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

摘要 克罗恩病（CD）是一种自身免疫性疾病，在美国影响70万人。病理 CD的特征在于阻塞由于炎症、纤维化或两者的组合引起的肠狭窄。 狭窄的准确表征是至关重要的，因为炎性狭窄可以治疗 然而，在医学上，纤维化狭窄是不可逆的，必须通过外科手术切除。 标准程序 切除组织， 组织病理学 与炎性狭窄相比，纤维化狭窄的特征在于： 胶原蛋白含量增加和分层组织结构丧失。 由于抽样数量有限 由于狭窄的位置不同，很难通过内窥镜活检对狭窄进行全面评估。单物理学 诸如超声、磁共振和X射线成像之类的成像方式已经证明， 解决结构中分层结构的能力。然而，CD的主要诊断因素 是狭窄中组织化学成分的变化（即胶原含量）。光学（photo） 诱导超声（声）成像，即光声成像（派），是一种多物理场、非电离 和非侵入性成像模式。派是目前用于CD诊断的任何成像方式都无法比拟的， 能够分辨出生物体内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派可以 通过以下方式表征不去除组织的肠狭窄：1）定量组织化学的相对含量， （2）评估 分层 狭窄处的组织结构 该项目的目的是利用研究团队在派、内镜下 系统，动物模型和CD的临床管理，是开发一种诊断策略， 在体肠狭窄的研究。本项目的具体目标包括：1）表征和优化 原型派探针在大鼠原位模型和人肠狭窄成像中性能 离体标本，和2）验证提出的肠狭窄内镜派诊断策略 家兔体内模型。内窥镜派探针呈小胶囊的形状，其延伸穿过微囊。 内窥镜器械通道。在太空舱内，一个小型化的一维平移台 聚焦换能器和光纤，以制定B扫描（2维）派能力，提供诊断 与组织学相当的信息。建议的内窥镜派程序无缝地适合临床 内窥镜检查框架，并且因此是高度平移的。一旦完成，建议的诊断 无限制采样位置的策略将有助于对肠狭窄进行全面评估 实现“体内活检”，改善CD患者的个性化治疗计划和生活质量。

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.