The objective of this Phase-I SBIR project is to develop a novel transrectal optoacoustic-ultrasonic (OU) imaging system for guiding cryotherapy of prostate cancer via real-time monitoring of ice ball formation and temperature distribution within the area of healthy tissues adjacent to the rectal wall. The proposed system will be capable of (i) non-invasive monitoring of spatial temperature distribution in areas of important innervation around rectal wall during cryotherapy and (ii) monitoring of development of the ice ball boundary. After encouraging additional preliminary studies we decided to restructure our Research Strategy and resubmit this proposal for development of a commercial prototype of the image-guided cryotherapy system and its in vivo evaluation of two canine prostates in the course of treatment. The proposed system will operate in real time and will be capable of imaging the prostate gland and assist in computer-controlled treatment procedure. Current methods of prostate cryotherapy often result in serious side effects including impotence (15-85%), incontinence (13%), and more severe thermal damage of rectum (2%) as a result of insufficient control of the damage done to the areas with sensitive innervation located next to the rectal wall. Additionally, the cryotherapy costs significantly increase if an expensive imaging modality (CT) or (MRI) is used alongside to enhance the control over the growing ice ball. Optoacoustic imaging utilizes high optical contrast of blood to visualize healthy and cancerous (angiogenesis) prostate tissues. The optoacoustic effect of stress generation after absorption of a short laser pulse is temperature sensitive and optoacoustic tomography was shown to provide excellent in vivo resolution (<0.5 mm) for deep tissue imaging (10 mm and more) typical of ultrawide- band ultrasonic imaging. Moreover, optoacoustic signals are sensitive to local changes of acoustic impedance and can provide a high-quality image of an impedance boundary, for example, forming ice ball. The optoacoustic imaging system has already demonstrated its clinical feasibility in oncology, based on diagnostic imaging results from 100 breast cancer patients in the course of recent FDA guided clinical trial. We will utilize the experience gained during the course of commercialization of a clinical breast imaging system to develop a more advanced optoacoustic system for guiding cryotherapy of the prostate. The focus of the Phase I project will be on (1) Development of a methodology based on 2D optoacoustic imaging that allows accurate temperature monitoring of non-frozen biological tissues (healthy areas adjacent to the rectal wall), (2) Development of a methodology based on 2D optoacoustic imaging that allows visualization of the boundary of frozen biological tissue (ice ball), and (3) Development of a preclinical prototype of the optoacoustic imaging unit for real-time temperature mapping and ice ball monitoring during cryotherapy of prostate cancer. A preclinical prototype will be developed based on a commercial transrectal ultrasound probe. The development will include computer simulations, extensive studies on biologically-relevant optoacoustic phantoms, and pre- clinical in vivo validation using canine prostate models. Successful accomplishment of this project will demonstrate feasibility of the proposed approach making the optoacoustic imaging system available for further clinical evaluation as a key component of the hybrid transrectal optoacoustic-ultrasonic cryotherapy guiding system. During the course of the Phase I project, we will define the technical parameters for a commercially viable laser optoacoustic imaging and monitoring system. Should results of Phase I project show promise, we will apply for the Phase II to integrate the optoacoustic imaging system with transrectal ultrasound in order to obtain coregistered images showing temperature distribution in non-frozen critical healthy tissues and high- quality monitoring of the ice ball formation. Laser Optoacoustic Ultrasound Imaging System (LOUIS) will be further incorporated as a guiding component of the commercial cryotherapy system. We envision that our optoacoustic imaging technology will provide a more accurate and versatile non-invasive alternative to the currently used thermal sensors, reducing the recurrences of undertreated cases of prostate cancer and diminishing complications from the excessive thermal damage of healthy tissues.
Prostate cancer is the most common cancer in American men, and is the second leading cause of cancer death in men, exceeded only by lung cancer. The National Cancer Institute estimates that during 2012, approximately 242,000 new cases of prostate cancer were diagnosed, and 28,000 men died of this disease in the United States. Cryotherapy is an effective minimally-invasive modern treatment for prostate cancer, which does not involve radiation beams or radioactive seeds and is recommended by physicians to many men diagnosed with T1-T3 stages of prostate cancer. Presently, application of this potentially highly effective treatment is hampered by occasional serious complications caused by the lack of appropriate non-invasive temperature monitoring in the physiologically important healthy area adjacent to the patient's rectal wall. Also, the cost of cryotherapy significantly grows when an extra level of procedure control is added by using expensive computed tomography or magnetic resonance imaging modality. In this project we propose to develop a cost-effective novel transrectal optoacoustic-ultrasonic imaging system for guiding cryotherapy of prostate cancer via real-time monitoring of ice ball formation and temperature distribution within the area of healthy tissues adjacent to the rectal wall. The proposed system will allow reduction of dangerous side effects of cryotherapy via non-invasive monitoring of temperature distribution and increase the efficiency of procedure by extra control over the forming ice ball.
| Petrova, E V; Brecht, H P; Motamedi, M et al. (2018) In vivo optoacoustic temperature imaging for image-guided cryotherapy of prostate cancer. Phys Med Biol 63:064002 |
| Petrova, Elena; Liopo, Anton; Oraevsky, Alexander A et al. (2017) Temperature-dependent optoacoustic response and transient through zero Grüneisen parameter in optically contrasted media. Photoacoustics 7:36-46 |
