MRI, MTI AND MRS AND MPS VII AND KRABBE DISEASE

MCSDA候选人是一名兽医神经学家，有兴趣开发 并应用核磁共振方法研究了人类的动物模型 神经退行性疾病 应聘者的长期目标是一份职业 在生物医学研究中， 使用磁共振成像在人类疾病动物模型中的神经变性 磁共振成像（MRI磁化传递成像（MTI）和 磁共振波谱（MRS）。 职业发展计划 包括MR物理学和医学遗传学课程， 与代谢磁共振研究计算机的互动 中心，以及一个研究计划与具体的和可测试的假设 将为候选人提供必要的培训，以实现 在神经退化研究中的科学独立性。 的 宾夕法尼亚大学兽医学院和我的导师，博士。 宾夕法尼亚大学医学院的杰里·格利克森说， 热情地承诺在未来三年内， 训练 本申请涉及犬和鼠动物模型的研究 溶酶体贮积症：粘多糖样沉积症（MPS）VII和 球状细胞脑白质营养不良（GCL）。 溶酶体贮积症影响 大约1/1500的人，目前还没有有效的治疗方法。 为那些有中枢神经系统表现的患者开发 疾病。 骨髓移植和神经系统移植的有效性 在犬和小鼠模型中进行祖细胞移植， 疾病已经产生了关于治疗的有希望的数据 神经变性 事实上，骨髓移植治疗这些疾病， 人类患者的疾病目前正在根据 在动物模型中取得了成功。 MRI、MTI和MRS提供令人兴奋的 增加组织表征的潜力，并可用于 在体内确定神经变性是否正在进展，是否已经停止， 或在治疗后正在消退。 具体来说，动物 MR扫描仪将用于收集MRI、MTI和MRS数据，以便 比较体积数据和特定MR可检测浓度 受影响动物和给药动物之间的代谢产物。 “黄金标准” 对于治疗效果将进行死后组织肛门分析 酶和底物的活性。 这些尸检数据 与体积数据和MR可检测的浓度相比， 代谢物，以便识别高度相关的MR数据 有效的治疗。

The MCSDA candidate is a Veterinary Neurologist interested in developing and applying NMR methods to study animal models of human neurodegenerative diseases. The candidates long-term goal is a career in biomedical research studying the pathophysiology and therapy of neurodegeneration in animal models of human disease using magnetic resonance imaging (MRI magnetization transfer imaging ((MTI) and magnetic resonance spectroscopy (MRS). A career development plan including coursework in MR physics and medical genetics, consistent interaction with the Metabolic Magnetic Resonance Research Computer Center, as well as a Research Plan with specific and testable hypotheses will provide the candidate with the training necessary to achieve scientific independence in the study of neurodegeneration. The Veterinary School of the University pf Pennsylvania and my mentor, Dr. Jerry Glickson, of the Medical School of the University of Pennsylvania, have enthusiastically pledged their support for the next three years of training. This application concerns the study of canine and murine animal models of lysosomal storage disorders: mucopolysaccharidosis (MPS) VII and globoid-cell leukodystrophy (GCL). Lysosomal storage disorders affect approximately 1/1500 humans and no effective therapy has yet been developed for those patients with central nervous system manifestations of disease. The effectiveness of bone marrow transplantation and neural progenitor cell transplantation in canine and murine models of these diseases has yielded promising data regarding the treatment of neurodegeneration. Indeed, bone marrow transplantation to treat these disorders in human patients is currently being pursued based on the success demonstrated in animal models. MRI, MTI, and MRS offer exciting potential for increased tissue characterization and can be used to determine, in vivo, whether neurodegeneration is progressing, has ceased to progress, or is regressing following therapy. Specifically, animal MR scanners will be used to collect MRI, MTI, and MRS data in order to compare volumetric data and the concentrations of specific MR detectable metabolites between affected and treated animals. The "gold standard" for the efficacy of treatment will be post mortem tissue anal analysis for enzyme and substrate activity. These post mortem data will be compared to volumetric data and to the concentrations of MR detectable metabolites in order to identify MR data which are highly correlated with effective therapy.