Novel diffusion MRI analysis for detection of mild traumatic brain injury

 描述(由申请人提供)：我们的总体长期目标是开发方法，准确地测量由于最被低估的损伤之一--轻度创伤性脑损伤而引起的细微的大脑变化。在目前的项目中，我们建议研究慢性创伤性脑病(CTE)，这是一种与先前暴露于重复头部撞击(RHI)相关的神经退行性疾病，例如接触运动引起的头部撞击。我们计划与创伤性脑病研究中心合作，对作为其R01(慢性创伤性脑病：临床表现和生物标记物)一部分的神经成像数据进行复杂的白质束分析。这些数据包括国家橄榄球联盟(NFL)退役球员的样本，他们被认为患有CTE的风险很高，以及与年龄匹配的对照运动员的样本。这个激动人心的项目提出将先进的扩散磁共振成像(DMRI)分析方法应用于CTE的生物标记物的研究。DMRI对轻度创伤性脑损伤(MTBI)引起的脑变化很敏感，但目前还不知道如何最好地检测这些变化。在mTBI的dMRI分析中，大多数先前的工作仅限于单张量模型(在穿过白质束区域有缺点)和基本扩散指数的测量，例如分数各向异性(其存在可能的潜在生物学机制的非特异性)。相反，我们建议评估单个和更复杂的多张量模型，使用我们开发的基于轨迹的测量和多壳dMRI的微结构测量，并经验性地确定哪些扩散指数是最具信息量的潜在生物标志物。我们假设dMRI测量将提供脑白质(WM)神经变性的敏感标记。我们建议通过与我们将根据对照运动员数据构建的正常大脑模型进行比较来测量白质变化。该模型将描述沿主要白质纤维束的扩散指数。我们将把单个受试者与这个模型进行比较，以检测异常扩散的区域。实验将选择表现最好的指标(潜在的生物标志物)，然后这些指标将被用来描述和量化病理变化。这项提议预计将有助于开发CTE的生物标记物，并探索这种疾病的临床表现，可能会影响到各级运动员以及我们社会的其他成员，如战斗军事人员。我们的方法有可能促进我们对mTBI和CTE的理解，朝着在临床上提供更好的诊断和预后信息的长期目标前进。

 DESCRIPTION (provided by applicant): Our overall long-term goal is to develop methods to accurately measure subtle brain changes due to one of the most under-diagnosed injuries, mild traumatic brain injury. In the current project, we propose to study chronic traumatic encephalopathy (CTE), a neurodegenerative disease associated with prior exposure to repetitive head impacts (RHI), such as those incurred from contact sports. We plan to work with the Center for the Study of Traumatic Encephalopathy to perform sophisticated white matter tract analyses of neuroimaging data acquired as part of their R01 (Chronic Traumatic Encephalopathy: Clinical Presentation and Biomarkers, PI Robert Stern). The data includes a sample of retired National Football League (NFL) players who are believed to be at high risk of developing CTE and a sample of control athletes matched for age. This exciting project proposes to apply advanced diffusion magnetic resonance imaging (dMRI) analysis methods to the study of biomarkers of CTE. dMRI is sensitive to brain changes caused by mild traumatic brain injury (mTBI), but it is not yet known how best to detect these changes. Most prior work in dMRI analysis for mTBI has been limited to single tensor models (with shortcomings in regions of crossing white matter tracts) and measurement of basic diffusion indices such as fractional anisotropy (which suffers from non-specificity regarding possible underlying biological mechanisms). In contrast, we propose to evaluate single and more sophisticated multi-tensor models, using tract-based measurements we have developed and microstructure measures from multishell dMRI, and to empirically determine which diffusion indices are the most informative as potential biomarkers. We hypothesize that dMRI measures will provide a sensitive marker of white matter (WM) neurodegeneration. We propose to measure white matter changes by comparison to a model of the normal brain that we will construct from the control athlete data. The model will describe the diffusion indices along major white matter fiber tracts. We will compare individual subjects to this model to detect regions of abnormal diffusion. Experiments will be performed to select the best-performing indices (potential biomarkers), then those indices will be employed to describe and quantify pathological changes. This proposal is expected to help develop biomarkers for CTE and to explore the clinical presentation of this disease likely to affect athletes at all levels of play, as well as other members of our society, such as combat military personnel. Our approach has the potential to advance our understanding of mTBI and CTE, towards the long-term goal of providing better diagnostic and prognostic information in the clinic.