Download Basic techniques and sequences of MRI

Contents
Letter from the President
(J. Tamraz, Lebanon)
Faculty and Program of the IVth PANRS Congress and Categorical course
Letter from the Honorary President
(M. Al Thagafi, S. Arabia)
A short history of neuroradiology in Lebanon
(J. Tamraz, Lebanon)
Opening Lecture: Neuroradiology: from ethics to nanotechnologies
(L. Picard, France)
Introduction to morphofunctional imaging of the brain
(J. Tamraz, Lebanon)
Part 1: FUNDAMENTALS OF MRI, MRS, F-MRI, SPECT & PET
Basic principles of MRI and F-MRI in neurosciences
(M.F. Secca, Portugal)
Basic principles of MR Spectroscopy in neurosciences
(B. Soussi, Sweden)
Basic principles of Nuclear medicine in neurosciences
(J.L. Stievenart, France)
Part 2: INTERVENTIONAL NEUROANGIOGRAPHY
Interventional neuroradiology: what about future ?
(L. Picard, France)
Middle cerebral artery aneurysm’s. 187 cases
(L. Picard, France)
Spontaneous dissections of cervical and intracranial arteries
(S. Bracard, France)
Endovascular treatments of ischemic stroke
(S. Bracard, France)
Part 3: DIAGNOSTIC NEURORADIOLOGY
Résultats de l’utilisation du scanner multibarrettes en neuroradiologie
Infectious diseases of the central nervous system
(C. Marsault, France)
(J. Ruscalleda, Spain)
CT and MR of neurocritic Patient: diagnostic and prognostic value (J. Ruscalleda, Spain)
Spinal cord tumors
(D. Balériaux, Belgium)
1
Preface
Twenty five years have slipped by since first MR essays performed in vivo. The efficiency of MRI
lies in many specific characteristics inherent to this method as its multiplanar ability to explore the patient
without moving his body in the three planes, and in fact in any oblique orientation, or to bring out almost
all the intracranial and spinal anatomical structures such as the leptomeningeal spaces, the CSF, the white
and grey matter, the cranial and spinal verves and the vessels spontaneously visualized even without
administration of any paramagnetic contrast media. The absence of beam hardening artifacts from bony
structures as those generated in the posterior fossa or at the skull base vicinity, favors the explorations of
tumoral processes developing in the orbitofacial region or in the base of the skull. The absence of ionizing
radiation makes MRI the modality of choice for follow-up exams, which is of crucial importance in the
pediatric field.
MRI is a multiparametric technique that largely depends upon the operator skill. It is also a
complicated and highly evolutive imaging method. The choice of the appropriate pulse sequences is
largely tributary of knowledge of the patient's clinical history, which contribute consistently to the final
positive diagnosis. 3D reformations and volume renderings are powerful complimentary procedures
available that add much to the preoperative planning of brain tumors. MR angiography is replacing to a
large extent diagnostic conventional angiography.
The need for contrast administration such as the paramagnetic Gadolinium chelates contrast
media, is relatively limited as compared to the wide use of iodine solutions with CT. Contrast infusion is
usually restricted to infectious or inflammatory diseases, intraaxial and more particularly extraaxial
tumoral conditions, base of skull lesions and most of the intraspinal and cord lesions.
Sophisticated techniques are presently used in a routine clinical basis: MR angiography without
the need to invariably inject any contrast agent IV, evaluation of CSF flow circulation, without intrathecal
injection of a contrast media, perfusion-diffusion imaging, ultra-fast imaging using Echo Planar Imaging,
functional imaging, and in vivo MR spectroscopy. These recently implemented techniques on most
available systems permit to obtain perfusion measurements using MRI, and identification of an infarct
within the first few minutes following the clinical onset. MRI is the sole method available for direct study
of the spinal cord. It is the technique of choice to perform to rule out non invasively spinal cord
compression.
The search for an optimal cost/efficiency ratio requires first the prescription of the most
informative exam. MRI stands as the modality of choice in many of such clinical conditions because it
provides most of diagnostic necessities in the neuroimaging field. However, CT scanner remains useful in
patients presenting absolute contraindications to MR exams (patients with pacemaker, vascular clips,
neurostimulator, ferromagnetic devices etc...), or in cranial traumatology during the acute phase, or in case
of suspicion of a subarachnoid hemorrhage in the first 48 hours. A combined approach may be needed for
the evaluation of osseous abnormalities or the detection of minute calcifications.Conventional radiography
of the skull or spine remain often useful and complementary of the MR exploration. Diagnostic
angiography, remains the gold standard procedure for imaging of the vascular system, and MR
angiography may be proposed as the primary screening method in conjunction with ultrasonography for
the evaluation of extracranial and intracranial vascular systems. They are highly powerful non-invasive
methods expanding in the routine practice.
MRI and MRA, MRS and f.MRI, may presently be considered as widely recognized diagnostic tools that
have to be performed whenever possible even prior to CT, in any clinical circumstances necessitating to
achieve an anatomical or a functional exploration of the head or spine.
2
A short history of neuroradiology in Lebanon (*)
Jean Tamraz, MD, DSc,
Professor and Chairman, Department of Imaging,
CHU Hôtel-Dieu de France, Université Saint-Joseph,
POB : 16 6830, Beirut, Lebanon
Soon after the discovery of X-Rays by Roentgen (1895), the first chest X-ray was performed in
thirty minutes using rudimentary equipment, in the French School of Medicine in Beirut, under the
leadership of the French Maurice Collangettes S.J., chairman of physics (from 1900 to 1925).
At the same period of time, at the American University School of Medicine, were installed X-Ray
systems (in 1900 and 1902), under the chairmanship of Arthur Bacon MD, who performed the very first
X-ray of a chest, assisted by Nader Kaddoura MD (1907) and Toufic Hajjar MD (1910). From that time
and until 1937, Professor Edward St-John Ward took in charge the radiology department, followed by
Professor Kingsley Blake (1931-1934) then Albert Oppenheimer (1934-1934) with his assistants, William
Shehadé MD and Georges Saleeby MD who became the head for two years.
The French School of radiology has undergone a major development in the year 1925 with the
creation of the “Institut de Radiology et de Lutte contre le Cancer” inaugurated by Professor Regaud from
the “Institut du Radium” of Paris. Doctor Lemarche was the first director, followed by Professor Chaumet
(1934) who started giving courses in radiology and radiotherapy, and then by François Dupré La Tour S.J.
(1941) and Professor Joseph Jalet (1943). From 1946 to 1975 the Institute was directed by Professor Paul
Ponthus assisted by Afif Berbir MD and Fouad Boustany MD.
During the second half of the XXth century, general radiology developed under the leadership of
several radiologists: Fouad Boustany MD, Fathi Homsy MD, Zahi Hakim MD, Jean Haddad MD, Joseph
Haddad MD, and Riad Ghorra MD, from the French school, and Rafic Melhem MD, Philippe Issa MD,
Naim Atallah MD, and Ghassan Rizk MD at the American University hospital. Georges Comair MD,
trained at the Hôpital d’Instruction des Armées du Val de Grâce, in Paris, returned to Beirut and
established a radiology department at the military hospital.
Neuroradiology emerged and individualised in the fifties thanks to the interest of neurologists and
neurosurgeons. Early in the fifties, Fouad Sabra, Head of Neurology at the American University Hospital
(AUH) performed the first pneumoencephalography and myelography with lipiodol (1951).Vertebral and
carotid angiography by direct puncture were first performed respectively by Professor Fuad S Haddad,
head of Neurosurgery at the AUH (1955) and by Professor Joseph Hajjar, neurologist (1957), followed
immediately by Professor Sami Tohmé, Head of Neurology, at Hôtel-Dieu de France (HDF) University
hospital, who performed also pneumoencephalography, angiography and myelography and developed
EEG (1959). Ventriculography was initiated in 1962 by Professor Gedeon Mohasseb, Head of
Neurosurgery and neuroangiography performed by Professor Raymond Chemaly, at HDF, until the
installation of a seriograph for global or selective catheterisation using Seldinger procedures developped
by Professor Pierre Zalzal, neurologist at HDF who devoted part of its time to neuroradiology and
particularly angiography and air myelography until 1983. In the same period of time (1968) Professor
Naim Atallah, Head of Neuroradiology, was performing all neuroradiological invasive techniques at the
American University Hospital of Beirut.
With the advent of CT and MR, modern neuroradiology expanded. The first CT scanner (CGR
ND 8000) dedicated to head explorations was installed at Hôtel-Dieu de France in 1980 by Professor Sami
Tohmé, Head of Neurology department, who performed brain exams, long before the acquisition of a total
3
body scanner (CGR CE 12000) in the Radiology department under the chairmanship of Professor Fouad
Boustany. Then came the MR era mostly devoted to neuroimaging and which tended rapidly to replace
most neuroradiological exams. Three systems were purchased and installed in the country in 1991-1992,
two mid-fields (0.5 T) and one high field (Signa 1.5 T) installed at Hôtel-Dieu de France and running
under the direction of Professor Jean Tamraz, neuroradiologist and neurologist, Head of MR and
Neuroimaging department since 1992 and Chairman of the department Imaging and Neuroradiology since
2001. The country is at present very highly equipped: 15 mid and 10 high field MR systems, 60 CT
scanners, 4 multisclice CT, 22 angiography units, 15 nuclear medicine scanners, 8 centers for linear
accelerators, a PET scanner, an EBT scanner and a PET-CT scanner.
(*) from “A History of Neuroradiology (1895-2002), E.A. Cabanis and MT Iba-Zizen Editors,
Paris, 2002, pages 353-354, modified (published during the XVIIth symposium Neuroradiologicum, Luc
Picard, President, Paris, France, August 18-24, 2002).
P.S.: The invaluable historical data have been collected from Fouad Boustany, Honorary
Professor and Chairman of Radiology and Raymond Chemaly, Honorary Professor and Chairman of
Neurology, at Hôtel-Dieu de France, Université Saint-Joseph, Beirut, Lebanon.
4
Letter from the Past President and PANRS bylaws
Mohammed A. AL Thagafi, MD
Founder & Past President of the PANRS
Director of the Radiology Department
Armed Forces Hospital,
Riyadh, Saudi Arabia
It gives me great pleasure to write this introductory letter for the Pan Arab Neurological Society
(PANRS).
The concept of formulating this society started in May 1993 after the World Federation of
Neuroradiological Societies had taken a decision to encourage the establishment of regional
Neuro-radiological societies throughout the world, with the aim of improving this important sub
speciality.
Dr. Hassan Sharif was the representative at the founding committee of the World Federation and
attended the meeting in Vancouver. Under the guidance of the late Derek Harwood Nash, who
was then the Acting Secretary General WFNRS. The idea of the Pan Arab Neuroradiological
Society was born.
The Pan Arab Neuro-radiological society was established in 1994 at its founding meeting,
which took place in Beirut, Lebanon. Attempts were made to include all Arab representatives
but unfortunately, this proved to be logistically impossible. However, it was the President of the
Pan Arab Neurology Society, Dr. Khalaf Al Moutaery, Dr. R. Rizk, the President of the
Lebanese Radiology Society and Dr. Ashraf Kurdi, President of the Pan Arab Neurology
Society. Their attendance was to witness the birth of the society on behalf of the WFNS.
A second and equally important reason for establishing a regional Pan Arab Society was that it
was felt that the time had come to start putting together efforts to form serious scientific
societies, arrange symposiums and education, with the aim of improving the practice of
neuroradiology with this region.
As the society is still in its early stages, it is our intention to encourage the new generation of
neuro-radiologists to join and take advantage of what we, as a society, can offer. Our future is
reliant upon the support from each other so that we can ensure the best possible standards of
Neuroradiological practice and facilities are maintained.
Since the establishment of the PANRS, we have had the opportunity to organise two Pan Arab
African Society Symposiums. The first was in Cairo in 1996 for two days where both national
and international speakers presented lectures on a wide range of interesting topics.
The second meeting will take place in Tunisia where once again a national and international
faculty will be speaking about experiences within their field.
During the meeting, there will be an Executive Committee Board Meeting where we shall be
discussing both the future of the society and ways of improving it.
I hope to see you all in Tunisia and other eminent scientific meetings.
5
PAN ARAB NEURORADIOLOGY SOCIETY
(PANRS)
Constitution & By-Laws
ARTICLE I
NAME
The Pan Arab Neuroradiology Society (hereinafter called the Society) shall be composed of
Neuroradiological Societies. Colleges, Academies and Kindred Neuroscience Associations Throughout
the Arab World. The Society shall be based in (…) and shall have branches in other countries of tne Arab
World.
ARTICLE II
PURPOSE
1 – Objectives:
The purpose of the Society shall be the advancement of Neuroradiology in all its aspects and to
represent Neuroradiology in the Arab World on matters of common interest by:
a-
The establishment and maintenance of cooperation between Neuroradiological organizations in
the Arab World.
b-
The direction and enhancement of the prominent and effective position of Neuroradiology
within radiology and the neurosciences.
c-
The exchange and dissemination of knowledge ideas and recognized terminology in the field of
Neuroradiology.
d-
The development of the best possible standards of Neuroradiological facilities and practice.
e-
The recommendation and encouragement of Pan-Arab accepted standards of education, training
and research in Neuroradiology and its allied sciences.
f-
The support of scientific Symposia and annual scientific meetings of member Neuroradiological
sciences.
2 – Scientific Meeting of PANRS
A major activity that should evolve and progress shall be the holding of a timely and recurring
“Scientific Meeting”. This should represent the scientific arm of the Society and should involve all
members and allied neuroscience organizations and should be upholding the highest scientific ideas.
6
Whenever beneficial and advantageous, the Society should collaborate with established regional
and international neuroscience groups in order to achieve its objectives.
3 – Other Activities
The Society shall pursue and will achieve its objectives through the following activities:
a-
Promotion of scientific research and exchange of ideas in its fields and related topics and
publish distribute and exchange such results with relevant Societies.
b-
Holding regular conferences, symposia and seminars in the field of Neuroradiology throughout
the Arab World.
c-
Publish regular bulletins or periodicals to keep readers members up to date with Society’s
programmes and progress of research activities.
d-
Organize scientific expeditions and to award prizes for meritorious work in open competition.
4 – Foundation of the Society
The initial establishment of the Society shall be by a Founding Committee whose members are
either leaders of established Neuroradiological societies or are recognized senior members of the
subspecialty in their respective Arab countries. The founding committee shall cease to exist immediately
the General Assembly holds its first meeting and a president and members of the Executive Committee
and other officers of the Society are elected.
ARTICLE III
MEMBERS AND MEMBERSHIP
The Society shall be composed of the following types of Member and Memberships:
A. Members:
Organizations of duly constituted Neuroradiological Societies from the Arab World as Members.
B. Affiliate Members:
Kindred Neuroscience Societies from the Arab World as affiliated member.
Application for membership will be submitted to the Executive Committee and shall contain:
1. A copy of the Constitution of the Society.
2. A list of the officers and members.
3. A report of the previous years Annual General Meeting of the Society and a description of the
Societies Scientific activities, journals, etc.
7
C. Active Membership:
To be given to persons who satisfy the conditions of membership and whoever holds a University
degree in the area of specialization of Society (Radiology, Neuroradiology). An active member should be
resident of the Arab world and must pay the regular fees.
D. Associate Membership:
Associate membership shall be offered to qualified persons who would like to join but do not
reside in the Arab world. Associates will be non-voting members.
E. Honorary Membership:
Shall be offered to persons who have contributed financially or otherwise towards the
development of the Society within and outside the Arab world. An honorary member shall be chosen by
the General Assembly of the Society on the recommendation of the Executive Committee. An honorary
member is exempted from payment of registration and subscription fees. An honorary member may attend
the General Assembly sessions, and other Committee meetings and take part in the discussions, but will
not be eligible to vote on decisions or in elections.
F. Conditions and Procedures for Membership
An individual member of the Society should fulfil the following conditions:
(a)
(b)
(c)
(d)
Must pay all dues of the Society.
Must submit an application to join the Society.
May be recommended by two active members of the Society.
Application for active membership should be submitted to the Executive Committee Membership
is granted only after the approval of the Executive Committee.
All applications when complete shall review by the Executive Committee and its
recommendations shall be submitted to the General Assembly for approval at its next meeting.
Election of Members
Organizations upon recommendation of the General Assembly, may be elected as members of the
Society by two-thirds (2/3) affirmative vote of the members of the General Assembly, present and voting.
The organization must be truly Arab in its continental arena, and should be primarily concerned with the
general aspects of Neuroradiology.
Executive Committee
The Executive Committee, which manages the affairs of the Society, will be composed of not
more than ----------- members chosen by the General Assembly in secret ballot and from among the active
members of the Society.
The Executive Committee shall draw up the general policy of the Society and submit it to the
General Assembly for approval. The Executive Committee shall also ensure that the functions of the
Society are carried out and its objectives are realized.
8
Membership of the Executive Committee shall be for two years, which will be renewable. The
Executive Committee shall hold an ordinary session at least once every two years. An extraordinary
session may be held when requested by half or more of the members or by one fifth of the General
Assembly or by the President of the General Assembly to discuss specific urgent matters (Define a
quorum? 1/3 of voting members).
A member who is absent for more than three sessions without an acceptable excuse will be
considered as having forfeited his membership.
Duties of the Executive Committee:
The Executive Committee shall issue rules and regulations necessary for the implementation of
this statute. Other responsibilities of the Executive Committee shall include drawing the annual budget.
Preparation of annual activities, future plans and fixes membership dues. The Executive Committee shall
submit the above activities for approval to the General Assembly during the regular session.
President and Vice-President of the Executive Committee:
The General Assembly shall elect by secret ballot a President of the Executive Committee from
the active members of the Society. The position shall be held for a period of two years, which will be
renewable. The President of the Executive Committee shall be the President of the Society. The President
has the right to suggest or choose names for the different committees of the Society.
Officers of the Society:
A.
B.
C.
D.
E.
F.
President
Vice-president
Secretary General
Treasurer
President of the scientific meeting
Historian
Officers of the Scientific Meeting:
A.
B.
C.
D.
President
Secretary
Treasurer
Members – at – Large (2)
General Qualifications of Officers:
All officers of the Societies and Scientific Meeting shall be active Neuroradiologists and full
members of one of the Members of the Society. Officers may or may not have been delegates to the
General Assembly.
Election of Officers. Terms and Duties:
All officers of the Societies and the Scientific Meeting shall be elected by an affirmative majority
vote of the members of the General Assembly present and voting during the Meeting. The President may
not be re-elected to this position.
9
Officers of the Societies :
1 - President
The President shall serve as the Chair of the Executive Committee and the General Assembly and
shall be an ex-officio member of all Committees of the Society. The President shall exercise the usual
authority and assume the responsibilities similar to that of the President of a scientific society. The
President may appoint Special (Ad Hoc) Committees and the President with approval of the General
Assembly shall be empowered to fill any vacancy which may arise in the offices of the Society, the
Scientific Meeting and their committees if not otherwise provided in these by-laws.
2 - Vice President
The Vice President, who shall also be the President-Elect, shall assume the duties of the President
if the President is absent or, for any reason, is unable to fulfil the duties of the office.
3 – Secretary General
The Secretary General shall be an ex-officio member of all committees of the Society. The
Secretary General shall assume the usual duties and responsibilities of a Secretary General of a scientific
society and those duties relating to the Society itself. The General Assembly and the Executive. The
Secretary General shall be responsible for the day-to-day activities of the Society.
4 – Treasurer
The Treasurer shall assume the duties and responsibilities common to this office and shall chair
the Finance Committee.
The Treasurer shall perform those duties typically related to dues and other monies received by
the Society and expend such funds of the Society in accordance with the policies and approval of the
Executive Committee and the General Assembly. The Treasurer shall provide the Executive Committee
with an operating statement of the Society and the Scientific Meeting and balance sheet at intervals of no
longer than twelve (12) months and then specifically at the meeting of the General Assembly during the
Scientific Meeting. The Treasurer shall supply to the Audit Committee copies of treasury records prior to
the Scientific Meeting.
7 –Historian
The Historian shall be elected by the General Assembly for the term of eight (8) years and may be
re-elected.
The Historian shall keep the archives of the Society and of the past, present and future Scientific
Meeting.
8 – All elected officers shall serve from the close of the Scientific Meeting at which they were
elected until the end of the next Scientific Meeting with the exception of the Historian. This term shall be
at least four (4) years.
10
Officers of the Scientific Meeting
All Scientific Meeting officers shall be active neuroradiologists and members of a
neuroradiological society of the country in which the Scientific Meeting is to be held. They shall be
nominated by the President of that Scientific Meeting and will be ratified by the Governing Council.
Scientific Meeting officers shall serve in office from the close of the Scientific Meeting at which
they were elected to the end of the Scientific Meeting for which they were elected to manage its affairs
until they are concluded and all financial matters sealed.
1 – President of the Scientific Meeting
The President of the Scientific Meeting shall be an ex-officio member of all committees of the
Scientific Meeting and shall be a member of the Executive Committee of the Society. The President of the
Scientific Meeting shall exercise the usual duties and responsibilities of a President of a scientific society
but shall confine his her attention to those matters related to the Scientific Meeting. The President of the
Scientific Meeting shall appoint all special (Ad Hoc) committees of the Scientific Meeting as are
necessary to carry out its functions, and will chair its Scientific Program Committee. The President of the
Scientific Meeting shall nominate the officers of the Scientific Meeting for ratification by the General
Assembly.
The President shall propose the site and date of the Scientific Meeting for ratification by the
Governing Council.
The President and Officers of the Scientific Meeting will be responsible for the high standard of
the scientific contents of the Scientific Meeting, its scope and duration, and shall respect the principles
customs and traditions of the past Scientific Meeting. The prime objective of the Scientific Meeting up to
the time of creation of these By-laws was the presentation and discussion of research.
2 – Secretary of the Scientific Meeting
The Secretary of the Scientific Meeting shall be an ex-officio member of all Scientific Meeting
Committees and a member of the Program Committee of the Scientific Meeting. The Secretary of the
Scientific Meeting shall exercise the usual duties and assume the responsibilities of a secretary of a
Scientific Society, which will confine attention to those matters related to the Scientific Meeting.
