Real-time In Vivo MRI Biomarkers for Breast Cancer Pre-Operative Treatment Trials

 描述(由申请人提供)：该项目的目标是开发和优化磁共振成像生物标记物，用于评估乳腺癌对术前治疗的反应。该项目是学术-产业伙伴关系R01奖CA 13270题为“乳腺癌手术前试验的实时在体磁共振生物标记物”的继续努力。在之前的资助周期中，加州大学旧金山分校和霍洛奇(前身为Sentinelle Medical)的研究人员开发和部署了专用工作站，在多中心I-SPY临床试验(通过成像和分子分析预测您的治疗反应的系列研究调查)中对乳腺MR图像进行体积分析。我们成功地将加州大学旧金山分校开发并在美国放射成像网络(ACRIN)试验6657中使用的信号增强比(SER)肿瘤体积测量方法移植到霍奇宙斯盾软件平台。Aegis SER软件插件于2010年获得IDE批准，可用于I-SPY 2试验，并在20个I-SPY 2临床中心安装了Aegis系统。Aegis SER插件软件产生的肿瘤体积测量现在被纳入I-SPY 2的适应性II期试验设计，并用于患者随机化算法。在最初项目期间的第二个目标下，我们开发了自动图像分析工具，以探索量化参数如何影响预测临床结果的成像指标的有效性。继续进行的项目侧重于扩展Aegis软件功能，包括实时分析扩散加权磁共振成像(DWI)以评估反应，并前瞻性地测试已使用前一个项目期开发的自动化工具进行优化的成像指标。建议的工作将与I-SPY 2试验及其成像子研究ACRIN 6698协调进行，ACRIN 6698测试乳腺DWI以评估肿瘤反应。在特定目标1下，我们将在Aegis工作站上增加DWI图像分析和报告功能，用于测量乳腺肿瘤的表观扩散系数(ADC)。在特定目标2下，我们将前瞻性地测试通过对I-SPY 1数据的回顾分析而估计的乳腺癌亚型优化的FTV指标的预测性能。前瞻性研究将使用I-SPY 2控制组中登记的独立队列患者的数据进行。还将进行探索性研究，以使用I-SPY 2的DCE和DWI图像数据调查和比较替代指标。

 DESCRIPTION (provided by applicant): The goal of this project is to develop and optimize MR imaging biomarkers for the assessment of breast cancer response to pre-operative treatment. The project is a continuation of effort under Academic-Industrial Partnership (AIP) R01 grant award CA 13270 entitled "Real-time in vivo MRI biomarkers for breast cancer pre-operative trials". In the prior funding cycle researchers at UCSF and Hologic (formerly Sentinelle Medical) developed and deployed dedicated workstations to perform volumetric analysis of breast MR images in the multi-center I- SPY TRIAL (Investigation of Serial studies to Predict Your Therapeutic Response with Imaging And molecular analysis) clinical trial. We successfully migrated the signal enhancement ratio (SER) tumor volume measurement method, developed at UCSF and used in the American College of Radiology Imaging Network (ACRIN) trial 6657, to the Hologic Aegis software platform. The Aegis SER software plug-in received IDE approval in 2010 for use in the I-SPY 2 TRIAL and Aegis systems were installed at the 20 I-SPY 2 clinical centers. Tumor volume measurements generated from the Aegis SER plug-in software are now incorporated in the adaptive phase II trial design for I-SPY 2 and used in the patient randomization algorithm. Under a second aim in the original project period, we developed automated image analysis tools to explore how quantification parameters influence the effectiveness of imaging metrics for predicting clinical outcomes. The continuing project focuses on expanding Aegis software functionality to include real-time analysis of diffusion-weighted MRI (DWI) for assessing response, and prospectively testing imaging metrics that have been optimized using the automated tools developed in the previous project period. The work proposed will be coordinated with the I-SPY 2 trial and its imaging sub-study ACRIN 6698, testing breast DWI for assessment of tumor response. Under Specific Aim 1 we will add DWI image analysis and reporting capabilities to the Aegis workstation for measuring breast tumor apparent diffusion coefficient (ADC). Under Specific Aim 2 we will prospectively test the predictive performance of breast cancer subtype-optimized FTV metrics estimated by the retrospective analysis of I-SPY 1 data. The prospective studies will be performed using data from an independent cohort of patients enrolled in the control arm of I-SPY 2. Exploratory studies will also be performed to investigate and compare alternative metrics using DCE and DWI image data from I-SPY 2.