High speed automated intraoperative microscopy of the prostate circumference to ensure tumor-free margins in radical prostatectomy

前列腺周围的高速自动化术中显微镜检查可确保根治性前列腺切除术中的无肿瘤边缘

• 批准号: 10172866
• 负责人: JONATHAN QUINCY BROWN
• 金额: $ 39.78万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-06-25 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10172866
• 关键词: Address; Adopted; Adoption; Affect; Algorithms; Area; Atlases; Automation; Behavior; Biopsy; Cadaver; Case Series; Clinical; Clinical Management; Clinical Research; Color; Computer Assisted; Custom; Data; Detection; Development; Devices; Engineering; Ensure; Equilibrium; Excision; Frozen Sections; Future; Generations; Genitourinary system; Goals; Gold; Histology; Human; Image; Image Analysis; Image Enhancement; Image-Guided Surgery; Ink; Intervention; Left; Lighting; Machine Learning; Malignant Neoplasms; Malignant neoplasm of prostate; Manuals; Measurement; Measures; Mechanics; Methods; Microscopy; Modeling; Multi-Institutional Clinical Trial; Nerve; Online Systems; Operating Rooms; Operative Surgical Procedures; Optics; Organ; Pathologist; Pathology; Patient-Focused Outcomes; Patients; Pattern; Postoperative Period; Prognostic Factor; Progression-Free Survivals; Prostate; Prostatic Neoplasms; Radical Prostatectomy; Residual Tumors; Resolution; Risk Factors; Sampling; Scanning; Sensitivity and Specificity; Series; Site; Specificity; Specimen; Speed; Stains; Structure; Surface; Surface of the Prostate; Surgical margins; System; Techniques; Technology; Testing; Time; Tissues; Training; Translations; Validation; Visual; Work; accurate diagnosis; analog; authority; base; cancer diagnosis; cancer imaging; cancer risk; cancer surgery; classification algorithm; clinical imaging; clinical practice; clinical translation; cohort; computer aided detection; contrast imaging; diagnostic technologies; high risk; histological image; imaging system; improved; machine learning algorithm; men; microscopic imaging; neoplastic cell; neurovascular; novel; overtreatment; preservation; prospective; prostate biopsy; prostate surgery; rapid detection; recruit; technology development; tissue processing; tool; tumor; tumor progression; visual search; web-enabled

Project Summary: In prostate cancer (PCa), the presence and amount of residual tumor at the surface of the excised prostate is the only prognostic factor that is affected by surgical technique, vs. other factors, which are fixed and non-modifiable. Yet, positive surgical margins (PSM), defined as the presence of tumor cells at the inked surface of the removed specimen, are common, especially in advanced stage cancers, and are a strong independent risk factor for clinical progression and secondary treatment. In addition, elevated post-operative PSA, which is understood to be related to tumor left behind in the patient, is also associated with high risk of progression and secondary treatment. Thus, complete tumor removal is important to achieve to improve patient outcomes and reduce overtreatment, yet there is a delicate balance between resection radicality and minimizing damage to the neurovascular bundles to preserve post-operative function. The NeuroSAFE trial demonstrated that real-time detection and correction of PSMs by comprehensive histology of the prostate circumference results in improved patient outcomes, yet there are no widely adoptable methods to achieve this. In an effort to address this technical gap, we have developed video-rate structured illumination microscopy (VR-SIM) and demonstrated that it enables accurate diagnosis of PCa in the biopsy setting, and that it can rapidly deliver gigapixel microscopic images of the entire prostate surface for detection of PSMs. VR-SIM delivers the surface area coverage and resolution needed to detect PSMs, yet it is also fast and relatively simple and inexpensive, opening the possibility for widespread adoption. In this project, our interdisciplinary team of engineers and clinicians with significant prostate expertise will further advance this technology towards clinical translation, by completing critical technology development steps and by prospectively validating it in a large patient series. Specifically, we will increase the mechanical automation speed of the device, and will develop a fully automated system for handling of the removed prostate, to enable gigapixel panoramas of the entire prostate circumferential surface to be delivered within 10 minutes of removal and with minimal tissue processing and user intervention. We will then leverage our recently developed dual-color fluorescent stain that replicates standard H&E with high specificity, to develop expert-validated clinical image atlases using biopsies and cadaveric specimens to enhance image interpretation of VR-SIM prostate panoramas. These improvements will be combined to test the system in a prospective 250-patient clinical study, to determine the accuracy of the device for intra-operative detection of PSMs and prediction of post-operative PSA based on measurement of PSM extent. Finally, we will measure and model expert reviewer behavior using a novel web-enabled visual observer tracking method, which could be used in future computer-assisted search algorithms to expedite intra-operative image review. Successful completion will set the stage for multi-center clinical trials to validate the clinical utility of VR-SIM for real-time detection and correction of PSMs, and improvement of patient outcomes.

