Download Magnetism : biomedical applications - NMR

Magnetism : biomedical applications
A. Lascialfari
Department of Molecular Sciences Applied to Biosystems (next at
Department of Physics), Università degli studi di Milano,
Milano (Italy)
Also at :
Dept. of Physics “A.Volta”, Univ. degli studi di Pavia, Pavia (Italy)
CNR-S3, Istituto di Nanoscienze, Modena (Italy)
Consorzio INSTM, Firenze (Italy)
OUTLINE
NOT EXHAUSTIVE !!
ƒ Magnetism in medicine : brief “recent”
“recent” history
ƒ Some techniques in medicine (MRI, MEG, MFH, BNCT...)
ƒ magnetic nanoparticles
ƒ MRI contrast agents
(MFH) agents
ƒ magnetic fluid hyperthermia (MFH)
ƒ some hints on magnetic biosensors
ƒ some hints on multifunctional nanoparticles
results,
faced. When presenting experimental results,
ƒ Toxicity problems will not be faced.
be, if ideal)
ideal) characterized
take into account that the new systems are (or must be,
from this point of view
eds. W. Andrä
Andrä and H. Nowak,
Nowak, Wiley-VCH
Wiley-VCH
Suggested book : Magnetism in Medicine, eds.
Thanks are due to Q. Pankhurst and C. Sangregorio for contributions to slides
Magnetic therapy through the ages
• a medical doctor
• He studied the influence of planets and living beings on sick persons
• Animal gravity : the forces among things and living beings penetrate the body
and harmonize it. When they are contrasted, a disease is developed
• Mesmer’s magnetic stones, animal magnetism, “magnetic” fluid
• He founded (in his house) the Landstrasse nursing home
• A book : Mémoire sur la découverte du magnétisme animal
Magnetic therapy through the ages
Dr (!!!) James Graham
(1745–1794)
•
He left medical school without taking a degree
• elaborated electro-magnetic apparatus, treated patients with musical therapy
• sold medicines such as “Electrical Aether” and “Nervous Aetherial Balsam.”
• converted a large house in an opulent section of London into Temple of Health.
• Young woman involved : Emma Lyon, in later years wife of Sir William
Hamilton and Lord Nelson's lover.
• The centerpiece of the Temple of Health was the 'Celestial Bed' (fee of £ 50 a night)
Magnetic therapy through the ages
More serious stuff … biomagnetic fields
Mechanisms and magnetism
Sensing
(MRI, Sentimag, MEG-SQUID,…)
Moving
(navigation)
Heating
(Magnetic
Hyperthermia)
Magnetic navigation (FDA approved)
Magnetic navigation system
Niobe system by Stereotaxis inc
Two large permanent (H~0.1÷0.2 T) magnets guide :
* a magnetic tipped-guide wire
* an electrophysiology mapping catheter
through the patient’s vascular system
Applied to :
- diagnosis of congenital heart disease in neonates
- cardiac bypass
- repair of chronic occlusions
- drug delivery of angiogenic factors to damaged
heart
Magnetic cell selection (FDA approved)
Isolex 300i
magnetic Cell Selection system
(from Baxter)
…. for removing tumor cells in stem cell
transplants.
Monoclonal anti-tumor antibodies (antiCD34) conjugated to magnetic polystirene
microspheres (Dynabeads M-450) to
purificate bone marrow from tumor cells
Sensing lymphnodes (FDA approved)
approved)
Sentimag® for sentinel lymphnodes approach
NP
+
For surgery of
breast tumour.
Used SP in place of
radio-isotopes
MEG (FDA approved)
Magneto encephalography (MEG)
MFH treatment (FDA approved)
Magnetic Fluid Hyperthermia (MFH) or Magnetothermia
• Heating through application of AC
magnetic field via activation of 12
nm amino-silane coated Fe3O4 MNP
directly implanted in the tumour mass
at high doses (ca. 50 mg/cm3)
• Typically : ν ~ 100 kHz, amplitude 10
kA/m
• Minor side effects
• Typical values of the reported specific loss of
power, SLP or SAR (the energy converted into heat
per mass unit) are : 10÷200 W/g
• Exceptions :
- 35 nm bacterial magnetosomes (960 W/g at
410 KHz and 10 kA/m)
- 16 nm γ-Fe2O3 N P ( 1650 W/g
at 700 kHz and 24.8 kA/m, 300 W/g at 11 kA/m)
Magnetic Resonance Imaging (MRI)
Typical MRI apparatus for
clinical use, magnetic field
H = 1.5 Tesla
MRI Timeline
1946 MR phenomenon - Bloch & Purcell
1952 Nobel Prize - Bloch & Purcell
1950-70 NMR developed as analytical tool
1972 Computerized Tomography
1973 Backprojection MRI - Lauterbur
1975 Fourier Imaging - Ernst
1977 Echo-planar imaging - Mansfield
1980 FT MRI demonstrated - Edelstein
1986 Gradient Echo Imaging - NMR Microscope
1987 MR Angiography - Dumoulin
1991 Nobel Prize - Ernst
1992 Functional MRI
1994 Hyperpolarized 129Xe Imaging
2003 Nobel Prize - Lauterbur & Mansfield
Special role in biomedical applications :
nanomagnetism in biomedicine
(involves physics, chemistry, biology, medicine,
engineering,…….)
