MR Spectroscopy of the Brain during Acute HIV infection

急性艾滋病毒感染期间大脑的磁共振波谱

• 批准号: 6893540
• 负责人: MARGARET R LENTZ
• 金额: $ 14.85万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-12-01 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6893540
• 关键词: AIDS therapy; HIV infections; acute disease /disorder; antiviral agents; bioimaging /biomedical imaging; brain edema; brain imaging /visualization /scanning; brain metabolism; cerebrum; clinical research; combination chemotherapy; cytotoxic T lymphocyte; flow cytometry; helper T lymphocyte; human subject; human therapy evaluation; leukocyte count; nerve injury; neural degeneration; neuroimaging; noninvasive diagnosis; nuclear magnetic resonance spectroscopy; patient oriented research; statistics /biometry; virus load

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：拟议的跨学科研究使候选人能够进一步发展她的 MR 物理知识和神经艾滋病成像研究的专业知识，同时严格接触本研究的临床和生物学方面。目标是提高候选人在其拟议的研究项目和未来职业发展所需的多个领域的专业知识。这些领域包括免疫学、神经生物学、病毒学和临床研究。候选人处于世界知名的 MR 成像和艾滋病研究环境中。该奖项将为她成为一名成功的独立研究员提供必要的指导和工具。拟议的 5 年研究培训计划包括 1）候选人目前缺乏的所有生物学领域的课程作业和指导关系，2）为期 4 个月的临床实习轮换，这将使候选人能够加强与患者的互动并提供对患者入组机制，3）为将来组织更大规模的合作临床研究（单中心和多中心）做准备，4）将她之前的动物研究（重点关注神经艾滋病）应用于艾滋病毒感染患者。该应用程序的研究部分将使她能够检查 MRS 从未研究过的独特 HIV 感染人群，以及将最近发表的 SIV 猕猴结果转化为 HIV 感染患者而不是病理学的独特方法。早期中枢神经系统感染期间急性感染艾滋病毒患者大脑内发生的代谢变化将通过磁共振波谱（MRS）测量，并与HAART治疗前和治疗期间外周免疫细胞数量、激活和病毒载量的变化相关。假设包括：1) HIV 病毒最初进入中枢神经系统会导致脑脊液和脑实质发生短暂变化，这反映了炎症和局部免疫反应。 2) 随着高效抗逆转录病毒治疗 (HAART) 的诱导，这些异常现象将会消退。 MRS 将证明脑代谢异常的广泛模式，这些模式是短暂的并且与外周的病毒学/免疫学事件相关。如果发现与 SIV-猕猴模型中看到的结果类似的结果，我们将验证使用光谱标记物作为一种非侵入性手段来确定其他患者群体的早期神经元功能障碍，同时它仍然是可逆的。这项技术的验证可能会对未来的艾滋病毒感染者的治疗产生影响，有可能改善他们的生活质量。