The proposed interdisciplinary study allows the candidate to further develop her knowledge of MR physics and expertise in imaging studies of neuroAIDS, while providing rigorous exposure to the clinical and biological side of this research. The goal is to increase the candidate's expertise in multiple areas necessary to her proposed research project and future career development. These areas include immunology, neurobiology, virology and clinical research. The candidate is in a world-renown environment for both MR Imaging and AIDS research. This Award will provide the guidance and tools necessary for her to become a successful, independent researcher. The proposed 5-year research training program consists of 1) Coursework and mentoring relationships in all biological areas the candidate is currently lacking, 2) a 4 month clinical clerkship rotation which will allow the candidate to strengthen her interactions with patients and provide insight to the patient enrollment mechanism, 3) preparation for organizing larger collaborative clinical studies in the future, both single site and multi-center and 4) application of her previous animal studies focusing on neuroAIDS to HIV infected patients. The research portion of this application will allow her to examine a unique HIV infected population that has never been studied by MRS, as well as a unique means of translating recently published SIV-macaque results to HIV infected patients in lieu of pathology. Metabolic changes occurring within the brains of the acutely infected HIV patients during early CNS infection will be measured by magnetic resonance spectroscopy (MRS), and correlated to changes in the peripheral immune cell numbers, activation and viral load both before and during HAART therapy. Hypotheses include: 1) The initial movement of HIV virus into the CNS leads to transient changes in the cerebrospinal fluid and brain parenchyma, which reflect inflammation and a local immune response. 2) These abnormalities will recede with the induction of highly active antiretroviral therapy (HAART). MRS will demonstrate widespread patterns of abnormal cerebral metabolism, which are transient and correlate to the virologic/immunologic events in the periphery. If similar results are found to those seen in the SIV-macaque model, we will validate using spectroscopic markers as a noninvasive means for determining early neuronal dysfunction in other patient populations while it is still reversible. Validation of this technique could impact future HIV-infected patients therapeutically, potentially improving their quality of life.
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