We’ll talk in more details about physical
mechanisms in :
• MRI contrast agents
• magnetic fluid hyperthermia (MFH) agents
Magnetic Nanoparticles (MNP)
Magneto-plasmonic
Data Storage
surface
Fe3O4
Au
Bio-medicine
Light modulation of the relaxation
dynamics on CoNi NPs in SiO2 thin
film
Why magnetic nano-particles (MNP) ?
Typical dimensions in biomedicine
nanoparticles
pollen
Gene (width)
0.1 nm
1 nm
Aspirin
molecule
DNA
10 nm
Human
hair
Bacteria
100 nm
1 µm
10 µm
Cells
Proteins
Virus
100 µm
Why Magnetic Nanoparticles are appealing for
Biological and Medical Applications
They can be manipulated by a
external magnetic field
In MRI, they provide an important
decrease of the T1 and/or T2 nuclear
relaxation per unit of metal
They may interact with time-varying
field and convert the electromagnetic
energy in local heat (MFH)
Ideal magnetic nanoparticle
Magnetic Nanoparticles in Theranostics:
Diagnostics :
Therapy :
MRI, sensing, fluorescence
magnetothermia, drug delivery
Biocompatible
shell
Fluorescent
molecule
Antibody
Drug
Magnetic nucleus
Molecular
Imaging
Sensing : diagnostics
MRI contrast agents
Why MRI ?
Nuclear Medicine:
•
Poor spatial resolution
•
Poor temporal resolution
•
High sensitivity
•
Reporters: radionuclides
Optical Imaging:
• Poor spatial resolution
• Poor temporal resolution
• high sensitivity
• Reporters: luminescent probes
X-Ray (CT):
• Good spatial resolution
• Good temporal resolution
• Low sensitivity
MRI:
•
Non-invasive
• Good spatial resolution
• Good temporal resolution
• Low sensitivity
Why MRI with MNP ?
-TE/T2 (1-e-TR/T1
MRI signal is s(t) ∝ N(H) e-TE/T2
(1-e-TR/T1)
The MRI image intensity (the contrast)
contrast) thus depends on :
Extrinsic Parameters
Intrinsic Parameters
§
§
§
§
• Magnetic field
Local proton density N(H) (water, fat)
Nuclear Relaxation times T1 and T2
Magnetic susceptibility differences
Diffusion processes
• Timing of the pulse sequence
• Contrast Agents (CA)
with MNP (contrast agents)
the nuclear relaxation times change
(much better idea than protons’ density)
⇓
better image contrast and pathology evidence
agents: features
MRI contrast agents:
TWO KINDS OF CA, BASICALLY
NON-SPECIFIC CA
NON-SPECIFIC
BIO-DISTRIBUTION
SPECIFIC CA FOR BIO-DISTRIBUTION
(Gd-based systems,
systems, ferrites-based
ferrites-based systems)
systems)
(Gd-based
•
•
•
•
Extracellular CA (Gd-DTPA)
Blood-Pool CA
Organ-Specific CA (tissutal targeting)
Molecular Imaging CA (cell targeting)
MAGNETIC PROPERTIES
Paramagnetic CA
(i.e. paramagnetic core)
(Gd-based CA)
Superparamagnetic (SP) CA
(i.e.superparamagnetic core)
EFFECT ON THE IMAGES
Positive CA (signal increase)
Negative CA (signal decrease)
Main missing scientific
investigations/results on SP-CA
SP-CA
investigations/results
ƒ Molecular Imaging. Examples of MI-MRI : stem cells targeting,
specific tumoral cells targeting , macrophages, etc.
ƒ Higher relaxivities optimization compounds (both T1 and T2)
ƒ Understanding the mechanism of nuclear relaxation
All the above depend on the control of
dimensions, shape,
shape, bulk anisotropy,
anisotropy, kind of magnetic ion,
ion, coating
dimensions,
in SP NP
“positive” CA
MRI angiography by “positive”
(contrast agents=CA
can be considered MNP)
ƒ
Evaluate blood
vessels non-invasively
⇒ MR angiography (MRA).
ƒ head and neck vessel narrowing (stenosis),
blood vessel blockage, cerebral aneurysm,
arteriovenous malformation (AVM) and blood
vessel dissection.
ƒ Contrast enhanced MRA
utilizes an intravenous injection of MRI contrast
media (Gd-DTPA).
Edema detection by “positive”
“positive” Gd-based
Gd-based CA
MRI
histology
“negative” SP-CA
SP-CA
Liver tumour detection by “negative”
ƒ
Generally the negative
CA are based on superparamagnetic nanoparticles
Example : liver tumour
without CA
with CA