Validation, Calibration, and Translation of Restriction Spectrum Imaging Signal Maps to enhance MRI diagnostic capabilities in Prostate Cancer

项目摘要/摘要 前列腺癌影响美国近七分之一的男性，但早期侵袭性癌症的诊断 仍然难以捉摸，代价是许多不必要的活组织检查，由于活组织检查抽样错误而延误诊断， 或诊断为惰性疾病。为了做出临床上有意义的前列腺癌的诊断，有一个 迫切需要找到一种既能统一实施，又能提供临床实用的成像模式。核磁共振- 引导下的前列腺活检已经迅速成为一种常见的前列腺活检方式；然而，有限的 重点放在图像采集的质量和准确性上。 我们的提案支持学术和行业合作，以开发和成像生物标记物， 革命性地使用限制谱成像(RSI)-MRI来诊断和监测前列腺癌。 我们试图通过一种新的、非侵入性的方法来改善前列腺MRI的操作特性。 持续时间，目标磁性RSI-MRI序列然后接受FDA批准的II类后处理软件 (OnQ ProState)将值归因于前列腺的可疑区域。RSI-MRI采用多个b值 在每个b值具有多个扩散梯度方向的采集以获取原始数据；图像是后处理 处理后将信号从各向同性、受限的水箱中分离出来，这些水箱通常存在于癌细胞中。一个 得到与肿瘤位置相对应的合成的“受限信号图”，并将其量化，作为输入信号 肿瘤分级的活体生物标志物，并提高了读者检测肿瘤的显着性。在目标1中，我们尝试验证 我们先前关于RSM值的操作特征及其与临床的关联的研究结果 严重前列腺癌(2级或以上)。我们将使用非随机、单臂临床试验来 调查具有和不具有RSM值的PI-RADS得分。在目标2中，我们看到要校准RSM映射 制造商(西门子、通用电气和菲利普斯核磁共振扫描仪)的价值。我们将使用两次扫描的方法， 将邀请一组PI-RADS值在一定范围内的男性进行研究参考扫描 在特定MRI供应商所在的三个地点之一接受了他们的标准护理扫描。两个人 将比较扫描，并使用几种校准和归一化来校准RSM值 有针对性的活检结果的技术。在一些确实接受了前列腺切除术的男性中，我们将进一步 使用术前MRI制作前列腺模型，然后进行整体切片、扫描和对齐 使用RSI-MRI获得正常和癌症区域的准确读数。在目标3中，我们将RSM与当前进行比较 可用FDA批准的生物标记物和临床风险来确定临床实用性。 在拟议的项目中，我们试图使用RSI来提高前列腺MRI的特异性。具体的交付成果将 包括使用特定的RSM输出阀修改标准辐射报告系统(PI-RADS)的能力。 我们寻求验证供应商之间的受限信号映射，并提供临床评估工具 展示了临床效用的衡量标准。

Project Summary/Abstract Prostate cancer affects nearly 1 in 7 men in the United States yet the diagnosis of early aggressive cancer remains elusive at the expense of many unnecessary biopsies, delay in diagnosis from biopsy sampling error, or the diagnosis of indolent disease. In order make a diagnose clinically significant prostate cancer, there is an urgent need find an imaging modality that can be implemented uniformly, yet also provide clinical utility. MRI- guided prostate biopsy has rapidly become a common modality to perform prostate biopsy; however, limited emphasis has been placed on the quality and accuracy of the image acquisition. Our proposal supports an academic-industry partnership to develop and imaging biomarker that could revolutionize how prostate cancer is diagnosed and monitored by using restriction spectrum imaging (RSI)-MRI. We seek to improve the operating characteristics of prostate MRI with a novel, non-invasive method of a short- duration, targeted magnetic RSI-MRI sequences then undergo FDA-cleared, class II post-processing software (OnQ Prostate) to attribute values to suspicious areas of the prostate. RSI-MRI employs multiple b-value acquisitions with multiple diffusion gradient directions at each b-value to acquire raw data; images are post- processed to isolate the signal from isotropic, restricted water compartments typically found in cancer cells. A resultant “restricted signal map” corresponding to tumor location is derived and quantified functioning as an in vivo biomarker of tumor grade and enhances tumor conspicuity for reader detection. In Aim 1, weseek to validate our previous findings regarding the operating characteristics of the RSM values and its association with clinically significant prostate cancer (grade group 2 or higher). We will use a non-randomized, single arm clinical trial to investigate both PI-RADS scores with and without the RSM values. In Aim 2, we see to calibrate the RSM map values across manufacturers(Siemens, GE, and Phillips MRI scanners). We will use a two-scan approach which will invite a sample of men with a range of PI-RADS values to undergo a research reference scan after they have undergone their standard of care scan within one of three locations housing a specific MRI vendor. The two scans will be compared and used to calibrate the RSM values using several calibration and normalization techniques with targeted biopsy results. In some men that do undergo prostatectomy, we will further make a mold of the prostate using the preoperative MRI then perform whole-mount sectioning, scanning, and alignment with RSI-MRI to obtain accurate reads of normal and cancer areas. In Aim 3, we will compare RSM to currently available FDA-approved biomarkers and clinical risk to determine clinical utility. In the proposed project, we seek to improve specificity of prostate MRI using RSI. Specific deliverables will include the ability to amend the standard radiological reporting system (PI-RADS) withspecific RSM output vales. We seek to validate the restricted signal maps between vendors and provide clinical assessment tools demonstrating a measurement of clinical utility.