Focal Laser Ablation for Prostate Cancer Treatment

Introduction

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.

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).

Focal Laser Ablation: The CASIT Approach

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

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.

Technology Development

• Interstitial Probes – Widespread adoption of FLA is contingent upon the development of a low cost monitoring modality. To this end, we are developing interstitial sensors that monitor both temperature and laser-tissue interaction. Our work includes simulations, fabrication and characterization of novel sensors. An example of optical monitoring is shown in Figure 3.
• Damage Models – We are developing computational models to provide real-time feedback during FLA. These models quantify cellular destruction based on thermal and optical data gathered by interstitial probes during FLA.
• Micro Ultrasound – This project is an industry collaboration with Exact Imaging to explore the utility of a high resolution ultrasound system for monitoring FLA.

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

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.