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Vladislav Toronov, Ph. D. Using Physics to Image Brain Function

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Using Physics to Image Brain Function. ____________ _________ _______ ___________. Vladislav Toronov, Ph. D. outline. Functional MRI: lack of physiological specificity Principles of Near Infrared Spectro-Imaging NIR study of the physiological basis of fMRI signal - PowerPoint PPT Presentation

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Page 1: ____________ _________ _______ ___________

Vladislav Toronov, Ph. D.

Using Physics to Image Brain Function

Page 2: ____________ _________ _______ ___________

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

outline

Page 3: ____________ _________ _______ ___________

Quantities used in MRI

Longitudinal relaxation time T1

Transverse relaxation time T2 (T2*)

Proton density

Page 4: ____________ _________ _______ ___________

Why MRI provides nice structural images?

Due to the large differences in T1 or T2 between tissues

Page 5: ____________ _________ _______ ___________

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

Page 6: ____________ _________ _______ ___________

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]?

Page 7: ____________ _________ _______ ___________

Blood Oxygen Level Dependent effect: Oxygen in the blood modifies T2*

Functional brain mapping

Page 8: ____________ _________ _______ ___________

Quantitative physiological model of the BOLD signal:

R. Buxton, 1998

q=[HHb]/[HHb]0 v=[tHb]/[tHb]0

where

v21 qS

Conclusion: MRI does not allow simple separation of oxygenation effects from blood volume effects

Page 9: ____________ _________ _______ ___________

Near-Infrared Spectro-Imaging

(NIRSI)

Page 10: ____________ _________ _______ ___________

Optical Spectroscopy

i

iia c

Beer’s law:

NIRSI

Page 11: ____________ _________ _______ ___________

Light Propagation in Tissues

NIRSI

Scattering

’s ~ 10 cm-1

Absorption

a ~0.1 cm-1

Page 12: ____________ _________ _______ ___________

Boltzmann Transport Equation

Where - radiance [W cm-2 steradian-1]L t

S t

a

s

( , , )

( , , )

r

r

- scattering coefficient [cm-1]

- absorption coefficient [cm-1]

- source term [W cm-3 steradian-1 s-1]

),ˆ,(ˆ)ˆ,ˆ(),ˆ,(

),ˆ,()(ˆ),ˆ,(),ˆ,(

v

1

trSdftrL

trLtrLt

trL

s

sa

Page 13: ____________ _________ _______ ___________

Diffusion Approximation

20

1, ,a

Dr r t q r t

c t c

Photon Density

SourceAbsorption

Diffusion coefficient (scattering)

Diffusion Equation:

a s s ' ( cos )1

Page 14: ____________ _________ _______ ___________

Type of the source modulation:

Continuous Wave

Time Domain (pulse)

Frequency-Domain

Page 15: ____________ _________ _______ ___________

Frequency-domain approach

Light Source: Modulation frequency: >=100 MHz AC, DC and phase

NIRSI

Page 16: ____________ _________ _______ ___________

Absolute measurements withfrequency-domain spectroscopy

a: absorption coefficients’: reduced scattering

coefficient

: angular modulation frequency

v : speed of light in tissue S: phase slopeSac: ln(r2ac) slope

multi-distance method

0 10 20 30 40

-9

-8

-7

-6

-5

-4

-3

-2

-1

AC

r (mm)

0

10

20

30

40

50

60

70

80

pha

se (

)

AC*r2

phase

S

SacLog

Frequency-domain solution for Semi-infinite medium

Page 17: ____________ _________ _______ ___________

Method of quantitative FD measurements: Multi-distance

Flexible pad

Detector fiber bundle

Source fibers

Direct light block

Page 18: ____________ _________ _______ ___________

Estimation of physiological parameters

22][][ 2 HHbHbO HHbHbOa

],[][][ 2 HHbHbOtHB

(%),100][][

][

2

2

HHbHbO

HbOOx

NIRSI

Beer’s law:

