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

双模态经直肠超声和光声成像检测侵袭性人类前列腺癌的临床转化

• 批准号: 10802712
• 负责人: Sri Rajasekhar Kothapalli
• 金额: $ 57.23万
• 依托单位: PENNSYLVANIA STATE UNIVERSITY, THE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-19 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10802712
• 关键词: American; Animal Model; Biopsy; Biopsy Specimen; Blood Vessels; Cancerous; Cessation of life; Chemicals; Classification; Clinic; Clinical; Clinical Research; Collaborations; Contrast Media; Detection; Development; Devices; Diagnostic Procedure; Ensure; Functional Imaging; Funding; Gleason Grade for Prostate Cancer; Heterogeneity; Human; Hypoxia; Image; Image Enhancement; Image Guided Biopsy; Imaging Techniques; Indolent; Institution; Intravenous; Light; Magnetic Resonance Imaging; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of prostate; Maps; Methods; Modality; Molecular; Needle biopsy procedure; Neoplasm Metastasis; Pathologic; Patient-Focused Outcomes; Patients; Performance; Perfusion; Permeability; Phase I/II Clinical Trial; Procedures; Prognosis; Property; Prostate; Prostate Cancer therapy; Prostatic Neoplasms; Provider; Rectum; Regional Cancer; Research; Resolution; Screening for Prostate Cancer; Statistical Data Interpretation; System; Systems Development; Technology; Time; Tissues; Translating; Translations; Transrectal Ultrasound; Ultrasonic Transducer; Ultrasonography; Validation; accurate diagnosis; anatomic imaging; cancer diagnosis; canine model; clinical diagnosis; clinical translation; clinically significant; cost; experience; fabrication; high resolution imaging; human subject; image guided; imaging biomarker; imaging detection; imaging modality; imaging platform; imaging system; improved; in vivo; in vivo imaging system; men; molecular imaging; novel; personalized medicine; photoacoustic imaging; prototype; rectal; safety assessment; structural imaging; tool; tumor; ultrasound; uptake; user-friendly

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.

抽象的 前列腺癌（PCa）的发病率逐年增加，已成为最常见的诊断癌症 准确诊断侵袭性前列腺癌对于患者的生存至关重要。 经直肠超声 (TRUS) 引导活检是评估是否存在和存在的当前标准程序 PCa 的侵袭性，核心产量低，导致临床采样不足和分级不足 为了填补 PCa 诊断中这一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态成像平台 技术与已建立的 TRUS 相结合，可改善具有临床意义的 PCa 的检测和分化 具有绘制反映病理的功能、化学和分子信息的独特能力。 提议的 TRUS 和 PA（即 TRUSPA）以非侵入方式体内检测整个人类前列腺的状况 成像可以灵敏地检测空间分布的肿瘤，更重要的是，可以区分侵袭性肿瘤和非侵袭性肿瘤。 非侵袭性 PCa 肿瘤。 这项拟议的多机构研究将利用 Kothapalli 博士实验室在以下方面的丰富经验： 开发和翻译用于体内人类前列腺成像的 TRUSPA 成像系统，以及 王博士的实验室正在开发 PCa 的新型功能成像生物标志物。 TRUSPA 能够以真实的方式绘制人类前列腺中的一系列功能和结构成像生物标志物 时间非侵入性方式检测和区分具有临床意义的 PCa 为了验证这一假设， 我们将通过与世界领先的 Verasonics Inc. 合作开发临床级 TRUSPA 平台 研究超声系统的提供商，以及提供定制超声的公司 Blatek Inc. 基于该平台的传感器阵列制造，一套用于检测前列腺的新成像生物标志物。 肿瘤和 PCa 侵袭性特征将通过平行临床研究进行严格检查 为了为成功翻译铺平道路，本研究将重点关注 以下具体目标： 目标 1. 开发并充分表征临床级 TRUSPA 双成像系统 PCa 检测；以及目标 2. 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，以区分侵袭性和惰性 PCa。 一旦所提议的 TRUSPA 前列腺癌成像的性能得到验证，这种低成本且用户友好的 技术将在下一个资助周期中为适当的 I/II 期临床试验做好准备，并提供 TRUSPA 成像。 体内、非侵入性、实时检测和区分具有临床意义的 PCa 的独特能力， 可以无缝融入当前TRUS图像引导活检的临床流程，具有巨大的潜力 改变 PCa 管理模式。