Rapid Needle Biopsy Assessment at Point of Care to advance personalized cancer therapy

护理点快速针活检评估以推进个性化癌症治疗

• 批准号: 9886701
• 负责人: Eric J Seibel
• 金额: $ 29.75万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9886701
• 关键词: Automation; Biological Markers; Biopsy; Breast; California; Carcinoma; Characteristics; Classification; Clinical; Computers; Core Biopsy; Data Analyses; Dehydration; Development; Devices; Diagnosis; Epidermal Growth Factor; Estrogen Receptors; Evaluation; Feasibility Studies; Feedback; Fluorescence; Formalin; Fresh Tissue; Future; Genomics; Goals; Guidelines; Histopathology; Human; Image; Immunophenotyping; Individual; Intervention; Legal patent; Lesion; Liquid substance; Lung; Malignant Neoplasms; Manuals; Measures; Methods; Microdissection; Microscopy; Microtomy; Molecular; Molecular Probes; Morphology; Multiomic Data; Needle biopsy procedure; Needles; Pancreas; Paraffin Embedding; Pathology; Phenotype; Precision therapeutics; Preparation; Procedures; Process; Progesterone Receptors; Proteomics; Pump; RNA; Sampling; Series; Shapes; Specimen; Speed; Stains; Standardization; Structure; Surface; System; Technology; Testing; Therapeutic; Time; Tissue Preservation; Tissue Procurements; Tissue Sample; Tissue Stains; Tissue Viability; Tissues; Triage; Tube; Universities; Validation; Washington; Work; base; breast cancer diagnosis; cancer biomarkers; cancer cell; cancer subtypes; cancer therapy; computerized; design; epigenomics; fluorescence imaging; image processing; instrumentation; malignant breast neoplasm; metabolomics; minimally invasive; molecular marker; multimodality; novel; personalized cancer therapy; personalized medicine; point of care; preservation; prevent; processing speed; protein expression; prototype; radiologist; response; robot control; sample fixation; tissue trauma; transcriptomics; treatment planning; tumor; ultraviolet; virtual

Project Summary Currently there are no standard guidelines followed for core needle biopsy (CNB) acquisition and preparation. Millions of CNBs are procured annually as the preferred minimally invasive procedure for diagnosing breast cancer and assessing therapeutic strategies based on biomarkers from these small biospecimens. However, the downstream steps in pathology were originally not designed for CNBs – a series of manual procedures that are not standardized. These are: adequacy testing, fixation & dehydration, paraffin embedding, thin-sectioning, staining for image-based morphological analysis, immuno-histochemical (IHC) analysis, and subsequent microdissection to enrich for RNA extraction. Our project is designed to rapidly evaluate the CNB for adequacy, the presence of cancer cells to make a diagnosis, using CoreView millifluidic device from the University of Washington, Seattle. Automated computer-controlled fluidic pumps help to remove the CNB from the needle, transport, clean and stain the tissue surface in a repeatable system designed for CNBs. In partnership with the University of California at Davis, the new method of microscopy with ultraviolet surface excitation will be used which rapidly produces images appear to match the standard H&E images used for adequacy testing. In addition, MUSE will be expanded to include multiplexed molecular of the same CNB. High clinical impact for personalized medicine is provided by this multiplexed fluorescence immunostaining of the biopsy to determine ER/PR and HER2 expression levels that are co-registered with the virtual H&E. The entire process of multiplexed MUSE imaging at the point of care allows the specimen to remain unfixed during this process, which triages one of the CNBs into genomic and other ‘omics analyses in the future that require high yield and quality of biomarkers. The other 1 or 2 CNBs can continue into formalin fixed paraffin embedded conventional histopathology work flow for the future validation of this rapid assessment system. In this feasibility study, the first molecular and morphological CNB instrumentation will be designed and fabricated based on CoreView-MUSE patented technologies. Testing will compare the CNB surface images compared to conventional thin section H&E and IHC as well as the quality and quantity of RNA from these two approaches. Pilot testing of full automation will determine the ultimate speed of processing from needle to multimodal adequacy determination that should range from 5 to 15 minutes at the point of care. Once developed and validated for breast cancer, the CoreView-MUSE system will be expanded to lung, pancreas, and other cancers that rely on CNB accurately sampling cancer from the lesion and providing phenotype classifications for precision therapies.

项目概要 目前，对于芯针活检 (CNB) 采集和采集没有遵循标准指南。 每年采购数百万个 CNB 作为首选的微创手术。 根据这些小分子的生物标志物诊断乳腺癌并评估治疗策略 然而，病理学的下游步骤最初并不是为 CNB 设计的 - 一系列未标准化的手动程序包括：充分性测试、固定和 脱水、石蜡包埋、薄切片、染色用于基于图像的形态分析， 免疫组织化学 (IHC) 分析，以及随后的显微切割以富集 RNA 提取。 我们的项目旨在快速评估 CNB 的充足性以及癌细胞的存在，以制造 使用西雅图华盛顿大学的 CoreView 微流体设备进行诊断。 计算机控制的流体泵有助于从针上去除 CNB、运输、清洁和染色 与大学合作设计的可重复系统中的组织表面。 加利福尼亚州戴维斯分校将使用紫外表面激发显微镜的新方法，该方法 快速生成的图像似乎与用于充分性测试的标准 H&E 图像相匹配。 此外，MUSE 将扩展到包括同一 CNB 的多重分子。 这种多重荧光免疫染色对个性化医疗产生了影响 活检以确定与虚拟 H&E 共同注册的 ER/PR 和 HER2 表达水平。 在护理点进行多重 MUSE 成像的整个过程使标本保持不固定状态 在此过程中，未来会将其中一个 CNB 分类到基因组和其他“组学”分析中 需要高产量和高质量的生物标记物的其他 1 或 2 个 CNB 可以继续进入福尔马林。 固定石蜡包埋的常规组织病理学工作流程，用于未来验证这种快速 在这项可行性研究中，第一个分子和形态 CNB 仪器。 将基于CoreView-MUSE专利技术进行设计和制造，测试将进行比较。 与传统薄切片 H&E 和 IHC 相比的 CNB 表面图像以及质量和 完全自动化的试点测试将确定这两种方法的 RNA 数量。 从针处理到多模式充分性确定的最终处理速度应在 一旦针对乳腺癌开发并经过验证，在护理点只需 5 至 15 分钟。 CoreView-MUSE系统将扩展到肺癌、胰腺和其他依赖CNB的癌症 从病灶中准确取样癌症并提供精确的表型分类 疗法。