Purpose: A real-time, functional imaging and tissue characterization technology that not only detects tumors but also differentiate aggressive tumors from non-aggressive ones will be highly valuable to clinical management of cancer. In this work, advanced photoacoustic (PA) imaging technologies were developed for characterizing cancer aggressiveness by assessing tumor microarchitecture and microenvironment in vivo.
Methods: Our recently invented PA physio-chemical analysis (PAPCA) method was adapted to characterizing the histological microstructures in human prostates. The interstitial PA measurements were achieved using a needle PA probe, which was inserted into the ex vivo prostates in the fashion of a biopsy needle. The power spectra of the PA signals from each sample at different wavelengths were analyzed, and the spectral parameters were quantified. The results from cancerous tissues and normal tissues were compared. In a parallel study on an animal model, functional imaging of cancer microenvironmental properties, specifically acidosis and hypoxia, was achieved using PA imaging powered by cancer-targeting hydrogel nanoparticles (NPs) containing pH sensing SNARF dye.
Results: The results from PAPCA of human prostates show significant differences between the individual spectral parameters of the nonaggressive and the aggressive cancerous regions (P < 0.005). Multivariate analysis of the quantitative features achieved a diagnostic accuracy of 78.6% for differentiating nonaggressive and aggressive prostate cancer tissues. Facilitated by the pH-sensing NPs and multi-wavelength PA imaging plus a spectral unmixing technique, the spatially distributed pH levels inside a solid tumor can be quantified without being affected by the background optical absorption of biomolecules, i.e., hemoglobin. As a result, both the pH levels and the hemodynamic properties across the entire tumor can be quantitatively evaluated with high sensitivity (<0.1 pH) and high spatial resolution.
Conclusion: The advanced PA imaging technology, by enabling quantitative assessment of tumor microarchitecture and microenvironment, shows great promise in the diagnosis of aggressive cancer.
Funding Support, Disclosures, and Conflict of Interest: This project is partly supported by NIH under grant numbers: R21AI12209801, R01AR060350, and R01CA186769, and American Gastroenterological Association Boston Scientific Career Development Technology and Innovation Award.