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MRI - functional MRI, spectroscopy, etc
Lecture 23
Functional MRI:
Principles
Magnetic susceptibility χ:
M is the magnetization of the material, H is the strength of the external magnetic
field
Prerequisites:
Oxyhemoglobin
(oxygen rich hemoglobin) which
delivers oxygen in arteries to brain cell is diamagnetic χ > 0
Deoxyhemoglobin
(oxygen poor hemoglobin) which gave some of
its oxygen molecules to brain cells is paramagnetic: χ <0
χdeoxy>>χoxy
ratio ~ 65
Paramagnetic substance produces microscopic field inhomogeneities that
decreases the transverse relaxation time T2 of the blood and surrounding
tissues.
T2* images and blood oxygen
level depend (BOLD) contrast
(Ogawa, 1990)
Oxygenated
blood
Diamagnetic
Neuron
De-oxygenated
blood
Paramagnetic
Oxyhemoglobin and Deoxyhemoglobin in
Veins during Brain Activation
Activation
Rest
Normal blood flow
High blood flow
Oxyhemoglobin
Deoxyhemoglobin
Neural activation
increased demand for oxygen
increased flow
increased blood flow
altered oxi /dioxi ratio
Naively, this would lead to decrease of T2. However the blood flow
overcompensates the demand so T2 actually increases in the area of the
neural activity.
One studies the difference between on and off task.
Perspectives:
Mapping of brain function in health and
disease in response to various stimulation
paradigm
Intensity
BOLD fMRI
Time
BOLD effect
Statistical map
t
Task mean  Re st mean
s tan dard deviation
activation
thresholded
Activation and structural image
Clinical applications
tumor
• Mapping motor
and language
areas in patients
with brain tumors
• Neurosurgeon
guided by fMRI
Activation upon Perception
of Disgust
Faces from a standard set were computer-transformed,
to create two levels of intensity of expressed fear and
disgust. Examples of faces depicting 100% neutral,
75 and 150% disgust, and 75 and 150% fear are
demonstrated, together with an example of a stimulus
depicting a mildly happy expression (75% neutral and
25% happy) which was used as the neutral baseline.
Phillips et al, Nature 389:495 (1997)
Figure 1 (next slide) Generic brain activations in seven right-handed normal
subjects during perception of faces depicting 75% (top row) and 150% (bottom
row) disgust intensity. The grey-scale template was calculated by voxel-by-voxel
averaging of the individual EPI images of all subjects, following transformation
into Talairach space. The transverse sections in each experiment are at 2 mm
below (left) and 9 mm above (right) the AC-PC line (right side of the brain on the
left side of each section, and vice versa). Major regions of activation (probability
of false activation <0.004) for perception of faces depicting 75% disgust versus a
neutral expression are demonstrated in the right insula (I) and right medial frontal
cortex (BA 32); those for faces depicting 150% disgust versus a neutral expression
are demonstrated in the right and left anterior insula (I), right anterior insula
bordering on inferior frontal cortex (BA 44), right putamen (P), and right middle
temporal gyrus (BA 21).
Figure 2 (next slide) The difference image demonstrating significant (P < 0.004)
differences in activation for perception of faces depicting 150% intensity of
disgust (versus a neutral expression) and faces depicting 75% intensity of disgust
(versus a neutral expression). The grey-scale template was as for Fig. 1. The
largest region of activation was in the right anterior insula (Talairach coordinates
38, 17, 9), with twice the number of activated voxels compared with other regions
of the difference image. Transverse (z = 9) and coronal (y = 17) sections are shown
depicting this activation in the right insula.
Activation upon Perception of Disgust
difference
75%
150%
Phillips et al, Nature 389:495 (1997)
Figure 1 (next slide) A representative axial slice from a 'late' bilingual
subject (A) shows all voxels that pass the multistage statistical criteria at P
< 0.0005 as either red (native language) or yellow (second acquired
language). An expanded view of the pattern of activity in the region of
interest (inferior frontal gyrus, Brodmann's area 44, corresponding to
Broca's area) indicates separate centroids (+) of activity for the two
languages. Centre-of-mass calculations indicate that the centroids are
separated on this plane by 7.9 mm. The green line on the upper right midsagittal view indicates the plane location. R indicates the right side of the
brain
Figure 2 (next slide) A representative axial slice from an 'early' bilingual
subject (G) who learned English and Turkish simultaneously during early
childhood shows all voxels that pass the multistage statistical criteria at P
< 0.0005. Red indicates the Turkish language task and yellow indicates
the English language task. An expanded view of the region of interest
(Broca's area) indicates multiple common voxels between the two
language areas. The geometric centers-of-mass indicate that the centroids
are within 1.5 voxels. R indicates the right side of the brain
Late vs. Early Second Language
Early-learned 2nd language
Late-learned 2nd language
Kim et al, Distinct cortical areas associated with native and second
languages, Nature 388:171 (1997)
QuickTime™ and a
Microsoft Video 1 decompressor
are needed to see this picture.
Functional MR imaging of the primary motor cortex, activated when the
subject’s hand repeatedly opens and closes. Note - this is NOT a real time
filming. It is produced by subtraction of measurements at rest and during the
activity.
MR Spectroscopy (MRS)
a non-invasive tool for quantitative biochemical analysis
The physical basis of the MRS. Protons in lipids have slightly
different resonance frequency than in water. This is because electrons
in the molecule interact with external magnetic field. They have
magnetic moments 1860 times larger than protons and may screen a bit
the external field as their orbitals are modified by the external field.
