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

摘要

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.