MR & Optical Diagnosis of Mitochondrial Metabolism and Dysfunction

描述（由申请人提供）：项目总结/摘要本BIRT补充的目标是开发一套定量MR成像和光谱工具，与已知的细胞事件相关，以获得识别肌肉炎症、损伤和恢复的替代标记物，并监测这些过程的时间过程和演变-非侵入性活检。拟议的项目将在狗和小鼠的营养不良疾病模型中进行。基于T2弛豫变化的成像是目前识别肌肉和软组织病理区域的临床标准。这些方法是有用的，因为它们对广泛的机制敏感，但这种普遍性意味着它们无法识别受影响区域的特定细胞过程。我们最近开始与Stephen Tapscott的实验室一起研究，以监测他们的营养不良犬模型，特别是制定MRI方法来监测炎症及其消退，这些炎症及其消退是在正常和cxmd犬中局部注射AAV-微肌营养不良蛋白基因构建体后进行的，以区分炎症与基因转移的积极影响，并使用常规工具监测针对炎症的治疗干预。这个新项目将测试1H，23 Na和31 P成像和光谱方法（除了传统的T2加权和STIR成像）的敏感性和特异性的基础病理学验证活检在Tapscott博士的实验室。与Jeff Chamberlain博士的实验室合作的相关实验将通过使用相同的MRI和MRS方法将布比卡因微量注射到胫骨前肌，股四头肌和小腿三头肌中，量化缺乏肌营养不良蛋白和/或utrophin的正常和敲除小鼠腿部肌肉中病变进展和恢复的时间过程。组织学检查和免疫组织化学的识别和成像区域将验证细胞机制。该结果有望应用于其他肌肉、关节和软组织疾病。

DESCRIPTION (provided by applicant): Project Summary/Abstract The goal of this BIRT supplement is to develop a set of quantitative MR imaging and spectroscopy tools that correlate with known cellular events to derive surrogate markers that identify muscle inflammation, damage and recovery and to monitor the time course and evolution of these processes - a non-invasive biopsy. The proposed project will be done in dystrophic disease models in dogs and mice. Imaging based on changes in T2 relaxation is currently the clinical standard to identify regions of pathology in muscles and soft tissues. These methods are useful because of their sensitivity to a wide range of mechanisms, but this generality means they are unable to identify specific cellular processes in the affected areas. We recently began studies with Stephen Tapscott's lab to monitor their canine model of dystrophy, and specifically to work out MRI methods to monitor the inflammation and its regression that follows focal injection of AAV-microdystrophin gene constructs in normal and cxmd dogs to distinguish inflammation from the positive effects of gene transfer, and to monitor therapeutic interventions against inflammation using conventional tools. This new project will test 1H, 23Na and 31P imaging and spectroscopy methods (in addition to conventional T2 weighted and STIR imaging) for sensitivity and specificity of the underlying pathologies verified by biopsy in Dr. Tapscott's lab. Related experiments in collaboration with Dr. Jeff Chamberlain's lab will quantify the time course of lesion progression and recovery in leg muscles of normal and knockout mice lacking dystrophin and/or utrophin by microinjections of bipivacaine into the tibialis anterior, quadriceps and triceps surae using the same MRI and MRS methods. Histological examinations and immuno-histochemistry of the identified and imaged regions will validate the cellular mechanisms. The results are expected to be applicable to other disorders of muscles, joints and soft tissues.