Correlative nonvital standard histopathology and vital multiphoton prehistopathology

相关非生命标准组织病理学和生命多光子组织前病理学

• 批准号: 10080978
• 负责人: Haohua Tu
• 金额: $ 15.59万
• 依托单位: LIVEBX, LLC
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-10 至 2022-08-09
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10080978
• 关键词: Address; Affect; Aftercare; Area; Binding; Biochemical; Biochemical Genetics; Biopsy; Chemicals; Clinical; Complement; Development; Diagnosis; Diagnostic; Diagnostic Procedure; Evidence Based Medicine; Formalin; Fresh Tissue; Functional Imaging; Future; Goals; Gold; Hematoxylin and Eosin Staining Method; Histology; Histopathology; Human; Image; Imaging technology; Immunohistochemistry; Label; Laboratories; Lasers; Meat Products; Medicine; Metabolic; Microscope; Microscopy; Microtome - medical device; Morphology; Optics; Outcome; Paraffin Embedding; Pathologist; Pathology; Patient Care; Phase; Phase Transition; Photons; Procedures; Process; Protocols documentation; Reproducibility; Rodent; Sample Size; Sampling; Slide; Small Business Technology Transfer Research; Specificity; Specimen; Stains; Structure; Surface Tension; Tattooing; Technology; Testing; Time; Tissue Embedding; Tissue Fixation; Tissue Preservation; Tissue Sample; Tissue imaging; Tissues; Training; Transportation; Validation; Work; base; clinical translation; cost; digital; empowered; evidence base; extracellular; genetic analysis; histological specimens; histological stains; human tissue; image registration; improved; multiphoton imaging; multiphoton microscopy; multiphoton process; novel; operation; optical imaging; point of care; sample fixation; standard of care; tool; tumor microenvironment; user-friendly; virtual

SUMMARY A common practice in medicine for handling freshly biopsied human tissue is to rapidly put it into a formalin solution. This “fixation” preserves the tissue from decay, allowing transportation to a (remote) pathology laboratory for standard histopathology or other biochemical/genetical analyses. However, formalin instantly “kills” the tissue, so that the biochemical and metabolic functions associated with its vital state are permanently lost. These functions likely contain diagnostic information not available from standard histopathology, e.g. the pristine picture of an active tumor microenvironment before the structural and chemical perturbations known in routine histological sample treatments. Thus, it will be highly beneficial to image “tissue vitality” noninvasively and rapidly (within minutes) before the fixation, by a novel optical imaging technology. Although numerous technologies have been developed for this purpose, their diagnostic capabilities independent from standard histopathology have not been unambiguously demonstrated, due to the lack of a correlative technology to co- register/co-localize the virtual optical sections of vital tissue (optical imaging) and the actual formalin-fixed paraffin-embedded sections of treated/nonvital tissue (standard histopathology). As a result, it is often difficult to justify the additional cost of novel optical imaging technologies in clinical standard-of-care processes. In this project, we aim to develop correlative microscopy between standard histopathology (operated in a linear/single-photon optical regime) and a novel optical imaging technology based on multiphoton processes, i.e. multiphoton pre-histopathology. The latter has been demonstrated in our prior work to visualize multiple unlabeled endogenous biomolecules and segment a rich set of cellular and extracellular components. The proposed correlative microscopy will retrace optical sections of fresh ex vivo tissue that were imaged using the label-free multiphoton pre-histopathology to the corresponding formalin-fixed paraffin-embedded sections with diverse histological stains. For proof-of-concept demonstration (Phase I), we will use discarded fresh rodent tissue specimens to mimic freshly biopsied human tissue specimens, and co-register a wide area (1x1 mm2) of image in the multiphoton pre-histopathology with its counterpart in standard hematoxylin and eosin (H&E) histology. In a future stage (Phase II), we will expand the co-registration area from 1x1 mm2 to 10x10 mm2 to accommodate larger sample sizes, extend the stains from H&E to diverse immunohistological stains, and switch the samples from the meat products to fresh human tissue biopsies in a clinical setting. The successful outcome of this project will equip pathologists with a real-time, label-free, slide-free, digital, and point-of-care or point-of-procedure tool to image “tissue vitality”, without affecting the existing histology workflow but with newly added critical information to complement the gold standard based on nonvital tissue.

