Cancer histology and QC via MUSE: Sample-sparing UV surface-excitation microscopy

通过 MUSE 进行癌症组织学和质量控制：保留样品的紫外表面激发显微镜

基本信息

批准号：
9901047
负责人：
RICHARD M. LEVENSON
金额：
$ 7.85万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-03-08 至 2021-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9901047
关键词：
Appearance Area Basic Science Biological Biological Assay Biopsy Biopsy Specimen Cancer Histology Cell Survival Cells Clinic Clinical Color Computer software Consumption Contrast Media DNA Detection Development Diagnostic Disease Dyes Effectiveness Ensure Eosine Yellowish Epithelial Experimental Animal Model Exposure to Fluorescence Fluorescent Dyes Formalin Frequencies Fresh Tissue Geometry Goals Harvest Histology Image Imaging Device Label Lasers Lesion Manuals Methods Microscope Microscopy Microtomy Molecular Molecular Analysis Morphologic artifacts Nervous System Neoplasms Optical Coherence Tomography Optics Organ Paraffin Embedding Pathologist Pathology Patients Penetration Preparation Process Proteins RNA Research Personnel Resolution Sampling Services Signal Transduction Slide Source Specimen Stains Surface Testing Time Tissue Sample Tissue Viability Tissues Toxicology Translational Research Ultrasonography Ultraviolet Rays Validation Visible Radiation Xenograft procedure base biobank cancer diagnosis cost file format high resolution imaging imaging capabilities instrumentation lens novel point of care preservation sample fixation software development tissue processing tool tumor validation studies whole slide imaging

项目摘要

PROJECT SUMMARY: Pathology—determining the causes and effects of disease, often by using a microscope to examine patients' tissue—is essential for arriving at a correct cancer diagnosis, but it has become increasingly important to submit relevant portions of often tiny tissue samples for DNA and other molecular and functional tests. Making sure that the submitted material actually contains tumor, in sufficient quantity, is not always easy, and sometimes just preparing conventional microscope slides can consume most or even the entire specimen. We have developed a new, simple and inexpensive approach we term MUSE, for Microscopy with UV Surface Excitation, that can provide high-resolution images directly and quickly from fresh tissue without consuming it, and thus can preserve intact, high-quality specimens for biobanking, downstream molecular and functional analyses. MUSE, by ensuring that acquired small biopsy specimens are indeed fit for purpose, can avoid the need to have a patient return at a later date for additional biopsies. In addition, the method will allow for lesion detection over larger cross-sections of tissue, such as organ whole-mounts, not currently practical with conventional instrumentation. Finally, we expect that MUSE will yield additional biologically informative imaging by avoiding artifacts inherent in conventional tissue processing and sectioning. We focus here on facilitation of tissue-based molecular studies, viable tumor harvest for xenografts and cultured spheroids, and biobanking, and include crucial validation studies to ensure that the MUSE process does not compromise sample utility due to possible impacts from exposure to intercalating dyes and/or UV light. MUSE relies on two mechanisms: 1) surface-restricted excitation of fluorescent dyes due to micron- scale penetration of sub-300-nm ultraviolet light; and 2) the fact that many conventional dyes excited in this way emit visible light. These signals are bright enough to be detected by conventional color cameras using sub-second exposure times, allowing rapid imaging of large areas. MUSE eliminates any requirement for conventional histology processing with formalin fixation, paraffin embedding, or thin-sectioning. It requires no lasers, confocal, multiphoton or optical coherence tomography instrumentation, can eventually cost in the range of a few thousands of dollars, and therefore affordable at the point of care (point of biopsy). MUSE samples are stained within seconds using familiar histology stains, such as eosin and DAPI, and the resulting high-resolution images converted from fluorescence to H&E-like brightfield appearance for interpretation in real time (but with novel and potentially useful features) easily interpreted by pathologists. While rapid cellular-scale imaging of fresh tissue can have significant benefits in clinical arenas, it can also empower basic and translational research use for essentially instant histology-, pathology- or toxicology-relevant images directly from experimental animal models—at the bench—and may help relieve such investigators from having to rely on often overworked, sometimes unavailable, conventional histology and pathology services.