Total HB ~CBV

Oxygenation

Page 19: ____________ _________ _______ ___________

source fibers

pmt a

RF electronics

multiplexing circuit

laser driver 1

pmt b

laser diodes

laser driver 2

detector bundles

Near-infrared tissue oximeter

NIRSI Instrumentation

Page 20: ____________ _________ _______ ___________

NIR Imaging System

Page 21: ____________ _________ _______ ___________

Advantages of NIRSI

Non-invasive

Fast (~ 1 ms)

Highly specific (spectroscopy)

Relatively inexpensive (~$100 K)

Can be easily combined with MRI

Page 22: ____________ _________ _______ ___________

Study of the physiology of the BOLD effect

BOLD= Blood Oxygen Level Dependent

NIRSI in Functional Magnetic Resonance Imaging

Page 23: ____________ _________ _______ ___________

fMRI Mapping of the Motor Cortex

Page 24: ____________ _________ _______ ___________

BOLD signal model

q=[HHb]/[HHb]0 v=[tHb]/[tHb]0

where

v21 qS

Study of the BOLD effect

Page 25: ____________ _________ _______ ___________

Multi-distance optical probe

Study of the BOLD effect

Detector fiber

Laser diodes690 nm&830 nm

Page 26: ____________ _________ _______ ___________

Collocation of fMRI signal and optical sensor

Study of the BOLD effect

Motor Cortex

Optical probe

Page 27: ____________ _________ _______ ___________

Activation paradigmActivation paradigm

Sti

mul

atio

n

Rel

axat

ion

Motor activation

Вlock Design - 10s/17s

Study of the BOLD effect

Time

Page 28: ____________ _________ _______ ___________

Data analysis:Folding (time-locked) average

Raw data

Folded data

Study of the BOLD effect

Page 29: ____________ _________ _______ ___________

Time course of hemodynamicand BOLD signals

Study of the BOLD effect

stimulation

Page 30: ____________ _________ _______ ___________

BOLD signal model

q=[HHb]/[HHb]0 v=[tHb]/[tHb]0

where

v21 qS

Study of the BOLD effect

Page 31: ____________ _________ _______ ___________

Biophysical Modeling of Functional Cerebral

Hemodynamics

Page 32: ____________ _________ _______ ___________

O2 Diffusion Between Blood and Tissue Cells

fin

fout

Modeling

Page 33: ____________ _________ _______ ___________

“Balloon” Model

in

outin

fE

tv

tqf

E

tEf

dt

dq

)(

)()(1

0q- normalized Deoxy Hb

v- normalized Total Hb

=V0/F0 – mean transit time

Oxygen Extraction Fraction

Modeling

Page 34: ____________ _________ _______ ___________

OEF as function of CBF(Buxton and Frank, 1997)

infin EfE /1

0 )1(1

Modeling

Page 35: ____________ _________ _______ ___________

“Balloon” Model

infin

outin

outin

EfE

ffdt

dv

tv

tqf

E

tEf

dt

dq

/10

0

)1(1

1

)(

)()(1

q- normalized Deoxy Hb

v- normalized Total Hb

Oxygen Extraction Fraction

Modeling

Page 36: ____________ _________ _______ ___________

Functional Changes in Cerebral Blood Flow from Balloon Model

0 5 10 15 20 25 3098

100

102

104

106

108

110f in,fout(%)

Time (s)

finfout

Stimulation

Modeling

Page 37: ____________ _________ _______ ___________

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.

Modeling

Washout Effect

Page 38: ____________ _________ _______ ___________

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

Page 39: ____________ _________ _______ ___________

Optical Mapping of Brain Activity

in real time

Page 40: ____________ _________ _______ ___________

detectors

light sources5

67

123

4 3 cmB A 8

Locations of the sources and detectors of light on the human

head

Brain mapping

Motor Cortex

Page 41: ____________ _________ _______ ___________

Backprojection Scheme

detectors

light sources(758 and 830 nm)

