Moriah ThomasonLara Foland

‘n Me

Radiological Sciences LaboratoryCenter for Advanced MR Technology*

Stanford University School of Medicine

Department of RadiologyNeurosciences Program

Towards Calibrating fMRI

*

fMRI Calibration: Not needed here

Examples where quantifying activation maybe important in drawing inferences aboutcognition:

fMRI Calibration: Motivation

• Inter-group comparisonsAge, health

• Longitudinal studiesnormal/abnormal development, therapy

• Multi-center studiesfBIRN schizophrenia fMRI trial

BH Task: Children vs. Adults

Thomason, et. al, 2005

BH Task: Children vs. Adults

Thomason, et. al, 2005

• BOLD contrast is indirect consequence ofchanges in regional metabolism

• Increased neuronal firing =>increased blood flow =>

increased HbO2 & decreased (paramagnetic) Hb =>

increased MR signal

Quantitative fMRI

• BOLD = Neuronal_Metabol HRF ( )NMR { }

HRF differences can modulate BOLD

• Measurement of HRF- ER- Fourier-wtd block (FM)

• Breath holding- motivation- mechanism- prospects for calibration

Outline

• Definition: BOLD response to an impulsivestimulus

• may include neuronal and vascular responses-> use a cognitively simple task to reduce neuronal component

• may be nonlinear -> superposition does not hold

Hemodynamic Response Function

HRF: Measure h(t) with 1s taskmotor auditory

Glover, NI 1999Finger tapping & tones at 3Hz, N=5

Spectral content of h(t)

• Event related

• Fourier-wtd block (FM method)

• Nonlinearities • Efficiency

Measurement of HRF

Measurement of h(t): Fourier (FM)

Design has on/off blocks of duration 4s, 6s, 8s, 10s, 12s, 16s, 20s, 30s, 40s, …4s

Measurement of h(t): Fourier (FM)

Analysis of Fourier Data: 1. GLM

h(t) aibi(t)i1

3

bi(t) i

te /(t 1)

yc (t) d(t) * h(t)

yc (t) ai bi(t) * d(t) i1

3

aix i(t)i1

3

Ym Yc ˜ N AX ˜ N A Ym X T XXT 1

Model h(t):

Then, calc. response is

GLM- Linear

Visual Auditory

Response to epochs of finger tappingcalculated measured

Glover, NI 1999

Finger tapping at 3Hz, 1.5T1/3s, 2/3s, 1s, 2s, 4s, 8s, 16s

Sensorimotor Activation maps

Glover, NI 1999

yc (t) h0 d(t')h(1)(t t') dt' d(t ' )d(t' ')h(2)(t t',t t ' ')dt'dt' '

h(1)(t) ai(1)bi(t')

i1

3

h(2)(t ',t' ') aij(2)bi(t')b j (t' ')

i, j1

3

yc (t) 0 i(1)x i(t')

i1

3

ij(2)x i(t ')x j (t ' ')

i, j1

3

x i(t) d(t) *bi(t)

Second order Volterra series (Friston, 1998)

Then, measurement isNonlinearities

GLM- Linear vs. Nonlinear

Linear Nonlinear

GLM- Linear vs. Nonlinear

• Event related

• Fourier-wtd block (FM method)

• Nonlinearities • Efficiency

Measurement of HRF

Measurement Efficiency

ER FM

= 0.32 = 1.85

CNR(FM)/CNR(ER)= 6.1

Measurement Efficiency

ER: 8 min FM: 6 min

Effect of HRF on Activation

Gamma variate

Linear HRF

Nonlinear HRF

Adult/Child HRF

Effect of HRF on Activation

Gamma variate

Linear h

JJEGAK

Adult Child

• Measurement of HRF- ER- Fourier-wtd block (FM)

• Breath holding- motivation- mechanism- prospects for calibration- fBIRN study- child/adult study of WM

Outline

• Breath-holding (BH) induces a systemic statechange in brain oxygenation…

Vascular Responsivity: BH

… which results in a BOLD contrast change…

… that does not derive from cognitive input.

BOLDBH = NMR { HRF ( O2-state change ) }

BOLDact = NMR { HRF ( CMRO2 change ) }

|BOLDact| ~ |BOLDBH| CMRO2act

BOLD Signal

Davis, PNAS (1998)Buxton, 2003

rCBF[HbO2]

OEF

[Hb]

CMRO2 = OEF x rCBF x [HbO2]

R2* rCBVa[Hb]a rCBV0[Hb]0

BOLD TER2 *

rCBV rCBF

BOLDa S0[ f (m

f) 1]

m CMRO2a /CMRO20

f rCBFa /rCBF0

BOLDBH S0[ fBH 1]

BOLD Signal

Kastrup (1999)Hoge (1999)

Block trial: 15s off/on - 8 cycles, 4 min, 15 s

BH Task

breathe normally 14s Breath in & hold 2s Hold 14s

ActivationBHSM

Vascular Responsivity: BH

lf121103 jshu112803

HbO2 vs. O2 in Lung

BH-induced BOLD signal

Vascular res. HR rCBF hypoxia

Basal metab. O2, CO2, NO, H+ vasodilation rCBF

BH Mechanism

Thomason, et. al, 2005