CoreView and FIBI for rapid-onsite evaluation and molecular profiling of core-needle breast biopsies.

CoreView 和 FIBI 用于对核针乳腺活检进行快速现场评估和分子分析。

• 批准号: 10613211
• 负责人: RICHARD M. LEVENSON
• 金额: $ 32.9万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10613211
• 关键词: Address; Antibodies; Antigen Targeting; Area; Artificial Intelligence; Biological Assay; Biopsy; Breast; Breast Cancer Patient; Breast biopsy; Caring; Chemistry; Classification; Clinic; Clinic Visits; Clinical; Collection; Computer Assisted; Consumption; Core Biopsy; Coupled; Development; Devices; Diagnosis; Diagnostic; Diagnostic Imaging; Disease; ERBB2 gene; Ensure; Evaluation; Fluorescence; Formalin; Goals; Hand; Histology; Histopathology; Human; Human Resources; Image; Immunohistochemistry; Immunophenotyping; Institutional Review Boards; Label; Laboratories; Ligands; Mammary Gland Parenchyma; Mass in breast; Mechanics; Molecular; Molecular Profiling; Nature; Needle biopsy procedure; Needles; Nucleic Acids; Optics; Paraffin Embedding; Pathologist; Pathology; Patient Triage; Patients; Peptides; Periodicity; Phenotype; Preparation; Procedures; Process; Rapid diagnostics; Reagent; Reproducibility; Research; Resolution; Resource-limited setting; Resources; Sampling; Site; Slide; Specimen; Specimen Handling; Stains; Stream; System; Technology; Testing; Time; Tissues; Training; Travel; Triage; Validation; Vial device; breast lesion; cloud based; digital; digital imaging; imaging software; improved; instrument; multiplexed imaging; point of care; preservation; rapid technique; rapid test; sample fixation; sensor; skills; tool; treatment planning; treatment site; validation studies; virtual

Abstract Patients with concerning breast masses require diagnosis, triage, and management. This proposal seeks to combine three recently developed technologies to provide rapid diagnostic support for patient breast tumor evaluation. Currently, this process consists of biopsy, standard histology, phenotype determination via im- munohistochemistry, and increasingly, molecular assays. In well-served areas, the challenges involve obtain- ing appropriate and representative biopsies, waiting for slide preparation, review by a pathologist, then im- munostaining (IHC), and optionally, submission for nucleic-acid based studies. We propose a simple tissue-direct-to-digital slide-free imaging solution (FIBI, fluorescence imitating brightfield imaging, UC Davis) coupled with a virtually hands-off millifluidic specimen handling device (CoreView, UW). Images, intrinsically digital, are of diagnostic quality, and can be interpreted locally by trained pathology per- sonnel, or streamed anywhere in the world for real-time evaluation. Eventually, on-site or cloud-based com- puter-assisted tools will be available. An additional goal is to achieve same-session multiplexed immunostain- ing and imaging, based on rapid-quench click chemistry approaches developed by Dr. Ko (Univ. Penn.) We will build and test versions of the combined imaging and automated sample handling of needle-derived specimens initially using excess fresh or recently fixed human breast tissue, and subsequently clinically ac- quired core-needle biopsies. Tasks involve optimization of staining, imaging, image display, reproducibility demonstration, and sample integrity assessments. Incorporation of single-step immunostaining with far-red la- bels will be included, and methods for rapid probe cycling (for multiplexing—ER, PR, HER2) will be applied and tested. Subspecialty pathology review will ensure that the FIBI images and immunostains are reliable and of diagnostic quality. The goal is to implement a context-appropriate, automated instrument that can capture his- topathology images from core-needle biopsies, while retaining their integrity for downstream processing as needed. Results will be available within minutes and allow for informed patient triage or even immediate on-site treatment, especially valuable if the patient has had to travel long distances to reach the clinic. Statement of Potential Impact: Current biopsy evaluation interposes at least 1-3 days delay, and involves consuming some or all of small tissue specimens. Immunostaining contributes additional delay. The situation is more challenging in poorly served areas, as histology laboratories and the pathologists capable of interpreting the results are rare outside major urban centers. The CoreView-FIBI approach could dramatically improve pa- tient-level care velocity, but also enterprise-level efficiency, allowing for same-day disease treatment planning. For biospecimen applications, preanalytical variables will be under complete control, the non-destructive nature of the imaging means that more tissue is available for storage and research, and imaging of the specimen prior to banking provide assurance of tissue content and abundance estimates of relevant components.

摘要 患有乳腺肿块的患者需要诊断、分诊和处理。这项建议旨在 结合三项最新开发的技术，为患者乳腺肿瘤提供快速诊断支持 评估。目前，这一过程包括活检、标准组织学、通过免疫组织化学进行表型测定。 免疫组织化学，以及越来越多的分子分析。在服务良好的地区，挑战涉及获得- 进行适当和有代表性的活检，等待幻灯片准备，由病理学家审查，然后- 免疫染色(IHC)，以及可选的提交基于核酸的研究。 我们提出了一种简单的组织直接数字无载玻片成像解决方案(FIBI，荧光模拟亮场 成像，加州大学戴维斯分校)与一个几乎不插手的毫微流样本处理设备(科雷维尤，威斯康星州)相结合。 图像本质上是数字化的，具有诊断性质量，并可由经过培训的病理学人员在当地进行解释。 Sonnel，或在世界上任何地方流传输以进行实时评估。最终，现场或基于云的COM- 计算机辅助工具将可用。另一个目标是实现同一节多路免疫染色- ING和成像，基于Ko博士(大学)开发的快速猝灭点击化学方法。宾夕法尼亚大学) 我们将构建和测试组合成像和自动样本处理的版本 标本最初使用过多的新鲜或最近固定的人类乳房组织，随后在临床上使用 针芯活组织检查。任务包括优化染色、成像、图像显示、重现性 演示和完整性评估样本。远红光一步免疫染色技术的应用 将包括BELS，并将应用快速探头循环的方法(用于多路复用-ER、PR、HER2)和 测试过。专科病理学检查将确保FIBI图像和免疫染色是可靠的 诊断质量。我们的目标是实现一种适合背景的自动化工具，可以捕获他的- 核心针活检的病理图像，同时保持其完整性以用于下游处理 需要的。结果将在几分钟内得到，并允许知情的患者分诊，甚至立即在现场 如果患者必须长途跋涉才能到达诊所，治疗尤其有价值。 潜在影响陈述：目前的活检评估至少会延迟1-3天，并涉及 消耗部分或全部小组织样本。免疫染色造成了额外的延迟。情况是这样的 在服务较差的领域更具挑战性，如组织学实验室和能够解释 这一结果在主要城市中心以外的地方很少见。CoreView-FIBI方法可以显著改善PAS- 临床级的护理速度，也是企业级的效率，允许当天的疾病治疗计划。 对于生物样品应用，分析前变量将处于完全控制之下，这是非破坏性的 成像意味着有更多的组织可用于存储和研究，并优先对标本进行成像 向银行提供组织含量和相关成分丰度估计的保证。