Approximately 175,000 men are diagnosed with prostate cancer in U.S. annually resulting in 30,000 deaths. The mortality to incidence ratio is relatively low, however, conventional therapies such as radical prostatectomy and radiation therapy are associated with numerous side effects and thus a substantial reduction in quality of life. Consequently there is a desire to develop minimally invasive therapies with fewer side effects. Recent advances in prostate cancer diagnosis (link to biopsy page) have enabled localization of the cancerous lesion within the prostate which can be subsequently treated via focal laser ablation (Figure 1).
Figure 1: A – Region of interest (ROI) identified via MRI with cancer confirmed via targeted biopsy. B – Cancerous lesion can be treated with focal laser ablation.Focal laser ablation (FLA) achieves oncologic control by inducing hyperthermic conditions throughout the target lesion. Successful treatment requires accurate guidance of the laser fiber to the target lesion as well as real-time monitoring. Both of these tasks can be achieved with magnetic resonance imaging, however, this method is time consuming and expensive. We are developing an alternative approach in which ultrasound and interstitial probes are used for laser fiber guidance and treatment monitoring respectively (Figure 2).
Figure 2: A – Setup during focal laser ablation. Ultrasound is used to guide a laser fiber to a target lesion with the resulting ablation monitored via four interstitial thermal probes. B – Thermal data acquired by the interstitial thermal probes for two laser activations at different locations in the prostate. Note that the probe monitoring the laser tip exceeds 60°C while safety probes outside the target treatment zone (rectal wall, lateral capsule, anterior) remain relatively cool. C – The treated tissue appears as a dark region on post-operative MRI. The location of each probe is indicated with the probe at the laser tip lying inside the treatment zone and all safety probes positioned in untreated tissue.
This project is a multi-disciplinary effort involving urologists, radiologists, pathologists, engineers and industry collaborators. The video below outlines our journey which started with the development of targeted biopsy for prostate cancer diagnosis.
Figure 3: A – Experimental setup for assessing the utility of interstitial optical monitoring. The insulated box contains a custom designed synthetic tissue that mimics the thermal and optical properties of the human prostate. Note that the optical probe is positioned at a known distance from the laser fiber (r). B – Detailed view of the optical probe which acts as an isotropic point detector (red arrows indicate light collection). C – The test was performed under MRI to enable quantification of the induced coagulation zone. The green line indicates the laser fiber with the optical probe visible to the left. D – The optical signal recorded for multiple laser fiber-probe seperations (r). An inflection point is observed when the coagulation radius reaches the optical probe, thus, demonstrating that the probe can be used to achieve predefined coagulation radii without the need for real-time MRI.
Selected Publications:
Geoghegan, R., Priester, A., Zhang, L., Wu, H., Marks, L., & Natarajan, S. (2020, July). Monitoring Focal Laser Ablation with Interstitial Fluence Probes: Monte Carlo Simulation and Phantom Validation. In 2020 42nd Annual International Conference of the IEEE Engineering in Medicine & Biology Society (EMBC) (pp. 5272-5275). IEEE.
Geoghegan, R., Santamaria, A., Priester, A., Zhang, L., Wu, H., Grundfest, W., ... & Natarajan, S. (2019). A tissue-mimicking prostate phantom for 980 nm laser interstitial thermal therapy. International Journal of Hyperthermia, 36(1), 992-1001.
Natarajan, S., Priester, A. M., Garritano, J., Marks, L., Grundfest, W., & Geoghegan, R. (2019). U.S. Patent Application No. 16/072,979.
Nassiri, N., Chang, E., Lieu, P., Priester, A. M., Margolis, D. J., Huang, J., ... & Natarajan, S. (2018). Focal therapy eligibility determined by magnetic resonance imaging/ultrasound fusion biopsy. The Journal of urology, 199(2), 453-458.
Natarajan, S., Jones, T. A., Priester, A. M., Geoghegan, R., Lieu, P., Delfin, M., ... & Grundfest, W. (2017). Focal laser ablation of prostate cancer: feasibility of magnetic resonance imaging-ultrasound fusion for guidance. The Journal of urology, 198(4), 839-847.
Natarajan, S., Raman, S., Priester, A. M., Garritano, J., Margolis, D. J., Lieu, P., ... & Marks, L. S. (2016). Focal laser ablation of prostate cancer: phase I clinical trial. The Journal of urology, 196(1), 68-75.
