The long-term goal of this research is to improve the utility of functional magnetic resonance imaging (fMRI) in the studies of brain disorders, in particular psychiatric disorders. For this project, the goal is focused on the establishment of MRI measures of baseline venous oxygenation as a physiologic normalization factor for fMRI. The first application of this approach to Schizophrenia will demonstrate the clinical feasibility.
The specific aims are: 1) Optimization and validation of T2-Relaxation-Under-Spin-Tagging (TRUST) MRI. 2) To show the effect of baseline oxygenation on fMRI signals and demonstrate that TRUST MRI can be used as a normalization factor across subjects. 3) To compare the fMRI responses to a memory task between a schizophrenia group and a control group using TRUST MRI. FMRI has been widely used over the past fifteen years to noninvasively evaluate the brain functions. There is also great interest in the application of fMRI to psychiatric disorders, such as Schizophrenia and Alzheimer's Disease, with the goal of better understanding the cognitive consequences of these diseases and, importantly, for early diagnosis of these diseases based on the expectation that functional alterations precede structural/behavioral changes. These efforts, however, have met with some practical problems and many studies have found results to be negative, due to large variations within the subject groups. It is hypothesized that variation in baseline venous blood oxygenation is the main reason for individual variation of fMRI results between subjects and that measurement of this parameter should allow correction for such differences. A novel MRI technique, TRUST MRI, will be devised to quantitatively measure the baseline venous oxygenation non-invasively, and calibration and validation of this technique will be performed. The TRUST MRI will then be used to normalize the fMRI signals and to improve the sensitivity in detecting regional differences between two groups of subjects. A """"""""model"""""""" situation in which two subject groups are known to have different neural activities will be utilized to assess the utility of the approach and the improvement in fMRI sensitivity. As a clinical application of the technique, a memory task will be presented to the Schizophrenia patients and, from the fMRI responses, the brain regions that are responsible for the memory deficits will be determined, which may guide future treatment strategies for patients with Schizophrenia.
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