CORE II: Functional MRIP.I.:John A. Detre

Co-I: Jiongjiong Wang (Project 1)Co-I: Andrew Newberg (Project 2)

Fellows:Maria Fernandez-Seara

Wen-Chau Wu

Core 2: Specific Aims• Project 1 Translational Applications of ASL

– Aim 1. To develop ASL perfusion MRI for adult brain at 3T– Aim 2. To develop ASL in other organs and populations– Aim 3. To reduce susceptibility effects and temporal noise in

ASL methods

• Project 2 Metabolic Correlates of Functional MRI– Aim 1. To use the combined fMRI/PET technique for coupling

of CBF and CMRGlc at rest and during activation– Aim 2. To use the fMRI/PET technique during a psychomotor

vigilance task (PVT)– Aim 3. To use the fMRI/PET technique during the acute

administration of caffeine (±PVT)

behavior

Physiological Basis of fMRI

disease

blood volume

BOLD fMRIBOLD fMRIASL fMRI

RR

Non-RR

neural*function

metabolism

blood flow

Core II Publications

• 32 since 2005 related to topic of core andcollaborations– 15 specifically cited RR02305

Core II Major Collaborations• ASL and Brain Function

– EB004349 (Reddy) Methodology for Oxidative Metabolism– HL077699 (Yodh) Diffuse Llight Imaging of Flow, Oxygen, and Brain Metabolism– MH08729 (Detre) Perfusion MRI for Multisite Studies of Brain Function

• ASL in Vascular Disease– HL30300 (Floyd) MRI Correlates of Limb Ischemia in PVD– NS057400 (Cucchiara) Circle of Willis Variability and Migraine

• ASL in Cognitive Neuroscience– AG17586 (Lee) Frontotemporal Dementia– HD050836 (Whyte) Neuroimaging for Cognitive Rehabilitation– NS045839 (Detre) Neuroscience Neuroimaging Center

• ASL in Pediatric Populations– DA014129 (Hurt) Neurocognitive Outcome of In Utero Cocaine– HD049893 (Wang) Hemodynamic Neuroimaging of Pediatric Stroke

• ASL is Substance Abuse– DA005186 (O’Brien) Center for Research in Drug Abuse– CA084718 (Lerman) Center for Tobacco Use Research

• ASL in Sleep– NR004281 (Dinges) Neurobehavioral Effects of Partial Sleep Deprivation

Core II: Collaboration Within RR

• Project 4 Optical (Yodh)– ASL+Optical CBF

• Muscle/PVD (Papers and Grants)

• Stroke and Neurointensive care monitoring (Papers andGrants, including BRP)

• Project 1 “Multinuclear” (Reddy)– Potential convergence in AD biomarker

– Potential Na+ functional MRI (esp. 7T)

Progress:Project 1 Translational Applications of ASL

Aim 1. To develop ASL perfusion MRI for adultbrain at 3T– Amplitude-modulated CASL implemented (head coil)– Pulsed ASL implemented (dual coil)– Pseudocontinuous ASL (Garcia et al ISMRM 2005

and modifications) implemented (dual coil)

CASL

PASL

PASL

0.77%54AM-CASL(Tx/Rx coil)

0.79%74pCASL(array coil)

0.58%56PASL(array coil)

ΔM/M0BCNR

PASL AM -CASL pCASL

Calculated from gray matter

Imaging parameters:> TR/TE = 4000/17 ms (GE EPI readout)> 60 repetition (surround subtraction)> For CASL/pCASL: PLD = 1000 ms; tagduration = 1500 ms> For PASL: TI1/TI2 = 700/1700 ms (QUIPSS II)

Comparison of PASL and CASL at 3TWu et al., MRM 2007

ModerateYesHighestpCASL

HighNo(excepthybrid)

HighAM-CASL

HighYesModeratePASL

Robust-ness ofLabeling

Body Xmit+Array Coil/

Parallel

LabelingEfficiency

Progress:Project 1 Translational Applications of ASL

Aim 2. To develop ASL in other organs andpopulations– CASL in skeletal muscle for functional assessment

of peripheral vascular disease• Collaborative with Floyd R01

– ASL in pediatric populations• Stroke: Collaborative with Wang R21, Ichord R01• Development: Collaborative with Wang R21 (R01 pending)

– Preliminary efforts in cardiac ASL• Limited progress

Heterogeneity of Muscle FlowWu et al, Am J Physiol 2007

SoleusDeep flexorAnterior ExtensorLateral Gastrocnemius

Hyperemic flow response to 5-min ischemia is significantlyhigher in the soleus muscleand deep flexors

cuff deflation

Time (min)