3 – Treasurer of the Scientific Meeting
The Treasurer of the Scientific Meeting shall assume the duties and responsibilities common to
this office and that of a Scientific Society and be responsible to the President of the Scientific Meeting and
the Executive Committee. The Treasurer shall accept all monies received by the Scientific Meeting,
handle them suitably and expend any of those funds of the Scientific Meeting in accordance with the
budget submitted to the Finance Committee of the Federation to whom the Treasurer is responsible and to
whom the Treasurer must provide a full financial report at the completion of the respective Scientific
Meeting.
4 – Members At-Large
One member at-large shall be the Chair of the local arrangements committee; the other Chair of
the Technical exhibits Committee. Both shall be members of the Scientific Program Committee.
11
The number and responsibilities of such officers may be altered when necessary to accommodate
local requirements according to geography or custom.
ARTICLE V
GENERAL ASSEMBLY
1 – Composition:
a.
b.
c.
d.
Officers of the Executive Committee
Delegates from Various Neuroradiological Societies from the Arab World
Delegates from Associated Kinder Neuroscience Societies
All Individuals Holding Membership of the Society
2 – Responsibilities
3 – Honorary President of the Society
The General Assembly shall comprise all active and eligible members who have paid or will pay
their annual subscription fees. It will hold an ordinary session, at a fixed date once every two (2) years.
The agenda of the meeting shall be prepared by the Executive Committee and invitations issued by the
President.
The General Assembly may hold an extraordinary session at the request of the Executive
Committee. Rules governing the ordinary session also apply to the extraordinary session meetings. The
General Assembly session meetings are valid only in the presence of the majority of its members.
The General Assembly has the following responsibilities:
A.
B.
C.
D.
E.
F.
To issue by-law regulations for the organization of work in the Society.
To approve the annual budget of the Society and the final financial statements every year.
To approve the annual report of the Society activities prepared by the Executive Committee.
To elect the President and members of the Executive Committee.
To approve the annual plan presented by the Executive Committee.
To discuss the items on the agenda and other matters that need to be studied by the members, within the
sphere of the Society activities and to take necessary actions; and to choose an honorary President to the
Society upon the suggestion of the Executive Committee.
Honorary President of the Society
The General Assembly appoints the honorary President of the Society upon the proposal of the
Executive Committee. The Honorary President is to be a known public figure whose interests are related
to the activities of the Society. The honorary President shall preside over meetings of the Society that he
attends.
The Society’s Financial Resources and Budget:
The Society’s Financial Resources include:
12
1. Registration and annual subscription of the members.
2. Proceeds from the sale of the Society’s publications and printouts.
3. Dues from any workshops or training programmes held by the Society, and other institutions
established to serve the purpose of the Society.
4. Gifts, grants, voluntary contributions and other financial support given to the Society by the
Government or the public or private institutions or individuals and which the Executive Committee
accepts.
The Executive Committee shall nominate from its members a Treasurer who will keep the
society’s accounts and prepare the budget. The budget will be reviewed by the Executive Committee and
ultimately be submitted to the General Assembly for approval.
The financial year of the Society shall begin on the first of November and end on the last day of
October of the year after.
An Auditor shall be appointed to audit the Society accounts at the end of each financial year. The
Auditor’s report shall be submitted to the Executive Committee and the General Assembly of the Society.
The Executive Committee may review and amend the responsibilities of the President, the Vice
President, the Treasurer and the Secretary when the need arises.
13
Chapter II – M.F. Secca
Basic Principles of MRI and F-MRI in Neurosciences
Mario Forjaz Secca, PhD
Professor de Biofisica, Departemento de Fisica
Faculdade de Ciencias e Tecnologia, Universidade Nova de Lisboa,
Lisbon, Portugal
Contents
Introduction
Basic principles of MR
The nucleus and the spin
The central equation in MRI
Faraday's Law
Spatial encoding
Proton density
Basic techniques and sequences of MRI
RF Pulses
FID
Spin Echo
Repetition Time
T1 Imaging
Gradient Echo
Echo Planar Imaging
Inversion Recovery
STIR (Short TI Inversion Recovery)
FLAIR
MR Angiography
Magnetization transfer
Contrast agents (Gadolinium)
Contrast Enhanced MRA
Functional Imaging: principles and techniques
Diffusion
Perfusion
Sequence comparison table
Image parameters and contrast
Signal to Noise ratio
Contrast
Spatial resolution
Image artifacts
Motion and Ghosting
Respiratory artifact
Magnetic Susceptibility
Partial voluming
Wrap around
Chemical shift
Bibliography
14
Introduction
Nuclear Magnetic Resonance (NMR) was originally a field of Physics, which overflowed into Chemistry,
Biochemistry and Medicine. Several Nobel prizes have been won in this field. In the prehistory of NMR
Isidor Rabi won the prize in Physics in 1944, because of his work on a resonance method for the
registration of the magnetic properties of atomic nuclei. In 1952, Felix Bloch and Edward Purcell won the
prize in Physics for the discovery of nuclear magnetic resonance in solids. Then, in 1991, Richard Ernst
won the prize in Chemistry for his contributions to the development of the methodology of high resolution
nuclear magnetic resonance spectroscopy; and in 2002, Kurt Wüthrich won the prize, also in Chemistry,
for his development of nuclear magnetic resonance spectroscopy for determination of the threedimensional structure of biological macromolecules in solution. Finally, in 2003, Paul Lauterbur and
Peter Mansfield won the only Nobel missing for NMR: the prize in Physiology or Medicine. The prize
was awarded for having made seminal discoveries concerning the use of magnetic resonance to visualize
different structures, leading to the development of modern magnetic resonance imaging, MRI, which
represents a breakthrough in medical diagnostics and research. The award came more than twenty years
after the original work was performed, but it recognized the extreme importance that MRI has had in the
field of Medicine.
One of the questions a physicist working in MRI is constantly asked by medical doctors is: What is
Nuclear Magnetic Resonance Imaging and how does it work? The physicist normally answers rhetorically:
How much Physics do you know? Or, how far are you prepared to go? Like everything else in life MRI
can be explained at different levels, advancing more and more as the physical knowledge progresses; a bit
like peeling an onion.
Starting from the outer layer we could explain how Magnetic Resonance Imaging works in a few lines, as
follows.
The body is made up of atoms, a large proportion of which is Hydrogen. The nuclei of Hydrogen, which
have only one proton, because they are charged and spin about themselves, behave like little magnets.
These little magnets, when placed in a magnetic field align with it and rotate around the axis of the field in
a movement called precession, similar to spinning tops on a table. This precession, or turning, movement
is faster the higher the magnetic field. If electromagnetic radiation, like radio waves, at exactly the same
frequency of the precessing nuclei is emitted near them they can absorb this radiation, which is said to be
at resonance, and they flip, becoming aligned in the opposite direction of the field. When the radiation is
switched off the nuclei get rid of the energy they absorbed by emitting back the radiation. Each tissue of
the body, because of its different chemical composition and physical state, re-emits radiation at a different
rate, known as the tissue relaxation time. This radiation is picked up by an antenna, transforming it into
electrical current, which is then used to construct the image we want. Because nuclei are used in a
magnetic field and absorb radiation at resonance the method is called Nuclear Magnetic Resonance
Imaging. However because of the bad connotations of the word "nuclear" it has been dropped from the
name and the method is usually know as Magnetic Resonance Imaging.
It is not the intention of this book to go too deeply into the Physics of MRI, so, to go to next layer, we will
keep things simple and show only the essential and easily understood equations.
15
Basic principles of MRI
The nucleus and the spin
All matter is composed of molecules, which in turn are composed of atoms. These atoms are constituted of
a positively charged nucleus, made up of protons and neutrons, surrounded by negatively charged
electrons. In the case of hydrogen the nucleus has only one proton and is surrounded by only one electron.
The nucleus rotates upon itself, it has spin. And because it is charged it produces a small magnetic field,
behaving like a tiny magnet. This produces what is called in Physics a nuclear magnetic moment.
The magnetic field
The magnetic field is a disturbance in space produced either by a permanent magnet or by the passage of
current through a loop of wire. It is a field of attractive or repulsive forces generated by moving or
spinning electric charges and can be described as a set of imaginary lines that indicate the direction a
compass needle would point at a particular position in space. Magnet fields strengths are measured in
either Tesla or Gauss, where 1 T equals 10,000 Gauss. In the case of MRI most magnets are made up of
loops of superconducting wire, which, because of their virtual zero electrical resistance at low
temperature, can withstand very high currents in very thin cross-sections, without dissipation of energy,
thus allowing very high fields in compact volumes. The main MRI field is commonly designated by B0.
The central equation in MRI
When a nuclear spin is placed in a magnetic field it tends to align itself with the main field. But, as in the
case of a spinning top, it doesn't align completely, forming an angle with the field and rotating about the
axis of the main field. This particular rotation is called precession and the angular frequency of precession
is called the Larmor frequency and designated 0.
If there is only one equation one should remember from Magnetic Resonance it has to be the Larmor
equation:
or
f0
0 = 2π f0
0
0
0/2π
This equation basically states that, for a particular nucleus, the higher the magnetic field the higher the
frequency of the precessing nucleus. And it is this dependence of the frequency on the magnetic field that
= 2.68108 rad/s/Tesla, and its precessing frequencies for the
more common magnetic fields are given in the following table.
Field
0.5 T
1.0 T
1.5 T
2.0 T
3.0 T
Frequency
21.3 MHz
42.6 MHz
63.9 MHz
85.2 MHz
127.8 MHz
These frequencies are in the range of VHF radio waves, from short wave to FM, hence they are referred to
as radio-frequencies. Another consequence of this equation is that for a 1 ppm (part per million) increase
in the magnetic field in a 1.5 T magnet the frequency will change from 42,600,000 Hz to 42,600,042.6 Hz.
It is changes like this that allow an image to be acquired as we will see later on.
It is possible to observe Nuclear Magnetic Resonance with many different isotopes, as is the case in the
human body, in decreasing order of abundance, with hydrogen, 1H, Fluor, 19Fl, Sodium, 23Na, and
Phosphor, 31P. However, because of its natural predominant abundance, Hydrogen is the nucleus of choice
for MRI. Each isotope has a different
For example, for a field of 1.5 T the Larmor frequencies of the previous nuclei are shown in the following
table.
16
Nucleus
1
H
19
Fl
23
Na
31
P
Frequency
63.9 MHz
60.1 MHz
16.9 MHz
25.9 MHz
The alignment of spins
In practice the nuclear spins do not all align with the magnetic field because of the thermal energy
associated with temperature. In the simplest case of Hydrogen, with only two spin quantum states, the
laws of physics state that there are only two possibilities for the spins: either aligned, in the direction of
the field, or anti-aligned, in the opposite direction. Because the anti-aligned spins have an energy slightly
superior to the energy of the aligned spins and this energy difference is of the order of the thermal energy
for temperatures around body temperature, the spins are almost evenly distributed among the two energy
levels. However, there is a slight difference, and it is this difference that allows us to obtain an image from
the body. For example, for a field of 1.5 T the spin excess, the difference between the aligned and the antialigned spins, at a temperature of 37˚ C (98˚ F), is only of the order of 5 ppm. And it is this fraction that
contributes to the signal. Fortunately, because of the very large number of nuclei, there are still enough
spins to obtain a signal. As an example, there are around 71019 hydrogen nuclei in a volume of 111
mm3 of water, and a fraction of 5 ppm still yields a spin excess of 31014.
The net magnetization
The net magnetization is then the sum of the magnetic moments of all the spins. In equilibrium it will be
pointing in the direction of the magnetic field. It is this net magnetization that will produce the MR signal
and to simplify the approach to MRI we will concentrate on the behavior of this magnetization as a single
varying vector rather than the behavior of the individual spins. This is normally referred to as the classical
approach as opposed to the quantum mechanical approach where we look at the individual spins.
The relaxation times T1 and T2
Now, if the spins are left on their own nothing in particular happens, but if electromagnetic energy, of the
same magnitude as the difference in energy between the spin levels, is emitted near the spins in the form
of radiation, they will absorb that energy, disturbing their equilibrium. Once that electromagnetic radiation
is switched off the magnetization will return to equilibrium by re-emitting the energy absorbed. The return
to equilibrium is not instantaneous and it can be decomposed in two parts, one along the direction of the
main field and the other in the plane perpendicular to the main field. In equilibrium the magnetization has
only a longitudinal component in the direction of the field and no transverse components in the
perpendicular plane, but after the disturbance the longitudinal component is smaller in general and the
transverse component appears. As the disturbance is switched off these components return separately to
their equilibrium states, one returning back to the maximum net magnetization value and the other
returning to zero. They both vary exponentially: the longitudinal component increases exponentially with
a characteristic time known as T1 and the transverse component decreases exponentially with a
characteristic time known as T2. The longitudinal time T1 is known as the 'spin-lattice' relaxation time
because of its origin in the interactions of the spins with their surroundings. The transverse time T2 is
known as the 'spin-spin' relaxation time because of its origin in the interactions between the spins, which
cause a dephasing between them. The important point in imaging is that different tissues, because of their
different chemical constitutions and different physical states, will have different relaxation times. In other
words, T1 and T2 contain tissue information.
17
T2*
In practice the transverse component is affected by external field inhomogeneities which cause additional
dephasing and suppression of the signal and destroy tissue information. This means that, due to the faster
transverse relaxation, T2 should be replaced by a smaller relaxation time designated T2*. Fortunately T2
can be extracted by recourse to a method known as spin echo.
Faraday's Law
Now that we have covered the basic physical principles of Magnetic Resonance, we have to understand
the practical side of it (the engineering), that is, how to obtain a signal, and for that we have to understand
the Law of Faraday. It states that if one moves a magnetic field inside a coil winding in the direction of the
main axis of the coil an electric current is produced at the terminals of the winding. In equilibrium no
signal can be detected because the net magnetization is constant, but by placing a coil perpendicular to the
main field it is possible to monitor the disturbance as a varying transverse magnetization vector moving
inside the coil. This will produce an electrical current that will be taken as the MR signal.
Spatial encoding
To construct an image it is essential to be able to tell what part of the body the signal is coming from. This
is achieved by spatially encoding the signal. To understand spatial encoding we will start with a simple
image. Let us suppose that we have a choir where each singer sings only one note and the singers for each
octave are standing on the same line, with the lower octaves at the back and the higher octaves at the front;
also, within each line, the singer on the left sings the lower note and the one next to him on the right sings
the next semitone higher. If someone falls, and sings as he does, we can know exactly where it happened,
even without looking, because we have encoded the frequencies. If the intensity of the singing is related to
the speed at which the singer stands up again, just by listening to the sounds we have a way of telling what
is happening to the choir.
In imaging this encoding is achieved in practice by making use of magnetic field gradients and taking into
account the Larmor equation. The gradients will produce a variation of the magnetic field along a
particular direction of space, which will cause a variation of frequencies in that direction. Thus each point
in space will produce a signal with a characteristic frequency which will enable the computer to separate
the different points in space and reconstruct the image. For practical reasons the gradients in the different
directions are not all switched on at the same time, but they are pulsed as the measuring sequence
proceeds. The gradients applied in the three main axis are called the slice selection (SS) gradient, the
frequency encoding (FE) gradient and the phase encoding (PE) gradient.
To make the image acquisition technically possible the signal is acquired line by line until a full slice is
obtained, going on then for the next slice.
Proton density
As the image is reconstructed it is divided in small equal volumes where all the spins inside each of them
contribute to only one signal value. This means that within each of these volume elements (voxels) the
signal assigned to it is an average of the signals of all the individual spins inside it. Each of these voxels
will have a different quantity of spins inside it because of the different tissues it encompasses. The
consequence of this is that different voxels will have initially different signals as a result of the particular
concentration of spins, or protons of hydrogen, hence the designation proton density, which reflects the
number of protons contributing to the signal that exist within a voxel.
18
Basic techniques and sequences of MRI
RF Pulses
In practice the emission of RF frequency radiation is achieved in the form of a temporary variation of a
magnetic field perpendicular to the main field. This field rotates at the resonant frequency and causes the
net magnetization to rotate about it, thus disturbing it from its equilibrium state. This burst of
radiofrequency energy is called an RF pulse. The longer the RF pulse is switched on the more the
magnetization will rotate about it. In this way, by adjusting the pulse time width or intensity, it is possible
to achieve a rotation of 90˚, 180˚ or any other angle desired. In MRI a group of RF pulses used to produce
a specific type of signal is called a pulse sequence.
FID
The Free Induction Decay (F.I.D.) is the simplest signal obtained from a Magnetic Resonance sequence.
By applying a 90˚ pulse the magnetization is rotated from the axis of the main field to a plane
perpendicular to it. Because it continues to rotate around the main field in the plane perpendicular to B 0, it
induces a current in the detecting coil and as the magnetization relaxes back to equilibrium, the signal
decreases exponentially. This decay however is dominated by T2*, and not T2, dependant on the field
inhomogeneities, which makes the FID very short in general.
Spin Echo
There is a way of recovering the T2 information that is masked by T2* and that is done by using a
technique called Spin Echo. In this sequence a 180˚ pulse is applied some time (TE) after the original 90˚
pulse and some of the signal, originally lost after the FID, is recovered as a kind of echo that comes and
goes. The best way to understand this process is to look at the system from the individual spin perspective.
Right after the 90˚ pulse the spins, which are originally in phase, begin to dephase, some turn faster and
others turn slower due to the spatial variations in magnetic field, causing the net magnetization to
disappear quickly. However, when the 180˚ pulse is applied some time later the spins are reversed, that is
the faster ones which moved further away from the origin now have a longer way to go to reach back the
origin, while the slower ones which didn't move so far have a shorter way to reach back the origin.
Because this movement of coming into phase is a mirror image of the dephasing movement they all reach
the starting point at the same time and then restart to dephase. It is this temporary coming into phase that
is called the spin echo. The main characteristic of the spin echo is that it retains the physical information
about T2 and eliminates the influence of T2*, therefore an image based on the signal height of the echo is
said to be T2 weighted. If, however, TE is very short, T2 relaxation has no time to occur, so the signal
height will be proportional to proton density. This means that a spin echo with a short TE will be DP
weighted and with a longer TE will be T2 weighted. The spin echo sequence implies that for a DP
weighted sequence, the higher the DP the brighter the signal, and for a T2 weighted sequence, the longer
the T2 the brighter the signal. (Fig.1)
19
Fig. 1 - Two axial images acquired in the same plane: (a) DP weighted image with a TE = 20 msec. (b)
T2 weighted image with a TE = 90 msec.
Repetition Time
The repetition time (TR) of a sequence is the time between repetitions of the basic sequence of the
imaging sequence. The sequence can be repeated for instance if it is necessary to improve the signal to
noise.
The repetition time is also the time taken to obtain each phase line measurement within a single slice,
therefore the time required to produce an image is determined by the product of TR by the number of
phase encoding steps. The TR can affect image contrast, making it one of the image parameters.
T1 Imaging
To obtain a T1 weighted image the spin echo sequence is repeated but with a short TR. This means that
the net magnetizations of the tissues with short T1's will have time to recover to equilibrium but the
magnetizations of the tissues with long T1's will have no time to recover. In this way tissues with shorter
T1 will show brighter signals than the tissues with longer T1's. By varying the value of TR the contrast
between the tissues with different values of T1 can be adjusted. (Fig. 2)
20
Fig. 2 - A spin echo T1 weighted axial image with a TR = 400 msec.
Gradient Echo
The spin echo sequence requires that the net magnetization recovers to its equilibrium position along the
direction of the main field before repeating the sequence, and for tissues with a long T1 this can greatly
increase the acquisition time. The incomplete recovery of the magnetization implies that there will be a
signal loss. The gradient echo method allows a much faster acquisition by a combination of two
techniques: a rotation of the magnetization less than 90˚ and a faster way of producing an echo. The
purpose of rotating the magnetization less than 90˚ can be seen in the following diagram (Fig. 3).
21
Z direction
F = 0Þ
E
E = 15Þ
D = 30Þ
D
C = 45Þ
C
B = 60Þ
B
E
D
C
B
A = 90Þ
XY direction
Fig. 3 - Variation of the XY and Z components of magnetization with flip angle.
Let us consider several rotations of the magnetization, known as the flip angle, as shown in the figure. For
a flip angle of 90˚ the magnetization only has components in the XY direction and no component in the Z
direction, taking its full time to recover (approximately five times T1). For a flip angle of 45˚ the
components in the XY and Z directions are equal, that is, about 71% of the net magnetization. For a flip
angle of 30˚, the component in the XY direction is 50%, but the Z component is 87% of the net
magnetization. For a flip angle of 15˚, the component in the XY direction is 25%, but the Z component is
97% of the net magnetization. As can be seen, the use of a small flip angle can produce a magnetization in
the XY direction which is sufficiently large to yield a detectable signal but reduce very little the
longitudinal magnetization, implying that it will recover to equilibrium more rapidly and allowing a much
shorter TR.
The faster way of producing an echo is achieved by the use of a special gradient rather than a sequence of
90˚-180˚ pulses. In this case a strong dephasing gradient, which will produce a dephasing faster than that
caused by the external field inhomogeneities, is applied for a short time. At some point the gradient is
reversed, causing the spins to rephase and go through a temporary echo a time TE after the original flip
angle pulse. In the gradient echo it is the reversing polarity of the readout gradient that produces the echo,
having no need for a 180˚ pulse. This allows the minimum TE to be reduced.
One of the problems with the gradient echo, as opposed to the spin echo, is that it does have T2* effects
from the external field inhomogeneities, manifesting themselves as a l oss of signal and geometric
distortion which becomes worse as TE increases. This problem is more pronounced in the vicinity of
interfaces with different magnetic susceptibilities, like air-tissue.
The increased sensitivity of gradient echo pulse sequences to susceptibility effects makes them the
methods of choice for perfusion imaging and brain functional imaging.
22
Echo Planar Imaging
Echo planar imaging (EPI) is a fast imaging technique that acquires an entire image within a single TR
period. To fully understand this technique it is important to understand the strange concept of k-space as
opposed to the image space.
