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

描述(申请人提供)：在美国，每年有300多万例针吸活组织检查，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。因为针刺活检比外科活检侵入性小，所以它们的成本效益更高。然而，所有针吸活检的一个主要限制是病理学家或细胞学家只能从两个维度观察组织或细胞，而重要的是 确定癌症和疾病侵袭性的结构在三维(3D)比二维更清晰。放射学上的道理在病理学上是可以期待的，3D成像将会给信息含量带来量子上的增加，有望提高癌症早期诊断的敏感性和特异性。对于许多疑似胰腺癌的病例，细针活检是临床团队在做出挽救生命的决定之前必须检测的所有组织。在这项建议中，胰腺癌诊断的首选标本是细针芯活组织检查，整个1-2厘米长的标本使用先进的光学成像技术进行3D可视化。在从体外胰腺获取针头后，所有处理和高质量3D成像的准备工作都将在一种新型微流体设备中进行原型和验证。固定、染色、清除和运输的每一个组织准备步骤 到3D的成像是在微流控通道内进行的，可以自动进行。该项目的目标是将活检组织准备的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结构将被保存下来，以用于第一次活检完整性的光学机械测量。自动准备后的针吸活检标本的诊断价值将由经验丰富的病理医生确定。在组织活检中可视化3D形态的能力也将使病理学家更好地比较体外诊断和新的体内3D成像。这些依赖于光学透明组织和传统明视场成像(Z堆叠成像和光学投影断层扫描显微镜)的体外技术可以成为病理学家更好地了解体内3D成像技术的桥梁，如共焦、光学相干断层成像和光声成像。该项目预计将导致病理学从2D向3D的转变，以及提供侵入性更小、低成本和快速的癌症诊断的能力，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.