Quantitiative MRI of prostate cancer as a biomarker and guide for treatment

描述(申请人提供)：前列腺癌是美国男性最常见的恶性肿瘤，也是癌症相关死亡的第三大原因。由于婴儿潮一代的老龄化，患有局限性前列腺癌的男性人数将会增加，对准确的非侵入性成像工具的需求也会增加。磁共振(MR)成像能够提供精确的肿瘤解剖图谱。较新的磁共振技术允许对前列腺组织进行药代动力学(PK)评估。MR成像的这一功能方面可以极大地提高肿瘤检测和定位的准确性，并有可能作为局部消融治疗的指南，或对新辅助治疗反应的前列腺组织微循环的功能方面进行非侵入性评估。因此，这项研究的目的是确定优化的MR分析工具和算法是否可以用作前列腺癌靶向治疗的生物标记物指南和疾病复发的替代物。我们计划通过四个具体目标来实现我们的目标： 1.开发和实施成像方法和分析工具，利用定量多参数磁共振成像(MpMRI)自动、可靠地定量评估前列腺肿瘤体积和功能特性(血管和通透性)。 2.为了在临床上验证AIM 1中描述的前列腺mpMRI定量分析工具，我们将对分析工具的结果进行多变量分析，并将获得患者特定的肿瘤定位参数图(汇总统计显示)，并将其与前列腺切除术中的病理相关联。 3.确定分析工具作为靶向治疗的生物标记物指南和低风险前列腺癌患者疾病复发的替代物的临床应用。我们将获得mpMRI图，详细描述指标性病变及其边缘，并将其与局部消融治疗计划图像配准。后续的mpMRI图将记录治疗前的mpMRI图以检测变化，并将其与PSA相关联，以确定预期的治疗范围和未治疗的前列腺mpMRI特征。 4.确定分析工具在评估肿瘤对以下治疗的反应方面的临床应用 高危前列腺癌患者的新辅助雄激素剥夺治疗(ADT)我们将评估ADT治疗12周后mpMRI图的变化，通过与前列腺切除标本的相关性，确定前列腺癌血管通透性变化是否可以作为预测病理反应的合适指标。

DESCRIPTION (provided by applicant): Prostate cancer is the most common malignancy and third leading cause of cancer-related mortality in American men. Due to the ageing "baby boomers", the number of men with localized prostate cancer will increase, as will the need for an accurate non-invasive imaging tool. Magnetic Resonance (MR) imaging has the ability to deliver precise anatomical mapping of tumor. Newer MR techniques allow for pharmacokinetic (PK) evaluation of prostate tissue. This functional aspect of MR imaging could contribute greatly to the accuracy of tumor detection and localization, and potentially serve as a guide for focal ablative therapy, or non-invasively assess functional aspects of prostate tissue microcirculation in response to neoadjuvant treatment. The objective of this study is therefore to determine if optimized MR analysis tools and algorithms can be used as a biomarker guide for targeted therapy and as a surrogate for disease recurrence in prostate cancer. We plan to achieve our objective through 4 specific aims: 1. To develop and implement imaging methodology and analysis tools for automated, robust quantitative assessment of prostate tumor volumetry and assessment of the functional properties (vascularity and permeability) using quantitative multi-parametric MR imaging (mpMRI). 2. To clinically validate the prostate mpMRI quantitative analysis tools described in Aim 1. We will perform a multivariate analysis of the results of the analyses tools, and patient-specific parameter maps for tumor localization (a summary statistic display) will be obtained and correlated with pathology at prostatectomy. 3. To determine the clinical use of the analysis tools as a biomarker guide for targeted therapy and as a surrogate for disease recurrence in low-risk prostate cancer patients. We will obtain mpMRI maps, detailing the index lesion and its margins, and register them with focal ablative therapy treatment planning images. Follow up mpMRI maps will be registered the pre-treatment maps to detect changes, and will be correlated with PSA to determine the "expected" treatment margin and untreated prostate mpMRI characteristics. 4. To determine the clinical use of the analysis tools in evaluating tumor response to treatment with neoadjuvant androgen deprivation therapy (ADT) in patients with high-risk prostate cancer. We will assess the changes in mpMRI maps after 12 weeks of ADT to determine if prostate tumor vascular permeability changes may be a suitable predictor of pathological response, by correlation with prostatectomy specimens.