Brain mapping

3&4 3 3 3 3 2&3 2 2 2 2 2 2 1&2 1 1 1 1 1&8

3&4 3 3 3 2&3 2 2 2 2 2 2 2 2 1&2 1 1 1 1&8

4 4 3 3 2&3 2 2 2 2&2 2&2 2 2 2 1&2 1 1 8 8

4 4 43&4

2&3 2 2 2&6 2&6 2&6 2&6 2 2 1&2 1&8 8 8 8

4 4 44&5

5&6 6 6 6&2 2&6 2&6 6&2 6 6 6&7 7&8 8 8 8

4 4 5 5 5&6 6 6 6 6&6 6&6 6 6 6 6&7 7 7 8 8

4&5 5 5 5 5&6 6 6 6 6 6 6 6 6 6&7 7 7 7 7&8

4&5 5 5 5 5 5&6 6 6 6 6 6 6 6&7 7 7 7 7 1&8

C34=.75*S3+.25*S413

6

7

8

2

4AB

5

C34=.5*S3 + .5*S4

Page 42: ____________ _________ _______ ___________

[Hb] (M)

-1.0

-0.5 0.0

0.5

Real time video of brain activation

Brain mapping

67

8

1

2

3

4AB

5

Page 43: ____________ _________ _______ ___________

3D NIR imaging of brain function using structural

MRIS D

Page 44: ____________ _________ _______ ___________

A small change in absorption

S D

an

nna

sd

sd LU

U

sdU

Ln –the mean time photon spends in voxel n relative to the total travel time

Page 45: ____________ _________ _______ ___________

Solve an equation:

Underdetermined Problem

Number of measurements<< number of voxels

3D imaging

n

nna

sd

sd LU

U

Page 46: ____________ _________ _______ ___________

Sensitivity is high near the surface and low in the brain

Source Detector3D imaging

Page 47: ____________ _________ _______ ___________

Cerebro-SpinalFluid

Scalp

Scull

BrainCONSTRAINT

3D imaging

Using structural MRI info

Page 48: ____________ _________ _______ ___________

How do we find Ln –the relative voxel time?

n

nna

sd

sd LU

U

Page 49: ____________ _________ _______ ___________

Monte Carlo Simulation

Structural MR imageis segmented infour tissue types:

• Scalp• Skull• CSF• Brain

10,000,000 “photons”

Source Detector3D imaging

Page 50: ____________ _________ _______ ___________

Image Reconstruction

Solution: Simultaneous Iterative Reconstruction Technique

Y=Ax

3D imaging

n

nna

sd

sd LU

U

Underdetermined Problem

Page 51: ____________ _________ _______ ___________

Activation of Human Visual Cortex

Flashing or reversing checkerboard

Page 52: ____________ _________ _______ ___________

EXPERIMENT

40 mm

10 mm

40 mm

10 mm

40 mm

10 mm

3D imaging

50 mm

Page 53: ____________ _________ _______ ___________

Probe for imaging human visual cortexin the MRI scanner

Page 54: ____________ _________ _______ ___________

Placement of the optical probe on the head inside the “birdcage” head coil of the MRI scanner

To/from the NIR spectrometer

Optical fibersOptical probe

Birdcage head coil

B0

Magnetic bore of the MRI scanner

Page 55: ____________ _________ _______ ___________
Page 56: ____________ _________ _______ ___________

Time course of hemodynamic changes in the activated region

0 10 20 30 40 50 60-1

-0.5

0

0.5

1

1.5

2x 10

-4

Time (sec)

Ave

rage

hem

o ch

ange

s (m

M)

Average changes in [HbR] and [HbO] at 2 Hz

[HbO]

[HbR]Vis. Stim.

Page 57: ____________ _________ _______ ___________

Results of the group statistical analysis of variance

BOLD -[Hb] [HbO2] 3D imaging

Using AFNI medicalImage processingsoftware

Page 58: ____________ _________ _______ ___________

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.

Page 59: ____________ _________ _______ ___________

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 ~Baby’s head has low size and

absorption Mammography ~ Non-ionizing, specific

Small animals ~ Neuroimaging, fast assessment in cancer

research