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

描述（由申请人提供）：MRI（磁共振成像）上的对比度增强提供了测量脑肿瘤和其他实体瘤对治疗的反应的当前最佳方法。因此，国际委员会制定了标准，通过测量造影剂增强肿瘤的肿瘤直径来指导肿瘤负荷的评估（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对比后MRI，但这种方法在脑肿瘤中的应用存在几个重要的局限性。首先，恶性胶质瘤在组织病理学和放射学上表现为异质性，具有地理上不规则的边缘，可变的增强，以及中央坏死或囊性变化的区域，使得主观和手动识别和测量增强ROI极具挑战性。第二，术后肿瘤体积的评估可能会受到血液制品的干扰，血液制品在增强后MRI上也显示明亮。虽然对比前后T1加权图像之间的视觉比较通常足以区分这种差异，但当增强很细微时，这可能非常具有挑战性。最后，随着抗血管生成剂（具有类固醇样作用）的使用越来越多，造影后轻微增强的病例越来越常见。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荷时观察者之间的巨大差异（大于50%）。为了克服这些局限性，我们建议开发delta T1（dT 1）方法，用于自动检测真正的造影剂增强和自动生成增强ROI，并选择生成RECIST/Macdonald/RANO指标。这些工具将与目标2中概述的评估肿瘤负荷的标准方法进行比较。[The dT 1方法的新奇源于它结合了专利的“图像强度标准化”技术，使新开发的工具比现有方法具有重要优势，并有可能改变临床实践模式。具体而言，标准化步骤已经获得专利并独家授权给Imaging Biometrics LLC，消除了由于正常MRI系统可变性、成像参数的微小差异等而导致的图像对比度的大部分正常可变性。因此，dT 1和相关的ROI工具，将被纳入成像生物识别低成本产品，IB SuiteTM，将广泛提供。它将使肿瘤ROI的鲁棒性和可重复性确定成为可能，从而消除或显著减少当前观察者间差异性问题。因此，将该工具产品化有可能导致在临床试验和日常实践中如何评估肿瘤负荷的范式转变，提高可靠性和工作流程，从而更好地护理脑肿瘤患者。 公共卫生相关性：该I期STTR提案的目标是开发急需的MR图像分析工具，用于稳健和自动确定脑肿瘤负荷。新的标准化算法，创建差异或“deltaT 1”地图，以及自动ROI方法，其阈值由生物指标决定，使开发的工具显着减少困扰当前方法的高观察者内和观察者间差异的可能性很高。这些工具的开发和验证将与Imaging Biometrics LLC合作进行，该公司是一家小型企业，在将有前途的实验室医学图像分析软件转化为临床工具方面拥有良好的记录。因此，开发的工具将广泛用于肿瘤对治疗反应的日常临床评估，以及更大规模的临床试验。这反过来又可以导致更有效和更具成本效益的临床试验，以及在个性化的基础上改善对患者的护理。

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.