Let us start with an example, if we look at a cylinder from the top we see a circle, but if we look at it from
the side we see a rectangle. One perspective shows us the roundedness of the cylinder while the other
shows us its squareness. The object we are looking at is the same but we are highlighting its different
properties by looking at it from different angles. And that is exactly what the image space and the k-space
do, they look at the MRI from different perspectives, but describe the same phenomena. Fortunately there
is a mathematical tool that allows us to convert from one perspective to the other and that is called the
Fourier transform. The image itself is in the image space and the k-space is equivalent to the space defined
by the frequency and phase encoding directions.
While conventional sequences acquire one line of k-space for each phase encoding step, which occurs
every TR seconds, EPI acquires all lines of k-space in a single TR period. This is achieved by cycling the
phase and frequency encoding directions so as to cover the k-space of the image. There are several
methods to obtain echo planar images, which include conventional EPI, spiral EPI and square-spiral EPI,
whose names refer to the way k-space is covered.
Because of the possibility of obtaining 15 to 30 images per second, depending on the acquisition matrix,
one of the important applications of echo planar imaging is in obtaining ultra-fast images allowing real
time acquisitions. There is, however, a price to pay for the extra speed and it is the image quality and
sharpness.
Inversion Recovery
By applying a 180˚ pulse at the beginning of a sequence it is possible to invert the alignment of the spins
from being aligned with the magnetic field to being anti-aligned. If the spins are then left to themselves
they return back to equilibrium which is the aligned position. As they do that the magnetization goes from
negative, through zero, to positive, that is, the magnetization recovers from inversion, hence the name
Inversion Recovery. Because different tissues have different longitudinal relaxation times (T1) their
magnetizations will go through zero at different times. If one starts a 90˚-180˚ spin echo sequence at
exactly the time the magnetization of a specific tissue is going through zero, then that tissue will produce
no signal. This time interval between the inversion pulse and the rest of the sequence is called the
inversion time or TI. The main reason for using inversion recovery sequences is either to increase T1
contrast or to eliminate the signal from a particular tissue.
STIR (Short TI Inversion Recovery)
One of the specific inversion recovery sequences is used to eliminate the signal from fat and is called
STIR (Short TI Inversion Recovery). This is achieved by using a short TI of around 150 to 180 msec,
which is the time the protons from fat take to reach zero magnetization after being inverted. The main
disadvantage of this sequence is the low signal to noise ratio because the magnetization of all the other
tissues is also close to zero.
FLAIR
The other common inversion recovery sequence is used to achieve heavy T2 weighting without signal
from the CSF. This sequence is called FLAIR (Fluid Attenuated Inversion Recovery).
The signal from the CSF can be attenuated using a TI around 2000 msec, which produces a heavy T2
weighting of the images without virtually any signal from the CSF. The main disadvantage of this
sequence is the necessity of very long TRs to allow the CSF to relax completely. (Fig. )
23
MR Angiography
MR angiography (MRA) is referred to as the ensemble of techniques that allows MR to image the flowing
fluids in the body. In the past angiography was only possible with the injection of contrast in the blood
vessels, but it would not distinguish between flowing and stationary blood. The methods of time-of-flight
and phase contrast MRA, however, are sensitive to the flow of blood.
Time-of-Flight Angiography
The Time-of-Flight (TOF) method makes use of the movement of blood through the imaging plane. For
instance, for the spin echo acquisition of a slice through which a blood vessel passes, a 90˚ pulse affects
the whole slice. However, when the 180˚ pulse is applied, the blood that has experienced the 90˚ pulse is
already out of the slice so it does not contribute to the signal leaving a signal void, as can be seen from the
figure. (Fig.4)
90Þ pulse
180Þ pulse
Flowing
blood
Flowing
blood
Imaging plane
Imaging plane
Fig. 4 - Movement of blood magnetization away from the imaging plane.
This can be used for angiography by applying a 90˚ pulse outside the imaging plane, so that only the blood
that flows into the plane within a time TE of the 90˚ pulse is prepared for the 180˚ pulse and will produce
an echo. The rest of the slice will produce no signal. (Fig. 5)
90Þ pulse
Flowing
blood
180Þ pulse
TE
Imaging plane
Flowing
blood
Imaging plane
Fig. 5 - Movement of blood magnetization into the imaging plane.
This method only works for flow into the plane and will not take into account flow in the plane.
Phase Contrast Angiography
24
The phase contrast (PC) method works on a different principle, making use of the dephasing produced on
the spins by a non-linear bipolar magnetic field gradient, that is, one which has two lobes, one positive and
one negative.
If the positive lobe comes first the bipolar gradient is said to be positive and if the negative lobe comes
first the gradient is negative. The positive lobe of the gradient will dephase the spins in one direction and
the negative lobe will dephase in the opposite direction. If the spins are stationary the total dephasing will
be zero, that is, the stationary spins will not be an affected. But if the spins have a velocity component in
the direction of the gradient, the dephasing of the different lobes of the gradient will not be compensated.
In PC angiography two imaging sequences are performed, the first one with a positive bipolar gradient
pulse and the second one with a negative bipolar gradient pulse. Then the raw data from the two is
subtracted. The signals of the stationary spins cancel and the moving spins have a net signal, producing an
image of the flowing spins.
To obtain the optimum signal, the spins of the fastest flowing blood should acquire 90˚ of phase after each
bipolar gradient pulse, or 180˚ in total. All the other spins with slower velocities will acquire smaller
phase shifts. Only those spins with a component in the direction the bipolar gradient will produce a signal.
.
With PC angiography it is possible to obtain quantitative measurements of velocities both for vascular
flow and for CSF flow, by means of adequate software, that will convert phase measurements into
velocity values. It is also possible, by measuring vessel areas, to obtain fluid flow rates. (Fig. 6)
Fig. 6 - (a) Axial oblique plane perpendicular to the Aqueduct showing the flow area measured. (b) Graph
of the average CSF flow through the cardiac cycle. (c) Summary table of the flow parameters calculated.
Magnetization transfer
The hydrogen nuclei in the body exist not only in water and fat but also in other macromolecules like
proteins. However these protons do not contribute to the MR signal because they have a very short T2
relaxation time, since they are tightly bound. They are in fact excited at the same time as the water
protons, but their signal decays in less than a millisecond. In MR a system that has a short T2 responds to
a very large range of frequencies and a system with a large T2 responds to a narrow range of frequencies.
This means that the protons bound to the macromolecules can respond to an RF pulse shifted, for instance,
1500 Hz, from the resonant frequency of the water protons, without affecting these. However, the protons
of water bound to these macromolecules will interact with them and will become partly saturated. In this
way the signal from highly proteinated tissues, like brain, liver and muscle, will become suppressed. (Fig.
7)
25
Water protons
Pres aturation
pulse
Protons bound to
macromolecules
1500 Hz shift
Fig. 7 - Diagram for the magnetization transfer process.
Magnetization transfer is used normally to improve the suppression of the signal from brain and muscle
when performing MRA TOF, but it can also be used to obtain information on the protein contents of some
tissues.
Contrast agents (Gadolinium)
Although MRI is a very powerful imaging technique not all pathologies are clearly contrasted using only
proton density or relaxation times weighting. For example, some meningiomas and small metastatic
lesions do not show on normal imaging. And considering that some of these intra-cranial lesions have an
abnormal vascular bed or a breakdown of the blood-brain barrier, a magnetic contrast agent that
distributes throughout the extracellular space became an obvious choice to improve image contrast.
Some purists believe that the fact that MRI is a non-invasive method is one of its strengths and should be
kept that way, but the clinical efficacy of the paramagnetic contrast is more than proven to amply justify
its use.
All the common contrast agents used in MRI are Gadolinium chelates, which are not directly imaged but
produce an effect, which is imaged. Gadolinium is the element of choice because of its high number of
seven unpaired electrons. Each unpaired electron has a magnetic moment 657 times bigger than that of a
proton, so seven unpaired electrons can induce relaxation a million times better than an isolated proton.
This implies that both T1 and T2 are reduced, although the enhancement caused by the shortening of T1 is
stronger than the signal loss caused by the shortening of T2; and that is why with Gadolinium contrast the
images obtained are normally T1 weighted. The actual amount of T1 shortening is dependent on the
concentration of Gadolinium injected and the signal enhancement depends also on TE and TR.
Contrast Enhanced MRA
One of the recent uses of MR contrast agents is in MR angiography. The injection of the contrast into the
blood reduces the T1 relaxation time in the blood vessels relative to surrounding tissues, therefore a rapid
volume imaging sequence with a short TR value will produce a large signal for blood and a very small
signal for the long T1 tissues surrounding the blood vessels.
This technique enables the acquisition of very good vessel images without recourse to the flow properties
of blood. It works in the same way as digital angiography but is not selective. One of the advantages is the
possibility of imaging vessels with awkward geometries and turbulent flow, which are difficult to obtain
using standard TOF or PC angiography. Because of the high quality of contrast enhanced MRA (CEMRA) images it is becoming the modality of choice in MR angiography. (Fig. 8)
26
Fig. 8 - A CE-MRA image showing the carotids all the way from the aorta.
Functional Imaging: principles and techniques
The term Functional Imaging in MRI is a very general term that covers any technique that gives functional
information rather than just anatomical information. That is, any technique that acquires time dependent
imaging data should be called functional imaging. Flow, perfusion, diffusion, tagging and brain activation
belong to this category. However, when functional magnetic resonance imaging (fMRI) is mentioned it is
normally referred to brain activation. In this section we are concentrating on this latter technique.
Brain activation can be studied either by direct methods, those that measure directly the electrical activity
of neurons, like EEG (electrical effect) and MEG (magnetic effect); or indirect methods, those that
measure the hemodynamic response to the neuronal electrical activity, like 15O PET (blood flow) and
fMRI (BOLD effect).
The indirect method used by fMRI can be understood by following the chain of physiological events that
describes it. When a set of neurons fire, there is a local increase in glucose consumption which in turn
produces an increase in oxygen consumption. This induces an increase in regional cerebral blood flow
(rCBF) and an increase in regional cerebral blood volume (rCBV) with a consequent increase in blood
velocity. In the blood there is a decrease in oxygen extraction fraction producing an increase in
oxyhemoglobin and a decrease in deoxyhemoglobin.
In this sequence of events the most common approach used in fMRI is the Blood Oxygen Level
Dependent (BOLD) contrast. The decrease in deoxyhemoglobin, because of its high paramagnetism,
produces a decrease in local microscopic field gradients, which in turn produces an increase in T2*. This
corresponds to an increase in signal, which is measured by the MR equipment. The ideal sequence to use
is a rapid sequence with T2* sensitivity, which detects changes in magnetic field, usually a Gradient Echo
EPI.
fMRI has its own limitations both in spatial resolution and temporal resolution. In terms of spatial
resolution, although for a standard image the voxel volume is, approximately, 3  3  5 mm3, it is
theoretically possible to go down to 0.5  0.5  1 mm3. The temporal resolution is limited by the
hemodynamic lag of 4 to 8 sec in the response to the neuronal electrical activity and the speed of the
scanner hardware, presently of the order of 10 frames per sec. To achieve optimal functional imaging it is
important to have the highest possible magnetic field, powerful and fast gradients and a powerful
computer with adequate software to manipulate the image.
27
The pulse sequence used will look for small variations in the signal of the T2* weighted image. Since
these variations are very small it is necessary to obtain a large number of images as the activation
paradigm is performed. The paradigms normally consist of blocks of 30 sec of rest followed by 30 sec of
activation. During rest no activity is maintained. During the activation period the task being studied is
performed. The activation can be motor, sensory, visual, auditory, language generation and others.
The images obtained directly from the system do not show any visible characteristic to the naked eye. It is
necessary to treat the images mathematically by comparing the variation of intensity of the pixels in a
certain image as a function of time with the variation that one would expected in the theoretical ideal case
of the particular activation paradigm, which corresponds to a square function. This comparison is done
statistically, pixel by pixel, and colour coded to indicate if they are more or less correlated with the
activation paradigm. The final images are then obtained by superimposing the statistically processed EPI
images on the anatomical images obtained for the same slices. It should be noted however that the images
obtained with the EPI sequence are very sensitive to changes in magnetic susceptibility and can be heavily
distorted. It is normally necessary to correct the EPI images by computer. It is important to stress that
there can be false positive signals, due in particular to blood vessels and eye movement. (Fig. 9)
Fig. 9 - A functional image showing the language premotor cortex activation for a phonetic language
generation paradigm.
There are several clinical applications for fMRI now being tried like tumor surgery planning, AVM’s,
epilepsy, addiction, schizophrenia and AIDS. Functional brain activation imaging with MR promises to be
clinically useful, but only with a more robust and complete image processing and being very careful with
the definition of the paradigm used and the verification of its implementation.
Diffusion
While MR angiography and flow measure the movement of spins from voxel to voxel, MR is capable of
measuring microscopic translational motion within each voxel. This motion can be the molecular diffusion
of water and the microcirculation of blood in the capillary network, referred to as perfusion. Diffusion is
the process by which molecules and other particles mix and migrate due to their random thermal motion.
Diffusion imaging is acquired in a similar way to phase contrast angiography, using a specific bipolar
gradient with very high strength and duration of the gradient lobes to detect the slow molecular diffusion
in the body. This bipolar gradient will cause a signal loss in the diffusing spins, which depends on the
28
diffusion coefficient and the b value. The b value is determined by the strength and duration of the
gradients and has units of s/mm2.
High b values can eliminate the T2 effect and improve the visualisation of the white matter fibres and can
be useful to differentiate sub-acute from chronic infarcts. (Fig…)
It is possible to obtain maps of diffusion in the three different orthogonal directions, or combine the three
images into a single map of overall diffusion.
With specific research software it is possible to calculate the diffusion tensor and deduce the actual
direction of the diffusion, and even obtain the direction of the neuronal axons. (Fig. 10)
Fig. 10 - Two images on the same location of a patient with infarcts. (a) A FLAIR image on the left and
(b) a diffusion image on the right.
Perfusion
Perfusion in MRI is the study of the net transport of magnetization into a volume of tissue, which refers to
the capillary blood flow to the tissue, measured in ml/min.g. This technique requires the use of a contrast
agent to distinguish the perfused from the unperfused tissue and it can be performed either with
endogenous or exogenous contrast agents.
The more common perfusion technique, known as Dynamic Susceptibility Contrast (DSC), is achieved by
injecting a bolus of contrast agent, like Gadolinium. A rapid EPI series of slices is acquiring through the
region of interest and then repeated at a rapid rate, of the order of one per second, as the contrast is
injected. This repetition is performed from just before the injection until about 30 seconds to a minute
after the arrival of the bolus. For most people best results are achieved with the use of a power injector,
which can produce a steady injection rate of between 3 and 5 ml/s, hard to achieve by hand.
After acquisition it is necessary to perform some quantitative analysis of the images to look for variations
in the arrival of the contrast agent between the pathological and normal regions. This is performed either
on the manufacturers workstations or with specific software. The blood flow to the brain tissue is known
as cerebral blood flow (CBF), but two other quantities are of interest in perfusion: the cerebral blood
volume (CBV) and the mean transit time (MTT). However, because these absolute quantities are difficult
to quantify, they are normally replaced by their relative values, indicated respectively by rCBF, rCBV and
rMTT, but it is normally preferable to compare the values from the ipsi-lateral and contra-lateral side. On
a first approach, the parameters measured directly from the concentration time curves, like the negative
enhancement integral, the bolus arrival time and the time to peak, and the peak height can be
29
approximately related to rCBV, rMTT and rCBF, however they are strongly dependent on the shape of the
bolus. The pixel by pixel analysis of the images for the required parameters is usually presented on a
colour coded scale, overlaid on an anatomical image, producing images similar to those of nuclear
medicine.
The other perfusion technique, known as Arterial Spin Labelling (ASL), uses the magnetic tagging of
protons in the arterial blood supply, thus avoiding the injection of an external contrast agent. This tagging
can be achieved by applying a saturation pulse to the feeding arteries, which prepares the blood before it
enters the slice of interest, and then acquiring an image of the slice. Following that, a second image
acquisition is obtained, but with a different tagging excitation. By subtracting the two images, signal
differences are obtained only in the regions where the tagged blood has reached. Because of the small
signal it is normally necessary to average over a large number of acquisitions. ASL has the disadvantage
of only producing CBF and not CBV or MTT, but it has the advantage of being sensitive to brain
activation.
Sequence comparison table
With the evolution of MRI many manufacturers started developing their own sequences, or their versions
of the standard sequences. Some of these sequences although slightly different and called different names
are practically equivalent. This diversity of nomenclature can introduce some chaos in the field when
dialoguing amongst different platforms, since it is important to know if the same sequences are being used
for a particular study. With this in mind we present a sequence comparison table where equivalent
sequences for four of the major manufacturers are presented on the same line.
Sequence comparison table.
Image parameters and contrast
Signal to Noise ratio
The main parameter to assess signal quality is the Signal to Noise Ratio, designated by SNR. This is
defined as the ratio of the average signal over the standard deviation of noise. The signal comes only from
the spins that were excited intentionally when selecting the slice, or volume, of interest and the noise
comes from many other sources, the main one being the patient. As mentioned above, only the spin excess
between the aligned and anti-aligned spins contribute to the signal, but all the other spins, as they jump up
and down from the two energy levels, can emit a random radio-frequency photon, which contributes to the
background noise. Obviously if the sensitive volume of the coil is large it will detect a large number of
these random transitions, producing a large noise. Therefore the smaller the coil the closer it will be to the
excited spins, producing a larger signal, and detecting fewer random transitions, consequently producing
less noise; that is, a smaller coil will have a higher SNR. For example, a head coil has a higher SNR than a
body coil, and a small surface coil placed close to the anatomy of interest will have an even higher SNR
than the head coil.
There are several factors affecting SNR, like voxel size, number of excitations and bandwidth. The voxel
size affects the signal and the other parameters affect the noise. The larger the voxel size the larger the
number of spins inside it, so the signal is directly proportional to the voxel size within a tissue of uniform
spin density. The SNR also depends on the number of excitations, but not in a linear way. In fact the SNR
is proportional to the square root of the NEX, for example, going from 1 to 4 NEX only improves the SNR
by a factor of 2. Another factor that influences the SNR if the receiver bandwidth, but here the dependence
is inverted, the SNR is inversely proportional to the square root of the bandwidth, that is, if the bandwidth
is increased by a factor of 4 the SNR is decreased by a factor of 2.
30
Contrast
Contrast is the relative difference between the signals of adjacent voxels and can be defined as the
difference of signal intensities divided by the average signal intensity in two adjacent regions. To
differentiate one tissue from another it is very important to increase the contrast between them.
The main factor determining the tissue contrast is the choice of sequence and its parameters, since for a
particular sequence each tissue will have a particular signal height. For example, to differentiate a tumor
from the surrounding tissue it is essential to choose a sequence that maximizes the contrast between the
tumor and the surroundings.
Once the image is acquired it is possible to improve the contrast by manipulating the image in the postprocessing stage, but this should be done very carefully because it can mask the original information
obtained.
Spatial resolution
The spatial resolution of an image is determined by the number and size of points composing it and it will
determine the smallest anatomical structure that can be resolved. It is inversely related to voxel size, the
higher the spatial resolution the smaller the voxel size. The two main factors determining spatial
resolution are the field of view (FOV) and the matrix size. If you diminish the FOV maintaining the same
matrix the voxel size goes down and if you maintain the FOV but increase the matrix the voxel size goes
down as well. We should bear in mind that if the matrix size is doubled, for instance from 256x256 to
512x512, the number of voxels goes up by a factor of four and their volumes go down by a factor of 4.
Therefore, as the resolution goes up the voxel size goes down and this implies that the SNR goes down as
well. As always in MRI there is a price to pay for a particular improvement.
Image artifacts
MRI has a multitude of factors that affect the appearance of the image and this makes it very interesting
and rich. However, one of the problems with this is that it is possible that a few of these factors will go out
of control producing an image that does not reflect the real state of the anatomy, in other words, the image
will have artifacts.
Although sometimes artifacts may destroy the quality of the image, with the possibility of making it
useless, some other times they can just be ignored, but the major danger of some of the artifacts is that
they can be confused with pathology, leading to misdiagnosis.
Therefore it is important to understand the aspects and the causes of the major artifacts and how to deal
with them. All manufacturers have a series of standard techniques to eliminate or compensate for the
major artifacts.
Motion and Ghosting
The most common cause of image artifacts is patient motion. Random motion will just produce a blurred
image and is avoided by asking the patient to be still or sedating in extreme cases.
However, not all movement can be controlled by the patient, for instance, the blood keeps on pulsating.
And any motion that occurs regularly in a repeating pattern will not cause a blurred image, but will
produce one or more 'ghosts' in the phase encoding (PE) direction. If the 'ghost' occurs inside the image it
can produce either a darker or brighter area in the surrounding tissue that can confused with pathology.
The way to avoid this artifact or at least reduce it is by using cardiac gating or a spatial presaturation pulse
on the side of the incoming blood. Sometimes, if it is unavoidable, changing the order of the phase
31
encoding and the frequency encoding gradients shifts the 'ghosting' to an area that is not important and
leaves the area of interest clear. (Fig. 11)
Fig. 11 - An image showing both a motion artifact on the left and right and a blood flow artifact running
from left to right.
Respiratory artifact
Another source of periodic motion is respiration, and this can also cause ghosting, but because it is the
whole chest and abdomen that moves the artifact appears above, below and throughout the body.
This artifact is avoided either by using respiratory gating, improving the quality of the image significantly
but doubling, or more, the acquisition time, or by using a method known as respiratory compensation,
which will clear the coherent 'ghosts' above and below the image but will produce a slight blur all across
it. (Fig. 12)
32
Fig. 12 - An image showing a respiratory artifact, from top to bottom.
Magnetic Susceptibility
To obtain good MRI images it is essential that the magnetic field is as homogeneous as possible, because
the spatial encoding is based on a precise distribution of the linear field gradients. Unfortunately there are
several things that can distort the magnetic field affecting adversely the quality of the image. The main
parameter affecting the homogeneity is the magnetic susceptibility, which says how much a substance will
be magnetized when placed in a magnetic field. This can be a problem not just due to the presence of
foreign objects within the body but also due to differences in magnetic susceptibilities of adjacent tissues.
