In vivo Imaging of Brain Damage in HTLV-I Associated Tropical Spastic Paraparesis

描述(由申请人提供)摘要HTLV-I相关性脊髓病/热带痉挛麻痹(HAM/TSP)是一种慢性进行性中枢神经系统疾病，在中南美洲人群中特别流行，在巴西等国家，它会造成重大的社会和经济影响。尽管最常见的中枢神经系统病变部位是胸部水平的脊髓，但有证据表明，HTLV-I感染后的脑损伤，尽管表现不佳，特征不如脊髓，但潜在的实质性，即使在无症状的HTLV-I携带者中也可能发生。这项建议的目标是描述和量化脑白质和皮质的变化，以及它们与巴西HAM/TSP患者认知功能障碍的关系。我们的研究计划建立在马萨诸塞州波士顿的马萨诸塞州总医院(MGH)阿蒂努拉·A·马蒂诺斯生物医学成像中心(Clinica de Diagnostio Por Imagem，CDPI)和巴西里约热内卢埃斯塔多大学(University Do Estado Do Rio De Janeiro)的研究人员之间的合作伙伴关系上。这项合作工作建议将先进的多光谱磁共振图像采集和分析方法与临床神经学和认知评估技术相结合。这项提议还寻求为巴西的神经成像专家和神经学家提供必要的培训，以应用阿蒂努拉·A·马蒂诺斯生物医学成像中心开发的先进神经成像工具来研究这种在他们的国家正在出现的公共重要性的大脑疾病。了解HAM/TSP相关脑损伤的体内致病机制及其神经学后果可能最终导致对这种地方性疾病及其许多临床表现的更有效的治疗和预防干预与公共卫生相关性：这项建议旨在利用先进的多光谱磁共振成像方法，表征和量化巴西人群中HTLV-I相关脊髓病/热带痉挛性瘫痪(HAM/TSP)患者的活体脑病理变化，及其与认知功能障碍的关系。HAM/TSP是一种慢性、进行性的中枢神经系统疾病，在巴西特别流行，它会造成重大的社会和经济影响。该项目将通过马萨诸塞州波士顿的马萨诸塞州总医院(MGH)阿蒂努拉·A·马蒂诺斯生物医学成像中心的研究人员与诊断成像诊所(CDPI)和巴西里约热内卢的埃斯塔多大学的研究人员建立合作伙伴关系来实施。了解HAM/TSP相关脑损伤的体内致病机制及其神经学后果可能最终导致对这种地方性疾病进行更有效的治疗和预防干预。

DESCRIPTION (provided by applicant): Abstract HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic, progressive disease of the CNS that is particularly prevalent among populations in Central and South America, where in countries like Brazil, it causes significant social and financial impact. Although the most frequently reported site of CNS pathology is the spinal cord at the thoracic level, there is evidence that brain damage following HTLV-I infection, although poorly and less characterized than spinal cord involvement, is potentially substantial and may occur even in asymptomatic HTLV-I carriers. The goals of this proposal are to characterize and quantify white matter and cortical changes in the brain and their relation to cognitive dysfunction in a Brazilian population of patients with HAM/TSP. Our study plan rests on the formation of a partnership between investigators at the Massachusetts General Hospital (MGH) Athinoula A. Martinos Center for Biomedical Imaging in Boston, MA, and the Clinica de Diagnostico por Imagem (CDPI) and the Universidade do Estado do Rio de Janeiro, Brazil. This collaborative work proposes to combine advanced multi-spectral MR image acquisition and analysis methods with clinical neurologic and cognitive assessment techniques. This proposal also seeks to provide the neuroimaging specialists and neurologists in Brazil with the training necessary to apply advanced neuroimaging tools developed at the Athinoula A. Martinos Center for Biomedical Imaging to study this brain disorder of emerging public importance in their country. Understanding the in vivo pathogenic mechanisms of HAM/TSP-associated brain damage and its neurologic consequences may ultimately lead to more effective therapeutic and preventive interventions of this endemic disorder and its many clinical manifestations PUBLIC HEALTH RELEVANCE: This proposal aims at characterizing and quantifying, using advanced multi-spectral MR image methods, in vivo brain pathological changes in a Brazilian population of patients with HTLV-I- associated myelopathy/tropical spastic paraparesis (HAM/TSP), and their relation to cognitive dysfunction. HAM/TSP is a chronic, progressive disease of the CNS that is particularly prevalent in Brazil where it causes significant social and financial impact. The project will be conducted through the formation of a partnership between investigators at the Massachusetts General Hospital (MGH) Athinoula A. Martinos Center for Biomedical Imaging in Boston, MA, and the Clinica de Diagnostico por Imagem (CDPI) and the Universidade do Estado do Rio de Janeiro, Brazil. Understanding the in vivo pathogenic mechanisms of HAM/TSP-associated brain damage and its neurologic consequences may ultimately lead to more effective therapeutic and preventive interventions of this endemic disorder.