Real time fine needle assessment of architectural heterogeneity in prostate cancer

前列腺癌结构异质性的实时细针评估

• 批准号: 10322417
• 负责人: Guan Xu
• 金额: $ 48.63万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-01-18 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10322417
• 关键词: 3-Dimensional; American; Animal Model; Anxiety; Architecture; Biopsy; Cancer Etiology; Cancer Patient; Cancerous; Cessation of life; Clinical; Clinical Trials; Collagen; Core Biopsy; Diagnosis; Diagnostic; Diagnostic Procedure; Dimensions; Discrimination; Early Diagnosis; Effectiveness; Excision; Future; Gleason Grade for Prostate Cancer; Hemoglobin; Heterogeneity; Histologic; Histology; Human; Individual; Knowledge; Lipids; Location; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of prostate; Maps; Measurement; Molecular; Molecular Bank; Needle biopsy procedure; Needles; Optics; Pain; Pathology; Patients; Penetration; Performance; Pilot Projects; Probability; Procedures; Prognostic Factor; Prostate; Prostatectomy; Research; Risk; Sampling; Screening for Prostate Cancer; Sensitivity and Specificity; Signal Transduction; Stains; Structure; Study Subject; System; Technology; Testing; Time; Tissue Sample; Tissues; Transrectal Ultrasound; Tube; base; blood-based biomarker; cancer diagnosis; clinical care; clinical practice; clinically significant; cost; design; diagnostic value; human subject; human tissue; improved; in vivo; in vivo Model; men; mouse model; non-alcoholic fatty liver disease; prostate biopsy; prototype; screening; tumor

ABSTRACT During the past two decades, prostate cancer (PCa) has become the most commonly diagnosed cancer and ranks as the second leading cause of cancer deaths for American men. Prostate biopsy is the standard procedure for evaluating the presence and aggressiveness of PCa. Guided by transrectal ultrasound (TRUS) and preprocedure magnetic resonance imaging (MRI), small pieces of tissues are removed from the prostate. The architectural heterogeneities are assigned a Gleason score as a quantitative description of the aggressiveness. However, TRUS has low sensitivity to PCa. MRI has limited availability, and a spatial mismatch can occur when co-registering the preprocedure MRI with the real-time TRUS. Therefore, standard TRUS-guided biopsy, either with or without additional MRI, suffers from missing or under-sampling clinically significant tumors, leading to under-grading of PCa. At-risk patients with rising blood-based biomarkers undergo repeated and saturated biopsies, causing extra diagnostic costs and time as well as anxiety and pain. We propose to solve this long-standing technical gap in PCa diagnosis by introducing a needle photoacoustic (PA) probe for online guidance of TRUS biopsy. As validated in our preliminary studies on both animal models and human tissues, quantitative multispectral PA signal analysis possesses the unique capability of objectively characterizing the architectural heterogeneities in prostate tissues and grading PCa in vivo. Our needle PA probe has an all-optical design that allows a small probe dimension to avoid causing additional invasiveness to the current biopsy procedure. Taking advantage of the optical penetration, the needle PA probe can assess the histopathological information in a tissue volume much larger than that of a standard biopsy core without tissue removal. Hence, PA pre-biopsy measurements, performed together with the TRUS needle biopsy, can provide highly valuable diagnostic information covering the whole prostate. Core extractions can then be focused within the suspicious cancerous region(s). The central hypothesis of this research is that a fine needle probe-based PA prostate pre-biopsy can guide prostate biopsy, improve the core yield, and decrease false negative rates. The objective of this study is to validate the correlation between the PA measurements and the PCa grading through an observational human subjects study. The specific aims include investigating the performance of the needle PA probe in accessing PCa using 1) biopsy tissue cores; 2) ex vivo human prostate samples procured through prostatectomy, and 3) human subjects. We will leverage the research team's extensive expertise in the clinical practice of PCa diagnosis and pathology as well as PA technology. The proposed pre-biopsy procedure is designed within the framework of current clinical practice and is, therefore, highly translational. The knowledge gained in this study will prepare us to conduct a future clinical trial of the proposed diagnostic procedure in detecting PCa. Once successfully tested, the PA pre-biopsy will benefit PCa patients by facilitating accurately targeted needle biopsies for the early detection of clinically significant PCa.

摘要 在过去的二十年里，前列腺癌(PCa)已经成为最常见的癌症和 成为美国男性癌症死亡的第二大原因。前列腺活检是标准检查 评估PCA的存在和侵袭性的程序。经直肠超声引导(TRUS) 以及手术前的磁共振成像(MRI)，从前列腺中取出小块组织。 体系结构异质性被指定为Gleason分数，作为对 咄咄逼人。然而，TRUS对PCa的敏感性较低。核磁共振成像的可用性有限，而且空间 当将术前MRI与实时TRUS共同配准时，可能会发生不匹配。因此，标准 经直肠超声引导下的活组织检查，无论有没有附加的mri，临床上都会有缺失或取样不足的问题。 显著的肿瘤，导致Pca分级偏低。血液生物标志物升高的高危患者 进行重复和饱和的活检，导致额外的诊断成本和时间，以及焦虑和疼痛。 我们建议通过引入针头光声来解决PCa诊断中长期存在的技术空白 (PA)用于在线引导经皮超声活检的探头。这在我们对两种动物模型的初步研究中都得到了验证 与人体组织相比，定量多光谱PA信号分析具有独特的客观能力 描述前列腺组织的结构异质性，并对活体前列腺癌进行分级。我们的针头PA 探头具有全光学设计，允许较小的探头尺寸，以避免对 目前的活组织检查程序。利用光学穿透的优势，针状PA探头可以评估 组织体积远大于无组织的标准活组织芯中的组织病理学信息 移走。因此，PA活检前测量与TRUS穿刺针活检一起进行，可以提供 涵盖整个前列腺的高度有价值的诊断信息。然后，核心提取可以集中在 可疑癌变区(S)。这项研究的中心假设是，基于细针探头的 PA前列腺术前活检可指导前列腺活检，提高活检核心率，降低假阴性率。 本研究的目的是验证PA测量和PCA分级之间的相关性 通过观察性的人类受试者研究。具体目标包括调查 针状PA探头在1)活检组织芯进入前列腺癌中的应用；2)体外采集的人前列腺样本 通过前列腺切除术，以及3)人类受试者。我们将利用研究团队在以下方面的广泛专业知识 前列腺癌的诊断、病理和PA技术的临床实践。拟议的前活组织检查程序 是在当前临床实践的框架内设计的，因此具有很高的翻译性。这个 从这项研究中获得的知识将为我们未来进行拟议诊断的临床试验做好准备 检测PCA的程序。一旦测试成功，PA预活组织检查将使PCA患者受益于 促进准确定位的针吸活组织检查，以早期发现具有临床意义的前列腺癌。