If the magnetic susceptibility of the region being imaged is fairly homogeneous there will be no major
changes in the magnetic field. However, if the magnetic susceptibility of adjacent tissues differs much,
like the transition between air and tissues (lungs and sinuses), there will appear an artifact at the separating
edges.
Because of their high magnetic susceptibility, the presence of metallic objects (like dental implants, clips
and shunts) within the volume to be imaged will distort drastically the local magnetic field and it is
possible to have a total loss of signal in a particular region, surrounded by a strong distortion of the signal.
Partial voluming
Normally the width of the voxels, that determines the resolution in the imaging plane, is smaller than their
depth, except in the case of 3D volume acquisitions. This depth, called the slice thickness, is normally of
the order of 5 mm. If a group of voxels incorporates the edge of a structure there will be a blurring of the
image around these voxels because their volume averages the signal from different tissues. This process is
called partial volume. The way to diminish this problem is to reduce the slice thickness.
Wrap around
The phase encoding (PE) gradient produces a phase shift in the spins that varies between 180˚ and –180˚.
However if the field of view is too small there will be excited tissue outside the FOV, producing phase
shifts above 180˚ and below –180˚. Because the equipment cannot measure phases outside the 180˚ and –
180˚ range, values above 180˚ will be confused with those near the –180˚ and values below –180˚ will be
confused with those near the 180˚. As an example, some tissue outside the FOV assigned a phase shift of
190˚ will be confused, in the reconstruction, with the tissue inside the FOV assigned a phase shift of -170˚.
This will produce what is called a wrap around in the PE direction. In a sagittal slice of the head this can
cause the nose to appear on the back of the head. (Fig. 13)
33
Fig. 13 - An image showing a wrap around artifact, with the nose and mouth appearing at the back of the
head.
Chemical shift
The different chemical environment of the nuclei of hydrogen in water and fat produces a slightly
different magnetic field around them, that causes the protons in fat to resonate at a frequency lower than
the protons of water. This difference is 3.5 ppm, which at 1.5 T corresponds approximately to 224 Hz.
One consequence of this is the appearance of white and dark bands at fat/tissue boundaries, as is
exemplified in the figure below. (Fig. 14)
Fig. 14 - Diagram showing the original object and the image obtained due to chemical shift.
34
The image reconstruction computer assumes that a spin with a particular frequency comes from a
particular point in space. However, because the fat protons have a resonant frequency lower than that for
the water protons, along the frequency encoding gradient all their spins will be considered to come from a
slightly displaced position when compared with the water protons. This can have two effects. One is
producing a dark band, or signal void, in an area where the fat signal should be but no water exists. The
other is the appearance of a white band due to the existence of two different signals, from water and fat,
with exactly the same frequency which add up.
By exchanging the frequency and phase encoding gradient directions these artifacts can disappear from
some of the boundaries.
Note
All the images shown were obtained on a 1.5 T GE CVi system at Ressonancia Magnética de Caselas,
Lisbon, Portugal.
Bibliography
– “All You Really Need to Know About MRI Physics” Moriel NessAiver. Simply Physics, Baltimore,
1997.
– “Physics of MR Imaging. Magnetic Resonance Imaging Clinics of North America. Volume 7, Number.
4, November 1999” Ed. J. Paul Finn. W. B. Saunders, Philadelphia, 1999.
– “Magnetic Resonance Imaging. Physical Principles and Sequence Design” e. Mark Haacke, Robert W.
Brown, Michael R. Thompson, Ramesh Venkatesan. Wiley-Liss, New York, 1999.
– “MR Imaging Abbreviations, Definitions, and Descriptions; A Review” Mark A. Brown, Richard C.
Semelka. Radiology, 647, Dec. 1999.
– “Magnetic Resonance in Medicine. 4th Completely Revised Edition” Peter A. Rinck. Blackwell
Wissenschaft-Verlag, Berlin, 2001.
– “MRI From Picture to Proton” Donald W. McRobbie, Elizabeth A. Moore, Martin J. Graves, Martin R.
Prince. Cambridge University Press, Cambridge, 2003.
– “Quantitative MRI of the Brain. Measuring Changes Caused by Disease” Paul Tofts (Ed.). Wiley,
Chichester, 2003.
35
Chapter III – B. Soussi
Basic principles of MR Spectroscopy in Neurosciences
Bassam Soussi, MD, PhD
Professor and Director of NMR Research Lab & Bioenergetics Grp,
Wallenberg Laboratory, Sahlgrenska University Hospital Gothenburg Unviersity
SE-413 45 Göteborg, Sweeden
AIM OF CHAPTER
The aim of this chapter is to provide a comprehensive introduction to the new possibilities that Magnetic
Resonance Spectroscopy (MRS) offers in clinical neurosciences. Focus will be on what MRS can do
rather than what MRS is. For simplicity, basic physical and chemical principles will not be much explored
and are referred to elsewhere.
INTRODUCTION
For over half a century, interest in Nuclear Magnetic Resonance (NMR) has bee n continuously
increasing. From structural analysis in smaller organic molecules, to biochemical macromolecules, tissue
extracts, isolated intact organs and in vivo studies in animals and humans.
For almost two decades, in vivo MRS has been a revolutionary technique in biomedical research. Today,
it is a powerful tool in neurosciences giving noninvasive access to the chemistry of the human brain in
health and in disease.
Nuclei like 31P, 1H, 13C, 19F and 23Na have been studied in various organs. However, early applications of
in vivo MRS began with the measurements of 31P metabolites in isolated organs and surface regions like
skeletal muscles from intact animals.
Historically, 31P has been the most studied nucleus. However, MRS of the brain today relies mostly on 1H
examination due to its relative ease i.e. high natural abundance (99.9%) and sensitivity (100%). Numerous
studies have shown that MRS can detect pathophysiological changes in the brain tissue in a number of
diseases.Therfore, this chemically specific technique with its ability to examine the mechanisms of disease
is continuously gaining attention from clinicians.
In vivo MRS should be seen as complementary to the well established clinical MRI, providing quantitative
nondestructive analysis of the biochemistry of the brain cells without the use of radioactive tracers.
It is possible to integrate spectroscopy with conventional MRI equipment of 1.5T or higher magnetic
field by adding appropriate hardware and software available from MR manufacturers.
Theoretical background
MR theory is described elsewhere. For more detailed physical and chemical aspects of the technique see
references.
The basic principles for MRS are the same as for MRI. It is suitable however, to mention some aspects
that are related to spectroscopy. Briefly, and put in its simplest form:
36
The interaction between atomic nulclei (possessing a spin that gives a magnetic moment) and radio waves
when an external static magnetic field is applied gives rise to a electromagnetic signal.
The electromagnetic signal obtained after the application of a 90° radiofrequency pulse is called free
induction decay (FID).
At the same time, each nucleus is charecterized by the time constants T 1 (longitudinal relaxation) and T2
(transveral relaxation).
The decaying signal is the result of the relaxation of the nuclei from their excited state to their relaxed
state.
The FID is then converted to a spectrum by a Fourier transformation (mathematical algorithm).
stic of the
variation in resonance frequency. Its specific dependency on the chemical environment of a particular
nuclei makes it like a “finger print“ of the analyzed substance. Figure 1 shows the conversion of a FID to
a spectrum by Fourier transformation.
Localization
“Image guided spectroscopy“
Figure 2 (A, B) ilustrates the selection of a volume of interest (VOI) based on a topographical MR image
in order to acquire a proton MR spectrum.
The same strategy is used in the example in figure 3 to get a 31P MRS localization based on a
topographycal MRI.
Localization methods
Early localization methods started with surface coil localization which is based on RF pulses and the use
of surface coils for spatial localization.
A disadvantage of this procedure is surface tissue contamination of the spectra.
Multi-shots methods
ISIS
Image -selected in vivo spectroscopy (ISIS) uses a combination of 8 pulses. The VOI is pre-selected,
based on MRI scan and is repeatedly excited. The ISIS method has been applied to both 31P and 1H. One
advantage of this method is that it can be used without T 2 weighing. However, the eight phase cycles used
in localization might make shimming difficult.
Single-shot methods
Two methods are widely used and basically similar.
1) STEAM
Stimulated Echo Aquisition Mode (STEAM) uses a stimulated echo generated by three 90°pulses (90°90°-90°). It is mostly used in 1H spectroscopy. Signal loss due to motion sensitivity at long echo times is
a disadvantage. This method is suitable for short TE acquisitions.
37
2) PRESS
Point Resolved Spectroscopy (PRESS), involves a double spin echo scheme (90°-180°-180°) which
theoretically gives improved S/N. This method is most suitable to 1H spectroscopy where small volumes
and/or metabolites with long relaxation times T2 are of interest.
Chracteristic patterns seen in STEAM and PRESS spectra in patients with acute brain injury are shown in
fig 6.
Spectroscopic imaging
Spectroscopic imaging is the simultaneous acquisition of spectra from many volumes using phase
encoding. It is suitable for both 1H and 31P. This method offers the advantage of investigating many slices
simoulnateously. However, the S/N is lower the an in single-voxel techniques.
Water and lipid suppression
The 1H peak from brain water is dominant as well as the resonance from precranial lipids. Since most 1H
signals from brain metabolite are present at concentrations less than 10 mM, water and lipid suppression
techniques are essential in 1HMRS. Water suppression can be done using Gaussian chemical shift
selective pulses (CHESS). The water signal is pre-saturated by using frequency selective 90° pulses.
Outer volume selective pulses may be applied to pre-saturate the lipid resenance. However, by using
localization technique such as PRESS and STEAM lipid areas can be kept outside the VOI.
Sensitivity
The analytical limit is around 1 mM. MRS is thus not a very sensitive technique. However, many of the
100% naturally abundant 31P and 1H metabolites are present in cellular concentrations in the mM range.
In localized in vivo spectroscopy, theoretical minimum resolution is around 1 ml for 1H and 15 ml for 31P.
Generally, volumes for brain 1H MRS vary from 4 - 30 ml at 1.5T and typically used VOI is around 8 ml.
Resolution can be improved at longer aquisition times and with increasing magnetic field strength.
Several factors can influence the sensitivity during an MR examination. For example, the presence of
paramagnetic species, or the slow exchange between bound and unbound forms of molecules, can cause
signalbroadening.
Changes in viscosity, inhomogeneity of magnetic field and many exchamge processes could also affect the
line shape of a resonance.
However, despite this relative insensitivity, no other method can do today what MRS can.
Field strength
Most clinical MRS is performed at 1.5T to this date. Higher field strength permits better resolution of
overlapping peaks. Field strengths of 3 and 4 T for clinical research have been available for a few years.
Today, in vivo magnets of 9 T for experimental research are commercially available. A comparison
illustrating improvment in resolution with increased magnetic field strength is shown in figure 4 (a, b).
Spectral quantitation
For calculation of in vivo metabolite concentrations it is important to apply quantitaion methods using
38
internal and/or external standards.
Absolute quantitation is possible but remains difficult. Relative concentrations and areas of peak ratios are
also useful and widely used.
Problems associated with spectral quantitation
Common technical problems encountered arise from:
motion artifacts
magnetic susceptibility effects
partial volume effects
Motion artifacts may arise from breathing or any other movement. Susceptibilty effects may arise from
the variety of adjacent tissue to the VOI complicating shimming and affecting field homogeneity.
Partial volume effects are caused by the region surrounding the VOI affecting adequate metabolite
quantitation. This is particularily problematic when large volumes (> 8 ml) are selected. Smaller VOI can
can chosen at the cost of lower signal/noise ratio. Higher magnetic field might solve this problem.
Additionally, general factors like lower field strength, poor shimming and the low concentration of a
particular metabolite may complicate calculation of peak areas due to, non-Lorentzian lineshapes, base
line distortions and resonance overlap.
Metabolic information
1. 31P MRS
A representative 31PMRS spectrum of the human brain at 1.5T is shown in figure 5a. where peaks of major
metabolites observed are assigned.
-ATP, and of PCr and Pi can be clearly identified. Phosphomonoesters such as
phosphocholine, phosphoethanolamine and sugar phosphates are under normal conditions are also present
on both sides of the Pi resonance and might partly overlap the Pi peak at lower fields.
-ATP peak is the most reliable in analyzing ATP concentrations, while the a and g resonances
contain contributions from NAD and ADP respectively.
Free Cytoplasmic ATP can be calculated from the creatine kinase reaction
PCr2- + ADP- + H+
<----> ATP2- + Cr
assumed to be at equilibrium:
Keq = [ATP][Cr]/[H+][ATP][PCr]
The intracellular pH is calculated from chemical shift of Pi relative to Pcr according to the formula where
d is the chemical shift:
-3.27)/(5.692. 1H MRS
Figure 5b shows a representative 1H MRS spectrum of the human brain aquired at 1.5T with major
39
observable peaks are assigned.
1
H MRS detects a number of metabolites present in relatively low concentrations (< 10 mM), when water
and fat suppression techniques are used.
Major 1H metabolites observed are commented below:
N-acetyl -aspartate (NAA) produces a large resonance in a H2O suppressed 1H spectrum. The peak may
contain up to 20% contributions from Aspartyl-glutamate (NAAG). NAA is generally associated with
neurons and axons in the adult brain. It has received considerable interest in several disorders where there
is neuron loss. However, its function is largely unknown.
The creatine (Cr), resonance originates from intracellular Cr and PCr these are involved in the creatine
kinase reaction and consequently in energy metabolism.
The Choline (Cho) peak arises from a mixture of glycero-phosphoethanolamine and glycerophosphocholine. Both phospholipids are present in cellular membranes. This resonance can provide
information about cell density and membrane integrity (or peroxidation).
A glutamate and glutamine (Glu, Gln) peak can be detected in the human brain. Glutamine is a precursor
of glutamate. Glutamate is involved in neurotransmission. Gamma-aminobutyric acid (GABA), also
present but in lower concentrations during normal physiological conitions may overlap with the Glu, Gln
resonance at 1.5T field strength.
Myo-Inositol (MI) provides a relatively large resonance and is involved in osmotic regulation across the
cellular membrane and could be specific for glial cells. The amino acid glycine may also contribute to the
myo-inositol resonance.
Scyllo-inositol, an isomer of inositol appears also as a singlet peak more downfield. Taurine resonates
close to the scyllo-inositol region.
Glucose, an important substrate in brain metabolism gives rise a week but observable coupled resonance.
It is more easily detected under hyperglycemic conditions. Lactate can be detected as a boublet resonance
in brain tissue. Under normal conditions, lactate is present at around 1 mM concentration and is increased
during ischemic conditions as a result of anaerobic glycolysis leading to a more distinct peak.
The brain tissue is rich in lipids. These might be detected as broad resonances with contributions from
several fatty acyl chains. Measurement of lipids may be useful in evaluating myelination and membrane
breakdown.
The dominant 1H and 31P biochemicals in the human brain are also listed in tables 1 and 2 respectively.
Resonance frequencies are given in ppm. The concentrations and ratios are mean values from the
literature and are rather orientational than absolute.
MRS and bioenergetics
High energy phosphates such as ATP and Pcr are markers of cellular ability to perform chemical and
mechanical work. The PCr /Pi is a direct thermodynamic measure of mitochondrial oxidative
phosphorylation.
Extensive experimental studies duing the past 15 years have confirmed the high value of 31P MRS in the
understanding of cellular bioenegetics. Numerous studies have used the bioenergetic behaviour as a
marker in monitoring disease development and drug effect. Figure 6 illustrates this. The series of spectra
40
show on one hand the behaviour of phosphorous metabolites in an experimental skeletal muscle ischemia
and reperfusion model; and on the other hand, the effect of treatment with ascorbate, a potent antioxidant,
on the recovery of high energy phosphates during post ischemic reperfusion.
In clinical applications, 31P MRS has been useful for diagnosis and therapy follow-up of metabolic
myophapthies. Calculation of the intracllular pH and PCr degradation and resynthesis during muscle
exercise and recovery from exercise in patients with muscular and metabolic diseases according to
suitable potocoles has been used successfully.
31
PMRS have been helpful in studying metabolic diseases of mitochondrial origin where changes in
lactate and PCr/Pi are taken as markers like in KearnsSayre syndrome.
Aerobic oxidation of glucose provides the human brain cells with energy.
31
P MRS can register of metabolic changes during brain hypoxia where a reduction in oxygen and
substrate supply leads to energetic failure and consequently to neuronal dysfunction and membrane
breakdown. Thus loss in Pcr and ATP can be dected as well as decreases in intracellular pH. Possible
structural membrane changes can be demonstrated from changes in PDE and PME. Intracellular pH
and/or lactate are useful markers of low oxygen availability in the cell. It is well that anaerobic
metabolism leads to lactate accumulation and in the brain tissue the resulting acidocis might in turn lead to
neuronal damage.
Metabolic encephalomyopathies
Brain ischemia and hyoxic/ischemic disease in newborns where cerebral energetics can be monitored to
study oxidative and glycolytic metabolism where parameters like pH, Pi/ATP has proven to be good
markers.
Anaerobic glycolysis in brain is an indication of impairment in mitochondrial function. Decreased PCr/Pi
and elevated lactate levels are indications that could help the diagnosis of that metabolic disorders.
In cases of hepatic encephalomyopathy, Kearns-Syre syndrome and pyrovate dehydrogenase deficiency,
MRS is used to monitor therapy.
Brain trauma
Posttraumatic brain injuries might affect cerebral energy metabolism. Decreases in ATP and in
intracellular pH were shown by 31PMRS. Elevated lactate probably due to increased anaerobic glycolysis
and diminished NAA were also reported from 1HMRS examinations. In neonateswith acute brain injury
1
HMRS examination was able to predict outcome through variations in NAA, Glu/Gln and lactate as
illustrated in figure 7.
Stroke
Stroke is associated with degradation of high-energy phosphates (ATP, Pcr) ans increase in inorganic
phosphate (Pi) and intracellular acidocis as documented from early 31P MRS insvestigations. Additionally,
Typical 1H MRS of patients with stroke show levated lactate and reduced NAA. Follow-up after the acute
infarction period might reveal continued loss in NAA as well as acidocis in the ischemic regions of the
brain. These parameters are certainly useful in monitoring the affect of medication.
Alzheimer Disease
41
1
H MRS using short TE STEAM revealed that myo-inositol is increased in AD. NAA is also decreased in
the brain indicating diminished number of healthy neurons.
Figure 8 illustrates abnormalities in 1H MRS spectum in a patient with AD.
AIDS
Neurologic disorders such as AIDS-encephalitis and AIDS -dementia resulting from HIV infection have
been successfully studied by MRS. Reductions in NAA and increases in Cho have been detected.
Brain tumor
MRS can distinguish between recurrent tumor and tissue necrosis.
Adequate tumor diagnosis and therapy monitoring during the various stages of a tumorous disease are
important for optimal treatment. Both 31P and 1H MRS have been utilized for diagnosis and therapy
monitoring of brain tumors. NAA is decreased in brain gliomas. Studying changes in tumor-type
dependent metabolites is an area of active research.
Lipids and lactate peaks corelate well with necrotic tumor. High-energy phosphate and phospholipid
(ATP, PCr, PDE, PME) levels vary in reponse to radiation therapy, chemotherapy and even to nutrition
(in experimental cancer).
This suggests to utility of 31PMRS in tumor therapy monitoring focusing on cellular bioenergetics and
phospholipid metabolism.
However, biochemical heterogeneity within the tumor tissue is still difficult to study because of poor
resolution on commonly available clinical equipment (1.5T).
Brain tumor classification though network analysis and and pattern recognition might shed further light on
the different tumor types and degree of activity.
Multiple Sclerosis
Changes in NAA, cho and lactate correlate with axonal damages, demyelination and inflammation
observed in MS patients during various stages of the disease. These metabolites can be monitored to the
study the outcome of new treatment.
Epilepsy
31
P MRS showed that the PCr/Pi is dramatically decreased during seizures and normalized after seizure
discharge.
The glutamine and glutamate peak is elevated in the hippcampus while NAA is diminshed in patients
with chronic epilepsy .
Changes in GABA have been correlated with drugs affecting GABA metabolism.
An increase in lactate has also been reported in focal epilepsy of extratemporal origin.
These biochemical changes in epiteptogenic region of the brain indicate that 1HMRS can be clinically
useful in the diagnosis of this disease as a complement to MRI.
Schizophrenia
31
P spectroscopy studies revealed increases in PDE and decreases inPME in the prefrontal cortex of
schizophrenics. Alterations in these lipids vary with different brain regions and stages of the disease.
42
Reductions in NAA and glutamate have been reported from 1H spectroscopy investigations.
These reductions were largely found in the hypocampal area/mesial temporal lobe
Additional neurological diseases under evaluation include:
Huntington disease
Increases in lactate and in Pi and decreases in PCr in Huntington disease implicate mitochondrial
oxidative phosphorylation in the disease process.
Migraine
31
P studies showed diminished PCr and increased Pi and ADP which indicates energetic disturbances in
brain tissue in patients with migraine.
Parkinson Disease
A decrrease in the neuronal marker NAA and an increase lactate/NAA ratio were reported by 1HMRS.
Psychiatry (mood disorders)
Both 31P and 1HMRS have been used in investigation mood disorders where changes in energy
metabolism , lipids and Cho were observed. This indicates the potential of MRS in monitoring the effect
of psychopharmacological drugs.
CONCLUSIONS
MRS is a unique and powerful technique that has been applied to a number of brain diseases. It can be
correlated with imaging and other clinical data for confirmation. It is useful in diagnosis and prognosis of
disease and mostly in the evaluation of the noninvasive monitoring of response to treatment.
Metabolic information from MR spectra is an emerging component in modern neurochemistry.
In neuroresearch MRS is definitely a revolutionary tool that will help understand the brain biochemistry
of mechanisms of disease. MRS if introduced into a clinical practice could be very supportive in clinical
decision making.
Spectral quantification is still difficult therefore
calculated.
relative concentrations of metabolites are usually
Most reports are difficult to compare due variations various parameters in the methodological set up.
