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BIOMARKERS AND PATHOGENESIS OF MS: FROM MOUSE TO HUMAN

多发性硬化症的生物标志物和发病机制：从小鼠到人类

基本信息

批准号：
9275041
负责人：
DOROTHY ANNE CROSS
金额：
$ 32.76万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-25 至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/9275041
关键词：
Acute Advocate Affect Animal Model Area Atlases Autopsy Axon Biological Markers Biological Preservation Biopsy Blood Brain Cellularity Chronic Classification Clinical Clinical Trials Cognitive Data Demyelinations Detection Deterioration Development Diffuse Diffusion Diffusion Magnetic Resonance Imaging Disease Edema Enrollment Evolution Fiber Funding Gadolinium Histologic Histology Histopathology Human Image Imaging Techniques Individual Inflammation Inflammatory Injury Lead Lesion MRI Scans Magnetic Resonance Imaging Measures Methods Modeling Multiple Sclerosis Multiple Sclerosis Lesions Mus Myelin Nerve Fibers Outcome Pathogenesis Pathologic Pathology Patients Play Population Process Relapse Resolution Role Sampling Scanning Severities Specificity Specimen System Techniques Testing Therapeutic Time Tissue Sample Tissues Translating Validation Water axon injury base black hole clinical imaging clinical predictors disability forest imaging approach imaging modality improved in vivo innovation mind control mouse model multiple sclerosis patient neuropathology novel novel therapeutics outcome forecast predict clinical outcome relating to nervous system remyelination repaired spectrograph white matter

项目摘要

During the initial funding period, our group developed a novel Diffusion Basis Spectrum Imaging (DBSI) method to simultaneously detect and quantitate inflammation, demyelination and axon injury in vivo using diffusion imaging (Wang et al. 2011). DBSI has substantially improved the accuracy and specificity of our prior diffusion tensor imaging (DTI) approach, by overcoming the main inadequacies of DTI. We hypothesize that DBSI can quantitate the proportions of axon injury, demyelination, and inflammation in CNS of MS patients. We previously showed using a mouse model that DBSI detects and quantitates axonal and myelin injuries that had escaped detection by standard imaging, and by DTI. Our preliminary data now include validation of DBSI using autopsied and biopsied human specimens, with favorable correlations with human histology. We also now have longitudinal data spanning 1.5 yrs, and comparisons of DBSI with magnetization transfer imaging (MTI). In Project 3, we will apply DBSI to humans with MS, comparing it to standard MRI, DTI and MTI. Project 3 will classify MS lesion subtypes by measures of axon injury, demyelination, and inflammation (cellularity and increased free water due to edema or tissue loss), and follow the patients over 4 years to identify predictors and correlates of clinical deterioration. We expect to achieve this using DBSI by differentiating prominent axonal injury vs. axon preservation, and demyelination vs. myelin preservation/ remyelination. We will examine established persistent black holes (PBHs) (new sub-aim), and perform longitudinal assessments of gadolinium-enhancing (Gd+) MS lesions to determine if DBSI will predict PBH formation, representing severe axon loss. With its ability to profile lesions and normal-appearing CNS, DBSI could help non-invasively elucidate the substrate of MS lesion formation and detect inflammation behind an intact blood-CNS-barrier (not detected by Gd+). DBSI has potential to aid development and testing of new therapies for progressive MS where loss of axons and tissue integrity are believed to play a large role.

在最初的资助期间，我们的团队开发了一种新的扩散基谱成像（DBSI）