概括 处理新鲜活检的人体组织的医学中一种常见的做法是将其迅速放入福尔马林 解决方案。这种“固定”可保留组织免于衰减，使运输到（远程）病理 标准组织病理学或其他生化/遗传分析的实验室。但是，福尔马林立即 “杀死”组织，以使与其重要状态相关的生化和代谢功能是永久的 丢失的。这些功能可能包含标准组织病理学中无法获得的诊断信息，例如 原始肿瘤微环境的原始图片在结构和化学扰动之前已知 常规的组织学样本处理。这是无创图像“组织活力”非常有益的 并在固定前（几分钟之内）通过一种新型的光学成像技术。虽然很多 为此目的开发了技术，其诊断功能与标准无关 由于缺乏相关技术，组织病理学并未得到明确的证明 注册/共定位重要组织的虚拟光学部分（光学成像）和实际的福尔马林固定 治疗/非重要组织的石蜡包裹的部分（标准组织病理学）。结果，通常很难 为了证明在临床标准过程中，新型光学成像技术的额外成本是合理的。 在这个项目中，我们旨在发展标准组织病理学之间的相关显微镜（在A中进行操作 线性/单光子光学制度）和基于多光过程的新型光学成像技术， 即多光子前病理学。后者已在我们​​先前的工作中证明了多个 未标记的内源性生物分子和一组丰富的细胞和细胞外成分。这 拟议的相关显微镜将在使用该新鲜的外体组织的光学切片中进行反剖面 与相应的福尔马林固定石蜡包裹的切片的无标签多光子前病理学 潜水员组织学染色。为了证明概念证明（I阶段），我们将使用丢弃的新鲜啮齿动物 组织标本以模仿新鲜活检的人体组织标本，并共同注册广泛的面积（1x1 mm2） 多光子前病理学中的图像及其在标准苏木精和曙红（H＆E）中的图像（H＆E） 组织学。在未来的阶段（第二阶段），我们将将共同注册区域从1x1 mm2扩展到10x10 mm2 容纳更大的样本量，将皮肤从H＆E扩展到潜水员免疫组织学皮肤，然后 在临床环境中，将样品从肉类产品转换为新鲜的人体组织活检。成功 该项目的结果将为病理学家提供实时，无标签，无幻灯片，数字和即时的护理 或加工点工具，用于图像“组织活力”，而不会影响现有的组织学工作流程，而是 新添加的关键信息以基于非重要组织完成黄金标准。

项目成果

Intratumor graph neural network recovers hidden prognostic value of multi-biomarker spatial heterogeneity.

• DOI: 10.1038/s41467-022-31771-w
• 发表时间: 2022-07-22
• 期刊: Nature communications
• 影响因子: 16.6

Computational Photon Counting Using Multithreshold Peak Detection for Fast Fluorescence Lifetime Imaging Microscopy.

• DOI: 10.1021/acsphotonics.2c00505
• 发表时间: 2022-08-17
• 期刊: ACS PHOTONICS
• 影响因子: 7
• 作者: Sorrells, Janet E.;Iyer, Rishyashring R.;Yang, Lingxiao;Martin, Elisabeth M.;Wang, Geng;Tu, Haohua;Marjanovic, Marina;Boppart, Stephen A.
• 通讯作者: Boppart, Stephen A.

Large-scale tumor-associated collagen signatures identify high-risk breast cancer patients.

• DOI: 10.7150/thno.55921
• 发表时间: 2021
• 期刊: Theranostics
• 影响因子: 12.4
• 作者: Xi G;Guo W;Kang D;Ma J;Fu F;Qiu L;Zheng L;He J;Fang N;Chen J;Li J;Zhuo S;Liao X;Tu H;Li L;Zhang Q;Wang C;Boppart SA;Chen J
• 通讯作者: Chen J