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: 8631484
• 负责人: KATHLEEN Marie SCHMAINDA
• 金额: $ 44.95万
• 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/8631484
• 关键词: Address; Algorithms; Angiogenesis Inhibitors; Biological Markers; Blood Volume; Brain Neoplasms; Cell Density; Cerebrum; 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; Hybrids; Image; Image Analysis; Laboratories; Lead; Magnetic Resonance Imaging; Maps; Measurement; Measures; Methods; Modification; Monitor; Multi-Institutional Clinical Trial; Patient Care; Patients; Perfusion; Perfusion Weighted MRI; Predisposition; Primary Brain Neoplasms; Principal Investigator; Process; Protocols documentation; Publications; Recurrence; Relative (related person); Research; Software Tools; Solutions; 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; chemoradiation; cost; cost effective; data exchange; design; drug discovery; imaging modality; improved; neoplastic cell; novel; public health relevance; response; standard measure; standard of care; time interval; treatment planning; treatment response; tumor; tumor growth

ABSTRACT: 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 suceptibility 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 ROIs 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 lacking, 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.

摘要：总体目标是开发和验证标准和新型灌注加权 MRI (PWI) 和弥散加权 MRI (DWI) 生物标志物，用于监测治疗临床的治疗反应 脑肿瘤患者的试验和标准护理治疗计划。这个目标解决了迫切的需求 寻找更好的方法来监测靶向治疗，而增强肿瘤体积的标准措施尚不存在 足够长的时间。将用于临床试验的两种 PWI 方法基于多年的经验 Schmainda 博士实验室的 PWI 研究。第一个更广泛应用的 DSC（动态磁化率 对比）方法提供了在预治疗后获得的肿瘤 rCBV（相对脑血容量）测量值。 造影剂的负载并校正混杂的造影剂泄漏效应。多年比较 对 rCBV 方法的研究表明，该算法是目前可用的最准确的方法之一。 第二种方法虽然尚未得到充分证实，但很有可能成为最全面的方法 灌注液。它包括使用双回波梯度回波 (DEGES) 螺旋方法，该方法 能够同时收集 DSC（动态磁化率对比）和 DCE（动态 对比增强）仅使用单剂量造影剂的灌注数据并结合 对泄漏影响进行全面校正。此外，新开发的用于纵向 监测是 rCBV 图像的“标准化”，其中 rCBV 值被转换为标准 测量规模，以便在研究中保持更大的视觉和定量一致性。主观 由于量化不再需要用户定义的参考 ROI，因此误差得以最小化。这些 进展显然有利于轻松纳入临床试验和标准实践。 近年来，越来越清楚的是，脑肿瘤反应的全面评估也 需要评估肿瘤细胞密度、死亡和侵袭，特别是在非增强肿瘤中。在这个 在此背景下，我们的实验室付出了巨大的努力，最近的几篇出版物证明了这一点，以开发和 验证监测肿瘤生长和侵袭的扩散方法。通过计算表观变化 随时间变化的扩散系数（ADC），我们在非对比范围内创建了功能扩散图（fDM） 代理增强区域。我们发现 ADC 的变化表明细胞密度增加 与标准造影剂增强 MRI 相比，可以预测抗血管生成药物贝伐珠单抗的反应。 虽然 PWI 和 DWI 都在治疗监测方面表现出了巨大的前景，但研究定义了它们 缺乏在临床试验中使用这些技术所必需的重测重复性，因此 代表了目标 1 的重点。此外，早期结果表明混合 PWI/DWI 地图可能会提供 对治疗反应最完整的评估，这一假设将在目标 2 中得到检验。最后，为了 以稳健且经济高效的方式提供优化的 PWI/DWI 技术和工作流程 临床试验和标准实践，目标 3 涉及商业集成图像分析的开发 用于大规模多中心临床试验的平台。 总而言之，这些努力应该会产生一个强大且随时可用的先进成像平台。 常规和靶向脑肿瘤治疗的高级成像评估。这应该会导致 更高的临床试验效率，实现更快速的药物发现和转化，并改进个体化 照顾病人。