Automating MRI Delta T1 Methods for the Routine Assessment of Brain Tumor Burden

用于脑肿瘤负担常规评估的自动化 MRI Delta T1 方法

• 批准号: 8253047
• 负责人: Scott D Rand
• 金额: $ 10.51万
• 依托单位: IMAGING BIOMETRICS, LLC
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8253047
• 关键词: Algorithms; Angiogenesis Inhibitors; Appearance; Biometry; Blood - brain barrier anatomy; Brain; Brain Neoplasms; Businesses; Caliber; Characteristics; Clinical; Clinical Trials; Clinical assessments; Collaborations; Computer software; Contrast Media; Data; Detection; Development; Enhancing Lesion; Evaluation; Exhibits; Generations; Glioma; Goals; Image; Image Analysis; International; Interobserver Variability; Laboratories; Legal patent; Lesion; Licensing; Magnetic Resonance Imaging; Malignant Glioma; Malignant neoplasm of brain; Manuals; Maps; Measurement; Measures; Medical Imaging; Methods; Metric; Necrosis; Organ; Output; Patient Care; Patients; Performance; Phase; Plague; Plug-in; Postoperative Period; Process; Recurrence; Recurrent tumor; Seeds; Series; Small Business Technology Transfer Research; Software Tools; Solid; Solid Neoplasm; Standardization; Steroids; Sum; System; Technology; Testing; Time; Translating; Tumor Burden; Tumor Volume; Validation; Visual; Weight; base; blood product; clinical practice; cost; cost effective; experience; image processing; improved; novel; phase 2 study; prospective; response; software development; tool; tumor

DESCRIPTION (provided by applicant): Contrast enhancement on MRI (magnetic resonance imaging) provides the best currently available approach for measuring tumor response to therapy in brain and other solid tumors. Accordingly, criteria have been formulated, by international committees, to guide the assessment of tumor burden by measuring tumor diameters of contrast-enhancing tumor (eg RECIST, Macdonald and RANO criterion). Despite the widespread use of post-contrast MRI in daily practice and most clinical trials, there exist several important limitations to this approach for use in brain tumors. First, malignant gliomas are histopathologically and radiographically heterogenous in appearance with geographically irregular margins, variable enhancement, and regions of central necrotic or cystic changes, making the subjective and manual identification and measurement of enhancing ROIs extremely challenging. Second, assessment of postoperative tumor volume can be confounded by the presence of blood products, which also appear bright on post-contrast MRI. Though a visual comparison between pre and post-contrast T1-weighted images is often sufficient to make this distinction, this can be very challenging when the enhancement is subtle. Finally, with the increasing use of anti-angiogenic agents, which have a steroid-like effect, the number of cases with subtle post-contrast enhancement is becoming increasingly common. These challenges may explain the large inter-observer differences (greater than 50%) in assessing tumor burden that plague most clinical trials. To overcome these limitations, we propose to develop the delta T1 (dT1) method for automatic detection of true contrast-agent enhancement and the automatic generation of enhancing ROIs with options to generate RECIST/Macdonald/RANO metrics. These tools will be compared against standard approaches for the assessment of tumor burden as outlined in Aim 2. [The novelty of the dT1 method derives from the fact that it incorporates a patented "image intensity standardization" technology, giving the newly developed tools an important advantage over existing methods and the potential to shift clinical practice paradigms.] Specifically, the standardization step, which has been patented and exclusively licensed to Imaging Biometrics LLC, eliminates much of the normal variability in image contrast due to normal MRI system variability, slight differences in imaging parameters and the like. Thus, the dT1 and associated ROI tools, which will be incorporated into Imaging Biometrics low-cost product, IB SuiteTM, will be made available on a widespread basis. It will enable the robust and reproducible determination of tumor ROIs that eliminate or significantly minimize current issues of inter-observer variability. Accordingly, productizing this tool has the potential to result in a paradigm shift in how tumor burden is assessed in clinical trials and daily practice, improving reliability and workflow resulting in better care for patients with brain tumors. PUBLIC HEALTH RELEVANCE: The goal of this Phase I STTR proposal is the development of much needed MR image analysis tools for the robust and automatic determination of brain tumor burden. The incorporation of novel standardization algorithms, creation of difference or "deltaT1" maps, as well as automatic ROI methods whose thresholds are dictated by biologic indicators, give the developed tools a high likelihood of significantly diminishing the high intra- and inter-observer differences that plague current methods. The development and validation of these tools will be performed in collaboration with Imaging Biometrics LLC, a small business concern, who has a proven track record of translating promising laboratory medical image analysis software into clinical tools. Therefore the developed tools will be made widely available for the daily clinical assessment of tumor response to therapy, as well as for larger scale clinical trials. This in turn can result in the performance of more efficient and cost-effective clinical trials, as well as improved care of patients on an individualized basis.

