Quantitative DCEMRI of Prostate Cancer Correlation with Gold Standards

描述（由申请人提供）：动态对比增强MRI （DCEMRI）有可能为指导前列腺癌（PCa）患者的治疗和改善预后提供关键信息。然而，敏感性和特异性尚不足以用于常规临床应用。DCEMRI尚未被证明能够可靠地区分高Gleason评分的癌症和低Gleason评分的癌症。目前尚不清楚诊断准确性差是由于测量误差还是由于潜在的生物学变异性。虽然已经提出了各种各样的方法来改进DCEMRI，但很少有人尝试用金标准来验证这些方法，以确定是否准确地测量了对比动力学。为了解决这些问题，我们建议：a)开发创新的DCEMRI定量方法，有可能提高诊断的准确性。b)根据“金标准”对DCEMRI进行测试，以确定准确性和可变性，并指导开发减少错误的改进。c)确定定量DCEMRI是否可以提高对高Gleason分级和低Gleason分级癌症的区分。我们提出以下具体目标：使用芝加哥大学开发的创新方法定量测量造影剂浓度、动脉输入功能和生理参数（如Ktrans）。验证造影剂浓度、动脉输入功能、Ktrans和ve的测量，使用金标准测量，包括动态增强CT、直接测量造影剂血药浓度和心输出量。3. 评估从DCEMRI数据中提取的参数的可变性。识别可变性的来源-基于金标准测量和修改程序，以减少可变性。4. 将Gleason分级与定量DCEMRI结果相关联。5. 建立一个由注册的多参数体内MRI，金标准测量和体外组织学图像组成的策划成像数据库。这包括来自DCEMRI、扩散加权成像（DWI）、CT、校准扫描、定量分析参数和组织学的数据。这将为其他机构的研究人员提供一个可用于测试定量分析方法的有价值的数据库。本研究将提供有效的DCEMRI方法，以改善Pca的诊断和分期，并将影响DCEMRI的其他应用。这项研究将为前列腺癌研究界提供重要的资源，国际公认专家的支持信证明了这一点。此外，与飞利浦医疗系统的合作（见支持信）将确保结果快速转化为临床实践。

DESCRIPTION (provided by applicant): Dynamic contrast enhanced MRI (DCEMRI) has potential to provide critical information to guide therapy and improve outcomes for prostate cancer (PCa) patients. However, sensitivity and specificity are not yet adequate for routine clinical use. DCEMRI has not been demonstrated to reliably differentiate between high Gleason score cancers and low Gleason score cancers. It is not known whether poor diagnostic accuracy is due to measurement error or to underlying biological variability. While a wide range of methods have been proposed to improve DCEMRI, there have been few attempts to validate these methods against gold standards, to determine whether contrast dynamics are accurately measured. To address these problems, we propose to a) Develop innovative quantitative approaches to DCEMRI that have the potential to increase diagnostic accuracy. b) Test DCEMRI against 'gold standards', to determine accuracy and variability, and guide the development of improvements that reduce error. c) Determine whether quantitative DCEMRI can improve discrimination of high Gleason grade from low Gleason grade cancers. We propose the following specific aims: 1. Quantitatively measure contrast media concentration, arterial input function, and physiological parameters (e.g. Ktrans) using innovative approaches developed at the University of Chicago. 2. Validate measurements of contrast media concentration, the arterial input function, Ktrans, and ve, using gold standard measurements, including dynamic contrast enhanced CT, direct measurements of blood concentration of contrast media, and measurements of cardiac output. 3. Evaluate variability of parameters extracted from DCEMRI data. Identify sources of variability - based on the gold-standard measurements and modify procedures to minimize variability. 4. Correlate Gleason grade with quantitative DCEMRI results. 5. Establish a curated imaging database consisting of registered multiparametric in vivo MRI, gold standard measurements, and in vitro histological images. This includes data from DCEMRI, diffusion- weighted-imaging (DWI), CT, calibration scans, parameters from quantitative analysis, and histology. This will provide researchers at other institutions with a valuable database that can be used to test quantitative analysis methods. The proposed research will provide validated DCEMRI methods that improve diagnosis and staging of Pca, and will also impact other applications of DCEMRI. The research will provide important resources for the prostate cancer research community, as evidenced by letters of support by internationally recognized experts. In addition, the collaboration with Philips Medical Systems (see letter of support) will insure rapid translation of results to clinical practice.