Clinical Translation of dual-modality transrectal ultrasound and photoacoustic imaging for detection of aggressive human prostate cancer

摘要 前列腺癌(Pca)的发病率逐年上升，已成为最常见的诊断 美国男性罹患癌症。侵袭性前列腺癌的准确诊断对患者的生存至关重要。 经直肠超声(TRUS)引导的活检，目前评估存在和 PCA的进攻性，核心产量低，导致临床抽样不足和分级偏低 重要的肿瘤。为了填补PCA诊断中长期存在的严重技术空白，我们建议开发 集成新兴光声(PA)分子成像的新型双模成像平台 利用已建立的TRUS技术改进临床有意义的PCa的检测和鉴别诊断 肿瘤。具有独特的绘制反映病理的功能、化学和分子信息的能力 活体、非侵入性、拟议的TRUS和PA(即TRUSPA)对整个人类前列腺的影响 成像可以敏感地检测到空间分布的肿瘤，更重要的是，可以区分侵袭性和 非侵袭性前列腺癌。 这项拟议的多机构研究将利用Kothapalli博士实验室在 开发和翻译用于活体人体前列腺成像的TRUSPA成像系统，以及 王博士的实验室正在开发新的PCA功能成像生物标记物。中心假设是 TRUSPA能够绘制一系列人类前列腺的功能和结构成像生物标志。 时间无创性方法检测和鉴别临床有意义的前列腺癌。为了验证这一假设， 我们将通过与世界领先的Verasonics公司的合作，开发临床级别的TRUSPA平台 研究超声系统提供商，以及提供定制超声的Blatek Inc. 换能器阵列制作。基于该平台，开发了一套新的前列腺癌影像生物标志物 肿瘤和特征的前列腺癌侵袭性将通过平行的临床研究在 两个参与机构。为了为翻译的成功铺平道路，本研究将重点放在 以下具体目标：目标1.开发和充分表征临床级别的TRUSPA双重成像系统 通过对人类受试者的研究，检查TRUSPA的临床表现，通过 评估一系列结构和功能成像生物标志物，以区分好斗和懒惰的前列腺癌。 一旦所提出的主成分分析的TRUSPA成像的性能得到验证，这种低成本和用户友好的 这项技术将在下一个资金周期为适当的I/II期临床试验做好准备。TRUSPA成像，带 独特的能力，在活体内，非侵入性，实时， 可以无缝地适应当前的TRUS图像引导活检的临床过程，并具有巨大的潜力 转变PCA管理模式。

ABSTRACT Prostate cancer (PCa), with an annually increasing incident rate, has become the most commonly diagnosed cancer in American men. The accurate diagnosis of aggressive PCa is critical for the survival of patients. Transrectal ultrasound (TRUS) guided biopsy, the current standard procedure for evaluating the presence and aggressiveness of PCa, suffers from low core yield, leading to under-sampling and under-grading of clinically significant tumors. To fill this long-standing and serious technical gap in PCa diagnosis, we propose to develop a novel dual-modality imaging platform which integrates the emerging photoacoustic (PA) molecular imaging technique with the established TRUS for improved detection and differentiation of clinically significant PCa tumors. With the unique capability to map functional, chemical, and molecular information reflecting pathological conditions over the entire human prostate in vivo, non-invasively, the proposed TRUS and PA (namely TRUSPA) imaging can sensitively detect spatially distributed tumors and, more importantly, differentiate aggressive vs. non-aggressive PCa tumors. This proposed multi-institutional research will leverage the extensive experience of Dr. Kothapalli’s lab in developing and translating TRUSPA imaging systems for in vivo human prostate imaging, and the expertise of Dr. Wang’s lab in developing novel functional imaging biomarkers of PCa. The central hypothesis is that the TRUSPA is capable of mapping a list of functional and structural imaging biomarkers in human prostate in a real- time non-invasive manner for detecting and differentiating clinically significant PCa. To validate this hypothesis, we will develop a clinical grade TRUSPA platform through the collaborations with Verasonics Inc., a world leading provider of research ultrasound systems, and Blatek Inc., a company providing customized ultrasound transducer array fabrication. Based on this platform, a set of new imaging biomarkers for detecting prostate tumors and characterizing PCa aggressiveness will be rigorously examined via the parallel clinical studies at the two participating institutions. To pave the road toward successful translation, this research will focus on the following specific aims: Aim 1. Develop and fully characterize a clinical grade TRUSPA dual imaging system for PCa detection; and Aim 2. Via the studies on human subjects, examine the clinical performance of TRUSPA, by assessing a list of structural and functional imaging biomarkers, in distinguishing aggressive from indolent PCa. Once the performance of the proposed TRUSPA imaging of PCa is validated, this low-cost and user-friendly technology will be ready for appropriate phase I/II clinical trials in the next funding cycle. TRUSPA imaging, with the unique capability of detecting and differentiating clinically significant PCa in vivo, non-invasively, in real time, can seamlessly fit into the current clinical procedure of TRUS image-guided biopsy, and holds great potential to shift the paradigm of PCa management.