Additional complicating factors are the diversity in clinical material studied and exact anatomical
localization (including gray-white matter separation). Discrepancies in results can thus be expected .
In vivo MRS is a complex technology that requires the simultaneous optimal adjustment of multiple
parameters during an examination.The most critical task in MRS however, is not spectral aquisition but
rather spectral analysis . This latter is time demanding and necessitates appropriate know-how in order to
interprete the results, eliminate arifacts and quantitate data often by complex procedures and finally
statistically analyze the findings.
The precise role of many identified metabolites is still unclear. Therefore, along with experimental
43
mechanistic research, incorporation of MRS in clinical practice as much as possible would increase the
body of information since what is still needed is the characterization of spectral patterns in disease
conditions and in healthy control conditions.
Major benefits
High chemical specificity in studying:
energy metabolism,
lipid metabolism,
amino acid and intermediary metabolism,
noninvasive regional serial measurements of metabolite in patients and controls subjects.
Therapy response.
Mechanistic studies of inherited and acquired brain metabolic diseases.
Generally, MRS is well suited for the exploration of diffuse brain diseases where it provides new insights.
Technical improvements
Major technical improvments by manufacturers in terms of hardware and user friendly software has
contributed largely to the increase in the number of clinical studies using 1HMRS along with conventional
MRI.
Automation of methods for shimming, water suppression and peak integration will replace the manual
adjustment of several parameters thus increase reproducibility and certainly spread the use of this
technique.
FUTURE STUDIES
Future studies should focus on multidisciplinary multicentre projects for the development of standardized
reproducible measurements e.g. :
Instrumental calibration protocoles (internal/extern standards)
Protocoles for quality assessment
Comparison of methodologies used for data aquisition, analysis and metabolite quantitation betwen
different centres
Collaborative efforts are necessary for the evaluation of the value of MRS in diagnosis, prognosis and
therapy monitoring in order to enhance clinical workability.
Future technological improvements in magnetic field strength, gradients, data processing and analysis will
also encourage more applications of 13C and 19F.
And last, envision in vivo non-invasive access to highly localized and reliable chemical information as a
routine clinical procedure in health and in disease... Life would become much easier for both patient and
clinician.
Until then MRS continues to be an area of intensive investigation.
44
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45
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23. Hajek M, Burian M, Dezortova M. Application of LCModel for quality control and quantitative in
vivo 1H MR spectroscopy by short echo time STEAM sequence. Magma 10 (1): 6-17, 2000.
24. Podo F, Henriksen O, Bovee WM, Leach MO, Leibfritz D, de Certaines JD. Absolute metabolite
quantification by in vivo NMR spectroscopy: I. Introduction, objectives and activities of a
concerted action in biomedical research. Magn Reson Imaging 16 (9): 1085-92, 1998.
46
25. Chen W, Adriany G, Zhu XH, Gruetter R, Ugurbil K. Detecting natural abundance carbon signal
of NAA metabolite within 12- cm3 localized volume of human brain using 1H-[13C] NMR
spectroscopy. Magn Reson Med 40 (2): 180-4, 1998.
Epilepsy
26. Duc CO, Trabesinger AH, Weber OM, Meier D, Walder M, Wieser HG, Boesiger P. Quantitative
1H MRS in the evaluation of mesial temporal lobe epilepsy in vivo. Magn Reson Imaging 16 (8):
969-79, 1998.
27. Hajek M, Dezortova M, Komarek V. 1H MR spectroscopy in patients with mesial temporal
epilepsy. Magma 7 (2): 95-114, 1998.
28. Rothman DL, Behar KL, Prichard JW, Petroff OA. Homocarnosine and the measurement of
neuronal pH in patients with epilepsy. Magn Reson Med 38 (6): 924-9, 1997.
29. van der Grond J, Gerson JR, Laxer KD, Hugg JW, Matson GB, Weiner MW. Regional
distribution of interictal 31P metabolic changes in patients with temporal lobe epilepsy. Epilepsia
39 (5): 527-36, 1998.
30. Vainio P, Usenius JP, Vapalahti M, Partanen K, Kalviainen R, Rinne J, Kauppinen RA. Reduced
N-acetylaspartate concentration in temporal lobe epilepsy by quantitative 1H MRS in vivo.
Neuroreport 5 (14): 1733-6, 1994.
Stroke and acute brain injuries
31. Blamire AM, Graham GD, Rothman DL, Prichard JW. Proton spectroscopy of human stroke:
assessment of transverse relaxation times and partial volume effects in single volume steam MRS.
Magn Reson Imaging 12 (8): 1227-35, 1994.
32. Ford CC, Griffey RH, Matwiyoff NA, Rosenberg GA. Multivoxel 1H-MRS of stroke. Neurology
42 (7): 1408-12, 1992.
33. Friedman SD, Brooks WM, Jung RE, Chiulli SJ, Sloan JH, Montoya BT, Hart BL, Yeo RA.
Quantitative proton MRS predicts outcome after traumatic brain injury. Neurology 52 (7): 138491, 1999.
34. Gideon P, Rosenbaum S, Sperling B, Petersen P. MR-visible brain water content in human acute
stroke. Magn Reson Imaging 17 (2): 301-4, 1999.
35. Holshouser BA, Ashwal S, Shu S, Hinshaw DB, Jr. Proton MR spectroscopy in children with
acute brain injury: comparison of short and long echo time acquisitions. J Magn Reson Imaging
11 (1): 9-19, 2000.
36. Ross BD, Ernst T, Kreis R, Haseler LJ, Bayer S, Danielsen E, Bluml S, Shonk T, Mandigo JC,
Caton W, Clark C, Jensen SW, Lehman NL, Arcinue E, Pudenz R, Shelden CH. 1H MRS in acute
traumatic brain injury. J Magn Reson Imaging 8 (4): 829-40, 1998.
37. Wardlaw JM, Marshall I, Wild J, Dennis MS, Cannon J, Lewis SC. Studies of acute ischemic
stroke with proton magnetic resonance spectroscopy: relation between time from onset,
47
neurological deficit, metabolite abnormalities in the infarct, blood flow, and clinical outcome.
Stroke 29 (8): 1618-24, 1998.
Schizophrenia
38. Keshavan MS, Sanders RD, Pettegrew JW, Dombrowsky SM, Panchalingam KS. Frontal lobe
metabolism and cerebral morphology in schizophrenia: 31P MRS and MRI studies. Schizophr Res
10 (3): 241-6, 1993.
39. Nasrallah HA, Skinner TE, Schmalbrock P, Robitaille PM. Proton magnetic resonance
spectroscopy (1H MRS) of the hippocampal formation in schizophrenia: a pilot study. Br J
Psychiatry 165 (4): 481-5, 1994.
40. Riehemann S, Volz HP, Smesny S, Hubner G, Wenda B, Rossger G, Sauer H. Phosphorus 31
magnetic resonance spectroscopy in schizophrenia research. Pathophysiology of cerebral
metabolism of high-energy phosphate and membrane phospholipids. Nervenarzt 71 (5): 354-63,
2000.
41. Sigmundsson T. TBK, Maier M., Williams SCR., Simmons A., Greenwood K., Ron MA. Frontal
lobe in vivo proton magnetic resonance spectroscopy in schizophrenic patients with negative
symptoms. Schizophrenia Research 24 (1-2): 182, 1997.
Cancer
42. Castillo M, Kwock L. Clinical applications of proton magnetic resonance spectroscopy in the
evaluation of common intracranial tumors. Top Magn Reson Imaging 10 (2): 104-13, 1999.
43. Kim SH, Chang KH, Song IC, Han MH, Kim HC, Kang HS, Han MC. Brain abscess and brain
tumor: discrimination with in vivo H-1 MR spectroscopy [see comments]. Radiology 204 (1):
239-45, 1997.
44. Leach MO. Introduction to in vivo MRS of cancer: new perspectives and open problems.
Anticancer Res 16 (3B): 1503-14, 1996.
45. Negendank W, Li CW, Padavic-Shaller K, Murphy-Boesch J, Brown TR. Phospholipid
metabolites in 1H-decoupled 31P MRS in vivo in human cancer: implications for experimental
models and clinical studies. Anticancer Res 16 (3B): 1539-44, 1996.
46. Sijens PE, Levendag PC, Vecht CJ, van Dijk P, Oudkerk M. 1H MR spectroscopy detection of
lipids and lactate in metastatic brain tumors. NMR Biomed 9 (2): 65-71, 1996.
Multiple sclerosis and ALS
47. Arnold DL, Matthews PM, Francis G, Antel J. Proton magnetic resonance spectroscopy of human
brain in vivo in the evaluation of multiple sclerosis: assessment of the load of disease. Magn
Reson Med 14 (1): 154-9, 1990.
48. Block W, Karitzky J, Traber F, Pohl C, Keller E, Mundegar RR, Lamerichs R, Rink H, Ries F,
Schild HH, Jerusalem F. Proton magnetic resonance spectroscopy of the primary motor cortex in
patients with motor neuron disease: subgroup analysis and follow-up measurements. Arch Neurol
48
55 (7): 931-6, 1998.
49. Leary SM, Brex PA, MacManus DG, Parker GJ, Barker GJ, Miller DH, Thompson AJ. A (1)H
magnetic resonance spectroscopy study of aging in parietal white matter: implications for trials in
multiple sclerosis. Magn Reson Imaging 18 (4): 455-9, 2000.
50. Rooney WD, Miller RG, Gelinas D, Schuff N, Maudsley AA, Weiner MW. Decreased Nacetylaspartate in motor cortex and corticospinal tract in ALS. Neurology 50 (6): 1800-5, 1998.
51. Sarchielli P, Presciutti O, Tarducci R, Gobbi G, Alberti A, Pelliccioli GP, Orlacchio A, Gallai V.
1H-MRS in patients with multiple sclerosis undergoing treatment with interferon beta-1a: results
of a preliminary study. J Neurol Neurosurg Psychiatry 64 (2): 204-12, 1998.
Encephalmyopathy and metabolic diseases
52. Soussi B, Schersten T, Waldenstrom A, Ronquist G. Phosphocreatine turnover and pH balance in
forearm muscle of patients with syndrome X [letter]. Lancet 341 (8848): 829-30, 1993.
53. Ronquist G, Soussi B, Frithz G, Schersten T, Waldenstrom A. Disturbed energy balance in
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1995.
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correlation of P-31 exercise MR spectroscopy with clinical findings. Radiology 192 (1): 223-30,
1994.
55. Mathews PM, Andermann F, Silver K, Karpati G, Arnold DL. Proton MR spectroscopic
characterization of differences in regional brain metabolic abnormalities in mitochondrial
encephalomyopathies. Neurology 43 (12): 2484-90, 1993.
Alzheimer¥s Disease and Dementia
56. Cuenod CA, Kaplan DB, Michot JL, Jehenson P, Leroy-Willig A, Forette F, Syrota A, Boller F.
Phospholipid abnormalities in early Alzheimer's disease. In vivo phosphorus 31 magnetic
resonance spectroscopy. Arch Neurol 52 (1): 89-94, 1995.
57. Moats RA, Ernst T, Shonk TK, Ross BD. Abnormal cerebral metabolite concentrations in patients
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49
Legends to figures and tables
Figure 1.
The free induction decay is converted to a spectrum by a Fourier transformation.
The FID signal (= amlitude vs time) is converted to a spectrum (= amplitude vs frequency).
Figure 2.
Volume selection and spectral acquisition.
A: MRI of normal human brain, illustrating the VOI = 50 x 40 x 50 mm.
B: Proton MRS spectrum of the selected volume showing the major proton metabolites. (Reproduced
from 47)
Figure 3.
In vivo 31P MR spectrum localised from rat brain with ISIS ( VOI = 10 x 10 x 10 mm). Mannetic field
strength = 2.35 T. The peaks of the adenosine triphosphates a-, b-, and g-ATP, the phosphocreatine, PCr,
the inorganic phosphate Pi as well as the phosphomonoesters PME and the phosphodiesters DPE are
assigned.
Figure 4.
Improved resolution with improved magnetic field strength.
a) In vivo 31P MR spectrum of rat skeletal muscle at 2.35T.
b) In vitro 31P high resolution NMR spectrum of skeletal muscle extract acquired at 11.74 T. The peaks of
the adenosine triphosphates a-, b-, and g-ATP, the phosphocreatine, PCr, the inorganic phosphate Pi are
well resolved. Peaks at 6.3-7.3 ppm are PME including G-6-P at 7.17ppm. The large Pi peak arises from
artifactual degradation of PCr.
Figure 5.
Localized MRS spectra of of normal human brain illustrating the major metabolites observed.
(A) is an ISIS 31P MR spectrum obtained at 2 T (VOI = 100 ml). The adenosine triphosphates a-, b-, and
g-ATP, the phosphocreatine, PCr, the inorganic phosphate Pi as well as the phosphomonoesters PME and
the phosphodiesters DPE are well resolved.
(B) is a proton MR spectrum at 1.5 T obtained with STEAM combined with CHESS to suppress the water
signal, (VOI = 8 ml). The assigned proton metabolites are: N-acetylaspartate NAA, glutamate and
glutamine GLU-GLN, creatine and phosphocreatine Cr-PCr, choline CHO, inositol INS scyllo-inosito
Scy-INS, taurine TAU, glycine GLY and glucose. (Reproduced from 3)
Figure 6.
Illustration of the dynamics of cellular energetics by in vivo 31PMRS The potential of MRS in therapy
monitoring is also demontrated.
The spectra are from a skeletal muscle from a control rat and a rat treated with ascorbate. At rest (A), after
2 h of ischemia (B), after 4 h if ischemia (C) and after 4 h of ischemia + 150 minutes of reperfusion (D).
The treated rat showed higher levels of PCr and ATP after reperfusion. Spectra were obtained by
accumulating 128 FIDs with a repetition time 1 s at 2.35 T. (Reproduced from 13)
Figure 7.
50
1
H MRS illustrating patterns seen in STEAM spectra (a, c) and in PRESS spectra (b, d) from the brain of
two children with after birth brain injury.
Spectra (a, b) are from a patient with a mild brain injury and show good outcome.
Spectra (c, d) are from a patient with a traumatic brain injury and show poor outcome (Note the low
NAA signal and the elevated lactate signal).
Figure 8.
A proton MRS spectrum from the brain of a normal patient (A) compared with a spectrum of a patient
with Alzheimer disease (B). (Reproduced from 58)
Table 1. Major proton metabolites with approximate mean concentrations and corresponding resonance
frequencies detected in normal human brain by in vivo MRS.
Table 2. Summary of 31P metabolites in normal human brain obtained by in vivo MRS. Relative mean
metabolite ratios are also given.
51
Chapter IV – J.L. Stievenart
Basic principles of Nuclear Medicine in Neurosciences
Jean-Louis STIEVENART,
Praticien Hospitalier, Service de Médecine Nucléaire,
C.H.U. Hôpital Beaujon, Clichy, France
The aim of this presentation is to draw a broad overview of the functional brain imaging in Nuclear
Medicine. A more in depth description of these techniques and of their applications can be found in a
recent reference (1).
All these methods have in common two fundamental steps :
-
injection of radioactive substance to a patient at some time during which the status of the brain
activity is known (« basal », seizure free, drug action, etc….) ;
-
Tomographic imaging of the radioactive distribution after a delay that is important to monitor.
The radioactive substance is a radiopharmaceutical which has two components : a molecule of biologic
interest and a radioactive atom tightly bound to it.
Thus, questions to deal with to get a better understanding of these examinations become self-evident :
What are the available radiopharmaceuticals, and which aspects of brain functions do they allow to
explore ?
How can we make an image of a radioactive distribution and what are the spatial and temporal resolutions
of the instruments ?
In which clinical situations do these methods give relevant and irreplaceable information ?
The radiopharmaceuticals.
1 the radioactive atoms.
They have an unstable nucleus which spontaneously emits energy to reach a stable state. This
transformation is inexorable and its rate is characterized by the half-life, that is the time period during
52
which half of the atoms of a sample have experienced it. The number of these transformations occurring in
one second is the activity of the sample (unit of activity : 1 Becquerel (Bq) = 1 decay per second ;
equivalence with an older unit the Curie 1 mCi = 37 MBq ).
As far as we are concerned, they fall into two categories :
-
the gamma emitters for which the transformation is associated with the emission of a photon of a
precise energy.
-
The beta-plus emitters for which the transformation is associated with the emission of a positive
electron or positron of variable energy. Secondary, these positrons will slow down and collide with
electrons of the medium. This event takes place after a travel of about 2 mm. depending on the initial
energy of the positron ( the mean of this travel distance is called the range). A dematerialisation
occurs and the mass of the electron and of the positron transform in energy resulting in an emission of
two photons in two opposite directions, each one with the precise energy of 511 kiloelectron-volts
(keV). Figure 1.
The gamma-emitters are used to perform single photon computed emission tomography (SPECT), the
main representative of this class are the technetium 99m (99mTc half-life 6 hours, energy 140 keV), and the
iodine 123 (123I, half-life 13 hours, energy 159 keV. In spite of its relatively short half-life
99m
Tc is the
most easily used radionuclide, being available from a 99Mo/99mTc generator. The beta plus emitters are the
core of the positron emission tomography (PET). Fluor 18 (18F, half-life 110 minutes) plays a major role
in PET examinations. Other atoms can be used : oxygen 15 (15O half-life 2 minutes), carbon 11 (11C halflife 20 minutes), 13 nitrogen (13N half-life 10 minutes). They can be easily included in molecules of
biological interest but their short half-lives require their on site production (cyclotron) and coupling with
the other parts of the molecule.
2 the molecules of biological interest.
2.1 perfusion and energetic metabolism
53
Hexa-methyl-propylenamine-oxime-99mTc (HMPAO, Ceretec®) and Ethyl-cysteinate-dimer-99mTc
(ECD, Neurolite®) are the radiopharmaceuticals with which SPECT perfusion brain studies are routinely
performed. They are lipophilic molecules that easily go through the blood brain barrier and cellular
membranes. Then they become hydrophilic in the cells (neurons and astrocytes) and thus unable to go
backward across lipids layers. The involved chemical transformations are for the HMPAO a reaction with
glutathione (2) and for the ECD an esterification catalyzed by a primate specific enzyme (3). So, the
radioactivity is rapidely trapped in the brain cells, proportionally in first approximation, to the local blood
flow. Because of this behavior these molecules are sometimes referred to as « chemical microspheres ».
2-Fluoro-2-deoxy-D-glucose (18FDG ) has been used for more than 20 years as a metabolic tracer of cells
functioning. This substance diffuses through the cell membrane, this diffusion being facilitated by glucose
transporters. It then undergoes a phosphorylation step by hexokinase and cannot follow further the glucose
metabolic pathway. Thus the trapped activity by cells reflects their glucose consumption
201Tl-chloride and 99mTc-metoxyisobitytilisonitrilme (MIBI) are radiopharmaceutical designed to study
cardiac perfusion and they reflect another aspect of cell functioning. The Tl+ ion is analogous to K+ and is
actively transported across membrane by Na+/K+-ATPase. SestaMIBI (Cardiolite®) has an uptake
dependant upon membrane electrical potential and accumulates in mitochondria.
2.2 The dopaminergic pathways.
Since the beginnings of the PET this pathway (figure 2) has received a considerable attention due to its
implications in psychiatric symptoms and movements disorders (4). 18F –fluoro-DOPA was used to assess
the activity of dopaminergic neurons. The presynaptic components of the synapse have also been studied
with ligands for dopamine transporters (DAT) which are tropane derivatives. They were at first labeled
with 11C as the [11C]CFT (5). Now,
and
123
123
I labeled agents are commercially available such as
123
-CIT (6)
IFP- -CIT (Ioflupane, DatScan®) (7). Work is in progress to develop 99mTc labeled ligands that
would be more convenient for routine clinical use (8). One of them, the 99mTc-TRODAT is already in a
Phase I clinical study (9). Numerous ligands for D2 and D3 receptors have been developed, most of them
54
belonging to the benzamides family. The 11C-raclopride has been the first of them (10). More recently this
kind of molecules has been labeled with
18
F, which is a more appropriate radionuclide for performing
kinetic studies, such as fluoropropylbenzamide (11) and with
123
I, such as
123
I iodobenzamide (IBZM)
(12) which opens the possibility to study D2 and D3 dopamine receptors with SPECT.
2.3 other receptors ligands
The benzodiazepine receptors
The central benzodiazepine site is a part of the gamma-aminobutyric acid (GABA) channel receptor –
(GABA)A. This site has been thoroughly studied by PET with
SPECT radiopharmaceutical is
123
11
Cflumazenil (13,14). The equivalent
Iiomazenil and efforts are currently done to reach a PET-like accuracy
for estimation of binding parameters of this tracer (15,16).
Many other ligands have been designed for PET imaging of the serotonine system (17-19), the cholinergic
system (20). SPECT tracers are less numerous. Up to now, none of them is available for clinical routine.
2.4 Labeled amino acids
Proteins synthesis is an aspect other than the glucose metabolism by which malignant lesions may be
distinguished from the benign ones. Among the different synthesized labeled amino acids the
11
C
MethylMethionine (CMET) has had a relatively wide usage. [18F] fluoro- -metyl-tyrosine has also been
tried as a tumor marker (21). The SPECT version of this agent,
123
I iodo- -methyl-tyrosine is currently
under tests (22).
2.5 molecules kinetics modeling.
If the labeled molecules were completely extracted from circulation during the first pass of blood in brain
tissue and irreversibly trapped there, the radioactivity distribution would be an image of the local blood
flows. Even for the so-called chemical microsphere it is not exactly the case. For neuroreceptors or
transporters studies, such a weighting by perfusion conditions would rather be a confounding factor, the
parameter of interest being the availability of specific sites for a given ligand. Making the distinction
55
between the delivery and the binding of a molecule and separately measuring both, are the main tasks
assigned to tracer kinetic modeling (23). It is usually assumed that the labeled ligand participates to
exchanges between several compartments, and that the tissue in which the activity is measured can be
modelized as a sum of these exchanging compartments. A sequence of acquisitions is done to give the
time course of activity in every voxel of interest. This evolution is compared to other ones in plasma or in
some reference organ or region. Fitting to the expected evolutions derived from the model can give access
to its parameters. But it must be underlined that with a single injection it is not always possible to estimate
all the parameters. For this purpose more sophisticated protocols are needed, such as coinjection of cold
ligand or continuous infusion (24).
