Label-free intraoperative photoacoustic microscopy for rapid diagnosis of tissue biopsies with specimen integrity

无标记术中光声显微镜可快速诊断组织活检并保持样本完整性

• 批准号: 9803571
• 负责人: MASSIMO D'APUZZO
• 金额: $ 66.29万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9803571
• 关键词: Address; Adjuvant Study; Algorithms; Archives; Benign; Biopsy; Collagen; Core Biopsy; Custom; Devices; Diagnosis; Diagnostic; Diagnostic Imaging; Diagnostic Procedure; Diagnostic tests; Discrimination; Edema; Excision; Forcep; Formalin; Freezing; Frozen Sections; Generations; Goals; Gold; Healthcare Systems; Hematoxylin and Eosin Staining Method; Hospitals; Hour; Human Resources; Image; Image-Guided Surgery; Imaging Device; Immunohistochemistry; Label; Lesion; Light Microscope; Malignant - descriptor; Methodology; Methods; Microscope; Microscopy; Morphologic artifacts; Nature; Needles; Nuclear; Operating Rooms; Operative Surgical Procedures; Paraffin Embedding; Pathologist; Patient Care; Patient risk; Patients; Performance; Preparation; Procedures; Process; Property; Resolution; Savings; Series; Slide; Specimen; Stains; System; Technology; Thinness; Time; Tissue Embedding; Tissue Procurements; Tissues; Training; Translations; Universities; base; cost; imaging modality; improved; light transmission; next generation sequencing; novel; photoacoustic imaging; preservation; public health relevance; rapid diagnosis; sample fixation; scalpel; tumor; virtual

ABSTRACT (30 Lines) Frozen section diagnoses are typically requested intraoperatively to guide the surgery. While this methodology is still irreplaceable, it suffers from a series of limitations: tissue loss, freezing artifacts, suboptimal cutting of fatty specimens, inability to diagnose bony lesions, and prolonged turnaround time. The aim is to develop a multi-channel subcellular resolution photoacoustic microscopy (PAM) system capable of addressing all the aforementioned limitations and providing pathologists with diagnostic images comparable or identical to the state of the art, with magnification matching or exceeding that of standard transmission light microscopes, and requiring no additional training for pathologists to diagnose. To achieve our objective, we will pursue the following two specific aims: Specific Aim 1: Develop a multi-channel subcellular resolution PAM system for rapid analysis and diagnosis of tissue biopsies A. Develop a multi-channel subcellular resolution PAM system B. Develop a customized tissue biopsy holder for rapid tissue biopsy handling and imaging by PAM Specific Aim 2: Optimize and validate the multi-channel subcellular resolution PAM for translation into a robust, accurate, and efficient intraoperative device A. Optimize image acquisition in order to maximize discrimination of nuclear, cytoplasmic, and stromal properties with minimal tissue degradation B. Optimize post-acquisition algorithms to generate pseudocolored images resembling classical hematoxylin and eosin (H&E) sections with superimposed unique imaging modalities (edema and collagen) C. Validate the utilization of PAM generated images for diagnostic purposes by comparing with H&E sections, which are prepared by formalin-fixed paraffin-embedding (the current gold standard) D. Validate the utilization of PAM generated images for intraoperative diagnostic purposes by comparing with H&E sections, which are prepared by frozen section (the current intraoperative gold standard) Impact: The proposed technology will represent a major breakthrough by addressing all the limitations of current frozen section-based diagnoses and providing images with H&E equivalent qualities intraoperatively. It aims to introduce a rapid and tissue saving diagnostic method for surgical biopsies, positively impacting the healthcare system and patient care. Reducing the turnaround time on the frozen section interpretation will significantly reduce the time spent in the operating room, and therefore, decrease patient risks and costs. The ability to evaluate adequacy of small specimens with no loss in tissue will decrease the need for re-biopsy procedures. The virtually generated images can be interpreted remotely so that smaller hospitals can benefit from procedures currently available only to larger tertiary hospitals and university centers.

摘要（30 行） 术中通常需要冰冻切片诊断来指导手术。虽然这种方法论 仍然是不可替代的，它受到一系列限制：组织损失、冷冻伪影、脂肪切割不理想 标本，无法诊断骨病变，以及延长的周转时间。 目的是开发一种多通道亚细胞分辨率光声显微镜（PAM）系统 解决所有上述限制并为病理学家提供可比的诊断图像 或与现有技术相同，放大倍数匹配或超过标准透射光的放大倍数 显微镜，并且不需要病理学家进行额外的培训即可诊断。 为了实现我们的目标，我们将追求以下两个具体目标： 具体目标1：开发多通道亚细胞分辨率PAM系统，用于快速分析和诊断 组织活检 A.开发多通道亚细胞分辨率PAM系统 B. 开发定制的组织活检支架，用于通过 PAM 快速进行组织活检处理和成像 具体目标 2：优化和验证多通道亚细胞分辨率 PAM，以转化为强大的、 准确、高效的术中设备 A. 优化图像采集，以最大限度地区分细胞核、细胞质和基质 具有最小组织降解的特性 B. 优化采集后算法以生成类似于经典苏木精的伪彩色图像 和曙红 (H&E) 切片，叠加独特的成像模式（水肿和胶原蛋白） C. 通过与 H&E 切片进行比较，验证 PAM 生成的图像用于诊断目的的利用率， 通过福尔马林固定石蜡包埋（当前的金标准）制备 D. 通过比较来验证 PAM 生成的图像用于术中诊断的用途 H&E 切片，通过冷冻切片制备（当前术中金标准） 影响：所提出的技术将解决当前技术的所有局限性，代表着一项重大突破。 基于冰冻切片的诊断并在术中提供具有 H&E 同等质量的图像。其目的是 引入一种快速、节省组织的手术活检诊断方法，对医疗保健产生积极影响 系统和患者护理。减少冰冻切片解释的周转时间将显着 减少在手术室花费的时间，从而降低患者的风险和费用。有能力 评估小样本是否足够且不损失组织将减少重新活检程序的需要。 虚拟生成的图像可以远程解读，以便小型医院可以从手术中受益 目前仅向较大的三级医院和大学中心提供。