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.

摘要 克罗恩病(CD)是一种自身免疫性疾病，在美国有70万人患病。《病理学》 CD的特点是因炎症、纤维化或两者兼而有之而导致的肠梗阻。 由于炎性狭窄是可以治疗的，因此对狭窄的准确描述是至关重要的。 在医学上，纤维性狭窄是不可逆转的，必须手术切除。狭窄的特征是内窥镜活检，其中一小块 标准程序 切除组织是为了 组织病理学。 与炎症性狭窄相比，纤维性狭窄的特点是 胶原含量增加，失去层状组织结构。 由于抽样数量有限 对于狭窄部位，很难通过内窥镜活检对狭窄进行全面评估。单物理学 超声、磁共振和X射线成像等成像手段已经证明 解决狭隘中的层次化架构的能力。然而，CD的主要诊断因素 是狭窄处组织化学成分的变化(即胶原含量)。光学(照片-) 诱导超声(声)成像，又称光声成像，是一种多物理、非电离的成像技术 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所无法比拟的， 可以分辨体内生物组织中个别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。这个项目的中心假设是PAI可以 在不切除组织的情况下，通过1)定量组织化学的相对含量来表征肠狭窄 组件和2)评估 分层 狭窄处的组织结构。 这个拟议项目的目标是，通过利用研究团队在PAI、内窥镜方面的专业知识 CD的系统、动物模型和临床处理，是为了制定一种诊断策略来表征 以PAI为基础的在体肠管狭窄模型。该项目的具体目标包括：1)特征化和优化 原型式PAI探头在大鼠在体肠狭窄模型和人肠狭窄成像中的应用 体外标本，以及2)验证所提出的内窥镜PAI对肠狭窄的诊断策略 以兔为模型进行体内实验。内窥镜下的PAI探头呈小胶囊状，穿过 内窥镜的仪器通道。在太空舱内，一个微型的一维平移工作台 聚焦换能器和光纤形成B超(2维)PAI能力，提供诊断 可与组织学媲美的信息。提出的内窥镜下血管内注射技术与临床完全吻合。 内窥镜检查框架，因此具有很高的转换性。一旦完成，建议的诊断 战略，无限制的抽样地点，将有助于全面评估肠道狭窄 实现活体活检，提高CD患者的个性化治疗方案和生活质量。