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，残留肿瘤的存在和数量 切除的前列腺是唯一受外科技术影响的预后因素，而不是其他因素 固定和不可修改。然而，阳性手术边缘（PSM），被定义为肿瘤细胞在 去除的样品的墨水表面很常见，尤其是在高级阶段癌症中，并且是一个强的 临床进展和继发治疗的独立危险因素。此外，术后升高 PSA被认为与患者留下的肿瘤有关，也与高风险有关 进展和次要治疗。因此，完全清除肿瘤对于改善很重要 患者的结果并减少过度治疗，但切除激进性和 最大程度地减少对神经血管束的损害，以保留术后功能。 Neurosafe试验 证明了通过前列腺的全面组织学对PSM的实时检测和校正 周长会改善患者的结局，但没有广泛采用的方法来实现这一目标。 为了解决这一技术差距，我们开发了视频速率结构化照明显微镜 （VR-SIM）并证明它可以在活检环境中准确诊断PCA，并且可以 快速提供整个前列腺表面的吉吉像微小图像，以检测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，并且 廉价，开放了广泛采用的可能性。在这个项目中，我们的跨学科团队 具有重要前列腺专业知识的工程师和临床医生将进一步将这项技术推向临床 翻译，通过完成关键的技术开发步骤并前瞻性地验证它 患者系列。具体而言，我们将提高设备的机械自动化速度，并将发展 全自动系统用于处理被删除的前列腺，以启用整个吉米金斯全景 前列腺圆周表面将在去除后10分钟内交付，并且随着最小的组织加工 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来复制 具有高特异性的标准H＆E，以使用活检和 尸体标本以增强VR-SIM前列腺全景图的图像解释。这些改进将会 在前瞻性的250名患者临床研究中合并以测试系统，以确定 基于测量 PSM范围。最后，我们将使用新颖的网络视觉效果来衡量和建模专家审阅者的行为 观察者跟踪方法，可以在未来的计算机辅助搜索算法中使用来加快 术中图像综述。成功完成将为多中心临床试验奠定阶段，以验证 VR-SIM对PSM的实时检测和校正以及患者预后的改善的临床实用性。

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