In vivo photoacoustic biopsy for intestinal strictures in Crohn's disease

体内光声活检治疗克罗恩病肠道狭窄

• 批准号: 9304857
• 负责人: Peter D.R. Higgins
• 金额: $ 19.38万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9304857
• 关键词: Acute; Affect; Animal Model; Architecture; Autoimmune Diseases; Biological; Biopsy; Chemicals; Chronic; Clinic; Clinical; Clinical Management; Colitis; Collagen; Crohn' s disease; Devices; Diagnostic; Diagnostic Factor; Diagnostic Imaging; Diagnostic Procedure; Diagnostic radiologic examination; Dimensions; Disease; Edema; Endoscopes; Endoscopic Biopsy; Endoscopy; Excision; Fiber Optics; Fibrosis; Hemoglobin; Histologic; Histology; Histopathology; Human; Image; Imaging Techniques; Imaging technology; In Situ; Individual; Inflammation; Inflammatory; Intestines; Lighting; Lipids; Location; Magnetic Resonance; Magnetic Resonance Imaging; Medical; Microscopic; Modeling; Mono-S; Normal tissue morphology; Operative Surgical Procedures; Optics; Oryctolagus cuniculus; Outcomes Research; Pathology; Patients; Performance; Physics; Procedures; Quality of life; Rattus; Research; Resolution; Sampling; Scanning; Shapes; Signal Transduction; Specimen; Surface; System; Testing; Tissues; Transducers; Translating; Translations; Trinitrobenzenesulfonic Acid; Ultrasonic Transducer; Ultrasonics; Ultrasonography; United States; Water; X-Ray Computed Tomography; absorption; acoustic imaging; base; capsule; design; disease diagnosis; human tissue; imaging capabilities; imaging modality; imaging probe; imaging system; improved; in vivo; in vivo Model; instrument; miniaturize; non-invasive imaging; personalized medicine; personalized therapeutic; photoacoustic imaging; prototype; translational diagnostics; two-dimensional

ABSTRACT Crohn's disease (CD) is an autoimmune disease affecting 700,000 people in the United States. The pathology of CD is characterized by obstructing intestinal strictures due to inflammation, fibrosis, or a combination of both . The accurate characterization of the strictures is critical, as the inflammatory strictures can be treated medically, yet the fibrotic strictures are irreversible and have to be removed surgically.for characterizing the strictures is endoscopic biopsy, in which a small piece of The standard procedure tissue is removed for histopathology. Compared to the inflammatory strictures, the fibrotic strictures are characterized by the increased collagen content and the loss of stratified tissue architecture. Due to the limited number of sampling locations, comprehensive assessment of the strictures by endoscopic biopsy is hard to achieve. Monophysics imaging modalities such as ultrasound, magnetic resonance and X-ray imaging have demonstrated the capability of resolving the stratified architecture in the strictures. However, the primary diagnostic factor of CD is the change of histochemical components in the strictures (i.e. the collagen content). Optically (photo-) induced ultrasonic (-acoustic) imaging, namely photoacoustics imaging (PAI), is a multiphysics, non-ionizing and non-invasive imaging modality. PAI, unmatched by any imaging modality currently used for CD diagnosis, can resolve the microscopic distributions of individual histochemical components in biological tissue in vivo with optical sensitivity and ultrasonic resolution. The central hypothesis of this project is that the PAI can characterize intestinal strictures without tissue removal, by 1) quantifying the relative contents of histochemical components and 2) assessing the stratified tissue architecture in the strictures. The objective of this proposed project, by leveraging the research team’s expertise in PAI, endoscopic systems, animal models and clinical management of CD, is to develop a diagnostic strategy for characterizing the intestinal strictures in vivo based on PAI. Specific aims of this project include: 1) Characterize and optimize the performance of a prototype PAI probe in imaging intestinal strictures with rat model in situ and human specimens ex vivo, and 2) validate the proposed endoscopic PAI diagnostic strategy for intestinal strictures with rabbit model in vivo. The endoscopic PAI probe is in the shape of a small capsule extending through the instrument channel of an endoscope. Inside the capsule, a miniaturized 1-dimensional translation stage holds a focused transducer and fiber optics to formulate a B-scan (2-dimensional) PAI capability, providing diagnostic information comparable to histology. The proposedendoscopic PAI procedure fits seamlessly into the clinical endoscopy framework and is thereby highly translational. Once accomplished, the proposed diagnostic strategy, with unlimited sampling locations, will facilitate comprehensive assessment of the intestinal strictures to achieve "in vivo biopsy", improving personalized therapeutic planning and the life quality for CD patients.

抽象的 克罗恩病 (CD) 是一种自身免疫性疾病，影响着美国 70 万人。病理学 CD 的特征是由于炎症、纤维化或两者的组合而导致肠道狭窄。 狭窄的准确表征至关重要，因为炎症性狭窄是可以治疗的 在医学上，但纤维化狭窄是不可逆的，必须通过手术切除。为了表征狭窄，需要进行内窥镜活检，其中一小块 标准程序 组织被移除 组织病理学。 与炎症性狭窄相比，纤维化性狭窄的特点是 胶原蛋白含量增加和分层组织结构的损失。 由于采样数量有限 位置，通过内镜活检对狭窄进行全面评估是很难实现的。单物理场 超声、磁共振和 X 射线成像等成像方式已证明 解决分层架构中的限制的能力。然而，CD 的主要诊断因素 是狭窄处组织化学成分的变化（即胶原蛋白含量）。光学（照片-） 诱导超声（声）成像，即光声成像（PAI），是一种多物理场、非电离 和非侵入性成像方式。 PAI 是目前用于 CD 诊断的任何成像方式都无法比拟的， 可以解析体内生物组织中单个组织化学成分的微观分布 具有光学灵敏度和超声波分辨率。该项目的中心假设是 PAI 可以 通过 1) 量化组织化学的相对含量来表征无需去除组织的肠道狭窄 组件和2）评估 分层 狭窄处的组织结构。 该拟议项目的目标是利用研究团队在 PAI、内窥镜检查方面的专业知识 CD 系统、动物模型和临床管理，旨在开发一种诊断策略来表征 基于PAI的体内肠道狭窄。该项目的具体目标包括：1）表征和优化 原型 PAI 探针在大鼠原位模型和人类肠道狭窄成像中的性能 离体标本，2) 验证所提出的肠道狭窄内镜 PAI 诊断策略 与兔子体内模型。内窥镜 PAI 探头呈小胶囊形状，延伸穿过胃腔 内窥镜的仪器通道。胶囊内部有一个小型化的一维平移台 聚焦传感器和光纤形成 B 扫描（二维）PAI 功能，提供诊断 与组织学相当的信息。拟议的内窥镜 PAI 手术无缝融入临床 内窥镜框架，因此具有高度的转化性。一旦完成，建议的诊断 采样位置不受限制的策略将有助于对肠道狭窄进行全面评估 实现“体内活检”，改善CD患者的个性化治疗计划和生活质量。