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，影响了美国70万人。病理 CD的特征是由于炎症，纤维化或两者的结合而阻塞肠道狭窄。 狭窄的准确表征至关重要，因为可以治疗炎症狭窄 从医学上讲，纤维化狭窄是不可逆的，必须通过外科手术去除。对于狭窄的表征是内窥镜活检，其中一小部分 标准过程 将组织取出以供 组织病理学。 与炎症狭窄相比，纤维化狭窄的特征是 增加胶原蛋白含量和分层组织结构的丧失。 由于采样数量有限 位置，对内窥镜活检对狭窄的全面评估很难实现。单物理学 超声，磁共振和X射线成像等成像方式已证明 解决狭窄的分层结构的能力。但是，CD的主要诊断因素 是狭窄中组织化学成分的变化（即胶原蛋白含量）。光学上（照片） 诱导的超声（ - 声学）成像，即光声成像（PAI），是一种多物理学，非电离 和非侵入性成像方式。 PAI，当前用于CD诊断的任何成像方式无与伦比， 可以解决体内生物组织中各个组织化学成分的微观分布 具有光敏性和超声分辨率。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组织切除的肠道狭窄 组件和2）评估 分层 狭窄的组织结构。 通过利用研究团队在PAI，内窥镜检查中的专业知识，这一拟议项目的目的 系统，动物模型和CD的临床管理是为了制定表征诊断策略 基于PAI的体内肠狭窄。该项目的具体目的包括：1）表征和优化 原型在肠道狭窄中具有大鼠模型的原位和人类的原型PAI探针的性能 标本离体和2）验证提议的内窥镜PAI诊断策略以限制肠道狭窄 与兔模型在体内。内窥镜PAI探针的形状是一个小胶囊，延伸 内窥镜的仪器通道。在胶囊内部，一个微型的一维翻译阶段支架 专注的传感器和光纤形成B扫描（二维）PAI功能，提供诊断功能 与组织学相媲美的信息。建议的内部镜面PAI程序无缝地适合临床 内窥镜检查框架，因此被高度翻译。完成后，建议的诊断 具有无限抽样位置的策略将有助于对肠道狭窄的全面评估 为了实现“体内活检”，改善了个性化治疗计划和CD患者的生活质量。