To present some definitions and techniques let us consider the one-tissue model (figure 3).
Cp(t) is the plasma tracer concentration (activity) at time t (units: kBq.ml-1)
C(t) is the local tracer concentration in brain tissue (kBq.ml-1)
K1 is the rate constant for transfer from plasma to the tissue across the blood brain barrier
(ml(plasma).min-1.ml-1(brain))
k2 is the rate constant for transfer from tissue to plasma (min-1)
The evolutions of radioactive concentrations is ruled by the differential equation:
dC(t)/dt = K1.Cp(t) – k2.C(t)
(1)
If the system is in a steady-state dC(t)/dt = 0 and K1.Cp(t) = k2.C(t)
Then C(t)/Cp(t) = K1/k2 = cst.
Considering the units of K1 and k2 this ratio is expressed in ml(plasma).ml-1(brain).
It represents the volume the radioligand would occupy if it were in the brain at the same concentration as
in the plasma. It defines the volume of distribution of the radioligand which reflects the binding potential
of the brain tissue.
To illustrate how these parameters can be estimated let us integrate the equation
[1]
t
t
0
0
Ct   K1 . Cpu du  k 2 . C(u)du
56
Division of both sides of this equation by C(t) and k2 followed by some rearrangements yields
t
 Cu du
0
Ct 
t
Cpu du
K 1 0
1

.

k2
Ct 
k2
This relation is the basis of Logan’s graphical analysis (25). One disposes of two sets of measurements
Cp(ti) (from blood sampling), C(ti) ( from PET or SPECT acquisitions). Two series of values (expressed in
min.)
ti
ti
 Cu du  Cpu du
0
Ct i 
,
0
Ct i 
can thus be calculated. If the model is valid, the points defined by these couples of values are aligned
along a straight line, the slope of which is the distribution volume of the radioligand. Its ordinate at origin
is an estimation of 1/k2. Usually, adjunction of a second tissue compartment (the receptor rich
compartment), introducing two new rate constants k3 and k4 is needed to improve the fit to the
experimental data.
The instrumentation
1 detection of photons.
In both modalities photons have to be detected. This is done by use of scintillating crystal, converting the
energy of an incident photon in light photons. These light photons, the number of which depends on
incident photon energy, are multiplied by a photomultiplier, detected and, if the energy has a suitable
value, the scintillation origin is determined. The main difference between SPECT and PET is that in
SPECT, a single photon does not bear information about its direction when it hits the crystal. Whereas, in
PET, two photons are to be detected simultaneously (or near simultaneously) and thus it is known that the
annihilation point is on the line joining the two detected points.
57
2 The gamma camera.
the collimator selects photons before they hit the sodium iodide (NaI) crystal. It may be designed with
parallel channels or with converging channels in the transverse plane and parallels in the axial ones,
resulting in a “fan-beam” geometry (26). Detector and collimator are grouped in a head that orbits around
the patient. Most cameras have now 2 or 3 heads arranged for example as shown on figure 4. Only
photons travelling accordingly to the direction of collimator channels are detectable. Among those ones,
some are scattered and others are absorbed by the patient tissues.
3 the PET scanner.
The collimator is no longer necessary. Yet selecting devices are sometimes used to perform 2D imaging
where coincidences are looked for in slices. Due to higher energy of incident photons more dense crystals
are used. Critical parameters of these crystals are their energy resolution and the duration of the
scintillation after one hit, the shorter being the better in order to get a sharp time resolution to detect true
coincidences. Gadolinium oxyorthosilicate (GSO) and lutetium oxyorthosilicate (LSO) are recently
developed scintillators for which these parameters are well suited. The coincidences are detected inside a
temporal “coincidence window” the length of which is of the order of 8 nanoseconds. Potentially, all the
annihilations occurring in the object and emitting in the solid angle encompassed by the camera could be
detected. But some phenomena adversely affect this sensitivity: random coincidences causing non existent
events to be detected, scatter causing to misposition true events, attenuation in the patient preventing one
or two photons of the pair to reach the detector.
Nowadays, PET scanner is frequently coupled to a high quality X-rays scanner. So attenuation correction
is simplified and functional and morphologic data can easily be merged.
4 imaging capabilities
What the camera yield is a set of projections of a radioactive distribution. It is the task of the
reconstruction algorithm to go back to this volumic distribution (inverse problem). For years, this step was
quasi exclusively based on the filtred backprojection algorithm (preceded by a rebinning (rearrangement
of projections) in case of fan beam collimator or 3D acquisition). In this method a low pass filter is
58
involved, the properties of which are important to know to achieve an adequate balance between
resolution and noise. Recently, iterative methods gains a more widespread usage. They include a more
realistic modeling of the acquisition process and rely on the principle of maximum-likelihood expectation
maximization (MLEM). That is to say they try to compute the distribution, the acquired projection of
which are the most likely the observed ones. This method is implemented for PET and SPECT with a
procedure to accelerate its convergence: ordered-subset expectation maximization (OSEM) (27). For
direct reconstruction of 3D PET acquisitions an analogous algorithm can be used: row action
maximization likelihood (RAMLA) (28).
An important issue is the attenuation correction which can be relatively exact in PET but more
problematic in SPECT where the Chang’s method (29) is the most popular.
With 30 min. acquisitions the resolution (axial and transversal FWHM) is about 9 mm. for SPECT and 45 mm. for PET.
For an in depth review of characteristics of current PET systems see reference (30).
When the best temporal and spatial resolutions are researched one must use dedicated brain camera. This
is the case for quantitative molecular kinetics studies. In the majority of the described applications this is
not mandatory and the tomoscintigraphies can be performed with general purpose systems equipped with
an adequate head-holder.
The clinical applications
1 cerebrovascular diseases
In this domain a lot of work was done with PET tracers not detailed in the radiopharmaceutical section as
H215O, , C15O,
15
O2 , which allowed to study and measure perfusion (cerebral blood flow: CBF), blood
volume (CBV), oxygen consumption (CMRO2) etc…. It was an extensive research field. Concerning the
blood flow, many studies (31,32) reported quantitative approach to measure it in ml.min-1.100g-1 with
59
HMPAO or ECD but no universally accepted quantification method, usable in clinical routine, emerged
up to now
Let us simply recall the main results (33-35). Glucose consumption (CMRGlu) and local blood flow are
coupled in most of the clinical situations (36), (there may be exception during coma, anesthesia or in postictal periods). Face to a decline of perfusion pressure, the first compensating mechanism is an
augmentation of local blood volume. When its maximum is reached (autoregulation threshold) the CBF
begins to decrease but, due to the second compensation mechanism, the augmentation of the Oxygen
extraction fraction (OEF), the CMRO2 is maintained. This phase corresponds to the misery perfusion.
Then the brain tissue enters the true ischemic zone, experiencing first a reversible dysfunction (the
penumbra) then an irreversible one (37). The situation of maximum local vasodilatation was termed
« oligemia » by Lassen and is a potentially dangerous one. To recognize it, in complex vascular
malformation for example, a pharmacological trial with Acetazolamide
(Diamox®) is proposed. Oligemic regions look like normal in basal examination and like hypoperfused in
the examination after Acetazolamide (38). In some circumstances the Acetazolamide reactivity may be
normal in a brain territory having a low baseline perfusion. This occurs in patients with occlusive carotid
artery diseases and is the sign of a blood supply adapted to a low demand. It suggest possible incomplete
infarction (not visible in MRI). This hypothesis is reinforced by a diminution of benzodiazepine receptors
ligands binding in these regions (39). This situation is not predictive of a subsequent ischemic stroke.
When an ischemic or already damaged brain tissue is reperfused a luxury perfusion may occur,
characterized by a reduction of OEF (40) and thus an oxygen supply in excess of demand. It is considered
that this period, if associated with an increased cerebral blood flow, can be visualized by HMPAO, but not
by ECD. However this hyperfixation of HMPAO is equivocal and may be due an altered blood-brain
barrier (41)
Perfusion SPECT and FDG PET had been, for a time, the only imaging modalities to unveil abnormalities
and to allow a prognosis assessment at the very initial phase of stroke (42). Now this is routinely done
using MRI and especially diffusion weighted imaging (43). The isotopic methods are used in a secondary
60
period to evidence deafferentation and thus explain deficits which are not clearly related with the site of
ischemic lesions (44). The crossed cerebellar diaschisis was the first example of such a phenomenon (45).
Figure 5 shows an example of sub-cortical / cortical deafferentation.
The accumulation of these ischemic lesions, both cortical and sub-cortical, may lead to vascular dementia
which is characterized by an heterogeneous aspect of the perfusion. The heterogeneity of the brain
perfusion is a frequently observed aspect in normal aging (46) and one must be accustomed to
examinations of this population to decide if a perfusion heterogeneity is definitely pathologic or not.
2 dementia
Of particular importance is the distinction between vascular dementia and Alzheimer’s disease (AD).
Numerous studies show that this is possible (47-49). Parietal and temporal hypoperfusion or
hypometabolism, more or less symmetric is the major sign of AD. An important negative sign being the
sparing of the primary cortex (visual and sensori-motor) figure 6. This pattern can be evidenced with PET
or SPECT. In this domain more than anywhere else, the confrontation with clinical presentation and
morphological data is mandatory. For example, memory impairment is a prerequisite to evoke the
diagnosis. Longitudinal studies are possible to assess the treatment effect (50). Moreover, functional
imaging allows one to go further in differential diagnosis of dementia. A first group is the one of the
fronto-temporal lobes atrophy, which have different clinical expressions.
The primary progressive aphasia, where language dysfunctions (syntactic and phonologic) are on the
foreground. Morphologic imaging shows an atrophy of the left perisylvian region and functional
examinations reveal a concordant hypoactivity (51,52).
The fronto temporal dementia. In this complex syndrome, where behavioral problems are typically the
initial sign, the morphologic aspect is a frontal atrophy with an enlarged sylvian fissure. PET (53) and
SPECT (54) scans show a frontotemporal decreased metabolism or perfusion. In this context, an isolated
posterior hypoactivity excludes the diagnosis.
61
The semantic dementia is characterized by a loss of conceptual knowledges enabling to produce and
understand language. This syndrome is associated with atrophy of anterior temporal lobes, usually
asymmetric and more marked on the left side. This atrophy relatively spares medial regions such as
hippocampus. Functional imaging shows the same pattern (55).
The posterior cortical atrophy.
Here visual functions are altered. According to the main involved region the presentation is different:
visual agnosia, color agnosia or prosopagnosia when ventral pathway is concerned, alexia, agraphy,
Balint’s syndrome when it is the dorsal one. The functional aspect is an hypoactivity of the posterior
regions associated with a relatively preserved activity on the medial temporal lobes (56).
Dementia with extra-pyramidal signs.
Some pathologies of this neurodegenrative group raise difficult differential diagnosis problems with AD.
At the first rank is the dementia with Lewy bodies (DLB) in which fluctuation of consciousness and
visual hallucinations are much more frequent than in AD. Yet, the positive diagnosis is difficult and the
nosographic classification is not well established among AD variant with Lewy bodies, pure DLB (
without senile plaques and neurofibrilar degeneration), Parkison’s disease with dementia. For the
diagnosis of pure DLB, morphologic imaging does not appear helpfull. In functional imaging, the extent
of hypoactivity towards the occipital lobes looks more pronounced than in AD (57-59). Cortico basal
degeneration is another circumstance where functional imaging could be useful. In typical cases, the
hypoactivity is asymmetric, predominant on posterior frontal and parietal lobes (60-61). The evolution is
towards a more widespread involvement of the entire hemisphere including the deep structures: striatum
and thalamus (61).
In these 2 latter pathologies the functional study of the dopaminergic pathway is promising. The
nigrostriate function assessed by FDOPA or a tracer of the dopamine transporter is more altered in DLB
than in AD.
62
Mild cognitive impairment
An important issue in the dementia domain is the early diagnosis of AD in a clinical situation termed
“mild cognitive impairment”. More generally it can be assumed that for the involved brain cortex region
hypofunction precedes atrophy. To be detected on an individual basis this hypofunction must occurs in
region were normal variations are limited. Although it is known that AD begins in the entorhinal cortex,
an hypometabolism of this region is difficult to recognize. It appears more reliable to look for an
hypometabolism in the posterior cingulate cortex (62,63)
3 movements disorders.
Parkinson’s disease (PD) is the most frequent pathology encountered in this field. But number of
neurodegenerative diseases include tremor, rigidity and bradykinesia in their presentation. Since the
development of ligands for dopamine membrane transporter and for D2 receptors labeled with
123
I or
99m
Tc the study of dopaminergic pathways is more feasible in the clinical setting (64,65). The reduction of
the striatal uptake of dopamine transporters tracers is the sign of the nigrostriatal dysfunction. In PD, this
reduction is predominant in the putamen and, most of the time, asymmetric (Figure 7). These results
reproduce those ones of 18F-DOPA PET explorations (66). Moreover, there is a correlation between the
uptake reduction and the disease severity, and the time course of dopaminergic degeneration can be
measured (67). In essential tremor, the uptake of such tracers is normal. In multiple system atrophy
(MSA), or in progressive supranuclear palsy (PSP) (71) the reduction is more diffuse in the putamen
and the caudate. But it does not seem possible with these examinations to discriminate these pathologies
for individual patient. Nevertheless, imaging of dopamine transporter has an impact on management of
patients presenting with a possible PD or a supposed drug induced parkinsonism (study on 90 patients)
(68).
Imaging of D2 receptors show a reduced striatum uptake in MSA and PSP whereas it is normal in
Parkinson’s disease (69).
63
Metabolism and perfusion studies are also used to explore these extra-pyramidal syndromes. It is
noticeable that the striatal CMRGlu is normal in PD (70). It is diminished in MSA and allows
discrimination between PD and nigrostriate degeneration (72).
Current studies focus on relations between severity of the nigrostriatal dysfunction, assessed by the
18
FDOPA and the presence of a genetic mutation (73). Possible side-effect of long term treatment by
levodopa had been explored by brain blood flow (74) showing an alteration of the response to an acute
dose of levodopa in sensori motor and ventrolateral prefrontal cortex. The neuroprotective effect of
dopamine receptor agonist had been evaluated by a randomized study using the
123
I
-CIT (82 patients)
(75).
4 epilepsy
The main issue in medically untractable epilepsy is to correctly localize the epileptogenic zone in order to
determine the site and the extent of the cortical resection to be done. For this purpose several
methodologies had been developed using ictal and/or inter-ictal functional studies. The general pattern is
an hypometabolism in the inter-ictal phase and an hyperperfusion during the ictal period. For temporal
lobe epilepsy it is now well established that inter-ictal FDG PET (76) and ictal/interictal perfusion SPECT
(77) have the same efficiency in identifying the epileptogenic zone. The situation is less clear for
neocortical epilepsy where subtraction from the ictal examination of the inter-ictal one, both coregistered
with Magnetic Resonance Imaging (SISCOM) proved to be helpful to improve the interpretation of the
SPECT data (78,79).
In all these procedures the timing of the radiopharmaceutical injection in relation to the onset of the
seizure activity is of paramount importance (80,81). The localizing power of an ictal study is as much
greater as the perfusion tracer is injected earlier after the seizure onset. Delayed injection results in spread
hyperactivity in which the epileptogenic zone cannot be isolated. Perfusion abnormality can last a long
time after the seizure and could be related to psychotic episodes after complex partial seizure (82).
64
The classical pattern is sometimes missing or even inverted. Hypermetabolism during a supposed
interictal phase had been thought to occur during discharge of deep epileptic focus not recorded by the
surface EEG. On the contrary, hypoperfusion observed during an ictal examination could in fact unveil a
« steal » phenomenon (83).
Repeated seizures can cause subtle lesions that had been evidenced by imaging the benzodiazepine
receptors. A diminution of the binding potential in the cerebellum controlateral to the temporal region
responsible of partial epilepsy (17 patients), mimicking some kind of « crossed cerebellar diaschisis » has
been found (84).
5 tumors
Probably due to the high background activity of the normal brain, the FDG PET does not appear here so
effective than in other regions. In a study including 331 patients (85) the relationship between the activity,
assessed by visual inspection , and the histologic grading has been established. The FDG uptake was
qualitatively measured on a four-value scale – no uptake : 0, uptake less or equal to normal white matter :
1, uptake greater than normal white matter but less than normal grey matter : 2, uptake greater than grey
matter : 3. Moreover, the degree of uptake with the survival – 94% of the patients with low uptake (0,1)
survived for more than one year ( survival median : 28 months ), whereas only 29% of those ones with
high uptake (2,3) did so (survival median 11 months). Yet, it remains many clinical situations where the
decision making is difficult. Differentiating tumor recurrence from necrosis or scar, especially in the case
of radionecrosis and low-grade tumors, is one of them. This gave impulse for the development of more
specific tracers exploring the amino acid transport across the cell membrane. 11C-Methyl-Methionine has
been frequently used to study brain tumors (86). With this agent, contrast of the tumor relative to the
normal brain tissue is better than with the FDG. It permitted to assess the response of glioma to
brachytherapy in 46 patients (87). It seems useful for differential diagnosis of low-grade gliomas (88). To
overcome technical difficulties in relation with the short half-life of the 11C, other tracers, labeled with 18F
has been proposed as the FluoroTyrosine (89). More recently, tracers suitable for SPECT imaging have
65
been synthesized. For example, the L-3-[123I]iodo- -methyl tyrosine (IMT) gives better results than FDG
in some circumstances, such as low-grade recurrences of gliomas (90). It is also better than MIBI to
distinguish progressive from non progressive low-grad astrocytomas after irradiation (91). In fact,
201
Tl or
99m
Tc-MIBI had been used since a very long time (92) to make a positive image of brain tumors and assess
their malignancy. The physiological uptake of MIBI by choroid plexus may be confusing. A review of
201
Tl examinations in 90 patients with various brain tumors or processes concluded to a sensitivity of 72%
and a specificity of 81 % for detecting the malignancy (93). In this study, imaging was done 15 minutes
after the injection of tracer. More delayed acquisition (3 h.) is useful to further characterize the focal 201Tl
accumulation. The kinetic of Tl uptake can be grossly quantified by computing a tumor/non-tumor ratio in
two mirror ROIs. A retention index may be defined as the ratio between the delayed and the early
tumor/non-tumor ratios (94).
A strategy based upon 201Tl and 123I IMT has been proposed to differentiate brain tumors and was
evaluated in 65 patients. (95).
Conclusion
Since a 1995 partial review of the topic (96) a lot of events have occurred:
Clinical PET has become more affordable,
Resolution of SPECT camera steadily improves,
New tracers have been designed and some of them are commercially available,
Functional MRI has gained in maturity,
Spectroscopic MRI shows endless progress but supposes extended physico-chemical knowledge.
In this continuously changing landscape, nuclear techniques still produce effective results, useful in
management of dementia, medically untractable epilepsy, complex movements disorders.
The trend is to focus on more specific molecules and to more closely study their kinetics in the human
brain.
66
Efforts are also done to better characterize what a “normal” brain distribution of a specific activity is and
to quantify the pathologic deviations from it.
Thus, the concept of molecular imaging is emerging, which aims at detecting the pathologic processes
before they cause structural modifications, in a period where they are, hopefully, more amenable to
treatments.
67
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Chapter V – C. Marsault
Résultats de l’utilisation du scanner multibarrettes en neuroradiologie
Claude Marsault
Professeur des Universités et Chef de Service,
Service de Radiologie, Hôpital Tenon,
Paris, France
La neuroradiologie a d’emblée profité de l’acquisition spiralée en scanographie, essentiellement dans les
explorations vasculaires, comme les artères à destinée encéphalique (vertébrales et surtout carotides) et
également en intra-crânien (recherche d’anévrysme ou de malformations artério-veineuses). Par contre, les
reconstructions cérébrales multiplanaires n’ont pas été profondément modifiées.
Ainsi, l’angioscanner monobarrette était déjà un examen performant pour l’étude des axes vasculaires
cervico-encéphaliques (1, 2). Avec l’apparition des multibarrettes, cet examen devient probablement la
technique de choix non invasive dans l’exploration des artères cervicales et des vaisseaux encéphaliques.
Il permet de plus d’évaluer la perfusion cérébrale. Comparativement au scanner monobarrette, les
avantages majeurs du scanner multibarrettes pour l’étude des artères cervicales sont : la possibilité
d’obtenir des images en phase artérielle pure grâce à la réduction de la durée d’acquisition et du sens
crânio-caudal de l’acquisition ; la nette amélioration de la qualité de l’image reconstruite dans le plan
sagittal avec la disparition de l’effet en marche d’escalier par l’obtention de coupes inframillimétriques
avec reconstruction chevauchée; la réduction des artéfacts de mouvements et des artéfacts d’origine
dentaire par l’amélioration de la résolution temporelle et par une meilleure correction du durcissement du
faisceau de rayons X ; l’augmentation de la hauteur d’exploration avec la possibilité de visualiser au cours
de la même acquisition tout l’axe artériel cervico-encéphalique. Dans l’étude des sténoses
athéromateuses de l’artère carotide interne, ces améliorations permettent à la fois d’apprécier
exactement le degré de sténose (3), la morphologie de la plaque athéromateuse (Fig.1) et d’éventuelles
lésions associées au niveau des siphons carotidiens et de l’origine des TSA. Dans les dissections
artérielles, l’angioscanner multibarrettes permet de préciser la localisation et l’extension lésionnelle, la
présence de dissections multiples et l’existence d’un facteur favorisant comme la dysplasie fibromusculaire.
L’étude des vaisseaux encéphaliques a également bénéficiée de cette avancée technologique. La fiabilité
de l’angioscanner dans la recherche des anévrysmes intracrâniens se confirme avec l’utilisation des
multibarrettes (4). L’augmentation du volume exploré et la meilleure résolution spatiale longitudinale
permettent la détection de lésions artérielles sténo-occlusives sur des branches artérielles plus distales (5).
