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.

抽象的 患有乳腺肿块的患者需要诊断、分诊和治疗。 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 目前，该过程包括活检、标准组织学、通过免疫测定表型。 免疫组织化学，以及越来越多的分子检测，在服务良好的领域，面临的挑战包括获得—— 进行适当且有代表性的活组织检查，等待载玻片制备，由病理学家审查，然后进行成像 免疫染色 (IHC)，并可选择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，荧光模拟明场 成像，加州大学戴维斯分校）与虚拟免提微流体样本处理装置（CoreView，威斯康星大学）相结合。 图像本质上是数字化的，具有诊断质量，并且可以由训练有素的病理学人员在本地进行解释。 最终，在现场或基于云的计算机上进行实时评估。 另一个目标是实现同一会话多重免疫染色。 成像和成像，基于 Ko 博士（宾夕法尼亚大学）开发的快速猝灭点击化学方法 我们将构建和测试针衍生的成像和自动样品处理版本 样本最初使用多余的新鲜或最近固定的人类乳腺组织，随后临床上进行 所需的核心针活检任务涉及染色、成像、图像显示、再现性的优化。 演示和样品完整性评估与远红光单步免疫染色的结合。 将包括 Bels，并且将应用快速探针循环方法（用于多重检测 - ER、PR、HER2） 亚专业病理学审查将确保 FIBI 图像和免疫染色的可靠性和准确性。 目标是实现一种适合环境的自动化仪器，可以捕获他的信息。 来自芯针活检的拓扑病理学图像，同时保留其下游处理的完整性 几分钟内即可获得所需结果，并可以对患者进行知情分诊，甚至可以立即进行现场检查。 治疗，如果患者必须长途跋涉才能到达诊所，则尤其有价值。 潜在影响声明：当前活检评估至少延迟 1-3 天，并涉及 消耗部分或全部小组织样本会导致额外的延迟。 在服务较差的地区更具挑战性，因为组织学实验室和病理学家能够解释 在主要城市中心以外的地区，这种结果很少见。CoreView-FIBI 方法可以极大地改善帕 患者级的护理速度，还有企业级的效率，从而可以制定当天的疾病治疗计划。 对于生物样本应用，分析前变量将受到完全控制，且具有非破坏性 成像意味着更多的组织可用于存储和研究，并且可以提前对样本进行成像 为银行提供组织含量和相关成分丰度估计的保证。