Diametrically Patterned Dural Graft for Enhanced Dura Mater Regeneration

DESCRIPTION (provided by applicant): Prostate cancer affects one in every six men and remains the second leading cause of cancer related mortality in men. Permanent interstitial brachytherapy, the permanent placement of radioactive seeds in the prostate, is widely used in the treatment of prostate cancer. Despite the recent uptake in robotic surgery (with reported increased urinary morbidity) which has impacted both brachytherapy and conventional surgery, brachytherapy remains a widely used treatment. In the historical perspective, brachytherapy has been a definitive treatment option with potentially excellent long term results. The success of brachytherapy depends on adequately irradiating the prostate while avoiding excessive radiation to surrounding organs, most importantly the urethra and rectum. Despite improved outcomes from modifications in brachytherapy technique, contemporary reports document considerable variability in brachytherapy practice, with resultant suboptimal outcomes and toxicity. A recognized major contributor to these poor outcomes is the lack of real- time image guidance to visualize source placement and dose intra-operatively as it evolves due to seed positioning errors and the onset of prostatic edema. The proposed work is the development of a multi-modal image-guidance build in an intelligent platform with capability for real-time, precise, and quantitative evaluation of source position and target dosimetry during the course of a brachytherapy procedure, thereby allowing the physicianto continuously correct for source position alterations and adaptively achieve an optimal implant, resulting in both reduced toxicity and improved cancer control. The proposed work is the development, design and evaluation of a real-time imaging system based on integrated photo-acoustic and transrectal ultrasound image guidance and advanced image processing software that will produce real-time, precise, and quantitative evaluation of seed positions and dosimetry during the brachytherapy procedure and visualize prostate anatomy simultaneously. The proposed system will integrate imaging and planning tools that are already routinely used in current brachytherapy practice with an inclusion of low cost laser source. The real-time imaging will enable the physician to continuously correct for source position errors and adaptively achieve an optimal implant without disruption of existing surgical workflow, resulting in both reduced toxicity and improved cancer control. The research plan will be carried out in three aims: 1) study the optical properties of both prostate and metallic seed, 2) develop integrated photo-acoustic and transrectal ultrasound imaging system, and 3) perform system integration, testing and validation in tissue-mimicking phantoms, ex vivo prostrates and a limited in vivo animal study. The proposed integrated system will be first of its kind to have the capability of real-time imaging of brachytherapy implant and simultaneously visualizing prostate anatomy. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: Prostate cancer is diagnosed in approximately 240,000 men per year in the United States, making it the most common cancer afflicting men and second in the overall population. Brachytherapy (implantation of radioactive seeds into the prostate) is widely used in the treatment of prostate cancer, yet studies show that it is possible for men to receive suboptimal brachytherapy treatment, with doses either too high (leading to side effects and sometimes serious toxicity) or insufficient (leading to risk of cancer recurrence). A major contributor to these outcomes is the lack of existing techniques for physicians to visualize or quantify radiation dose within the prostate as seeds are implanted; the goal of the proposed research is to developa system that achieves this capability in a manner that can be readily implemented in operating rooms on a widespread scale nationwide. Over 50,000 brachytherapy procedures are performed in the U.S. annually. Prevalence of the use of brachytherapy is in part due to its minimally invasive nature and relatively brief time commitment on the part of the patient when compared to external beam radiation or surgery. The success of prostate brachytherapy hinges on adequately dosing the prostate while avoiding excessive radiation to adjacent organs, most notably the urethra and rectum. Despite some improvements in technique, the basic methods of prostate brachytherapy have changed little over the past decade, and contemporary multi-center reports document considerable variability in brachytherapy practice with resultant toxicity and suboptimal outcomes. A recognized major contributor to these poor outcomes are source positioning errors and the onset of prostatic edema, which create regions of both inadequate dose aswell as excessive dose. It is broadly recognized that there is a need for accurate image guidance, dynamic visualization of source positions, and intraoperative dose reconstruction as it evolves during the procedure. This work directly addresses these needs.