MRI - functional MRI, spectroscopy, etc Lecture 23.
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Transcript of MRI - functional MRI, spectroscopy, etc Lecture 23.
MRI - functional MRI, spectroscopy, etc
Lecture 23
Functional MRI: Principles
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
Paramagnetic substance produces microscopic field inhomogeneities that decreases the transverse relaxation time T2
of the blood and surrounding tissues.
Magnetic susceptibility χ:
M is the magnetization of the material, H is the strength of the external magnetic field
χdeoxy>>χoxy ratio ~ 65
T2* images and blood oxygen
level depend (BOLD) contrast (Ogawa, 1990)
Oxygenated blood
De-oxygenated blood
Diamagnetic Paramagnetic
Neuron
Oxyhemoglobin Oxyhemoglobin and and Deoxyhemoglobin Deoxyhemoglobin ininVeins during Brain ActivationVeins during Brain Activation
OxyhemoglobinDeoxyhemoglobin
Rest Activation
Normal blood flow High blood flow
Neural activation increased demand for oxygenincreased flowincreased blood flowaltered 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
BOLD fMRI
Time
Inte
nsi
ty
Rest
Task
BOLD effect
Statistical map
t =Taskmean−Restmean
standard deviationthresholded
activation
Activation and structural image
Clinical applications
• Mapping motor and language areas in patients with brain tumors
• Neurosurgeon guided by fMRI
tumor
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
Phillips et al, Nature 389:495 (1997)
difference
75%
150%
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 mid-sagittal view indicates the plane location. R indicates the right side of the brainFigure 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 aMicrosoft Video 1 decompressorare 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.
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.
where is the shielding constant expressed in units of 10-6
. Spectra are plotted as a function of with area under the peak proportional to the number of protons in this state.
MR Spectroscopy (MRS)
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,...
a non-invasive tool for quantitative biochemical analysis
MRI vs. MRS
With MRI you depict
WATERand
Fat
Water; Intramyocellulae Lipids, Acetate; Alanine; Aspartate; Choline;
N-acetylaspartate; Creatine; myo-Inositol; Ethanol; Lactate;
Glutamate; Phosphoryl-choline;
Glycerophosphoryl-choline; Keton Bodies; γ-Aminobutyrate; Glucose; Glutamine;
Glycine; scyllo-Inositol; Macromolecules; N-Acetylaspartylglutamate;
O-Phosphoethanolamine; Taurine; Threonine; Glycogen; Carnosine, Carnitine,
Acetylcarnitine, Phenylalanine; Succinate; Phosphocreatine; Adenosinetriphosphate; pH; NAD; 2,3-Diphosphoglycerol; Deoxymyoglobin; Deoxyhemoglobin; Citrate; Betaine; Propanediol;
Homo-Carnosine; Glutathione; .....
With MRS you determine
Single-Voxel MRS Studies of Alzheimer’s Disease(Neurology 2001; 57: 626-632)
Single-Voxel MRS Studies of Alzheimer’s Disease
Choline Creatine
Citrate
ppm 3.5 3.0 2.5 2.0 1.5 ppm 3.5 3.0 2.5 2.0 1.5 ppm 3.5
3.0
2.5
2.0
1.5
Atrophy or Necrosis Benign Tissue CancerKurhanewicz et al, Radiology,1996; 200:489-96.
MRS: Evaluation of Prostate TumorsH
isto
logy
Creatine
CitrateCholine
1 H-M
RS
beforeCryo-Therapy successfull
Cryo-therapy
failed Cryo-Therapy
Judged by Cho/Citrate ratio
Kurhanewicz et al
MRS: Therapy Control for Prostate Tumors
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. non-coordinated) ionic species accompanying the complex is termed the counterion.
Localization of Spectroscopic Voxel for a Patient with MetastaticSquamous Cell Carcinoma
Pre-therapy Post-therapy
1H MRS for Monitoring Head and Neck Cancer Response to Therapy
Proton Spectra of a Patient with SquamousCell 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 ImagingPolarization 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 5S1/2
state of Rb.
A collision will have a chance to exchange this polarization to the Xe. The N2
is present to keep fluorescence of the Rb to a minimum. Put all of this inside a weak magnet and one has polarized our xenon far greater then any magnet alone
MRI of the lung
129Xe
1H
QuickTime™ and aGIF decompressor
are needed to see this picture.
Volume rendering of lungs using hyperpolarized He. 3A 3D FLASH sequence was used to obtain the 60 sections (4.33mmthickness,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.
http://imaging.med.virginia.edu/hyperpolarized/rendering.htmmovie:
QuickTime™ and aGIF 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
In vivo visualization of gene expression using MRIAngelique Y. Louie et al. Nature Biotechnology 18, 321 - 325 (2000)
Gd3+ hidden Gd3+ exposed
If galactosidaseis present (i.e.gene expressed),it cleaves asugar residue toexpose (activate)Gd3+, a MRIcontrast agent.
Schematic of the transition of EgadMe from a weak to a strong relaxivity state.
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 model (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.