Open-top light-sheet microscopy for non-destructive 3D pathology of prostate biopsies

用于前列腺活检非破坏性 3D 病理学的开顶光片显微镜

基本信息

批准号：
10082154
负责人：
Nicholas Reder
金额：
$ 39.77万
依托单位：
ALPENGLOW BIOSCIENCES, INC.
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-05 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10082154
关键词：
3-Dimensional Address Adoption Age Algorithm Design Algorithmic Analysis Antibodies Archives Biological Assay Biopsy Biopsy Specimen Blinded Blood Cancer Detection Cancer Patient Carcinoma Cell Nucleus Clinical Clinical Research Color Perception Communities Core Biopsy Cytokeratin 8 Data Set Development Diagnosis Diagnostic Disease Disease Progression Evaluation Family Formalin Gleason Grade for Prostate Cancer Goals Grant Hematoxylin and Eosin Staining Method Histologic Histology Histopathology Human Image Image Analysis Immunohistochemistry Individual Keratin Label Laboratories Lead Light Malignant Neoplasms Malignant neoplasm of prostate Manuals Methods Microscope Microscopy Minority Molecular Molecular Weight NKX3-1 gene Optics PECAM1 gene PSA level Paraffin Embedding Pathologist Pathology Pathway interactions Patients Performance Phase Procedures Process Prostate Prostate carcinoma Prostate-Specific Antigen Prostatectomy Protocols documentation Recording of previous events Sampling Screening for Prostate Cancer Sectioning technique Slide Small Business Innovation Research Grant Specimen Stains Standardization Technology Technology Assessment Thinness Time Tissue Embedding Tissues Treatment Protocols Uncertainty Validation base cancer diagnosis cancer risk clinically relevant clinically significant cost density design digital image archival system improved innovation innovative technologies lightspeed novel novel strategies patient subsets programs prospective prostate biopsy rectal standard of care treatment optimization

项目摘要

Abstract We are proposing a new approach for prostate cancer pathology using 3D open-top light-sheet (OTLS) microscopy and optical clearing. Approximately 20% of patients with an initial negative prostate biopsy procedure are found to have prostate cancer on a subsequent biopsy procedure. Previous studies have shown that examination of 100% of biopsy tissue improved prostate cancer detection rate, but these studies used labor-intensive manual sectioning techniques that are practical for a clinical laboratory. We hypothesize that imaging 100% of prostate biopsy tissue using OTLS microscopy, rather than 1-2% of the biopsy using current pathology technology, can detect occult carcinoma that would have otherwise been missed in a subset of patients. Furthermore, we intend to show that 3D OTLS can be seamlessly integrated into the current clinical laboratory workflow. The specific aims of this proposal are: 1) Validate that our OTLS methods do not interfere with the current pathology practice of formalin-fixed paraffin-embedded (FFPE) tissue sections, hematoxylin and eosin (H&E) histology, and immunohistochemistry (IHC), and 2) To show that 3D pathology can detect occult cancer missed by traditional microscopy, we will compare diagnosis of “pseudo-H&E” 3D OTLS images to traditional H&E pathology. We will use archived FFPE biopsy blocks from patients with prostate cancer who had a negative initial biopsy result. Through the studies in this proposal, we will validate the non-interference of our innovative 3D OTLS methods with standard pathology practice, a necessary prerequisite for adoption within the pathology community and for regulatory considerations. We will also provide preliminary evidence to support the clinical value of 3D pathology. This project addresses the IMAT goal of developing substantially improved cancer detection and risk assessment technologies.

抽象的我们提出一种使用 3D 开顶光片进行前列腺癌病理学的新方法 (OTLS) 显微镜检查和光学透明化大约 20% 的患者最初呈阴性。前列腺活检程序在随后的活检中发现患有前列腺癌先前的研究表明，100% 的活检组织的检查得到改善。前列腺癌检出率，但这些研究使用劳动密集型手动切片对于临床实验室来说实用的技术我们敢于 100% 进行成像。使用 OTLS 显微镜对前列腺活检组织进行活检，而不是使用电流显微镜对 1-2% 的活检组织进行活检病理学技术可以检测出隐匿性癌症，否则这些癌症可能会被错过此外，我们打算证明 3D OTLS 可以无缝集成。该提案的具体目标是：1) 验证。我们的 OTLS 方法不会干扰福尔马林固定的当前病理学实践石蜡包埋 (FFPE) 组织切片、苏木精和伊红 (H&E) 组织学，以及免疫组织化学 (IHC)，以及 2) 证明 3D 病理学可以检测隐匿性癌症传统显微镜错过的，我们将比较“伪 H&E”3D OTLS 图像的诊断我们将使用来自患有以下疾病的患者的存档 FFPE 活检块。初始活检结果为阴性的前列腺癌患者。通过本提案中的研究，我们将验证我们创新的 3D 技术的无干扰性具有标准病理学实践的 OTLS 方法是在内部采用的必要先决条件我们还将提供初步的病理学界和监管考虑。支持 3D 病理学临床价值的证据该项目致力于实现 IMAT 目标。开发显着改进的癌症检测和风险评估技术。