-6
where
is the shielding constant expressed in units of 10 . Spectra
are plotted as a function of
with area under the peak proportional to
the number of protons in this state.
Since the shift is very small, MRS with fine tuning of the frequency to
suppress signal from water. This can be done only without gradient field.
Still localized measurements are possible - brain, kidneys, liver... . In
addition to protons, several other nuclei are used 31P, 13C,...
MRI vs. MRS
With MRI you depict
With MRS you determine
Water; Intramyocellulae Lipids, Acetate;
Alanine; Aspartate; Choline;
WATER
N-acetylaspartate; Creatine;
myo-Inositol; Ethanol; Lactate;
Glutamate; Phosphoryl-choline;
and
Fat
Glycerophosphoryl-choline; Keton
Bodies; -Aminobutyrate; Glucose; Glutamine;
Glycine; scyllo-Inositol; Macromolecules;
N-Acetylaspartylglutamate;
O-Phosphoethanolamine; Taurine; Threonine;
Glycogen; Carnosine, Carnitine, Acetylcarnitine,
Phenylalanine; Succinate; Phosphocreatine;
Adenosinetriphosphate; pH; NAD; 2,3Diphosphoglycerol; Deoxymyoglobin;
Deoxyhemoglobin; Citrate; Betaine; Propanediol;
Homo-Carnosine; Glutathione; .....
Single-Voxel MRS Studies of Alzheimer’s Disease
(Neurology 2001; 57: 626-632)
Single-Voxel MRS Studies of Alzheimer’s Disease
Histology
MRS: Evaluation of Prostate Tumors
Choline
1H-MRS
Creatine
Choline
ppm 3.5 3.0 2.5 2.0 1.5
Atrophy or Necrosis
Citrate
ppm 3.5 3.0 2.5 2.0 1.5
Benign Tissue
Creatine
Citrate
ppm
3.5 3.0 2.5 2.0 1.5
Cancer
Kurhanewicz et al, Radiology,1996; 200:489-96.
MRS: Therapy Control for Prostate Tumors
before
Cryo-Therapy
Judged by
Cho/Citrate ratio
successfull
Cryo-therapy
failed
Cryo-Therapy
Kurhanewicz et al
Cho - choline compounds (phosphocholine, glucero-phosphocholine)
Choline is a quaternary saturated amine with the chemical formula:
(CH3)3N+CH2CH2OHX−. where X− is a counterion such as chloride
Choline is a quaternary saturated amine with the chemical formula:
(CH3)3N+CH2CH2OHX−. where X− is a counterion such as chloride
A counterion is the ion that accompanies an ionic species in
order to maintain electric neutrality. In table salt the sodium
cation is the counterion for the chlorine anion and vice versa. In
a charged transition metal complex, a simple(i.e. noncoordinated) ionic species accompanying the complex is
termed the counterion.
1H
MRS for Monitoring Head and Neck Cancer
Response to Therapy
Localization of SpectroscopicVoxel for a Patient with Metastatic
Squamous Cell Carcinoma
Pre-therapy
Post-therapy
Proton Spectra of a Patient with Squamous
Cell Carcinoma
Pre-therapy
Post-therapy
MRI
of
Thin
Air
… but surely you can’t image air !
No, not thick air,
but if we add hyperpolarized gas,
…!
Hyperpolarized
129
Xe Imaging
Polarization is performed using a circularly polarized laser light
(s+, the red wavy line in left picture) tuned to the specific transition in Rb.
This causes population to build up in the 5S
state of Rb.
1/2polarization to the Xe. The N
A collision will have a chance to exchange this
is present to keep fluorescence of the Rb to a minimum. Put all of this inside2
a weak magnet and one has polarized our xenon far greater then any magnet alone
129
Xe
MRI of the lung
1
H
QuickTime™ and a
GIF decompressor
are needed to see this picture.
movie:
http://imaging.med.virginia.edu/hyperpolarized/rendering.htm
Volume rendering of lungs using hyperpolarized He. 3
A 3D FLASH sequence was used to obtain the 60 sections (4.33mm
thickness,each). TR/TE = 5.85/2.5ms; Flip angle = 2.2 degrees; matrix =
70*128; FOV = 300*400 mm and time to acquire the entire 60 sections was
24.6 seconds.
QuickTime™ and a
GIF decompressor
are needed to see this picture.
Dynamic images of the human lung
during inhalation and expiration of 3He
Contrast Agent for MRI of Gene Expression
Gd3+ hidden
Gd3+ exposed
If galactosidase
is present (i.e.
gene expressed),
it cleaves a
sugar residue to
expose (activate)
Gd3+, a MRI
contrast agent.
Schematic of the
transition of EgadMe from
a weak to a strong
relaxivity state.
In vivo visualization of gene expression using MRI
Angelique Y. Louie et al. Nature Biotechnology 18,К321К-К325 (2000)
EgadMe, a contrast agent, consists of chelated gadolinium caged by a galactopyranose molecule. The
cage door is removed only when EgadMe comes in contact with a beta-galactosidase enzyme.
(A) Schematic diagram representing the site-specific placement of the galactopyranosyl ring on the
tetraazamacrocycle (side view). Upon cleavage of the sugar residue by beta beta-galactosidase (at red bond), an
inner sphere coordination site of the Gd3+ ion becomes more accessible to water. (B) Space-filling molecular mode
(top view, from above the sugar residue) of the complex before (left) and after cleavage by the beta-gal (right),
illustrating the increased accessibility of the Gd3+ ion (magenta) upon cleavage: white, H; red, O; blue, N; gray, C.