D’autre part, nous avons observé une plus grande facilité dans la réalisation de l’examen, au cours des
situations d’urgences difficiles où les patients sont confus et agités, grâce à la rapidité d’acquisition de
l’examen et à l’absence de contrainte positionnelle de la tête du patient.
Pour l’étude des veines encéphaliques le scanner multibarrettes permet de diagnostiquer les
thrombophlébites cérébrales à partir d’un examen angioscanographique veineux dédié comme le faisait
déjà le scanner monobarrette (6). En revanche, un des avantages du scanner multibarrettes est de pouvoir
faire le diagnostic de thrombophlébite cérébrale a posteriori, après une acquisition spiralée banale réalisée
sans injection de produit de contraste, car pendant les deux premières semaines, le thrombus endoluminal
est spontanément hyperdense, très bien visualisé sur les coupes MPR millimétriques et les reconstructions
VRT (Fig.2).
L’intérêt du scanner multibarrettes, dans l’étude de la perfusion cérébrale au décours d’un infarctus au
stade aigu, permettrait de différencier la zone infarcie, de la pénombre ischémique et donc de sélectionner
76
les patients en vue d’une éventuelle thrombolyse (7, 8). La principale limite est la hauteur d’exploration,
24 mm avec un scanner 16 barrettes, responsable d’une méconnaissance des infarctus situées en dehors de
ce volume exploré. Nous avons également observé un manque de sensibilité pour les petits infarctus
territoriaux et lacunaires.
Cependant, une meilleure couverture volumique est apportée aujourd’hui par les scanners à 64 barrettes
(40 mm d’épaisseur en haute résolution) et l’évolution va encore se poursuivre.
Quant à l’étude des lésions parenchymateuses, elle bénéficie des possibilités d’excellentes reconstructions
tridimensionnelles. Mais, ceci concerne surtout les patients présentant une contre-indication à l’IRM.
En conclusion, les améliorations obtenues sont le volume exploré, la réduction des artéfacts de
mouvements et métalliques et l’amélioration de la résolution spatiale longitudinale et temporelle. Les
améliorations attendues concernent essentiellement la rapidité du post traitement des images,
l’amélioration de la résolution spatiale dans les trois plans de l’espace et l’augmentation de la zone de
couverture dans la perfusion cérébrale.
1- Randoux B, Marro B, Koskas F et al. Carotid Artery Stenosis: Prospective Comparison of CT,
Three-dimensional Gadolinium-enhanced MR, and Conventional Angiography. Radiology 2001;
220: 179-185.
2- Zouaoui A, Sahel M, Marro B et al. Three-dimensional computed tomographic angiography in
detection
of
cerebral
aneurysms
in
acute
subarachnoid
hemorrhage.
Neurosurgery. 1997 Jul; 41(1):125-30.
3- Chen CJ, Lee TH, Hsu HL et al. Multi-Slice CT angiography in diagnosing total versus near
occlusions of the internal carotid artery: comparison with catheter angiography. Stroke. 2004 Jan;
35(1):83-5.
4- Jayaraman MV, Mayo-Smith WW, Tung GA et al. Detection of intracranial aneurysms: multidetector
row
CT
angiography
compared
with
DSA.
Radiology. 2004 Feb; 230(2):510-8.
5- Skutta B, Furst G, Eilers J, Ferbert A, Kuhn FP. Intracranial stenoocclusive disease: doubledetector helical CT angiography versus digital subtraction angiography. AJNR Am J Neuroradiol.
1999 May; 20(5):791-9.
77
6- Ozsvath RR, Casey SO, Lustrin ES, Alberico RA, Hassankhani A, Patel M. Cerebral venography:
comparison of CT and MR projection venography. AJR Am J Roentgenol. 1997 Dec;
169(6):1699-707.
7- Eastwood JD, Lev MH, Wintermark M et al. Correlation of early dynamic CT perfusion imaging
with whole-brain MR diffusion and perfusion imaging in acute hemispheric stroke. AJNR Am J
Neuroradiol. 2003 Oct;24(9):1869-75.
8- Wintermark M, Reichhart M, Cuisenaire O et al. Comparison of admission perfusion computed
tomography and qualitative diffusion- and perfusion-weighted magnetic resonance imaging in
acute stroke patients. Stroke. 2002 Aug;33(8):2025-31.
Fig 1a
Fig 1b
Fig.1 : Sténose athéromateuse serrée de l’artère carotide interne. Thrombus endoluminal de la pointe du
bulbe bien visualisé sur les coupes MPR fines sagittale (a) et axiale (b)
78
Fig 2 : Scanner multibarrettes réalisé sans injection de produit de contraste. Reconstruction VRT.
Thrombophlébite du sinus longitudinal supérieur et des veines corticales adjacentes.
79
Chapter VI – J. Ruscalleda
Infections diseases of the central nervous system
Jordi Ruscalleda,
Professor and Director, Servicio de Radiologia-Neuroradiologia,
Hospital de la Santa Creu I Sant Pau,
President –Elect of the E.S.N.R..
Barcelona, SPAIN
In spite of the great advances in diagnostic imaging as well as in therapeutic availabilities, CNS infections
have not decreased their present morbi-mortality.
The incidence and characteristics of infectious processes that can affect CNS are very different when we
consider those processes in developed or undeveloped countries, when we analyse them from the
geographical point of view or as regard to the different periods of life.
Many factors are responsible for this different distribution and persistence of CNS infections.
1. - In the last two decades the increasing incidence of AIDS was under the major scope of CNS infections
and hopefully nowadays is much better under control.
2. - The present aggressive and different treatments that induce an immunodepressed state are responsible
of many CNS infections.
3. - Many viral infections with a not very effective treatment are involved in CNS infections
4. - The expansion of infections is made easier by the large movement of populations.
CNS has a limited mechanism of defence represented by skull, meninges and BBB their involvement
and failure is the first step in CNS involvement.
Present imaging studies, mainly CT and MR, allow a close and prompt diagnosis.
Learning objectives
To offer a large overview about the present different infectious processes involving CNS.
To learn the different neuradiological patterns and differential diagnosis of this infectious processes
To emphasise the progressive replacement of advanced MRI over TC as the method of choice in the
approach of CNS infections.
CNS INFECTIONS
Unfortunately CNS infections still represents a significative group of processes with a quite severe
dysfunction's in the follow-up of affected patients.
Several ways to present and describe CNS infections from the neuroradiological point of view:
Clinical point of view, like neurologist, talking about fever, headache, neck stiffness, and loss of
neurological functions or CSF findings.
Physio-Pathological aspects of CNS infections, explaining meningeal changes, the abscess process
formation, encephalitis or mechanisms of demielinated processes in AIDS.
The morphological point of view showing different meningeal thickenings and contrast uptakes,
describing round masses, granulomatous processes or focal and diffuse white matter diseases.
And other way to explain this topic would be Causal:
Traumatic infections
80
Surgical infections
Pediatric infections
AIDS related infections
Facial and petrous infections
In my opinion all the aspects are important and helpful in the management of CNS infections.
For all of that I insist on how important is the clinical and phisio-pathological knowledge of CNS
infections and diseases.
For academic and didactic purposes we classify CNS infections into:
Brains Abscess
Meningitis and Ventriculitis
Encephalitis
Parasitosis
MENINGITIS AND VENTRICULITIS. IMAGING
Inflammatory process of the dura matter, leptomeninges (pia and arachnoides) and CSF within the
subarachnoid space.
Meningoencephalitis represents an extension to the brain parenchyma.
Ventriculitis represents an extension to ventricular ependyma.
Meningitis needs a prompt diagnosis and specific treatment. Is an emergency because untreated patients
have a fatal outcome.
1. - Normal meninges and extra-axial spaces
Duramatter (pachymeninx): two layers:
Outer or periosteal. Highly vascularized, of not true meningeal origin ending at the foramen
magnum.
Inner layer, embryiologically derived from the meninx and continuous with the spinal duramatter.
Some reflections forms the falx cerebri, falx cerebelli and tentorium cerebelli.
Leptomeninges (arachnoid and piamatter)
The arachnoid is applied to the inner dura and the piamatter covers the brain.
2. - Clinical and pathophysiological features
Signs and symptoms are fever, nuchal rigidity as well as neurological signs and symptoms related to
stage of the illness, organism, age, state of previous health.
There are four routes of entry infectious agents into the CNS
Hematogeneous spread (arterial or venous) the most frequent
Direct implantation: traumatic, lumbar puncture or surgery
Local extension (air sinuses)
Along the peripheral nervous system. Viruses: rabies and herpes simplex.
The most important pathogens:
a) Acute Bacterial Meningitis
Streptococcus pneumoniae 47%
Neisseria meningitides
Haemophilus influenzae B 7%
Listeria monocytogenes
Streptococcus group B
25%
59% in patients 19 years and older
(part of human microflora)
8%
12%
45% in infants below 2 years
Meningococcal meningitides (13 different serogroups)
81
Tbc
b) Viral meningitis
Aseptic meningitis syndrome. LCR with pleocytosis with lymphocitic predominance.
Nonpolio enteroviruses
Mumps (the most common cause of aseptic meningitis)
Arboviruses (Encephalitis)
Herpes viruses (Encephalitis)
HIV
Adenoviruses (infants)
Polioviruses types 1,2,3
Meningitis are classified according to inflammatory exudate, CSF exam and clinical evolution.
Acute piogenic (bacterial)
Aseptic (viral)
Chronic (parasitic and fungi)
3. - Role of imaging
The first purpose of CT or MRI is to detect possible complications of meningitis: Hydrocephalus and
infarction.
Gd Contrast enhancement is positive in 55-70% of infectious cases but insensitive in viral meningitis.
4. - Bacterial meningitis
Acute bacterial (pyogenic) meningitis
Microorganism
Neonates
escherichia coli and group B streptoccoci
Infants, children: Haemophilus influenzae (basal)
Adolescents: Neisseria meningitides
80% convexity
Elderly: Streptococcus neumoniae. Lysteria monocytogenes
immunocompromised : klepsiella.
Anaerobic agents. (Ventriculitis)
Fungi.(Meningoencephalitis)
CSF cloudy or purulent. Meningeal vessels engorged.
Involvement of superficial arteries and veins, responsible of thrombosis and infarction.
Two patterns of contrast enhancement
Dural enhancement: follows the inner contour of the calvaria
Pia-subarachnoid enhancement: extends into the depths of the cerebral and cerebellar sulci and
fissures.
Differential diagnosis with neoplastic subarachnoid dissemination (carcinomatosis), more irregular and
nodular enhancement.
b. - Tbc Meningitis
Tbc is rising in the last two decades. 2-5% of patients with peripheral tbc have CNS tbc and in 10% of
AIDS-related patients.
Pattern: diffuse meningoencephalitis with a predominant characteristic of leptomeningeal opacification
and thick gelatinous infiltrates in the basal cisterns, sometimes with subarachnoid granulomas and blood
vessels involvement (spasm, arteritis, and thrombosis).
Mechanisms of CNS infection:
Rupture of subependymal or subpial granuloma into de CSF.
Hematogeneous spread to the meningeal vessels.
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c. - Neurosyphilis.
Basal predominance with obliterative endoarteritis.
d. - Neuroborreliosis (Lyme Disease)
Borrelia burgdorferi. Cranial nerve palsy, mild encephalopathy and polyneuropathy. Multiple unspecific
foci of brain infarction or borrelia granulomas.
5. - Complications or manifestations of bacterial meningitis
a. - Hydrocephalus.
Communicating hydrocephalus is the most frequent complication due to a leptomeningealependymal fibrosis secondary to gelatinous exudates are the main cause and block of CSF resorption
mainly at the level of the arachnoid villi
B- Extra-axial fluid and pus collections.
Subdural effusion and hygroma
They are sterile collections secondary to irritation of the dura or veins inflammation with an
increase of proteins and fluid in the subdural space.
Easily detected by imaging. No treatment. Spontaneously resolved.
Subdural Empyema
13-20% of intracranial infections. Bacterial and fungal infections of the calvaria and paranasal
sinuses can produce and Empyema. The mechanism is a thrombophlebitis via the calvarial emissary veins.
They are extra axial collections slightly hiperdense than CSF with a rim of contrast enhancement
(inflammatory membranes). Possibility of thrombophlebitis of bridging veins and cerebral infarctions.
Epidural empyema
c. - Cerebritis and parenchymal abscess formation
Spread from contiguous infections of the meninges by retrograde thrombophlebitis or direct
extension into the brain via de pia matter or along the penetrating perivascular spaces: early phase of
abscess formation.
d. - Abscess formation
e. - Central nervous system infarction
Secondary to inflammatory arterial spasm, o inflammatory infections of the arterial walls: arteritis.
Sometimes is difficult to differential infarction secondary to vascular involvement or focal brain
encephalitis. (MRA useful).
6. - VENTRICULITIS
Serious infectious process involving the cerebral ependyma secondary to meningitis, rupture of a
parenchymal abscess, surgery, catheter placement.
Imaging:
Some degree of ventriculomegalia
Subtle areas of periventricular low density
Enhancement along ventricular walls
IN chronic stages periventricular calcifications may be seen especially in perinatal ventriculitis especially
in the so-called TORCH infection:
Toxoplasma
Other (syphilis, HIV)
Rubella
Cytomegalovirus
Herpesvirus
7. - Acute aseptic (viral) meningitis
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Clinical syndrome with lymphocitic pleocytosis in the LCR
8. - Cytomegalovirus (CMV)
Is a ubiquitous DNA virus belonging to the herpesvirus family. Severe neurological dysfunction.
The hallmark in periventricular calcifications detected by CT. CMV has special affinity for the
metabolically active neuroblasts of the subependymal matrix and regional vasculature with a result of
subependymal degeneration and calcification.
9. - Fungal Meningitis
a) Criptococcus neoformans
The most frequent fungus that enters the body via the respiratory tract, then spread hematogeneously from
the lungs to the CNS.
Primary manifested as meningitis, although parenchymal mass lesions can also develop.
Highly prevalent in AIDS.
Imaging:
Meningitis with cystically dilated perivascular spaces filled with mucoid material as a response to the
immune system (gelatinous pseudocysts) and parenchymal criptococcomas formation.
10. Parasitic Meningitis
Cysticercosis (taenia solium)
Ingestion of eggs in contaminated water or food.
In the CNS Neurocysticercosis may be parenchymal, leptomeningeal or intraventricular.
When the scolex lodges de brain develops a cystic covering around it with a first inflammatory
parenchymal reaction with a granulation and connective capsule formation.
When the larva dies a secondary inflammation and posterior calcification
11. - Toxoplasmosis (TORCH group).
Toxoplasma gondii
Congenital: meningitis, chorioretinitis, hydrocephalus and intracranial calcifications.
12. - Non-infectious meningitis
Neoplastic meningitis
Sarcoidosis
Chemical meningitis
Cranial hypotension
Postsurgical states
ENCEPHALITIS. CEREBRITIS. BRAIN ABSCESS.
Encephalitis
Generalised and diffuse infection of the brain. Often as a result of a viral infection due to prevention and
treatment of bacterial diseases, increase of immunosuppresed patients (like AIDS) and in the course of
transplant and cancer patients.
Different types according to the site and tempo of infections.
Viruses can lead to:
Meningitis
Acute infective encephalitis
Acute disseminated encephalomielitis
Subacute or chronic encephalitis
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Encephalitis and myelitis
Herpes simplex encephalitis (type 2 predominantly in temporal lobe)
Enteroviruses and arboviruses encephalitis
Mechanism of CNS viral infection
Infections of the CNS by viruses begin with the local growth of virus in nonneural tissue. Spread of
viruses to the CNS primarily occurs by the Hematogeneous or neural route.
Most of them gains access through the bloodstream (viremia).
The viruses protect themselves against the reticuloendotelial system (RES) entering and growing in
lymphocytes (measles and mumps). HIViruses enter mononuclear cells that carry the CD4 antigen.
Poliovirus infects and grows in the lymphoid tissue of the gut. Arboviruses grow in the spleen and lymph
nodes.
From there viruses gain the CNS through perivascular spaces traversing the endothelium by pinocytosis
or growing into the endothelial cells. Entrance in the CSF is through the epithelial cells of the choroid
plexus.
Once in the CNS two major factors affect the general pathologic features:
The cell type infected (different susceptibility): specific viral receptors.
The host's immune response
The tempo leads to a varied appearance of CNS viral infections
a) Cells susceptibility
Coxsackie, echovirus and mumps rarely infect neurons but frequently meninges.
Poliovirus infects neurons (motoneurons) leaving sensory pathways untouched.
Rabies infects neurons and much less oligodendrocytes
Herpesvirus infects neuron and glial cells: predilection for cell population in limbic system.
JC virus attacks only oligodendrocytes leading to demielination
Host immune response
Humoral response against the virus
Acquired antibody after previous infections or vaccination. Local infections is quelled (sofocada) by
IgA in the respiratory tract, tears, saliva or gut. IgA or IgM restricts blood-borne dissemination.
Antibodies in tissue spaces prevent spread of infection between cells.
Cell-mediated response directed against the infected cell
Pathological features
Macroscopic: meningeal opacity, vascular congestion and brain swelling.
Microscopically: infiltration of brain by inflammatory cells.
Early on by polymorphonuclear cells
Later on by lymphocytes, plasma cells and large mononuclear cells. Perivascular cuffing of
mononuclear cells in the Virchow-Robin spaces in small venules and thicker cuffs of lymphocytes
around larger vessels are characteristic.
Microscopic response of host cells: hypertrophy and proliferation of microglial cells (mainly in the
cortex and deep grey matter), astrocytosis present when necrosis has occurred), neuronal changes (the
result of terminal hypoxia or brain swelling. Cytoplasm vacuolation specific of the spongiform
encephalopathy) and presence of inclusion bodies (specific of viral infection)
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ACUTE INFECTIVE ENCEPHALITIS
Brain damage is the result of viral intracellular growth and the host's inflammatory response.
Most common: herpes, rabies, arthropos-borne viruses and enteroviruses (polio).
Brain necrosis is frequent either selective or complete brain infarction.
Herpes viruses: simplex type 1 and 2 (HSV-1, HSV-2), CMV, Epstein-Barr V., varicella-zoster v., B
virus, herpesvirus 6 and 7.
Perivascular cuffing and inflammatory infiltrates are key features. Necrosis present in the more
aggressive.
HSV-1 is the cause of 95% of all herpetic encephalitis
Necrosis of temporal and Occ-frontal lobes. Less frequent in insula, occipital and cingulate gyrus.
Putamen frequently spared. Trigeminal ganglion is the site of viral reactivation o a latent
infection with spread along his branches. Biopsy is not needed because imaging is quite specific
and the non-toxic treatment with acyclovir.
Imaging HSV-1. Uptake of technetium pertechentate in various regions mainly in temporal lobe
positive in 85% of cases.
CT: hypodensity in 75% of cases present in the first 2-3 days. Hemorrhage frequent and highly
suggestive but sometimes difficult to be seen by CT.
MR study of choice. Temporal and inferior frontal lobes involvement. Basal ganglia spared. Often
bilateral involvement. Gyriform enhancement.
ACUTE DISSEMINATED ENCEPHALOMYELITIS (ADEM)
5 days-2 weeks after viral illness or a vaccination. Headache, fever and drowsiness and focal neurological
deficits.
Pervious demyelination is the hallmark of ADEM with a probably immunologic mechanism.
MR study of choice. Scattered plaques throughout the white matter of cerebellar and cerebral
hemispheres. No mass effect. Contrast enhancement very variable. Differential diagnosis with ME.
High-dose of steroids is the treatment.
SUBACUTE ENCEPHALITIS
Includes:
Subacute Sclerosing panencephalitis (measles virus)
Progressive Multiphocal Leucoencephalopathy (PML). JC-virus
HIC encephalitis
Tropical Spastic paraparesis (HTLV-1)
CMV encephalitis
Creutzfeldt-Jakob disease (proteinaceous particle: the prone)
All of them have and a relatively insidious onset.
Creutzfeldt-Jakob disease (proteinaceous particle: the prion)
Human spongiform encephalopathy as a result of infection by a slow unconventional virus. The infective
prion is a proteinaceous infectious particle that resists activation by procedures that modify nucleic acids.
They contain little or no nucleic acid and do not evoke an immune response.
1/1m. Dementia. Poor prognosis.
Brain atrophy non-specific. Pathologic changes: neuronal loss, reactive astrocytosis, neuronal vacuolation
with spongiform changes.
MR: to exclude treatable lesions. Hypersignal T2 in the corpus striatum (frequent). Cortical
hyperintensities have been described. Atrophy with rapid progression. MRE, decreased NAA/Cr. PET:
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decreased perfusion and hypometabolism.
CEREBRITIS ANS ABSCESS
Decline in the incidence and mortality (14%) thanks to the efficient use of antibiotics.
Source of infection: local or blood-borne. The first related to trauma or petrous and sinusal infections.
The second related to infections in the respiratory tract and in immunocompromised patients. 25% of brain
abscess have an unknown origin.
Abscess formation follows different stages described by Enzmann: 1) Early cerebritis 2) late cerebritis 3)
early capsule formation 4) late capsule formation. The abscess is preceded by focal cerebritis with
endothelium swelling of the local capillaries and migration of polymorphs, perivascular infiltration, focal
oedema, and petechial hemorrhage displayed on MRI as a focal area of unspecific edema. Progression to
abscess occurs when a central zone of necrosis becomes better defined and liquefied with a peripheral
collagen capsule. The collagen capsule is usually less well developed on the ventricular side likely related
to differences in blood supply a weak point for daughter abscess formation.
Abscesses from Hematogeneous origin are mainly located at the grey-white matter junction.
MR imaging features of brain abscesses display the capsule as an iso to slightly hyperintense signal on T1
and hypointense on T2 probably due to the presence of paramagnetic free radicals. The capsule enhances
with gadolinium. The centre of a mature abscess with necrotic material, displays on T1 a low signal higher
than CSF and high signal on T2 similar to CSF or perilesional vasogenic edema.
Thallium-201 scanning may be useful in differentiating an abscess from a necrotic tumour because there is
preferential uptake of thallium by tumors particularly of those of higher grade. (Not clear).
