Abstract
Positive surgical margins, or cancer cells found at the boundary of an excised tumor mass, are a significant problem in the management of many cancers resulting in worsened patient outcomes. The problem is exacerbated in organ sites such as the prostate, where unnecessarily wide local excisions can result in significant deterioration of post-operative quality of life due to collateral damage to neighboring structures. Yet, at the same time, incomplete tumor removal results in worsened prognosis and need for additional interventions. Here, we report the design and development of a rapid and completely automated system for intraoperative gigapixel ex vivo microscopy of the circumferential surgical prostate margin within intra-operative timeframes, called the Automated Prostate Positioning System (APPS). The APPS leverages the rotational geometry of the prostate and high speed structured illumination microscopy (SIM) to generate continuous gigapixel panoramas of the fresh intact prostate circumference, including areas of the prostate adjacent to the neurovascular bundles, the rectum, and the bladder wall. Our previous work using SIM and a manual prostate handling method demonstrated the promise of the imaging technique for accurate detection of positive surgical margins. Our work here advances the technology toward clinical adoption, by demonstrating 10% greater tissue surface coverage fraction, 1.6× faster imaging throughput, and reduced number of required operator steps, compared to our prior approach. The APPS may be operated by a single person in the operating room suite within intraoperative time limits, while simultaneously delivering nearly two orders of magnitude higher tissue surface coverage than destructive and labor-intensive frozen section analysis techniques.
Highlights
Our group has advanced structured illumination microscopy (SIM) for the ex vivo imaging of entire tumor surgical margins as an alternative to intensive FSA, with the goal of intra-operatively capturing gigapixel histologic panoramas of the resected tissue surface for use in the identification and correction of positive surgical margin (PSM) during the primary operation[10,11]
The potential for clinical utility of the method was established in that prior work, as 4/5 positive surgical margins were identified by visual analysis on gigapixel SIM images by blinded pathologist raters who had been trained on a prostate clinical imaging atlas of SIM versus standard H&E
We found that the automated prostate positioning system (APPS) system does enable improved surface coverage as well as higher image throughput, providing contiguous views of the organ circumference
Summary
Our group has advanced structured illumination microscopy (SIM) for the ex vivo imaging of entire tumor surgical margins as an alternative to intensive FSA, with the goal of intra-operatively capturing gigapixel histologic panoramas of the resected tissue surface for use in the identification and correction of PSMs during the primary operation[10,11]. Despite the advantages offered by SIM, the previous method for intra-operative imaging required manual re-positioning of the prostate organ on the microscope stage to image adjacent surfaces, and did not always allow for continuous imaging of the circumferential surface depending on the shape of the prostate[10]. We measure the surface coverage of whole prostate SIM imaging using our previously established manual sample handling method, by comparing scanned areas to theoretical computations and surface area measured using 3D structured light scanning of the prostate. The developments and findings from this work further advance the utility of SIM for the intra-operative detection of surgical margins, by demonstrating a practical automated prostate positioning system (APPS) that enables automated hands-free gigapixel prostate imaging with complete circumferential surface coverage within intra-operative timeframes.
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