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Improving biospecimen quality by verifying adequacy at the point-of-acquisition with ex vivo structured illumination microscopy

通过使用离体结构照明显微镜验证采集点的充分性来提高生物样本质量

基本信息

批准号：
9314384
负责人：
JONATHAN QUINCY BROWN
金额：
$ 30.24万
依托单位：
TULANE UNIVERSITY OF LOUISIANA
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-08-15 至 2019-07-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Ex vivo microscopy is an emerging set of imaging modalities intended to enable histological imaging of whole tissue specimens at the point-of-procedure. Ex vivo microscopy holds much promise for enabling rapid verification of cancer biospecimen quantity and quality at the time of specimen acquisition. Two areas in which such technologies would be extremely helpful to pathologists are in 1) screening of biopsies collected during a biopsy procedure with the aim of providing guidance for collection of additional tissues, and 2) non-destructively assessing and verifying cancer content in biospecimens collected for banking and downstream molecular analysis. In prostate cancer diagnosis, for example, 70-80% of the 1 million biopsies collected for diagnosis each year are ultimately found to be benign on permanent histopathology review. For tissue banking, the major limiting pre- analytical factor for downstream molecular and genetic analysis is the amount of cancerous tissue present in the banked biopsies. However, currently available in-procedure pathology methods to assess biopsy cancer content (such as frozen section analysis) are too destructive, slow, expensive, and labor-intensive to be widely adopted. Thus, there is a missing opportunity to improve the efficiency and efficacy of diagnostic biopsy, and to guide sample collection and improve cancer biospecimen quality in tissue banking, by non-destructive histological verification. Until now, methods for ex vivo microscopy with the resolution and contrast needed for accurate biopsy verification have been too slow and expensive to realistically be adopted for clinical workflows involving multiple biopsies (16-20 in the case of prostate diagnostic biopsy). Further, the contrast methods (typically topical fluorescent staining with a single dye) have left much to be desired in terms of providing images that leverage the extensive training of pathologists. We have recently developed a set of technologies to address these limitations in an effort to ease adoption. The first is a rapid microscopic optical sectioning scanner, based on video-rate structured illumination microscopy that provides high-resolution, high-contrast images of fluorescently-stained biopsies in seconds at the point-of-procedure. This technology has been optimized for ease-of-use in the pathology workflow, including novel autofocus functions that enable fully automated imaging with minimal user intervention. The second is our recent development of a dual-color fluorescent staining procedure that exactly recapitulates the H&E staining used in standard histopathology. In this R33 Advanced Development project, we will build on these developments to validate VR-SIM as a practical, adoptable ex vivo microscopy solution for point-of-procedure biospecimen verification. In this project we will develop a dual-color version of the VR-SIM system optimized for our fluorescent H&E analog stain, optimize the system for balancing image resolution, contrast, and image acquisition speed, and develop a robust secure web-based multi-resolution image viewer for fast and facile telepathology of the VR-SIM images from any computer with a web browser. The project will culminate in a direct validation challenge of VR-SIM versus frozen section analysis for point-of-procedure biopsy verification in 200 fresh prostate core biopsies.

描述（由申请方提供）：离体显微镜检查是一种新兴的成像模式，旨在实现手术时对整个组织标本进行组织学成像。离体显微镜具有很大的希望，使快速验证癌症生物标本的数量和质量在标本采集的时间。这种技术对病理学家非常有帮助的两个领域是：1）在活检过程中收集的活检物的筛选，目的是为收集额外的组织提供指导，以及2）非破坏性地评估和验证收集用于银行和下游分子分析的生物样本中的癌症含量。例如，在前列腺癌诊断中，每年收集用于诊断的100万个活检中的70-80%在永久组织病理学检查中最终被发现是良性的。对于组织库，下游分子和遗传分析的主要限制性预分析因素是存在于库活组织检查中的癌组织的量。然而，目前可用的用于评估活检癌症内容物的术中病理学方法（例如冷冻切片分析）太具破坏性、缓慢、昂贵且劳动密集型而不能被广泛采用。因此，通过非破坏性组织学验证来提高诊断活检的效率和功效，以及指导样本收集和提高组织库中的癌症生物样本质量的机会缺失。到目前为止，具有准确活检验证所需的分辨率和对比度的离体显微镜检查方法太慢且昂贵，无法实际用于涉及多次活检的临床工作流程（在前列腺诊断活检的情况下为16-20）。此外，对比方法（通常用单一染料进行局部荧光染色）在提供利用病理学家的广泛培训的图像方面还有很多需要改进的地方。我们最近开发了一套技术来解决这些限制，以便于采用。第一种是快速显微光学切片扫描仪，基于视频速率结构照明显微镜，可在手术点在几秒钟内提供荧光染色活检的高分辨率，高对比度图像。该技术经过优化，可在病理学工作流程中轻松使用，包括新颖的自动对焦功能，可实现全自动成像，只需最少的用户干预。第二个是我们最近开发的双色荧光染色程序，完全概括了标准组织病理学中使用的H&E染色。在这个R33高级开发项目中，我们将在这些开发的基础上验证VR-SIM作为一种实用的、可采用的体外显微镜解决方案，用于程序点生物样本验证。在这个项目中，我们将开发一个双色版本的VR-SIM系统，为我们的荧光H&E模拟染色进行优化，优化系统以平衡图像分辨率，对比度和图像采集速度，并开发一个强大的安全的基于Web的多分辨率图像查看器，用于从任何带有Web浏览器的计算机上快速轻松地远程病理学VR-SIM图像。该项目最终将在200例新鲜前列腺芯活检中进行VR-SIM与冷冻切片分析的直接验证挑战，以进行手术点活检验证。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Nondestructive Diagnosis of Kidney Cancer on 18-gauge Core Needle Renal Biopsy Using Dual-color Fluorescence Structured Illumination Microscopy.

DOI：
10.1016/j.urology.2016.08.036
发表时间：
2016-12
期刊：
Urology
影响因子：
2.1
作者：
Liu J;Wang M;Tulman D;Mandava SH;Elfer KN;Gabrielson A;Lai W;Abshire C;Sholl AB;Brown JQ;Lee BR
通讯作者：
Lee BR

Persistent Homology for the Quantitative Evaluation of Architectural Features in Prostate Cancer Histology