Differential diagnosis:
Primary brain tumors
Metastasis
Septic and aseptic infarction
Resolving hematoma
Thrombosed aneurysms
Arterio-venous malformations
Tumefactive MS
Lymphoma
MRE
Abscess cavity with a lack of normal metabolites often contains amino acids and lactate, succinate and
acetate that are not present in necrotic tumors.
CNS TUBERCULOSIS
Incidence variable in diferent countries and population.
1.5/105/year.
Hematogenous spread with small subpial or subependymal cortical focus of infection (Rich focus). When
such a focus ruptures it contaminates the subarachnoid spaces and cerebrospinal fluid and spreads along
the cereborspinal fluid pathways giving rise to tuberculous meningitis. Other manifestations are:
Tuberculomas
Tuberculous abscess
Tuberculous cerebritis
Pachymeningitis
Spinal areachnoiditis
Intraspinal tuberculoma
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TBC meningitis
Proliferative arachnoiditis and meningeal exudate predominantly in interpeduncular and
pontomesencephalic cisterns progressively impeding de CSF circulation (communicanting hydrocephalus)
and arteries and veins may become involved (vasculitis).
CT and MR imaging, obliteration of basal cisterns and contrast enhancement of basal meninges.
Hydrocephalus present in more than 50% of cases
Vasculitis by direct invasion of vessel wall may lead to spasm and thrombosis with hemorrhagic infarction
mainly at the basal ganglia present in more than 25% of cases.
Granulomatous tuberculous meningitis is uncommon with diffuse or circunscribed granulomas in the basal
cisterns.
A more diffuse chronic leptomeningeal infection is called leptomeningitis.
Parechymal tuberculomas is thougth to be secondary to an infective focos elswhere in the body. They can
be single or multiple, small or large and can be located enywhere in the cerebrum, brainstem and posterior
fossa. Two forms a) noncaseating granulomas with or without contrast enhancement and only abbormal
signal on MR or b) Caseating granuloma with a typical ring-enhancing lesion. A target sign with presence
of central calcification in a hypodense center of a ring enhancing lesion is characteristic but nor
pathognomonic.
Ricketsiosis
Gram.negative nonmotile bacteria
a) Rocky Monutain Spotted fever
Ricketsia rickettsii spreads hematogenously producing vasculitis with damage to the endothelial
blood vessels walls of any organ. Cutaneous rash (palms, soles and anterior aspects of distal extremities)
and mialgias.
Brain lesions: perivascular accumulations of mononuclear cells (typhus nodule) with arterial infarction,
cerebral edema and diffuse meningeal enhancement.
Epidemic typhus (R. Prowazekii). Inades the endothelial cells of blood vessels.
Q fever (Coxiella burnetii)
Spirochetes (gram.negatives organisms)
Syphillis
Lyme Disease (borrelia burgdorferi)
Leptospirosis
PARASITES
Cerebral malaria
Toxoplasmosis gondii
Amebiasis
Neurocysticercosis
Amebiasis (entamoeba histolitica). Fecal-oral transmission. Reproduction in the colon. Hematogeneous
dissemination can reach the CNS.
Brain abscesses caused by E. Histolytica are similar to those produced by bacteria, tuberculosis,
nocardia with an hipodense central zone, a ring-enhanced capsule and marked surrounding edema.
Schistosomiasis
More than 200 million in Asia, tropics and subtropic areas.
Schistosoma haematobium, japonicum and mansoni.
Infected water. Skin of humans. Systemic veins and lymphatics and maturation of the larvae in the
liver.
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Brain imaging ara homogeneous or heterogeneous lesions with contrast enhancement and edema. No
specific signs.
Toxoplasmosis. Toxoplasma gondii.
Intrauterine infection: chorioretinitis, encephalomyelitis, hydrocephalus and microcephaly.
AIDS. 28% of patients have toxoplasmosis.
Lesions typically located in the corticomedullary junction and in the basal ganglia.
CT and MR are useful for diagnosis and follow-up. Lesions dysplay tipical pattern of and abscess. The
enhancement of the capsule is in relation to the immunity capacity of inflammatory reaction.
Hyperintense masses on T2 represents areas of necrotizing encephalitis in early toxoplasmosis and
the isointense masses, seen after treatment, probably represents organizing abscesses.
Rapid response to treatment (12-15 days) confirms the diagnosis of toxoplasmosis and failure to
respond to antibiotic treatment suggest another diagnosis. Is frequent that two different diesease
processes may be occurring simultaneously.
In AIDS differential diagnosis is between toxoplasmosis and lymphoma
ToxoplasmosisLymphomaCTHyperdense noncontrast CT
Subapendymal spreadSPECT
PETNO increased uptakeHypermetabolism, resulting in increased tracer activityMREIncreased lipid and
lactate peaks and a deceased in other metabolitesMild-moderate increase in lipid and lactate but a large
increase in choline peaks.
Hydatidic disease
Echinococcus granulosus and E. Multiloculares. Dog and carnivore is the definite host (intestinal). Eggs
excreted and eaten by grazing animals and embrio released and through bowell wall go into the portal
venous or lymphatic system. Liver the embrio matures into a cyst.
Cerebral hydatidic cyst usually unilocular. CT shows a well-defined, smooth, thin-walled, homogeneous
cystic lesions similar in density to CSF. Capsule is difficult to be seen an enhancement in uncommon.
Edema rare. With MR the capsule is better seen.
Cysticercosis
Wide variety of neurologic syndromes induced by CNS infestation of cysticerci, le larva of Taenia
Solium.
Endemic in many areas (South America, Africa, Asia. East Europe.
The CNS is involved in 60-90% of patients with cystecircosis.
Parenchymas lesions of 10mm or less. Central hemisphere and basal ganglia.
Subaracnoid lesions: cortical sulci, basal cisterns, intraventricular.
ImagingEscobar's Stages
1.- Vesicular stage: the larva is seen as a small marginal nodule into a small cyst containing clear
fluid. The parasite may remain in this stage for years. No contrast enhancement.
2.- Colloidal vesicular stage. The larva beguins to degenerate as a result of host's immune
response. Scolex shows signs of hyaline degeneration and gradual schrinkage. Fluid becomes turbid and
the capsule thicker. Surrounding edema. Contradt enhencement and hiperdense contents.
3.- Granular nodule stage. Capsule thickens and scolex mineralise. Edema regresses.
4.- Nodular calcified stage. Lesion completely mineralized.. No edema.
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FUNGAL INFECTIONS
Criptococcus neoformans
Coccidioidomycosis
Histoplasmosis
Blastomicosis
Candidiasis
Aspergillosis
Mucormycosis
With The advent of immunosuppressive therapy in organ transplant patients and HIV disease fungal
infections has become less rare.
Fungi may exist as single cells (yeast) or in colonies (hyphal form) and may coalesce and form micelia.
Hematogeneous spread.
Yeast forms: blastomyces, Candida, Coccidioides, cryptococcus, histoplasma and torulopsis.
Hyphal forms: Aspergillus, mucormycosis, pseudallescheria.
Aspergillosis
Aspergillomas are close to the paranasal sinuses, and display abscesses not specific from other causes.
50% cases associated hemorrhage
Low density due to the presence ef calcium, magnesium, manganese and iron.and decreased signal
intensity on T2w.
Mucormycosis
Diabetes high risk.
The triade of diabetic ketoacidosis, meningoencephalitis and naso-orbital infection haigly suggest the
diagnositc of mucormycosis.
Other risk factors: metabolic acidosis: sepsis, severe dehydration, chronic renal failure.
Propensity for vascular structures: arteritis, ischemic changes, hemorrhagic infarcts and aneurysms
formations.
Hystoplasmosis.
Candidiasis
Coccidioidomycosis
Cryptococcal infection: the most common in AIDS patients. Meningitis producing hydrocephalus.
Noenhncing lesions in the basal ganglia filling the Virchow-Robin spaces produced by mucoid material.
CNS infections in Pediatric population.
Intrauterine and neonatal: malformations
Infants: destructive lesions
Congenital are infections transmited from the mother. Neonatal the first 4 weeks of life. The immune
system is not fully developed. TORCH infections.
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Chapter VII – J. Ruscalleda
CT and MR of neurocritic patient: diagnostic and prognostic value.
Jordi Ruscalleda
Professor and Director, Servicio de Radiologia-Neuroradiologia,
Hospital de la Santa Creu I Sant Pau,
President - Elect of the E.S.N.R..
Barcelona, SPAIN
All CNS lesions are relevant, however some of them, due to their nature, extension and/or form of
presentation, require the vigilance, control and management from part of specially trained medical and
nursing personnel, in order to foresee, identify of react to all critical situations that may provoke a
permanent brain damage.
Many CNS pathological processes require the assistance and benefit of Neurological Intensive Care
Units (NICUs) either from the beginning, or during the pathological course, or as a consequence of the
performed therapies. Among them we would like to mention the stroke, the severe cranio-encephalic
traumas and the anoxic encephalopaty secundary to cardiorespiratory failure.
The NICUs utilize several monitoring devices to control end record the events that may lead to an
irreversible neurological damage, such as the recording of the intracranial pressure (IPC), the evaluation
of the cerebral blood flow (Intracranial Doppler) in order to recognize the vascular spasm or obstruction,
the EEG monitoring of the cerebral acitivity, the hemodinamic arterial and venous control, and the
recording of the somatosensory, motor or auditory evoked potentials. These are some of the present
techniques that may be used to maintain a close and effective control of the vital parameters, as well as of
the brain parenchyma functions.
The advanced neuroradiological examinations, e.g. CT and MR, when applied with the objective to
reach a profound evaluation of the structural and functional alterations of the CNS, constitute an important
part in the activity of the NICUs, either as to the comprehension and management of these patients when a
life-threatening event related to a neurological cause occurs, or in order to define a short- or middle-term
prognosis with a high degree of sensitivity and specificity, or to foresee the degree of neurological
impairment that these lesions may provoke.
We present a review of the impact of the CT and MR studies in the management of these patients,
either in the diagnostic or the prognostic phase.
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Chapter X– L. Picard
Middle Cerebral Artery Aneurysm’s.
Interest and indications of Endovascular Treatment 187 cases
Luc Picard, Serge Bracard, L.Thuillier René Anxionnat, Ariel Lebedinsky,
Stephanos Finitsis, Francesco Ramos,
Department of Diagnostic and Interventional Neuroradiology
Hôpital Neurologique, Nancy, France
From October 1992 until December 2004, 940 patients who presented with 1120 aneurysms were
observed in the Department of Neuroradiology. 238 aneurysms ( 21,2 %) were located on middle cerebral
artery. This location concerned 21,5% of the patients. This study is realized on 174 patients ( 187
aneurysms ) with middle or long term follow up; the clinical and angiographic follow up has been realized
at 6 months, 1 – 3 and 5 years. 83 patients presented with ruptured aneurysms – 104 aneurysms were
unruptured ( fortuitous discovery or neurologic disturbances )
Indications :
According to an excellent cooperation between neuroradiological and neurosurgical team, as far it is
possible, we first try to treat the intracranial aneurysms by endovascular approach. Consequently 152
aneurysms ( 81,3 % ) were successfully treated by endovascular occlusion : 75 ruptured and 77
unruptured; for 7 patients ( 3,7 % ), the attempt of endovascular occlusion failed.
Anatomical Results in 174 patients ( 187 aneurysms ):
75 ruptured and 77 unruptured aneurysms were treated. Among the ruptured aneurysms, complete
occlusion ( 100 % ) was achieved in 22 cases ( 29,3 % ), good occlusion ( > 90 % ) in 38 cases ( 50,7 % )
and partial occlusion ( < 90 % ) in 15 ( 20 % ). For the unruptured aneurysms, the results were a little
better : complete occlusion in 24 ( 31,2 % ), good occlusion in ‘é ( 54,5 % ) and partial occlusion in 11 (
14,3 % ). If we add complete and good occlusion on both ruptured and unruptured aneurysms, good
anatomical results ( > 90 % ) were obtained in 126 cases ( 82,9 % ). The late middle term follow up is
characterized by 14 recanalizations but only 5 patients needed to be retreated either by neurosurgery or by
endovascular approach.
Clinical results :
According to the Glasgow Outcome Scale, 134 patients ( 72 % ) are Grade I and 28 ( 15 % ) Grade II what
means 87 % of very good clinical outcome. Only six patients ( all ruptured ) were Grade IV/V. When we
know the seriousness of the ruptured middle cerebral artery aneurysms, such results can be considered as
very interesting.
Incidents and Complications :
26 technical incidents and/or complications were observed on 187 procedures : 17 during the endovascular
approach and 9 during the post procedural week.
Among the per procedural complications, we find 3 aneurysmal sac ruptures ( 1,6 % ), 8 thrombo embolic
events ( 4,2 % ), 5 strokes and 1 erratic coil migration. It is interesting to emphasize that all the aneurismal
sac ruptures were and remained asymptomatic without any worsening.
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Post procedural complications : 4 rebleedings – 4 ischemic events – 1 hematoma related to the femoral
puncture. Among the precocious rebleedings, we observed 2 deaths directly related to this complication.
Learning curve : The analysis of the complication rate shows that the maximum of complications has been
observed during the first years of our experience, between 1992 and 1996. This first period was the
beginning of the techniques of coiling; now the complication rate is dramatically reduced.
Conclusions :
The evolution of treatment indications of MCA aneurysms is very slow but certainly inescapable. This
localization is reputed to be a poor indication of endovascular approach. The tridi angiography has really
modified our possibilities allowing us a better understanding of angioarchitecture. Thanks to these
technical improvements, the MCA aneurysms can be considered as an excellent indication for coiling
allowing excellent anatomical and clinical results.
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Chapter XI – S. Braccard
Extra and Intracranial dissection: diagnosis and therapy
Serge Bracard, René Anxionnat, Jean Christophe Lacour, Ariel Lebedinsky,
Francesco Ramos, Stephanos Finitsis, Luc Picard
Department of Diagnostic and Interventional Neuroradiology
Hôpital Neurologique, CHU de Nancy, Nancy, France
DISSECTIONS OF CERVICAL ARTERIES
Cervical artery dissection is one of the most frequent causes of stroke. The annual incidence of
spontaneous carotid- artery dissection is ranged from 2.5 per 100,000 to 3 per 100,000.
Dissections of the carotid and vertebral arteries usually arise from an intimal tear that allows blood to
enter the wall of the artery and to form an intramural hematoma. This hematoma is located within the
layers of the tunica media, but it may be eccentric. A subintimal dissection tends to result in stenosis of the
arterial lumen, whereas a subadventitial dissection may cause aneurismal dilatation of the artery.
Clinical Manifestations
Patients with carotid artery dissection typically present unilateral facial and cervical pain accompanied by
a partial Horner’s syndrome and followed hours or days later by cerebral or retinal ischemia. Cranialnerve palsies can be detected in more than 10 percent of patients. The lower cranial nerves are the most
commonly affected, particularly the hypoglossal nerve.
Patient with vertebral-artery dissection typically present pain in the back of the neck or head. Ischemic
symptoms occur in more than 90 percent of patients. Transient ischemic attacks are less frequent after
vertebral- artery dissections than after carotid-artery dissections.
Imaging
In about 15 to 25% of patients, dissections are detected in two or more vessels, and these multivessel
dissections often appear to have occurred at the same time.
Magnetic resonance techniques are replacing conventional angiography as the gold standard in the
diagnosis of dissections of the carotid and vertebral arteries, for it may display the intramural hematoma
itself as a crescentic shape adjacent to the vessel lumen and often spiraling along the artery. Fatsuppression techniques are important to differentiate intramural hematomas from the surrounding soft
tissues. Ultrasonographic techniques are useful in the initial assessment, an abnormal pattern of flow is
identified in more than 90 percent of patients
Prognosis
The reported rate of death from dissections of the carotid and vertebral arteries is less than 5 percent. The
local evolution is usually good: about 90 percent of stenosis eventually resolve, two thirds of occlusions
are recanalized, and one third of aneurysms decrease in size. This improvement takes place largely within
the first two to three months after the dissection and is rare after six months.
Persistent extra cranial aneurysms may exceptionally cause thromboembolic complications, but they never
rupture.
In our French multicentric study (432 patients, mean follow-up of 31 months), the risk of a recurrent
dissection is about 1% and the risk of recurrent ischemic stroke is also about 1 percent particularly during
the first month.
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Treatment
To prevent thromboembolic complications, anticoagulation with intravenous heparin followed by oral
warfarin for three to six months has been recommended for all patients with acute dissections of the
carotid or vertebral artery.
Endovascular treatment, consisting of percutaneous balloon angioplasty and placement of one or more
metallic stents, has supplanted surgery as the initial therapy of choice once medical therapy fails. If
needed in emergency, cervical angioplasty may be combined with intra arterial thrombolysis. Later,
aneurysms may be treated by covered or uncovered stents, however this treatment is seldom necessary and
the long-term results of carotid stenting are unknown.
DISSECTION OF INTRA CRANIAL ARTERIES
The real incidence of SAH due to a dissecting aneurysm rupture is unknown and is probably
underestimated. For histologic reasons the great majority of intracranial dissections related to SAH are
located in the posterior circulation. Despite the attention paid to this pathology in the past years the
published series remain short and there are still no consensus in the management of this group of patients.
Several series report a high rate of rebleeding especially in pseudoaneurysmal types. Most of these
rebleedings occur in the first few days after the haemorrhage and early treatment is thus recommended.
Our study involved a retrospective review of 27 patients with 29 dissections treated over a 16-year period
mainly by endovascular treatment (EVT).
Endovascular treatment was performed in the acute stage in 12/29 dissections, occlusion was performed
using coils at the dissection site in 6 and with proximal balloon occlusion in 6. Wrapping was performed
in one case. 16 dissections were not treated mainly for anatomical reasons. In this group, 3 patients died,
one of them from rebleeding. Angiographic follow-up performed in the 13 surviving patients
demonstrated initially misdiagnosed lesion in 1 and worsening lesions in 5 which led in delayed EVT in 5
and surgical clipping in 1. One of these dissections located on a dominant vertebral artery was treated after
a subsequent rupture using a stent and coils to preserve the patency of the parent vessel. Four ischemic
complications related to EVT resulted in a moderate disability in 2 patients. No rebleeding occurred after
EVT, 1 patient died due to a poor initial clinical status, other patients improved. In the 10 patients
conservatively treated, 4 patients died, 3 from a poor initial clinical status, 1 from rebleeding and 6 had a
good clinical outcome. Of the 27 patients, 3 had a rebleeding and 1 died from this rebleeding. Seventeen
patients (63%) had a good recovery, 6 (22%) had a moderate disability and 4 (15%) died.
Conclusion: EVT provides effective protection against rebleeding. Occlusion with coils at the dissection
site, when possible, is the current method of choice. Other options are parent artery occlusion with
balloons, while the use of stent may allow to preserve the permeability of the vessel in specific cases.
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Chapter XII– S. Braccard
Acute and chronic brain ischemia: diagnosis and treatment
Serge Bracard, René Anxionnat, Xavier Ducrocq, Ariel Lebedinsky, Stephanos Finitsis, Luc Picard
Department of Diagnostic and Interventional Neuroradiology
Hôpital Neurologique, CHU de Nancy, Nancy, France
Stroke Therapy
The majority of ischemic strokes are due to thromboembolic arterial occlusion. Over the past few
years, there have been intensive investigations regarding intravenous therapy for the treatment of acute
ischemic stroke. At the present time, tissue plasminogen activator (rt -PA), when administered within the
three hours of symptom onset has been shown to be an effective therapy. The benefits were demonstrated
in the NINDS trial in 1995.
Intra arterial thrombolysis is thought to be more effective than intravenous rt-PA. In PROACT II,
patients within 6 hours of symptom onset with ACM occlusion were randomised to receive intra arterial
thrombolysis with systemic heparinization versus heparinization alone. A good or excellent score on
modified Rankin scale was achieved in 40% in the intra arterial group versus 25% in the control group.
Intracerebral hemorrhage rates were increased in the intra arterial group, however no difference in overall
mortality was observed.
A combined approach that uses the speed of initiation of therapy with IV rtPA and the improved
recanalizations efficacy of rapidly administered local IA rt-PA may improve patient outcome from major
stroke. In the first studies, combined intravenous – intra arterial thrombolysis seems to be more efficient
but need larger studies to be accepted.
Further research is being conducted in the use of mechanical devices (like MERCI trial) with good
results. The advantages of theses approaches include lack of systemic and hemorrhagic complications.
Carotid stenting
Carotid stenosis may cause ischemic events by reducing cerebral blood flow or by acting as a
source of thromboemboly. Randomized studies have established carotid endarterectomy to be an effective
therapy for patients with significant carotid stenosis. Additionally, CEA may reduce the risk of ischemic
events and overall mortality for patients with asymptomatic stenosis.
Carotid stenting (CAS) is the less invasive percutaneous procedure that is being investigated as an
alternative to CEA. At the present time carotid stenting may be particularly useful for patients who are
poor surgical candidates, have received prior radiation or have restenosis or bilateral lesions.
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In the past few years, evidence is growing that CAS might be an alternative to CEA and some series
showed comparable major stroke and deaths rate of CEA and CAS. In order to reduce embolization of
plaque fragments to the brain during CAS, cerebral protection devices have been developed. In the French
EVA 3S study, the risk of any stroke within 30 days was about 3 times that of patients treated with
cerebral protection and the safety committee of EVA3 S recommended to stop unprotected CAS .
Intracranial stenosis
Atherosclerotic disease of the intracranial vessels accounts fort approximatively 10% of ischemic stroke.
Despite antithrombotic therapy many patients have recurrent ischemic events. In the French GESICA
multicentric study 44% of 102 patients who were treated with maximal antithrombotic therapy had
ischemic events during the 24 months follow-up period.
Studies of intracranial angioplasty and/or stenting have shown high technical success rates of more than
90%. However, compared with extra cranial vessels, angioplasty of intracranial vessels has a higher
complication rate.
In the GESICA study, 28 angioplasties were performed with 4 complications (14.2%), 2 deaths: 1 arterial
rupture, 1 reperfusion haematoma and 2 strokes. During the follow up period (mean follow-up: 19.5
months) only 1 TIA was observed but no stroke.
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