Mark Elliott, PhDAssociate Director of CMROI,

Department of Radiology, University of Pennsylvania School of Medicine, Philadelphia,

PA

CMROICMROI Slide Slide 22

Overview

Mechanisms of functional imaging with NIR light

Methodology of fNIRComparison with and without Difuse

Optical Tomography (DOT)

CMROICMROI Slide Slide 33

Methods for Imaging Neural Activity

electrical activity- excitatory- inhibitory- soma action potential

metabolic response

- glucose consumption- oxygen consumption

hemodynamic response- blood flow- blood volume- blood oxygenation

FDG PET

H215O PET

fMRIEEG

MEG

fNIRfNIRelectrophysiology

- ATP tightly regulated

Perfusion MRI

CMROICMROI Slide Slide 44

Vascular Sensitivity ofVascular Sensitivity offMRI and fNIR fMRI and fNIR

IIIIIIII

IIIIIVIV

Perfusion MRIPerfusion MRI

fNIRfNIRIIIIII

IIIIII IVIV

Vessel Size

Intravascular

Extravascular

Venous Arterial

fMRIfMRI

CMROICMROI Slide Slide 55

fMRI vs fNIR

fMRI fNIR

Spatial Resolution 8-27 mm3 “Blobs” 1-10 cm3

Temporal Resolution Slow (1-2 sec) Fast (50 Hz)Fast (50 Hz)important?important?

Measurement parameterMix of blood volume, blood

flow, and O2 metabolism [Hb] and [HbO]

Vascular Response

CMROICMROI Slide Slide 66

Mechanisms of fNIR:Overview fNIR = functional Near InfraRed

Measure changes in infrared light absorption and scattering

Primary source of signal contrast [Hb] and [Hb0]

Biological tissue is highly scattering in NIR window

Primarily used in vivo as a spectroscopic modality Not used to produce true images

DOT = Diffuse Optical Tomography Methods for accurate image reconstruction

CMROICMROI Slide Slide 77

Mechanisms of fNIR:Absortion of [Hb] and [Hb0]

Water Absorption

[Hb] & [HbO] Absorption

• Near infrared “window” ~ 650-900 nm• Water absorption is mimized• Hemoglobin species are dominant absorbers

CMROICMROI Slide Slide 88

Mechanisms of fNIR:Beer-Lambert Law

Beer-Lambert law models ballistic photon propagation in absorbing media

d

Io

I

solution [XX]

Transmittance, T = II//IIoo

Absorbance, A = -log(II//IIoo)

Beer-Lambert Law:A = [XX] d

where:d = distance between I0 and I = absorptivity (M-1 cm-1)[XX] = concentration of absorber (M)

CMROICMROI Slide Slide 99

Mechanisms of fNIR:Mechanisms of fNIR:Modified Beer-Lambert LawModified Beer-Lambert Law

Photons travelling through biological tissue are highly scattered (not ballistic)

Scattering adds to “pathlength” travelled by photons

DetectorDetector DetectorDetectorSourceSource

Fat

Muscle

dd

Modified Beer-Lambert Law: (A = -log(II//IIoo) = [XX] d DPF + G

where:

DPF = differential pathlength factorG = Scattering loss factor (generally unknown)

shallow

deeper

Source-detector spacing influences depth penetration

CMROICMROI Slide Slide 1010

Mechanisms of fNIR:Measures Changes in [Absorber]

Measure [Absorber]

A2–A1 = -log(II22//II11) = [XX] d DPF

where:

A2,A1 = absorption measured at two time points

• Scattering factor, G, is unknown• Absolute concentrations are not derivable• Can measure changes in [Hb] & [HbO]• Need baseline assumption or independent measure of [Hb]

CMROICMROI Slide Slide 1111

fNIR Methodology: Tissue Penetration

• NIR light penetration into biological tissue allows for surface imaging• Penetration increases with source light intensity• Limits on safe levels of source light intensity (~1mW/mm2)

• SNR sqrt(Io)• Highly sensitive detectors (PMTs) allow 2-6 cm deep probing

CMROICMROI Slide Slide 1212

fNIR Methodology:Quantitation of Multiple Chromophores

1 2 3

Multiple absorbers ([Hb], [Hb0]) multiple wavelengths

Extension of MBLL to multiple absorbers: (MBLL):

A1 = (Hb 1[HbHb] + HbO1[HbOHbO]) d DPFA2 = (Hb 2[HbHb] + HbO2[HbOHbO]) d DPF

Source illumination is time or frequencymultiplexed at several wavelengths.

CMROICMROI Slide Slide 1313

fNIR Methodology:Temporal Resolution

from Strangeman Biol Psych 2002

Extremely high temporal resolution possiblePractical systems ~ 10 – 100 HzfMRI ~ 1-2 Hz

Hemodynamic changes are slow ~ 2-5 sec

Fiber-optic systems for simultaneous fMRI

Fast signal – cell conformation and swellingScattering changes > 10 HzExtremely low signalEllusive to date

CMROICMROI Slide Slide 1414

fNIR Methodology:Spatial Localization

from Franceshini, NeuroImage, 2004

Discrete arrays of sources and detectors# voxels = # sources # detectorsTypical systems 10 – 100 voxels

Poorly localized “blobograms”Resolution 1-8 cm3

Surface FOV

Compare to low-res fMRI: 64x64x30 217 voxels!Whole brain coverage

CMROICMROI Slide Slide 1515

fNIR Methodology:Spatial Localization with DOT

from Strangeman Biol Psych 2002

True tomographic methods ~ 10,000 S-D pairs

Flying spot illumation

CCD detection

Low temporal resolution ~10 – 100 sec / imageill suited for functional assessment

“Hitting Density”, – poor basis setundetermined inversion problem

A = (r) (r) dr

= Hb[HbHb] + HbO[HbOHbO])

(r)(r)

CMROICMROI Slide Slide 1616

fNIR Methodology:MBLL vs DOT

Many fNIR implementations report [Hb] changes from individual S-D pairs w/o attempt at DOT

DPF in MBLL calculated from uniform background absorption and scattering. Focal changes not properly modelled.

“MBLL and DOT results did not agree in terms of absolute magnitudes, relative magnitudes, or even the relative sign for changes in [HbO] and [Hb].” (Boas, NeuroImage, 2001)

CMROICMROI Slide Slide 1717

Spatial Maps of HRF Spatial Maps of HRF Metrics:Metrics:TTP MapsTTP Maps

CMROICMROI Slide Slide 1818

fMRI: Mental Chronometry

ADC compartmentalization resolves events separated by 125ms.

TTP Map1 second right fovea & auditory delay