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.