Vladislav Toronov, Ph. D.

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Using Physics to Image Brain Function
____________ _________ _______ ___________
Vladislav Toronov, Ph. D.
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outline
Functional MRI lack of physiological
specificity Principles of Near Infrared
Spectro-Imaging NIR study of the physiological
basis of fMRI signal NIR imaging of brain function
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Quantities used in MRI

• Longitudinal relaxation time T1
• Transverse relaxation time T2 (T2)
• Proton density

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Why MRI provides nice structural images?
Due to the large differences in T1 or T2 between
tissues
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Can MRI be used for metabolic measurements?

• Answer it is very difficult to do because T1 and
  T2 can depend on many parameters
• Example
• Changes in the blood content during functional
  activity

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Oxygen Transport to Tissue

• Oxygen is transported in hemoglobin molecules of
  red blood cells
• Deoxy-hemoglobin HHb
• Oxy-hemoglobin HbO2
• Metabolic measurement Can MRI be used to measure
  HHb and HbO2?

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Blood content vs. blood flow
Conclusion MRI does now allow simple separation
of oxygenation effects from blood volume effects
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Blood Oxygen Level Dependent effect Oxygen in
the blood modifies T2
Functional brain mapping
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Quantitative physiological model of the BOLD
signalR. Buxton, 1998
where
DqDHHb/HHb0 DvDtHb/tHb0
Conclusion MRI does not allow simple separation
of oxygenation effects from blood volume effects
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Near-Infrared Spectro-Imaging

• (NIRSI)

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Optical Spectroscopy
Beers law
NIRSI
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Light Propagation in Tissues
NIRSI
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Boltzmann Transport Equation
Where
- radiance W cm-2 steradian-1
- absorption coefficient cm-1
- scattering coefficient cm-1
- source term W cm-3 steradian-1 s-1
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Diffusion Approximation
Diffusion Equation
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Type of the source modulation

• Continuous Wave
• Time Domain (pulse)
• Frequency-Domain

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Frequency-domain approach

• Light Source
• Modulation frequency gt100 MHz
• AC, DC and phase

NIRSI
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Absolute measurements withfrequency-domain
spectroscopy
multi-distance method
Frequency-domain solution for Semi-infinite
medium
SF

• ma absorption coefficient
• ms reduced scattering coefficient
• w angular modulation frequency
• v speed of light in tissue
• SF phase slope
• Sac ln(r2ac) slope

Log
Sac
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Method of quantitative FD measurements
Multi-distance
Detector fiber bundle
Source fibers
Flexible pad
Direct light block
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Estimation of physiological parameters
Beers law
Total HB
CBV
Oxygenation
NIRSI
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Near-infrared tissue oximeter
detector bundles
pmt b
RF electronics
pmt a
laser driver 2
laser driver 1
source fibers
multiplexing circuit
laser diodes
NIRSI Instrumentation
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NIR Imaging System
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Advantages of NIRSI

• Non-invasive
• Fast ( 1 ms)
• Highly specific (spectroscopy)
• Relatively inexpensive (100 K)
• Can be easily combined with MRI

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Study of the physiology of the BOLD effect
NIRSI in Functional Magnetic Resonance Imaging
BOLD Blood Oxygen Level Dependent
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fMRI Mapping of the Motor Cortex
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BOLD signal model
where
DqDHHb/HHb0 DvDtHb/tHb0
Study of the BOLD effect
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Multi-distance optical probe
Study of the BOLD effect
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Collocation of fMRI signal and optical sensor
Optical probe
Motor Cortex
Study of the BOLD effect
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Activation paradigm
Motor activation
?lock Design - 10s/17s
Time
Study of the BOLD effect
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Data analysisFolding (time-locked) average
Raw data
Folded data
Study of the BOLD effect
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Time course of hemodynamicand BOLD signals
stimulation
Study of the BOLD effect
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BOLD signal model
where
DqDHHb/HHb0 DvDtHb/tHb0
Study of the BOLD effect
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Biophysical Modeling of Functional Cerebral
Hemodynamics
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O2 Diffusion Between Blood and Tissue Cells
fout
fin
Modeling
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Balloon Model
q- normalized Deoxy Hb
v- normalized Total Hb tV0/F0 mean transit time
Oxygen Extraction Fraction
Modeling
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OEF as function of CBF(Buxton and Frank, 1997)
Modeling
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Balloon Model
Modeling
q- normalized Deoxy Hb
v- normalized Total Hb
Oxygen Extraction Fraction
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Functional Changes in Cerebral Blood Flow from
Balloon Model
Stimulation
Modeling
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Why oxygenation increases?

