Several lines of evidence derived from positron emission tomography (PET) studies suggest that measures of cerebral metabolic rate of oxygen utilization (CMRO2) provide an indication of brain tissue viability during cerebral ischemia. Although PET is a currently available technology to measure CMRO2, the need for an onsite cyclotron has limited its availability to only a few medical centers. Therefore, alternative approaches capable of providing similar physiological information as that of PET CMRO2 could have profound clinical implications. Towards this end, we have recently developed an MR imaging approach capable of measuring cerebral oxygen metabolic activity, which we have termed MR cerebral oxygen metabolic index (MR_COMI). Although physically different from PET CMRO2, preliminary results based on MR_COMI are encouraging, suggesting that this approach may indeed reveal similar physiological information as that of PET CMRO2. However, in order to determine if MR_COMI can delineate tissue viability during ischemia, a direct comparison between MR_COMI predicted tissue infarction and final tissue outcome under experimental conditions that are highly clinically relevant is of paramount importance. Therefore, the overall focus of this application is to first determine an MR_COMI threshold for irreversible injury and subsequently use this MR_COMI threshold to assess dynamic temporal and spatial evolution of MR_COMI defined lesions in response to cerebral ischemia (Aim 1) and second, empirically determine the predictive value of MR_COMI threshold, exploiting experimental conditions known to alter infarct volume (Aim 2). In addition, since this newly developed MR approach requires knowledge of regional cerebral hematocrit (Hct) which may change during cerebral ischemia, a parallel aim is proposed (Aim 3) to determine how cerebral ischemia induces alterations of cHct using small animal single photon emission computed tomography (SAI SPECT). Specifically, serial injections of two tracers: Tc-99m labeled red blood cells and Tc-99m labeled serum human albumin will be used to obtained SPECT images for the estimates of cHct. The success of the proposed studies will demonstrate that the newly developed MR approach is capable of delineate irreversibly injured from viable tissues under cerebral ischemia and may offer a tool for individualized treatment of acute stroke patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS054079-05
Application #
7760587
Study Section
Clinical Neuroscience and Disease Study Section (CND)
Program Officer
Wong, May
Project Start
2006-08-07
Project End
2013-01-31
Budget Start
2010-02-01
Budget End
2013-01-31
Support Year
5
Fiscal Year
2010
Total Cost
$278,951
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
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Wang, Jiaping; Zhu, Hongtu; Fan, Jianqing et al. (2011) Adaptively and spatially estimating the hemodynamic response functions in fMRI. Med Image Comput Comput Assist Interv 14:269-76

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