Practical high resolution microscopy of uncut, unembedded kidney biopsies

未切割、未包埋肾活检的实用高分辨率显微镜

• 批准号: 10017984
• 负责人: Michael John Levene
• 金额: $ 47.19万
• 依托单位: APPLIKATE TECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-15 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10017984
• 关键词: 3-Dimensional; Acute; Acute Kidney Failure; Acute Renal Failure with Renal Papillary Necrosis; Address; Adoption; Ancillary Study; Benchmarking; Biopsy; Biopsy Specimen; Chronic Kidney Failure; Clinical; Collagen; Collection; Computer Analysis; Computer Assisted; Computer software; Consumption; Core Biopsy; Cost Savings; DNA; Data; Detection; Development; Diagnosis; Diagnostic; Effectiveness; Elements; Evaluation; Fibrosis; Future; Gastric Parietal Cells; Generations; Grant; Health; Histology; Hospitals; Hour; Human; Image; Imaging technology; Immunohistochemistry; Immunologics; Injury; Kidney; Kidney Diseases; Kidney Transplantation; Laboratories; Liver diseases; Methods; Microscope; Microscopy; Modification; Molecular Analysis; Morphologic artifacts; National Institute of Diabetes and Digestive and Kidney Diseases; Neck; Nuclear Protein; Nucleic Acids; Pan Genus; Pathologist; Pathology; Patients; Phase; Preparation; Process; Protocols documentation; RNA; Remote Consultation; Research; Resolution; Sampling; Scanning; Signal Transduction; Slice; Slide; Small Business Innovation Research Grant; Specimen; Stains; Technology; Testing; Thick; Time; Tissue Preservation; Tissue imaging; Tissues; Tubular formation; Validation; Visualization; Visualization software; Waxes; cell injury; clinical application; clinical implementation; clinically relevant; comparative; cost; cost effective; design; digital; digital imaging; feature detection; global health; human tissue; improved; insight; instrument; kidney biopsy; machine vision; multiphoton microscopy; novel; novel therapeutics; physical process; precision medicine; preservation; prospective; second harmonic; second harmonic generation imaging; submicron; success; three-dimensional visualization; tissue processing; tool

Project Summary Applikate Technologies has developed Clearing Histology with Multiphoton Microscopy (CHiMP), a novel tissue processing and imaging protocol that provides direct-to-digital images from intact pathology tissue specimens, such as biopsies, without the need for wax embedding, slicing, or scanning of slides. The application of this technology to renal diagnosis is expected to improve considerably our ability to render accurate, cost-effective, and timely diagnoses in patients who suffer from a broad range of kidney problems. It will also expand our ability to study and understand kidney disorders by providing otherwise inaccessible data which can be analyzed with emerging computer analysis tools. The aim of this direct-to-Phase II SBIR proposal is to modify the hardware and software components of CHiMP for application to kidney biopsies and to validate CHiMP's non-inferiority for renal diagnosis compared to standard protocols and its integration into the renal pathology workflow in a clinical setting. CHiMP has many advantages for general histology, including: H&E-like images familiar to pathologists but with superior image quality, sub-micron effective thickness, and without artifacts common to slide preparation; non- destructive imaging that preserves intact tissue for ancillary molecular analysis and immunohistochemistry; rapid turnaround, with images ready within a few hours of receiving tissue; greatly reduced labor costs; true 3D prospective; and digitized images for remote consultation and machine vision. NIDDK has identified access to human kidney biopsies as an important bottle neck for progress in development of precision medicine for acute and chronic kidney disease. CHiMP directly addresses this by preserving tissue and increasing DNA yields. In addition, this proposal will extend CHiMP's imaging to include second harmonic generation from collagen, thereby enabling evaluation and quantitation of fibrosis, a key factor in renal health and applicable to other conditions such as liver disease. The specific aims of this proposal are to: 1) modify the CHiMP microscope and tissue cassettes to enable second harmonic generation imaging of collagen in kidney biopsies, 2) collect renal biopsy specimens in a clinical setting and evaluate integration into the clinical workflow and 3) add renal specific visualization features to Stackstreamer, our 3D visualization software, and demonstrate the utility of CHiMP for diagnosis. Successful completion of these aims will set the stage for a Phase III transition to regulatory approval and provide a proven platform for early implementation in select hospitals.

项目摘要 Applikate Technologies开发了一种新的组织--多光子显微镜(CHAMP)清除组织学 处理和成像协议，提供来自完整的病理组织样本的直接数字图像， 例如活组织检查，而不需要蜡包埋、切片或扫描载玻片。这一点的应用 肾脏诊断技术有望极大地提高我们提供准确、经济、 以及对患有广泛肾脏问题的患者进行及时诊断。它还将扩大我们的能力 通过提供原本无法访问的数据来研究和了解肾脏疾病，这些数据可以用来分析 新兴的计算机分析工具。 这项直接到第二阶段的SBIR提案的目的是修改CHINP的硬件和软件组件 应用于肾活检，并验证黑猩猩在肾脏诊断方面的非劣性。 标准方案及其在临床环境中与肾脏病理工作流程的整合。 黑猩猩在一般组织学上有许多优势，包括：病理医生熟悉的类似H&E的图像，但 卓越的图像质量，亚微米级的有效厚度，没有幻灯片准备常见的伪影； 为辅助分子分析和免疫组织化学保存完整组织的破坏性成像；快速的 周转，在收到组织后几个小时内就可以准备好图像；极大地降低了劳动力成本；真正的3D 以及用于远程会诊和机器视觉的数字化图像。NIDDK已确定可以访问 人肾活检是急诊精准医学发展的重要瓶颈 和慢性肾脏疾病。黑猩猩通过保存组织和增加DNA产量直接解决了这个问题。在……里面 此外，这项提议将扩展黑猩猩的成像，包括从胶原蛋白产生二次谐波， 因此，能够评估和量化纤维化，这是肾脏健康的关键因素，适用于其他 肝病等病症。 这项建议的具体目的是：1)修改黑猩猩显微镜和组织盒，以使第二 肾活检组织中胶原蛋白的谐波产生成像，2)在临床环境中收集肾活检标本 并评估与临床工作流程的集成，以及3)添加肾脏特定的可视化特征 StackStreamer，我们的3D可视化软件，并演示了黑猩猩用于诊断的效用。 成功完成这些目标将为第三阶段过渡到监管批准奠定基础，并提供 一个经过验证的平台，可在选定的医院早期实施。