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Physiologic Basis of fMRI Signals Focus on Perfusion MRI

. . . . . . . . . . . . MEG ERP. OpticalDyes. Single Unit. Patch Clamp. LightMicroscopy. PET. Lesions. 2-deoxyglucose. Microlesions. fMRI. Brain. Map. Column. Layer. Neuron. Dendrite. Synapse. Millisecond. Second. Minute. Hour. Day. Log Time. Log Size. Week. Spatiotemporal Scales for Neuroscience Methods adapted from Churchland.

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Physiologic Basis of fMRI Signals Focus on Perfusion MRI

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    1. Physiologic Basis of fMRI Signals Focus on Perfusion MRI John A. Detre, M.D. Center for Functional Neuroimaging Cognitive Rehabilitation Research Consortium University of Pennsylvania Moss Rehabilitation Institute Philadelphia, PA

    2. Spatiotemporal Scales for Neuroscience Methods adapted from Churchland

    3. Imaging Physiological Correlates of Neural Function

    5. Activation-Flow Coupling Blood flow and metabolism changes accompany brain activation First described in late 1800’s by Mosso (Italy) and Sherrington (England) Physiological basis remains poorly understood today

    7. Coupling of CBF, CMRGlu, and CMRO2 during Functional Activation Uncoupling of CBF, CMRGlu, and CMRO2 Fox and Raichle, PNAS 1996 ?CBF=?CMRGlu>>?CMRO2 Predicts reduction in deoxyhemoglobin with activation No increase in activated CBF with hypoglycemia Powers et al., Am. J. Physiol. 1996 Suggests ?CBF is not required to supply glucose substrate No increase in activated CBF with hypoxia Mintun et al., PNAS 2001 Suggests ?CBF is not required to supply O2 substrate

    12. Brain Activation Analysis

    13. fMRI with BOLD Contrast task activation

    14. Perfusion MRI with Arterial Spin Labeling

    15. Key Improvements in ASL MRI Transit time correction (Alsop and Detre, 1998) Multislice (Alsop and Detre, 1998) Background suppression (Ye et al., 2000) High Field (Wang et al., 2002) Multicoil/Parallel Imaging (Wang et al, 2005) Snapshot 3D Imaging (Duhamel and Alsop, 2004) (Fernandez-Seara et al., 2005) Improved Labeling (Garcia et al., 2005)

    16. Perfusion fMRI using ASL Observe CBF changes directly CBF changes are more linearly coupled to neural activity than BOLD effects Resting and activated CBF in absolute units (ml/g/min) Pathological conditions may affect resting CBF Despite reduced sensitivity vs. BOLD, advantages for: Spatial resolution (localizes to brain rather than vein) Low frequency designs (behavioral states) Group analyses (? reduced intersubject variability) Regions of high static susceptibility gradient (non-GE EPI) Statistical advantages (white noise)

    17. Localization of Functional Contrast

    18. Temporal Characteristics of Perfusion fMRI Control/Label pair typically every 4-8 sec “Turbo” ASL (Wong) can increase resolution by ~50% Qualitative ?CBF (no control) in ~2 sec S:N much lower than BOLD for event-related fMRI Control/Label pair eliminates drift effects White noise (instead of 1/f) Stable over long durations (learning, behavioral state changes, pharmacological challenge etc.) Sinc subtraction eliminates BOLD derivative

    19. Perfusion vs. BOLD: Very Low Task Frequency Wang et al., MRM 2002

    20. ASL Perfusion fMRI vs. BOLD Improved Intersubject Variability vs. BOLD Aguirre et al., NeuroImage 2002

    21. Utility of ASL Perfusion fMRI in Clinical Research Quantify CBF in cerebrovascular disorders Perfusion imaging may reveal “functional” deficits without a structural correlate Baseline CBF is a critical determinant of the capacity for activation-flow coupling with a task Correlate “resting” CBF with cognitive deficits in cohort Allows functional localization of affected regions Avoids confound of impaired task performance during fMRI Avoids need for cognitively impaired subject to perform during fMRI CBF should be a stable biomarker across space and time Ideal for multisite or longitudinal studies This advantage has yet to be formally proven in a clinical study

    23. Cognitive Correlations using Resting Perfusion MRI in Alzeimer’s Dementia

    24. Dissociation of Activation-Flow Coupling Patient with Left Intracranial Carotid Stenosis

    25. Considerations in Task-Activation fMRI (Summary)

    26. Conclusions FMRI is measures neural activity indirectly BOLD qualitatively reflects CBF and metabolism ASL quantitatively reflect CBF Clinical FMRI poses special challenges Task performance effects must be considered Underlying pathophysiology may alter coupling of activation and flow FMRI identifies putative regions supporting task function Does not establish necessity Correlation with outcome, lesions, or TMS lesions can disambiguate Many fMRI applications in neurorehabilitation Mechanisms of neuroplasticity Biomarker for therapy Prediction of outcome Bionic interfaces

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