CORE II: Functional MRI•Project 1 Translational Applications of ASL –Aim 1. To develop ASL...
Transcript of CORE II: Functional MRI•Project 1 Translational Applications of ASL –Aim 1. To develop ASL...
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)