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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Mentored Quantitative Research Career Development Award (K25)
Project #
5K25NS051129-04
Application #
7388902
Study Section
Special Emphasis Panel (ZNS1-SRB-S (06))
Program Officer
Wong, May
Project Start
2004-12-01
Project End
2009-11-30
Budget Start
2007-12-01
Budget End
2008-11-30
Support Year
4
Fiscal Year
2008
Total Cost
$149,237
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
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Burdo, Tricia H; Lentz, Margaret R; Autissier, Patrick et al. (2011) Soluble CD163 made by monocyte/macrophages is a novel marker of HIV activity in early and chronic infection prior to and after anti-retroviral therapy. J Infect Dis 204:154-63
Ratai, Eva-Maria; Annamalai, Lakshmanan; Burdo, Tricia et al. (2011) Brain creatine elevation and N-Acetylaspartate reduction indicates neuronal dysfunction in the setting of enhanced glial energy metabolism in a macaque model of neuroAIDS. Magn Reson Med 66:625-34
Lentz, Margaret R; Kim, Woong-Ki; Kim, Hyun et al. (2011) Alterations in brain metabolism during the first year of HIV infection. J Neurovirol 17:220-9
Wu, William E; Kirov, Ivan I; Zhang, Ke et al. (2011) Cross-sectional and longitudinal reproducibility of rhesus macaque brain metabolites: a proton MR spectroscopy study at 3 T. Magn Reson Med 65:1522-31
Ratai, E-M; Pilkenton, S; He, J et al. (2011) CD8+ lymphocyte depletion without SIV infection does not produce metabolic changes or pathological abnormalities in the rhesus macaque brain. J Med Primatol 40:300-9
Liu, Songtao; Fleysher, Roman; Fleysher, Lazar et al. (2010) Brain metabolites B1-corrected proton T1 mapping in the rhesus macaque at 3 T. Magn Reson Med 63:865-71
Lentz, Margaret R; Degaonkar, Mahaveer; Mohamed, Mona A et al. (2010) Exploring the relationship of macrophage colony-stimulating factor levels on neuroaxonal metabolism and cognition during chronic human immunodeficiency virus infection. J Neurovirol 16:368-76
Ratai, Eva-Maria; Pilkenton, Sarah J; Greco, Jane B et al. (2009) In vivo proton magnetic resonance spectroscopy reveals region specific metabolic responses to SIV infection in the macaque brain. BMC Neurosci 10:63
Liu, Songtao; Gonen, Oded; Fleysher, Roman et al. (2009) Metabolite proton T(2) mapping in the healthy rhesus macaque brain at 3 T. Magn Reson Med 62:1292-9

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