Needle biopsy preservation and preparation for rapid 3D pathology of pancreas

描述（由申请人提供）：美国每年进行超过300万次针吸活检，通常用于诊断乳腺癌、前列腺癌、甲状腺癌、肺癌、肝癌和胰腺癌。因为针吸活检比手术活检的侵入性更小，所以它们更具成本效益。然而，所有针穿刺活检的主要限制是病理学家或细胞学家仅在两个维度上观察组织或细胞，而重要的是， 与二维相比，用于确定癌症和疾病侵袭性的三维（3D）结构更清楚。放射学中的真实情况在病理学中也是如此，3D成像将使信息量大幅增加，有望提高早期癌症诊断的灵敏度和特异性。对于许多病例（例如疑似胰腺癌），临床团队在做出挽救生命的决定之前必须测试的所有组织都是小针活检。在该提案中，胰腺癌诊断的首选标本是细针芯活检，使用先进的光学成像在3D中可视化整个1-2cm长的标本。在从离体胰腺获取针之后，将在新型微流体装置中对用于最高质量3D成像的所有处理和准备进行原型制作和验证。固定、染色、清洁和运输的每个组织准备步骤 在微流体通道内进行3D成像，这可以是自动化的。该项目的目标是将活检组织制备时间减少到病理学实验室标准时间的一半以下。此外，组织的3D结构将被保留用于活检完整性的第一光学机械测量。将由经验丰富的病理学家确定自动制备后的穿刺活检标本的诊断价值。可视化组织活检内的3D形态的能力也将允许病理学家更好地将离体诊断与新的体内3D成像进行比较。这些依赖于光学透明组织和传统明场成像（Z-堆栈成像和光学投影断层扫描显微镜）的离体技术可以成为病理学家更好地理解体内3D成像技术的桥梁，例如共聚焦，光学相干断层扫描和光声成像。该项目预计将导致病理学从2D到3D的转变，并能够提供侵入性更小，成本更低和更快速的癌症诊断，每年直接影响数百万美国公民。

DESCRIPTION (provided by applicant): There are over three million needle biopsies performed every year in the USA, typically for the diagnosis of breast, prostate, thyroid, lung, liver, and pancreatic cancers. Because needle biopsies are less invasive than surgical biopsies, they are much more cost-effective. However, a major limitation for all needle biopsies are that the pathologist or cytologist views the tissue or cells in only two dimensions, while the important structures for determining cancer and invasiveness of the disease is more clearly seen in threes dimensions (3D) versus two dimensions. What is true in radiology is expected in pathology, 3D imaging will give a quantum increase in the information content, expected to increase sensitivity and specificity of early cancer diagnosis. For many cases such as suspected pancreatic cancer, the small needle biopsy is all the tissue that the clinical team has to test before making a lifesaving decision. In this proposal, the preferred specimen for pancreatic cancer diagnosis is a thin needle core biopsy, which the entire 1-2cm long specimen is visualized in 3D using advanced optical imaging. After needle procurement from ex vivo pancreas, all handling and preparation for highest quality 3D imaging will be prototyped and validated within a novel microfluidics device. Every tissue preparatory step of fixing, staining, clearing, and transporting to 3D imaging is conducted within the microfluidics channel, which can be automated. The goal of this project is to reduce the time for biopsy tissue preparation to less than half the standard time in a pathology lab. Furthermore, the 3D architecture of the tissue will be preserved for the first opto-mechanical measures of biopsy intactness. The diagnostic value of the needle biopsy specimens after automated preparation will be determined by experienced pathologists. The ability to visualize 3D morphology within tissue biopsies will also allow the pathologists to bette compare ex vivo diagnosis with new in vivo 3D imaging. These ex vivo technologies that rely on optically cleared tissue and traditional bright-field imaging (Z-stack imaging and optical projection tomographic microscopy) can become the pathologists' bridge for better understanding in vivo 3D imaging technologies, such as confocal, optical coherence tomography, and photo-acoustic imaging. This project is expected to lead to a transformation in pathology from 2D to 3D, and in the ability to provide less invasive, low-cost and rapid cancer diagnosis, directly affecting several millions of US citizens per year.