• 摘要: 内窥光学相干层析成像 (E-OCT)结合血管造影算法,可实现管腔组织高分辨率结构与血流动力学同步成像。针对近端控制内窥OCT受困于系统稳定性与非均匀旋转畸变 (NURD)影响而难以实现OCTA成像的问题,本课题组在前期工作中通过优化扭矩传输系统的机械稳定性并采用有效的NURD矫正算法,首次突破在近端控制内窥OCT系统中进行OCTA成像瓶颈。在此技术基础上本文进一步开展应用研究,将其成功拓展至多种细小管腔与血管结构的在体成像,包括大鼠直肠、小鼠膀胱、新西兰兔尿道及血管等部位,实现了从消化系统、泌尿系统及血管系统的多器官OCT/OCTA成像。实验结果表明,该方案能够稳定获取清晰的多层级组织结构信息,并准确呈现粘膜层及粘膜下层微血管网络分布。在尿道狭窄和膀胱癌模型中,成像结果进一步揭示了病变相关的组织结构异常及微血管灌注特征变化。综上,本文完成了近端控制内窥OCT/OCTA技术在多器官、多物种条件下的在体成像,为相关疾病的组织结构与微循环血流影像学研究提供了实验依据,并对该类技术由实验室研究向临床应用转化提供一定的参考价值。

       

      Abstract:
      Objective Narrow-lumen organs, including the urethra, bladder, esophagus, gastrointestinal tract, and blood vessels, are highly susceptible to pathological remodeling processes associated with inflammation, fibrosis, neovascularization, and microcirculatory dysfunction. Early-stage diseases occurring in these organs, such as urethral stricture, bladder cancer, esophageal lesions, and vascular abnormalities, are often accompanied by subtle structural alterations and local hemodynamic changes before obvious morphological narrowing becomes clinically detectable. Therefore, high-resolution visualization of tissue microstructure and microvascular perfusion is of great importance for early diagnosis, disease monitoring, and treatment evaluation. Conventional imaging modalities, including white-light endoscopy, ultrasound endoscopy, retrograde urethrography, and fluorescence imaging, still face limitations in simultaneously assessing tissue morphology and microcirculation. Endoscopic optical coherence tomography (OCT) provides micron-scale cross-sectional imaging of biological tissues, while optical coherence tomography angiography (OCTA) further enables label-free visualization of blood flow and microvascular networks. Compared with distal motor-driven probes, proximally controlled endoscopic OCT probes possess advantages in miniaturization, structural simplicity, and mechanical flexibility, making them more suitable for narrow and deformable luminal organs. However, proximally controlled endoscopic imaging systems are highly susceptible to non-uniform rotational distortion (NURD), rotational instability, and motion artifacts, which significantly degrade OCTA image quality and vascular visualization performance. In this study, a proximally controlled endoscopic OCT/OCTA system was developed and optimized for stable multi-organ in vivo imaging and pathological assessment in complex luminal environments.
      Methods  A swept-source OCT/OCTA imaging system centered at 1310 nm was employed in this study. The system achieved an axial resolution of 7.46 μm and a lateral resolution of approximately 15 μm. A side-viewing proximally controlled endoscopic probe was designed using a single-mode optical fiber, a GRIN lens, and a micro-reflector to achieve circumferential luminal imaging. To improve OCTA imaging stability under rotational scanning conditions, a complementary NURD correction strategy combined with a helical B-scan acquisition scheme was implemented to suppress rotational artifacts and improve inter-frame registration accuracy. Optical simulations were further performed using ZEMAX software to optimize probe focusing performance, working distance, and assembly tolerance.
      To validate imaging capability, multilayer adhesive tape samples were first imaged to evaluate structural resolution and imaging stability. Subsequently, in vivo OCT/OCTA imaging experiments were conducted across multiple organs and animal models, including rat rectum and esophagus imaging, mouse bladder imaging, and rabbit urethra and abdominal aorta imaging, covering digestive, urinary, and vascular systems. Furthermore, pathological imaging studies were performed using a rabbit urethral stricture model induced by electrocautery thermal injury and a C57 mouse bladder cancer model. Structural OCT images and vascular OCTA datasets were acquired simultaneously to evaluate disease-associated microstructural remodeling and microcirculatory alterations.
      Results and Discussions  The optimized proximally controlled endoscopic OCT/OCTA system demonstrated stable imaging performance in multiple narrow-lumen organs with different anatomical structures and motion characteristics. Imaging results of multilayer adhesive tape samples clearly resolved layered microstructures, validating the optical focusing capability and structural imaging performance of the designed probe.
      In vivo imaging experiments further demonstrated that the system could reliably visualize multilayer tissue architectures, including mucosal, submucosal, and muscular layers, in the rat rectum and esophagus. OCTA imaging successfully revealed superficial microvascular networks distributed within the mucosal and submucosal regions. In mouse bladder imaging, clear structural delineation of bladder wall layers and vascular distribution was achieved despite bladder deformation and motion. Imaging of rabbit abdominal aorta further demonstrated the capability of the system for vascular lumen imaging under pulsatile conditions.
      For pathological imaging applications, rabbit urethral stricture tissues exhibited obvious structural remodeling characterized by urethral wall thickening, disordered layered morphology, and localized arc-shaped hyperreflective bands associated with fibrosis formation. Correspondingly, OCTA imaging revealed reduced vascular density, interrupted vascular continuity, and localized hypoperfusion within stenotic regions, indicating progressive microcirculatory impairment during fibrosis progression. In the C57 mouse bladder cancer model, tumor-bearing tissues displayed irregular surface morphology, heterogeneous scattering features, decreased vascular density, and disorganized vascular architecture, reflecting tumor-associated angiogenic remodeling and microvascular disruption.
      Compared with conventional endoscopic imaging modalities, the developed endoscopic OCT/OCTA system provides simultaneous visualization of tissue microstructure and microvascular perfusion with micron-scale spatial resolution and without the need for exogenous contrast agents. The complementary NURD correction strategy significantly improved OCTA image stability and vascular continuity in rotational scanning environments, enhancing the applicability of proximally controlled endoscopic OCTA in deformable and dynamically moving luminal organs. These results demonstrate the capability of the system for reliable detection of disease-associated structural abnormalities and hemodynamic alterations in complex narrow-lumen environments.
      Conclusions  In summary, this study developed and optimized a proximally controlled endoscopic OCT/OCTA imaging system for multi-organ in vivo imaging and pathological assessment in narrow-lumen organs. The system demonstrated robust adaptability to complex anatomical and dynamic imaging environments and enabled simultaneous visualization of tissue microstructure and microvascular perfusion across digestive, urinary, and vascular systems. Pathological imaging experiments further verified the capability of the system for detecting fibrosis-associated hypoperfusion and tumor-related vascular remodeling. These findings indicate that proximally controlled endoscopic OCT/OCTA possesses significant potential for early, minimally invasive diagnosis, dynamic disease monitoring, and intraoperative guidance in luminal organ diseases.