View
216
Download
3
Category
Tags:
Preview:
Citation preview
Functional neuro-imaging methodsPET H2O15 -blood flow
CO215 , CO15 , O-O15 -blood volume
FDG -metabolism
Specific neuro-transmitters
Optical Signal Imaging -blood flow
-blood volume
fMRI Perfusion with contrast agents
Perfusion without contrast agents
Blood Oxygenated Level dependence (BOLD)
Connectivity
EEG MEG
PET Optical Imaging fMRI
Spatial resolution
Temporal resolution
Field ofview
4mm
1min
The wholebrain
The wholebrain
~50 <1mm
few ms <100ms
~2cm, cortex only
MRI Timeline
1946 MR phenomenon – Bloch & Purcell
1952 Nobel Prize – Bloch & Purcell
1960 NMR development as an analytical tool
1972 Computerized Tomography
1973 Backprojectionj MRI – Lautembur
1975 Fourier Imaging – Ernst
1980 MRI demonstration – Edelstein
1986 Gradient Echo Imaging
MRI Microscopy
Functional MRI demonstration
1988 Angiography – Dumoulin
1989 Echo-Planar Imaging – Mensfield
Perfusion imaging
1991 Nobel Price – Ernst
1994 Xe Imaginng Hyperpolarized (Xe-129)
2004 Nobel Price – Lautembur & Mensfield
Necessary Equipment
Magnet Gradient Coil RF Coil
Source: Joe Gati, photos
RF Coil
4T magnet
gradient coil(inside)
x 80,000 =
4 Tesla = 4 x 10,000 0.5 = 80,000X Earth’s magnetic field
Robarts Research Institute 4T
The Big MagnetVery strong
Continuously on
Source: www.spacedaily.com
1 Tesla (T) = 10,000 Gauss
Earth’s magnetic field = 0.5 Gauss
Main field = B0
B0
Microscopic Property Responsible for MRI
The human body contains ~63% hydrogen atoms
Single voxel cells Water molecules
Each hydrogen molecules can be thought of as a small magnetic field, and will cause the nucleus to produce an NMR signal
Spins
Spin is a fundamental property of nature like electrical chargeor mass. Spin comes in multiples of 1/2 and can be + or -. Protons, electrons, and neutrons possess spin. Individual unpaired electrons, and neutrons each possesses a spin of 1/2.
When placed in a magnetic field of strength H, a particle with a net spin can absorb
a photon, of frequency o. The frequency o depends on the gyromagnetic ratio,
of the particle.
=- Ho The Larmor frequency
For hydrogen = 42.58 MHz/T
Low energy state High energy state
E=hhEnergy for transition
Energy transitions
E=-1/2hoE=+1/2ho
o =- Ho
The Larmor frequency
N-/N+ = exp(-E/kT) – Boltzmann distribution
The magnetization vector
Two magnetic moments – procession
000 HM
dt
dM
The Bloch eq. (without relaxation)
Ho
Mo
DT- MRI Fiber Tract VisualizationDT- MRI Fiber Tract Visualization
Coronal Sagittal Axial
Diffusion ellipsoids in coronal slice of human brain
Diffusion ellipsoids in coronal slice of human brain
In 1890, Roy and Sherrington concluded that
“…the chemical products of cerebral metabolism contained in the lymph which bathes the walls of the arterioles of the brain can cause variations of the caliber of the cerebral vessels: that in this re-action the brain possesses an intrinsic mechanism by which its vascular supply can be varied locally in correspondence with the local variations of functional activity.”
This “neurovascular coupling” is the base of functional neuro-imaging.
E = mc2
???
The First “Brain Imaging Experiment”
“[In Mosso’s experiments] the subject to be observed lay on a delicately balanced table which could tip downward either at the head or at the foot if the weight of either end were increased. The moment emotional or intellectual activity began in the subject, down went the balance at the head-end, in consequence of the redistribution of blood in his system.”
-- William James, Principles of Psychology (1890)
Angelo MossoItalian physiologist
(1846-1910)
… and probably the cheapest one too!
Blood Oxygenation Level Dependent (BOLD) fMRI contrast
Based on modulation of blood susceptibility with activation.
Measures: Amount of deoxy-hemoglobin in the tissue. This indirectly is proportional to the ratio of oxygenated/deoxygenated hemoglobin (diamagnetic and paramagnetic)
Gradient echo - GEFI, GE-EPI
Spin Echo - FSE, SE-EPI
• changes in T2*
• changes in T2
T2* vs. T2
• Extravascular (~33%) contribution in T2* (none in T2 )
• T2* changes caused by signal dephasing
diffusion
out
in
• T2 changes caused by either: i) diffusion through the gradients surrounding the erythrocytes or by ii) exchange of water between regions of different susceptibility (erythrocyte-plasma)
B0 i
nhom
ogen
eity
Distance from blood vessel
Statistical Mapsuperimposed on
anatomical MRI image
~2s
Functional images
Time
Condition 1
Condition 2 ...