项目摘要：病理学——通常通过使用显微镜检查患者的组织——对于获得正确的癌症诊断至关重要，但它已经提交通常很小的组织样本的相关部分用于 DNA 和其他检测变得越来越重要分子和功能测试。确保提交的材料确实含有足够的肿瘤。数量并不总是那么容易，有时仅仅准备传统的显微镜载玻片就会消耗大部分我们开发了一种新的、简单且廉价的方法，我们称之为 MUSE，即 MUSE。带紫外表面激发的显微镜，可以直接快速地从新鲜的样品中提供高分辨率图像组织而不消耗它，因此可以保存完整的、高质量的样本用于下游生物样本库分子和功能分析。 MUSE 通过确保获得的小活检标本确实适合目的，可以避免需要稍后让患者返回进行额外的活检此外，该方法将允许病变。对较大横截面的组织进行检测，例如器官整体安装，目前尚不可行最后，我们预计 MUSE 将产生更多的生物信息成像。通过避免传统组织处理和切片中固有的伪影，我们在这里重点关注促进。基于组织的分子研究、异种移植物和培养球体的可行肿瘤收获以及生物库，并包括关键的验证研究，以确保 MUSE 过程不会因样本效用而妥协暴露于嵌入染料和/或紫外线可能产生的影响。 MUSE 依赖于两种机制：1) 由于微米级荧光染料的表面限制激发 300 nm 以下紫外光的尺度穿透；2) 许多传统染料在此过程中被激发这些信号足够明亮，可以被使用传统彩色相机检测到。亚秒级曝光时间，可实现大面积快速成像。 MUSE 消除了对福尔马林固定、石蜡等传统组织学处理的任何要求它不需要激光、共焦、多光子或光学相干断层扫描。仪器，最终成本可能在几千美元范围内，因此在护理点（活检点）使用熟悉的组织学染色剂在几秒钟内对 MUSE 样本进行染色，例如如曙红和 DAPI，所得高分辨率图像从荧光转换为类似 H&E 的图像明场外观可轻松进行实时判读（但具有新颖且可能有用的功能）由病理学家解释。虽然新鲜组织的快速细胞规模成像可以在临床领域带来显着的好处，但它可以还支持基础和转化研究用于基本上即时的组织学、病理学或毒理学相关图像直接来自实验动物模型（在工作台上），可能有助于缓解这些研究人员不得不依赖经常过度劳累、有时无法使用的传统组织学和病理学服务。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（1）

Multispectral analysis tools can increase utility of RGB color images in histology.

多光谱分析工具可以提高 RGB 彩色图像在组织学中的实用性。

DOI：
发表时间：
2018-04
期刊：
影响因子：
0
作者：
Fereidouni, Farzad;Griffin, Croi;Todd, Austin;Levenson, Richard
通讯作者：
Levenson, Richard

Banff Digital Pathology Working Group: Going digital in transplant pathology.

班夫数字病理学工作组：移植病理学走向数字化。

DOI：
发表时间：
2020-09
期刊：
影响因子：
0
作者：
Farris, Alton B;Moghe, Ishita;Wu, Simon;Hogan, Julien;Cornell, Lynn D;Alexander, Mariam P;Kers, Jesper;Demetris, Anthony J;Levenson, Richard M;Tomaszewski, John;Barisoni, Laura;Yagi, Yukako;Solez, Kim
通讯作者：
Solez, Kim

Beyond brightfield: a possible future of slide scanners.

超越明场：载玻片扫描仪的可能未来。

DOI：
发表时间：
2021-01
期刊：
影响因子：
2.7
作者：
Fereidouni, Farzad;Levenson, Richard
通讯作者：
Levenson, Richard

Dual-mode emission and transmission microscopy for virtual histochemistry using hematoxylin- and eosin-stained tissue sections.

使用苏木精和伊红染色的组织切片进行虚拟组织化学的双模式发射和透射显微镜。

DOI：
10.1364/boe.10.006516
发表时间：
2019-11-26
期刊：
Biomedical optics express
影响因子：
3.4
作者：
F. Fereidouni;A. Todd;Yuheng Li;Che;Keith Luong;A. Rosenberg;Yong;J. Chan;A. Borowsky;K. Matsukuma;Kuang;R. Levenson
通讯作者：
R. Levenson

New Technologies to Image Tumors.

肿瘤成像新技术。

DOI：
10.1007/978-3-030-38862-1_2
发表时间：
2020
期刊：
Cancer treatment and research
影响因子：
0
作者：
McNamara G;Lucas J;Beeler JF;Basavanhally A;Lee G;Hedvat CV;Baxi VA;Locke D;Borowsky A;Levenson R
通讯作者：
Levenson R