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: 6987884
• 负责人: MARGARET R LENTZ
• 金额: $ 14.87万
• 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/6987884
• 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）：拟议的跨学科研究允许候选人进一步发展她对神经辅助研究成像研究的MR物理学和专业知识，同时为这项研究的临床和生物学方面提供了严格的暴露。目的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。该候选人处于MR成像和艾滋病研究的世界享有盛誉的环境中。该奖项将为她成为一名成功的独立研究人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工作和指导关系，2）4个月的临床文员旋转，这将使候选人能够加强与患者的互动，并为患者提供见识并对患者入学机制，3）准备将来组织较大的协作临床研究的准备，无论是单位部位还是多中心，以及4）她以前的动物研究的应用，将关注神经辅助的动物研究应用于HIV感染患者。该应用的研究部分将使她能够检查MRS从未研究过的独特的HIV感染人群，以及将最近出版的SIV-Macaque结果转化为HIV感染的患者而代替病理学的独特手段。中枢神经系统感染期间急性感染的HIV患者的大脑中发生的代谢变化将通过磁共振光谱（MRS）来测量，并与HAART治疗前后的外周免疫细胞数量，激活和病毒载量的变化相关。假设包括：1）HIV病毒进入中枢神经系统的初始运动导致脑脊液和脑实质的短暂变化，这些变化反映了炎症和局部免疫反应。 2）这些异常将随着高度活性抗逆转录病毒疗法（HAART）的诱导而消退。 MRS将证明异常大脑代谢的广泛模式，这些模式与周围的病毒/免疫事件相关并相关。如果发现与SIV-MaCaque模型中看到的结果相似，我们将使用光谱标记作为一种无创手段来验证，用于确定其他患者种群中的早期神经元功能障碍，而该方法仍然是可逆的。对该技术的验证可能会影响未来的HIV感染患者治疗，从而有可能改善其生活质量。