Blo

od F

low

(ml/1

00g/

min

)

ABI: Ankle to brachial index

Hyperemic Response in PVDWu, Floyd et al, in preparation

ASL in Pediatric StrokeChen et al, JMRI submitted

N=10 with ischemic stroke (5-125hr)Perfusion lesion correlates with:

• degree of stenosis (P=0.002)• diffusion lesion (P=0.008)• follow-up T2 infarct (P=0.023)

↑Feasibility of longitudinalASL in pediatric AIS

Progress:Project 1 Translational Applications of ASL

Aim 3. To reduce susceptibility effects andtemporal noise in ASL methods– ASL with 3D-GRASE (collaboration with David

Feinberg, Advanced MRI Technologies)– Background-suppressed “snapshot” ASL– Physiological Noise in ASL time series

3T CASL with SS-3D-GRASEFernandez-Seara et al, MRM 2005

3DGRASE EPI

GRASE>EPI GRASE>EPI tSNR

GROUPVARIANCE

Applications of SS-3D-GRASE

• Imaging of narrative speech production– Collaborative: Grossman R01, P01– Trojiani et al, Neuroimage 2007

• Imaging of hippocampal activationduring memory– Collaborative: Detre R01 (expired)– Fernandez-Seara et al, HBM 2007

Snapshot ASL BS-SS-3D-GRASEFernandez-Seara et al, MRM 2008

SNR/Var SNR/Var vs. Averagesvs. Averages Retest 42s CBF MapsRetest 42s CBF Maps

0.75%0.75%

NO SUPPRESSION

8.2%8.2%

WITH SUPPRESSION

Physiological Noise in ASLWu et al, in preparation

ROI 1 ROI 2

0

0.01

0.02

0.03

0.04

0.05

0 1 2

Labeling time

Effic

iency s

tandard

devia

tion

Fernandez-Seara et al, ISMRM06

RETROICOR with cardiac monitoringdemonstrates noise is cardiac

Progress:Project 2 Metabolic Correlates of fMRI

• Aim 1. Combined fMRI/PET technique forcoupling of CBF and CMRGlc at rest and duringtask activation

• Aim 2. To use the fMRI/PET technique during apsychomotor vigilance task (PVT)

• Aim 3. To use the fMRI/PET technique duringthe acute administration of caffeine (±PVT)

Concurrent CBF and CMRGlc (Qualitative)Newberg et al, NeuroImage 2005

rCMRglc rCBF rCMRglc-rCBF

Concurrent CBF and CMRGlc (Quantitative)Underway; n=5 scanned

Pre Caffeine Post Caffeine Absolute Relative

30

35

40

45

50

55

60

Pre-Caffeine Post-Caffeine

Glo

bal C

BF (m

l/100

g/m

in)

Global CBF decreased 13.6% (p = 0.17)

Pre Caffeine FDG PET Scan

Post Caffeine FDG PET Scan

Qualitative(%) Quantitative(%)

Frontal 1.6 -28.7

Parietal 1.1 -33.0

Temporal 0.5 -36.3

Occipital -2.0 -32.3

Basal Ganglia 6.5 -36.8

Thalamus 1.7 -36.4

Whole Brain 0.0 -32.2

Quantitative GMRGlc

Concurrent CBF and CMRGlcApplications• Regional coupling of CBF and metabolism

(normal, pathological)• Caffeine effect

– Collaboration with sleep deprivation (Dinges lab)– Validation of ASL as a biomarker for Alzheimer’s

disease (AZ collaboration)

High Field ASL: T2/T2* Effects

St Lawrence & Wang MRM 2005

Core II Future Directions(2010 Renewal)• 7T ASL

– Optimum coil configuration and labeling strategy– Optical imaging strategies - Radial MRI

(collaboration with Wehrli lab)• Beyond CBF

– Using ASL signal to measure oxygenation,permeability, compartments

• Improved sensitivity for studies of metabolism– Resting CBF and metabolism in muscle

(collaboration with Wehrli R21)– CBF and metabolism in brain

Collaborations with Industry• ASL as a biomarker for assessing neurotherapeutics

– Presentation at Pfizer workshop, London 2007

• ASL as a biomarker for orally administeredpsychopharmaceuticals– Wyeth research grant (finalizing)

• Validation of ASL as a biomarker for AD usingconcurrent ASL and FDG-PET– Astra Zeneca proposal (finalizing)