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）每年增加入射率，已成为最常见的诊断 美国男性的癌症。侵略性PCA的准确诊断对于患者的存活至关重要。 经直肠超声（TRUS）引导活检，这是评估存在和的当前标准程序 PCA的侵略性，核心产量低，导致临床上的采样和上层 重要的肿瘤。为了填补PCA诊断中长期存在的严重技术差距，我们建议开发 一个新型的双模式成像平台，该平台整合了新兴的光声（PA）分子成像 具有既定TRU的技术，可改善临床意义的PCA的检测和分化 具有绘制功能，化学和分子信息的独特能力，反映了病理 整个人类前列腺的体内条件无创，拟议的TRU和PA（即Truspa） 成像可以灵敏地检测到空间分布的肿瘤，更重要的是，分化了侵略性VS。 非攻击性PCA肿瘤。 这项拟议的多机构研究将利用Kothapalli博士实验室的丰富经验 开发和翻译用于体内人类前列腺成像的TRUSPA成像系统， 王博士的实验室开发了PCA的新型功能成像生物标志物。中心假设是 TRUSPA能够绘制人类前列腺中的功能和结构成像生物标志物的列表 时间非侵入性方式用于检测和区分临床意义的PCA。为了验证这一假设， 我们将通过与Verasonics Inc.的合作开发临床级Truspa平台，Verasonics Inc. 研究超声系统的提供商和提供定制超声的公司Blatek Inc. 传感器阵列制造。基于此平台，一组用于检测前列腺的新成像生物标志物 肿瘤和表征PCA侵略性将通过平行的临床研究严格检查 两个参与机构。为了铺平成功翻译的道路，这项研究将重点放在 以下特定目的：目标1。开发并完全表征用于 PCA检测；和目标2。通过有关人类受试者的研究，检查TRUSPA的临床表现， 评估结构和功能成像生物标志物的列表，以区分侵略性和惰性PCA。 一旦验证了PCA的TRUSPA成像的性能，这种低成本和用户友好 在下一个资金周期中，技术将准备好进行适当的I/II期临床试验。 Truspa成像，带 在体内检测和区分临床意义的PCA的独特能力，无创地，实时，实时， 可以无缝地适合当前TRUS图像引导活检的临床程序，并具有很大的潜力 移动PCA管理的范式。