项目摘要：在前列腺癌 (PCa) 中，前列腺表面残留肿瘤的存在和数量 与其他因素相比，切除的前列腺是唯一受手术技术影响的预后因素 固定且不可修改。然而，阳性手术切缘（PSM）定义为肿瘤细胞存在于手术切缘处。 被移除的样本表面有墨水，很常见，尤其是在晚期癌症中，并且是一个强有力的证据。 临床进展和二次治疗的独立危险因素。此外，术后 据了解，PSA 与患者体内残留的肿瘤有关，也与高风险相关 进展和二次治疗。因此，彻底切除肿瘤对于改善病情非常重要。 患者的治疗结果并减少过度治疗，但切除激进性和 最大限度地减少对神经血管束的损伤，以保留术后功能。 NeuroSAFE 试验 证明通过前列腺的综合组织学实时检测和校正 PSM 圆周可以改善患者的治疗效果，但目前还没有广泛采用的方法来实现这一目标。 为了弥补这一技术差距，我们开发了视频速率结构照明显微镜 (VR-SIM) 并证明它能够在活检环境中准确诊断 PCa，并且它可以 快速提供整个前列腺表面的十亿像素显微图像，用于检测 PSM。 VR-SIM 提供 检测 PSM 所需的表面积覆盖范围和分辨率，但它也快速且相对简单， 价格低廉，为广泛采用提供了可能性。在这个项目中，我们的跨学科团队 具有丰富前列腺专业知识的工程师和临床医生将进一步推动这项技术走向临床 翻译，通过完成关键的技术开发步骤并在大规模中进行前瞻性验证 病人系列。具体来说，我们将提高设备的机械自动化速度，并将开发 用于处理切除前列腺的全自动系统，以实现整个前列腺的十亿像素全景 前列腺圆周表面将在切除后 10 分钟内交付，并且只需最少的组织处理 和用户干预。然后，我们将利用我们最近开发的双色荧光染色剂来复制 具有高特异性的标准 H&E，利用活检和 尸体标本，以增强 VR-SIM 前列腺全景的图像解释。这些改进将 结合起来在一项包含 250 名患者的前瞻性临床研究中测试该系统，以确定该系统的准确性 用于术中检测 PSM 并根据测量预测术后 PSA 的装置 PSM 范围。最后，我们将使用新颖的网络视觉效果来测量和建模专家审稿人的行为 观察者跟踪方法，可用于未来的计算机辅助搜索算法以加快 术中图像审查。成功完成将为多中心临床试验奠定基础，以验证 VR-SIM 在 PSM 实时检测和校正以及改善患者治疗效果方面的临床应用。

项目成果

Whole slide image data utilization informed by digital diagnosis patterns.

• DOI: 10.1016/j.jpi.2022.100113
• 发表时间: 2022
• 期刊: Journal of pathology informatics
• 作者: Ashman, Kimberly;Zhuge, Huimin;Shanley, Erin;Fox, Sharon;Halat, Shams;Sholl, Andrew;Summa, Brian;Brown, J Quincy
• 通讯作者: Brown, J Quincy

Rapid On-Site Microscopy and Mapping of Diagnostic Biopsies for See-And-Treat Guidance of Localized Prostate Cancer Therapy.

• DOI: 10.3390/cancers15030792
• 发表时间: 2023-01-27
• 期刊: Cancers
• 影响因子: 5.2