Quantitative (Perfusion and Diffusion) MRI Biomarkers to Measure Glioma Response

用于测量神经胶质瘤反应的定量（灌注和扩散）MRI 生物标志物

• 批准号: 9000135
• 负责人: KATHLEEN Marie SCHMAINDA
• 金额: $ 42.64万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-02-28 至 2019-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9000135
• 关键词: Address; Algorithms; Angiogenesis Inhibitors; Brain Neoplasms; Cell Density; Cessation of life; Clinic; Clinical; Clinical Oncology; Clinical Trials; Collaborations; Collection; Computer software; Contrast Media; Data; Data Storage and Retrieval; Databases; Development; Diffusion; Diffusion Magnetic Resonance Imaging; Dose; Evaluation; Extravasation; Glioblastoma; Glioma; Goals; Grant; Growth; Health; Hybrids; Image; Image Analysis; Laboratories; Lead; Magnetic Resonance Imaging; Maps; Measurement; Measures; Methods; Modification; Monitor; Multi-Institutional Clinical Trial; Patients; Perfusion; Perfusion Weighted MRI; Predisposition; Primary Brain Neoplasms; Principal Investigator; Process; Protocols documentation; Publications; Recurrence; Research; Software Tools; Standardization; Techniques; Technology; Testing; Therapeutic Clinical Trial; Time; Translating; Translations; Tumor Cell Invasion; Tumor Volume; Validation; Visual; Weight; Work; base; bevacizumab; cancer Biomedical Informatics Grid; cerebral blood volume; chemoradiation; contrast enhanced; cost; cost effective; data exchange; design; drug discovery; imaging biomarker; imaging modality; imaging platform; improved; neoplastic cell; novel; personalized care; predicting response; response; standard measure; standard of care; targeted treatment; time interval; treatment planning; treatment response; tumor; tumor growth

DESCRIPTION (provided by applicant): The overall goal is to develop and validate both standard and novel perfusion-weighted MRI (PWI) and diffusion-weighted MRI (DWI) biomarkers to monitor treatment response for both therapeutic clinical trials and standard of care treatment plans for patients with brain tumors. This goal addresses an urgent need for better ways to monitor targeted therapies, for which standard measures of enhancing tumor volumes are no longer sufficient. The two PWI methods that will be characterized for clinical trials are based on many years of PWI research in Dr Schmainda's laboratory. The first more wide-spread DSC (dynamic susceptibility contrast) approach provides tumor rCBV (relative cerebral blood volume) measurements obtained after a pre- load of contrast agent and corrected for confounding contrast agent leakage effects. A multi-year comparison study of rCBV methods suggests that this algorithm is one of the most accurate approaches currently available. The second approach, while less-proven has high-potential to become the most comprehensive perfusion solution. It consists of using a dual-echo gradient-echo (DEGES) spiral method, which enables the simultaneous collection of both DSC (dynamic susceptibility contrast) and DCE (dynamic contrast enhanced) perfusion data using only a single dose of contrast agent and incorporates comprehensive correction for leakage effects. Also, newly developed for purposes of longitudinal monitoring is the "standardization" of rCBV images where rCBV values are transformed to a standard measurement scale so greater visual and quantitative consistency is maintained across studies. Subjective errors are minimized since user-defined reference R0Is are no longer needed for quantification. These developments are clearly beneficial for ease of incorporation into clinical trials and standard practice. In recent years it has become increasingly clear that the full evaluation of brain tumor response also requires the assessment of tumor cell density, death and invasion, especially in non-enhancing tumors. In this context, our laboratory has put forth great effort, evidenced by several recent publications, to develop and validate diffusion methods to monitor tumor growth and invasion. By computing changes in the apparent diffusion coefficient (ADC) across time, we have created functional diffusion maps (fDM) within non-contrast- agent-enhancing regions. We have found that changes in ADC suggestive of increased cell density were more predictive of response to the anti-angiogenic drug, bevacizumab, than standard contrast-agent enhanced MRI. While both PWI and DWI have demonstrated great promise for treatment monitoring, studies defining their test-retest repeatability, necessary for use of these techniques in clinical trials, are lackng, and thus represent the focus of Aim 1. In addition, early results suggest that hybrid PWI/DWI maps will likely provide the most complete assessment of treatment response, a hypothesis that will be tested in Aim 2. Finally, in order to make the optimized PWI/DWI technology and workflow available in a robust and cost-effective manner for clinical trials and standard practice, Aim 3 involves the development of a commercial integrated image analysis platform for use in large-scale multi-center clinical trials. Taken together this effort should result in a robust and ready to use advanced imaging platform for the advanced imaging evaluation of both conventional and targeted brain tumor therapies. This should lead to greater clinical trial efficiency enabling more rapid drug discovery and translation and improved individualized care for patients.

描述（由申请人提供）：总体目标是开发和验证标准和新型灌注加权MRI（PWI）和扩散加权MRI（DWI）生物标志物，以监测治疗临床试验和护理标准治疗计划的治疗反应适用于脑肿瘤的患者。该目标迫切需要更好地监测目标疗法的方法，以增强肿瘤量的标准措施不再足够。将针对临床试验进行表征的两种PWI方法基于Schmainda博士实验室的PWI多年研究。第一个更广泛的DSC（动态敏感性对比度）方法提供了肿瘤RCBV（相对脑血体积）测量，后在预载造影剂后获得，并校正了对比度泄漏效应的混淆。 RCBV方法的多年比较研究表明，该算法是当前可用的最准确的方法之一。第二种方法虽然较少，但具有高潜力来成为最全面的灌注解决方案。它包括使用双回波梯度回声（度）螺旋方法，该方法可以同时收集DSC（动态敏感性对比度）和DCE（动态对比度增强）灌注数据，仅使用单剂量的对比剂并结合综合剂量纠正泄漏效果。同样，出于纵向监测的目的，新开发的是RCBV图像的“标准化”，其中RCBV值转化为标准的测量量表，因此在研究中保持了更大的视觉和定量一致性。主观错误被最小化，因为用户定义的参考R0I不再需要进行量化。这些发展显然有益于将临床试验和标准实践纳入易于纳入。近年来，越来越清楚的是，对脑肿瘤反应的全面评估还需要评估肿瘤细胞密度，死亡和侵袭，尤其是在非增强肿瘤中。在这种情况下，我们的实验室已经付出了巨大的努力，这证明了最近的几本出版物，以开发和验证扩散方法来监测肿瘤的生长和侵袭。通过计算跨时间的明显扩散系数（ADC）的变化，我们在非对比剂增强区域内创建了功能扩散图（FDM）。我们发现，ADC的变化表明细胞密度增加比标准对比剂增强的MRI更能预测对抗血管生成药物贝伐单抗的反应。尽管PWI和DWI都表现出对治疗监测的巨大希望，但定义其测试重复性的研究（对于在临床试验中使用这些技术所需的必要）是缺乏的，因此代表了AIM 1的重点。此外，早期的结果表明，结果表明混合PWI/DWI地图可能会提供对治疗反应的最完整评估，这是AIM 2中测试的假设。最后，为了使优化的PWI/DWI技术和工作流程以强大而成本效益临床试验和标准实践， AIM 3涉及开发用于大规模多中心临床试验的商业综合图像分析平台。综上所述，这项工作应导致强大的准备使用高级成像平台，以对常规和靶向脑肿瘤疗法进行高级成像评估。这将导致更高的临床试验效率，从而使药物发现和翻译更快，并改善了患者的个性化护理。