~ 5 min
Time
fMRISignal
(% change)
ROI Time Course
Condition
Activation Statistics
Region of interest (ROI)
The BOLD signal
neuronal activity
energy demand
need for oxygen/glucose
hemodynamic response
• Coupling between oxygen/glucose utilization and hemodynamic response• Control mechanism• Blood flow vs. blood volume ?
1 2 3
The BOLD signal - 2
Phase 1: Diamagnetic oxy-hemoglobin minus oxygen > paramagnetic deoxy
Effective T2* relaxation ; smaller T2* signal decreased
Localized to the activation neurons.
Phase 2: Over flow of arterial blood – uncoupling between flow and oxygen
Less paramagnetic material > inefficient relaxation > T2* increase
Signal increases
Phase 3: 1. Flow returns to rest, still high rate of oxygen utilization 2. Flow returns to rest, blood volume return slower
Increase dexoy > efficient relaxation > short T2* >> signal decrease
The fMRI BOLD signal The fMRI BOLD signal
• Aid in neurosurgery planning
• Used for brain mapping
fMRI mapping of the brain’s language areas replaces invasive pre-surgery electrocortical
stimulation mapping which requires a patient to be awake.
Medical imaging can now display changes in brain activity caused by normal thought processes, disease, or therapeutic drugs
Human brain circuitry for imagining one's hand in the posture of another's hand.
• The basis of cognitive research: e.g., relation
between perception cognition behavior mood
and health
• Used in neuropathology research
Dementia Patient Volunteer
Brain Iron Distribution as a Potential Biomarker for Neurodegenerative Diseases (NDD) (By short T2 mapping)
• Allow research on brain function, architecture and
organization
• Used to understand brain network
Neural architecture of emotion perception and affects-related cognition
Generation of cortical transient clusters during activation
Flow vs. volume
Increase in blood flow > less deoxy Hb > signal increases
Increase in blood volume > more deoxy Hb > signal decreases
• Increase/decrease in blood flow FASTER than blood volume
• In normal conditions, in the cortex - flow is dominant (~70%)
CBV=0.5CBF 0.5
Temporal resolution
fMRI speed:
• GEFI produces an image in few sec (1-2sec).
• EPI produces an image in few tens of ms (100-1000ms)
Brief Stimuli
• The shortest stimuli that gives fMRI signal is ~35ms
• The shortest distinguished time-difference between two stimuli is 200ms
Temporal resolution –2
Hemodynamic Delays
• A delay of ~1-2sec for the initial deep• A delay of ~5-8sec for the positive main BOLD signal
Neither of these effects seems to add up to the delay observed
• Some delay due to “plumbing” is expected
•The coupling between neuronal activity and blood flow is not direct it includes a cascade of events of chemical signaling of several messengers.
Temporal resolution -3
• The brain venous network is not uniform. Particularly, deep brain nuclei do not have the cortical venous structure.
• The yet unknown main mechanism of the BOLD delay
Limits the possibility to follow neuronal information processing relates to the serial order of events in
different brain areas.
Spatial resolution
Cortical Columns are radially oriented clusters of neurons processing similar task
• Functional connectivity within the columns is rich, between columns is much weaker
• Size of cortical column is 100-300 in diameter and ~3mm in length
Are cortical columns the brain elementary processing units?
What is the size element of neural data processing ?What is the size element of neural data processing ?
Spatial resolution -2
Typical fMRI voxel is 2-4mm, covering tens of columns
Practical needed resolution – ~2 mm for definition of area of activityand ~300 for detailed structure
Relationship of microvasculature to cortical elements:Relationship of microvasculature to cortical elements:
Cortical columns seems to be arranged about a single common artery and vein that presumably perfussed the column.
Using optical imaging it was shown that activity in single column affects vascular signal for several mm around
Linearity of BOLD responseDale & Buckner, 1997
Linearity:“Do things add up?”
red = 2 - 1
green = 3 - 2
Sync each trial response to start of trial
Not quite linear but good enough
Data Analysis
• Single voxel time course Vs. Cluster analysis
• Model driven Vs. Model free statistics
• Strength of activation Vs. Volume of activation
• Choice of threshold Signal and effect -to-noise ratio
Model based analysis
Knowledge of the neuronal response is assumed – • linear or non-linear with the stimulus• impulse response• hemodynamics delay• assuming no spatial dependence
Neuronal response, even strong, that do not mach themodel will be invisible !!!
Model based analysis - problems
• In pathological conditions the basis assumption for the BOLD signal might change. (i.e., the fraction of flow and volume)
• the model have to be modified –• spatial dependent model is needed but the dependency is unknown (i.e., tumor)
• For long stimulus or short rest intervals between stimulus – adaptation have to be included – how ?
Model-free statistics
• Pharmaceutical MRI - in most cases model is unknown
• In pathological conditions - BOLD basic assumption might change
When it is necessary:
• Non cortical areas
Possible approaches
Cluster analysis PCA ICA
Threshold
How sure we are that this is the area of activation ?
fMR
I S
igna
l
Area of activation
Threshold level
Recommended