描述（由申请人提供）：MRI上的对比度增强（磁共振成像）为测量脑和其他实体瘤治疗的肿瘤反应提供了当前可用的方法。因此，国际委员会已经制定了标准，以测量对比增强肿瘤的肿瘤直径来指导肿瘤负担的评估（例如，Recist，MacDonald和Rano标准）。尽管在日常实践和大多数临床试验中广泛使用了对比后MRI，但这种在脑肿瘤中使用的方法仍然存在一些重要的局限性。首先，恶性神经胶质瘤在组织病理学和Xogo骨上是异质的，具有地理不规则边缘，可变的增强和中央坏死或囊性变化的区域，从而使主观和手动识别以及对ROIS增强的主观和手动识别以及测量非常具有挑战性。其次，术后肿瘤体积的评估可能会被血液产物的存在混淆，这在对比后MRI上也显得明亮。尽管对比前和对比后T1加权图像之间的视觉比较通常足以使这种区别，但是当增强功能微妙时，这可能非常具有挑战性。最后，随着具有类固醇样作用的抗血管生成剂的使用越来越多，具有微妙的对比后增强的病例数量变得越来越普遍。这些挑战可能解释了在评估困扰大多数临床试验的肿瘤负担时，观察者间差异很大（大于50％）。为了克服这些局限性，我们建议开发Delta T1（DT1）方法，以自动检测真正的对比剂 - 代理增强功能，并自动生成增强ROI，并具有产生Recist/MacDonald/rano指标的选项。这些工具将与AIM 2中概述的肿瘤负担评估的标准方法进行比较。由于正常的MRI系统变异性，成像参数等的略有差异，消除了图像对比度的许多正常变异性。因此，将将DT1和相关的ROI工具纳入成像生物识别技术低成本产品IB SuteTM将被广泛提供。它将实现对肿瘤ROI的稳健和可重现的确定，从而消除或显着最大程度地减少观察者间变异性的当前问题。因此，生产此工具有可能导致临床试验和日常练习评估肿瘤负担的范式转移，从而提高了可靠性和工作流程，从而为脑肿瘤患者提供更好的护理。 公共卫生相关性：I阶段ISTTR提案的目标是开发急需的MR图像分析工具，以稳健和自动确定脑肿瘤负担。新颖的标准化算法，差异或“ deltat1”地图的创建以及自动ROI方法的结合，其阈值由生物学指标决定，使开发的工具具有很大的可能性，即显着减少了高大的内部和跨障碍者差异，使当前方法受到了当前方法。这些工具的开发和验证将与Imaging Biometrics LLC合作进行，这是一个小型企业问题，他在将有前途的实验室医学图像分析软件转换为临床工具方面具有可靠的记录。因此，开发的工具将被广泛用于肿瘤对治疗的反应以及大规模临床试验的每日临床评估。反过来，这可能会导致更有效，更具成本效益的临床试验的性能，并在个性化的基础上改善患者的护理。