Friday, May 9, 2025
5/9/2025
Detecting prostate cancer aggressiveness using photoacoustic chemical imaging with photoacoustic spectral analysis - 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 solve the long-standing challenges in PCa diagnosis, we propose to develop a real-time functional imaging platform with the unique capability of quantitatively evaluating both heterogeneous gland microarchitecture and anomalous chemical microenvironment in tumors for accurate diagnosis and prognosis of PCa. The proposed functional imaging platform is made possible by the recent advancement in photoacoustic (PA) imaging and biocompatible polyacrylamide hydrogel nanoscale probes (PAA NPs). Besides drastically enhancing the sensitivity and specificity of PA imaging in detecting the tumors, the PAA NPs conjugated with cancer-targeting ligands can be a carrier of versatile contrast agents for PA chemical imaging, offering unique opportunities for PCa diagnosis and characterization in both preclinical and clinical settings. The central hypothesis of this research is that the PA imaging, when powered by the functional PAA NPs, can enable sensitive detection of PCa tumors and accurate characterization of PCa aggressiveness in vivo by quantitatively assessing a list of imaging biomarkers reflecting prostate gland microarchitecture and cancer microenvironment. The objective of this project is to understand the performance and limitations of the PAA NP powered PA imaging in PCa tumor detection and characterization of cancer aggressiveness via the experiments in clinically relevant mouse models of PCa. To examine the central hypothesis and pave the road toward future clinical application, this research will focus on the following specific aims: Aim 1. Optimize PAA NPs for chemical imaging of the tumor microenvironment, targeting PCa tumors, and staining prostate microarchitectures; Aim 2. Understand the performance of PAA NP powered PA imaging in characterizing the aggressiveness of PCa via studies in clinically relevant mouse models of PCa; and Aim 3. Develop a multivariate strategy for PCa diagnosis and prognosis by combining the multiple cancer biomarkers from PAA NP powered PA imaging. The successful accomplishment of this project will lead to a prototype PA imaging platform with its performance in assessing the aggressiveness of PCa comprehensively evaluated. In the future, the proposed imaging procedure can be seamless integrated into the framework of TRUS guided PCa biopsy to improve the core yields and decrease the false negative rates. Moreover, the proposed PAA NP contrast agents specifically designed for PA molecular and chemical imaging can facilitate a platform technology for understand cancer microenvironment, not only for PCa but also for other types of solid tumors.
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