• The increase in cerebral blood oxygenation during
  functional activation is mostly due to an
  increase in the rCBF velocity, and occurs without
  a significant swelling of the blood vessels.

Washout Effect
Modeling
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Outcomes

• The time course of the BOLD fMRI signal
  corresponds to the changes in the
  deoxy-hemoglobin concentration
• BOLD fMRI provides no information about the
  functional changes in the blood volume
• This information can be obtained using NIRSI

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Optical Mapping of Brain Activityin real time
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Locations of the sources and detectors of light
on the human head
3
2
1
3 cm
4
detectors
B
A
8
light sources
6
5
7
Motor Cortex
Brain mapping
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Backprojection Scheme
C34.5S3 .5S4
C34.75S3.25S4
1
3
2
34 3 3 3 3 23 2 2 2 2 2 2 12 1 1 1 1 18
34 3 3 3 23 2 2 2 2 2 2 2 2 12 1 1 1 18
4 4 3 3 23 2 2 2 22 22 2 2 2 12 1 1 8 8
4 4 4 34 23 2 2 26 26 26 26 2 2 12 18 8 8 8
4 4 4 45 56 6 6 62 26 26 62 6 6 67 78 8 8 8
4 4 5 5 56 6 6 6 66 66 6 6 6 67 7 7 8 8
45 5 5 5 56 6 6 6 6 6 6 6 6 67 7 7 7 78
45 5 5 5 5 56 6 6 6 6 6 6 67 7 7 7 7 18
8
4
A
B
detectors
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light sources (758 and 830 nm)
7
5
Brain mapping
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Real time video of brain activation
D Hb (mM)
-1.0
-0.5
0.0
0.5
Brain mapping
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3D NIR imaging of brain function using structural
MRI
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Ln the mean time photon spends in voxel n
relative to the total travel time
A small change in absorption
S
D
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Solve an equation
Number of measurementsltlt number of voxels
3D imaging
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Sensitivity is high near the surface and low in
the brain
Source
Detector
3D imaging
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Using structural MRI info
Scalp
Cerebro- Spinal Fluid
Scull
Brain
CONSTRAINT
3D imaging
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How do we find Ln the relative voxel time?
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Monte Carlo Simulation

• Structural MR image
• is segmented in
• four tissue types
• Scalp
• Skull
• CSF
• Brain
• 10,000,000 photons

Source
Detector
3D imaging
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Image Reconstruction
Underdetermined Problem
YAx
Solution Simultaneous Iterative Reconstruction
Technique
3D imaging
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Activation of Human Visual Cortex
Flashing or reversing checkerboard
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EXPERIMENT
50 mm
3D imaging
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Probe for imaging human visual cortexin the MRI
scanner
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Placement of the optical probe on the head inside
the birdcage head coil of the MRI scanner
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(No Transcript)
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Time course of hemodynamic changes in the
activated region
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Results of the group statistical analysis of
variance
Using AFNI medical Image processing software
BOLD
-?Hb
?HbO2
3D imaging
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Outcomes

• In combination with structural MRI,NIRSI can
  be used for non-invasive 3D imaging of
  physiological processes in the human brain
• A two-wavelength NIR imaging provides
  independent spatially-resolved measurements of
  changes in oxy- and deoxyhemoglobin
  concentrations.

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General Conclusion and Perspective

• Alone or in combination with other imaging
  techniques, NIRSI can be used as a quantitative
  metabolic imaging tool in a variety of biomedical
  applications
• Neuronal activity 10 ms temporal resolution
• Neonatology Babys head has low size and
  absorption
• Mammography Non-ionizing, specific
• Small animals Neuroimaging, fast
  assessment in cancer research