Computational Tools for Research in Neuroscience, Behavioral Science and Mental H

描述（由申请人提供）：我们建议开发一个软件包来自动评估受试者的β -淀粉样蛋白PET扫描（使用C11-PIB， F18-florbetaben，或F18-florbetapir， f18 -氟替他莫），方法是将受试者的扫描正常化，掩盖非灰质组织（不依赖于共同注册的MRI扫描），将标准化的roi放置在横向切片上，并报告参考小脑灰质的单独脑区域的SUVr值。我们的目标是，该分析包最终将获得FDA-510(k)批准，并作为商业产品分发给医院和诊所（以及制药公司），以帮助评估和诊断患者。通过使用这种经过验证和标准化的分析包，可以客观地比较新的放射性示踪剂在定量大脑中β -淀粉样蛋白方面的准确性，更重要的是，可以在个性化的个体基础上客观定量地评估新疗法在预防或去除每个患者β -淀粉样蛋白方面的功效。测试、用户界面评估、ADER报告生成工具和临床应用的重要部分将在德克萨斯州达拉斯德克萨斯大学西南医学中心核医学中心Michael Devous博士的监督下进行。在纽黑文的MNI，我们将继续在我们的放射示踪剂评估计划（RTEP）计划中测试和评估ADER，在那里我们继续测试潜在的新β淀粉样蛋白PET和SPECT显像剂，同时由我们的内部神经科医生和支持人员对受试者进行临床评估。由于ADER分析包将为阿尔茨海默病的进展提供定量的生物标志物分析方法，从而实现个体化治疗效果，因此对社会的潜在益处是相当大的。阿尔茨海默病（AD）与显著的发病率相关，一个有用的标志物和/或脑扫描分析包，如拟议的ADER，将增加我们对AD疾病进展的理解，并提供神经保护和恢复性治疗的客观评估。这种完全自动化的图像处理也将允许在使用新的PET和SPECT放射配体的临床试验中研究更少的受试者（具有相同的临床能力）。随着新的示踪剂和治疗方法的开发，ADER将与这些研究共同发展成为一种用于诊断、分期和治疗阿尔茨海默病的优化图像分析方法。

DESCRIPTION (provided by applicant): We propose to develop a software package to automatically evaluate a subject's beta amyloid PET scan (using either C11-PIB, F18-florbetaben, or F18-florbetapir, F18-flutemetamol) by normalizing the subject's scan, masking away non-gray matter tissue (without relying on co-registered MRI scans), placing standardized ROIs onto the transverse slices, and reporting SUVr values in separate brain areas referenced to the cerebellar gray matter. Our goal is that this analysis package ultimately would be FDA-510(k) approved and distributed to hospitals and clinics (and pharmaceutical companies), as a commercial product, to aid in the evaluation and diagnosis of patients. Through the use of such a validated and standardized analysis package, new radio-tracers can be objectively compared for their accuracy in quantitating beta amyloid in the brain, and more importantly, new therapies can be objectively and quantitatively evaluated for their efficacy in preventing or removing beta amyloid for each patient, on a personalized individual basis. An important portion of the testing, user interface evaluation, and ADER's report generation utility and clinical application will be conducted in a subaward under the supervision of Dr. Michael Devous within the Nuclear Medicine Center at the UT Southwestern Medical Center, Dallas, Texas. At MNI, New Haven, we will continue to test and evaluate ADER in house within our Radio-tracer Evaluation Program (RTEP) program, where we continue to test potential new beta amyloid PET and SPECT imaging agents, while clinically evaluating subjects by our in-house neurologists and support staff. The potential benefit to society is considerable since an ADER analysis package would provide a quantitative biomarker analysis method for Alzheimer's disease progression for individualized therapy efficacy. Alzheimer's disease (AD) is associated with significant morbidity and a useful marker and/or brain scan analysis package, like this proposed ADER, would add to our understanding of AD disease progression and provide objective assessment of neuroprotective and restorative therapies. This fully automated image processing will also allow for fewer subjects to be studied (with the same clinical power) in clinical trials using new PET and SPECT radioligands. As new tracers and therapies are developed, ADER would co-evolve with these studies into an optimized image analysis method for diagnosing, staging and treating Alzheimer's disease. PUBLIC HEALTH RELEVANCE: Evaluation of Radiotracers (ADER) Project Narrative We propose to develop an automated package for analysis of beta-amyloid accumulation in Alzheimer's patients' brains which can be easily implemented by pharmaceutical companies for therapeutic drug discovery, as well as in a clinical setting, for high quality quantitative PET (and SPECT) imaging assessments. This analysis will remove subjectivity in the determination of the imaging outcome measure and permit a reproducible evaluation of new Alzheimer's radio- tracers' imaging potential. ADER can be used to test the efficacy of new Alzheimer's therapies in which FDA Phase II tested radiotracers are used as surrogate biomarkers. Our validated image processing package is highly relevant to the ongoing search for new diagnostics and treatments since it will serve as a new "medical device" (as defined by the FDA), which will improve the way in which medical care is delivered to Alzheimer's patients.