CORE II: Functional MRI

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1 CORE II: Functional MRI P.I.:John A. Detre Co-I: Jiongjiong Wang (Project 1) Co-I: Andrew Newberg (Project 2) Fellows: Maria Fernandez-Seara Wen-Chau Wu

2 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)

3 Physiological Basis of fmri behavior neural* function disease BOLD fmri blood volume Non-RR metabolism blood flow RR ASL fmri

4 Core II Publications 32 since 2005 related to topic of core and collaborations 15 specifically cited RR02305

5 Core II Major Collaborations ASL and Brain Function EB (Reddy) Methodology for Oxidative Metabolism HL (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 NS (Cucchiara) Circle of Willis Variability and Migraine ASL in Cognitive Neuroscience AG17586 (Lee) Frontotemporal Dementia HD (Whyte) Neuroimaging for Cognitive Rehabilitation NS (Detre) Neuroscience Neuroimaging Center ASL in Pediatric Populations DA (Hurt) Neurocognitive Outcome of In Utero Cocaine HD (Wang) Hemodynamic Neuroimaging of Pediatric Stroke ASL is Substance Abuse DA (O Brien) Center for Research in Drug Abuse CA (Lerman) Center for Tobacco Use Research ASL in Sleep NR (Dinges) Neurobehavioral Effects of Partial Sleep Deprivation

6 Core II: Collaboration Within RR Project 4 Optical (Yodh) ASL+Optical CBF Muscle/PVD (Papers and Grants) Stroke and Neurointensive care monitoring (Papers and Grants, including BRP) Project 1 Multinuclear (Reddy) Potential convergence in AD biomarker Potential Na + functional MRI (esp. 7T)

7 Progress: Project 1 Translational Applications of ASL Aim 1. To develop ASL perfusion MRI for adult brain 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) PASL PASL CASL

8 Comparison of PASL and CASL at 3T Wu et al., MRM 2007 Labeling Efficiency Body Xmit+ Array Coil/ Parallel Robustness of Labeling PASL Moderate Yes High AM- CASL pcasl High Highest No (except hybrid) Yes High Moderate Imaging parameters: > TR/TE = 4000/17 ms (GE EPI readout) > 60 repetition (surround subtraction) > For CASL/pCASL: PLD = 1000 ms; tag duration = 1500 ms > For PASL: TI 1 /TI 2 = 700/1700 ms (QUIPSS II) PASL AM -CASL pcasl AM-CASL (Tx/Rx coil) PASL (array coil) pcasl (array coil) CNR ΔM/M 0B 0.77% 0.58% 0.79% Calculated from gray matter

9 Progress: Project 1 Translational Applications of ASL Aim 2. To develop ASL in other organs and populations 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

10 Heterogeneity of Muscle Flow Wu et al, Am J Physiol 2007 Hyperemic flow response to 5- min ischemia is significantly higher in the soleus muscle and deep flexors Soleus Deep flexor Anterior Extensor Lateral Gastrocnemius

11 Hyperemic Response in PVD Wu, Floyd et al, in preparation ABI: Ankle to brachial index Blood Flow (ml/100g/min) cuff deflation Time (min)

12 ASL in Pediatric Stroke Chen 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 longitudinal ASL in pediatric AIS

13 Progress: Project 1 Translational Applications of ASL Aim 3. To reduce susceptibility effects and temporal 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

14 3T CASL with SS-3D-GRASE Fernandez-Seara et al, MRM DGRASE EPI GRASE>EPI GRASE>EPI tsnr GROUP VARIANCE

15 Applications of SS-3D-GRASE Imaging of narrative speech production Collaborative: Grossman R01, P01 Trojiani et al, Neuroimage 2007 Imaging of hippocampal activation during memory Collaborative: Detre R01 (expired) Fernandez-Seara et al, HBM 2007

16 Snapshot ASL BS-SS-3D-GRASE Fernandez-Seara et al, MRM 2008 WITH NO SUPPRESSION 8.2% 0.75% SNR/Var vs. Averages Retest 42s CBF Maps

17 Physiological Noise in ASL Wu et al, in preparation Efficiency standard deviation Labeling time Fernandez-Seara et al, ISMRM06 RETROICOR with cardiac monitoring demonstrates noise is cardiac ROI 1 ROI 2

18 Progress: Project 2 Metabolic Correlates of fmri Aim 1. Combined fmri/pet technique for coupling of CBF and CMRGlc at rest and during task 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)

19 Concurrent CBF and CMRGlc (Qualitative) Newberg et al, NeuroImage 2005 rcmrglc rcbf rcmrglc-rcbf

20 Concurrent CBF and CMRGlc (Quantitative) Underway; n=5 scanned Pre Caffeine Post Caffeine Absolute Relative 60 Global CBF (ml/100g/min) Pre-Caffeine Post-Caffeine Global CBF decreased 13.6% (p = 0.17)

21 Quantitative GMRGlc Pre Caffeine FDG PET Scan Post Caffeine FDG PET Scan Qualitative(%) Quantitative(%) Frontal Parietal Temporal Occipital Basal Ganglia Thalamus Whole Brain

22 Concurrent CBF and CMRGlc Applications 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)

23 High Field ASL: T2/T2* Effects St Lawrence & Wang MRM 2005

24 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

25 Collaborations with Industry ASL as a biomarker for assessing neurotherapeutics Presentation at Pfizer workshop, London 2007 ASL as a biomarker for orally administered psychopharmaceuticals Wyeth research grant (finalizing) Validation of ASL as a biomarker for AD using concurrent ASL and FDG-PET Astra Zeneca proposal (finalizing)