活体小动物脓毒症肠道模型的光声内窥成像研究

In Vivo Photoacoustic Endoscopy Imaging of Gastrointestinal Model of Septic Small-Animal

微循环功能是反映危重病人器官生理状态的关键指标,为确定后续治疗手段提供了重要依据。传统上采用显微镜等手段观察体表微循环状态,但仅能获得组织毛细血管的空间形态,获取的功能性信息有限,难以满足临床需求。针对肠道内微循环监测需求构建了小型化光纤光声内窥镜,将成像探头伸入活体小动物直肠内以旋转扫描的方式进行内窥成像。在扫描过程中通过逐点探测由激光脉冲在生物体内激发出的超声波,能够获得消化道内壁血管空间分布;基于动静脉血在光学吸收谱上的差异,采用双波长激发获得了血氧饱和度的空间分布。基于数小时的连续监测,发现小动物患脓毒症后直肠内壁血管结构与血氧饱和度均发生明显变化。实验结果表明,该技术能够以无创方式表征典型微循环疾病模型的功能性变化,为微循环的无创监测提供了一种新的技术途径。

Objective Microcirculatory dysfunction may cause circulatory failure,insufficient oxygen delivery,and fatal risks.Microscopes are used to observe microcirculation,but they can only image superficial tissues.In addition,they can hardly provide functional information.In this study,we report a photoacoustic endoscope for in vivo imaging of the gastrointestinal microcirculation.The imaging probe is inserted into the rectum of a small animal for rotational-scanning endoscopic imaging.The vascular structures in the gastrointestinal wall can be visualized by detecting the ultrasound excited by the pulsed laser.Moreover,the blood oxygen saturation can be measured and imaged with a dual-wavelength excitation based on the difference in the optical absorption spectrum between oxyand deoxygenated hemoglobin.We believe that this technology is capable of detecting the functional changes associated with microcirculation diseases with minimal invasion.Methods The imaging system consists of an endoscopic imaging probe,dual-wavelength pulsed laser source,rotary scanning device,and data acquisition and control module.First,we design an all-fiber endoscope probe containing two functional optical fibers as follows:one responsible for guiding and focusing the pulsed light and the other equipped with a laser ultrasonic sensor to detect the photoacoustic signal.Second,we design a rotational scanning device that rotates synchronously with the probe to achieve fast and unidirectional rotary scanning.This is achieved by miniaturizing the 980-nm pump laser,the optical amplifier,and the photodetector.Finally,we perform high-resolution in vivo endoscopic imaging of the rat rectum.Results and Discussions The endoscope probe has a diameter of 2.75 mm,a resolution of 12.5μm,signal jitter root mean square of 2.5%,and a B-scan frequency of 1 Hz.The instrument is stable and provides spatial resolution in high-speed scanning and is suitable for small animal digestive tract endoscopic imaging.The functional imaging results of the rectum of healthy rats show that we achieve 360°scanning,obtain the three-dimensional imaging results of hemoglobin concentration distribution,and show the vascular structure of the inner wall of the rat rectum.Along with the spatial distribution of blood oxygen saturation,the images show the distributions of the artery and vein in the inner wall(Fig.3).The imaging results of septic rats show the changes in microcirculation.According to the imaging result,the number of blood vessels in the intestine of rats gradually decreases,and the blood oxygen saturation also declines in 5 h(Fig.4).The above results reflect the phenomenon of insufficient tissue perfusion caused by sepsis.Conclusions In summary,we develop a photoacoustic endoscope for in vivo rectal imaging.By using fiber optic ultrasound sensors,the endoscope can image the vascular structure and visualize the changes in oxygen saturation.By using this endoscope,we can visualize the gastrointestinal microcirculatory disorder caused by lesions.The structure,number,and blood oxygen saturation level of blood vessels are significantly changed.The experimental results show that this technology can provide functional imaging results with high spatial resolution and high contrast in the endoscopic imaging of narrow cavity structures,thus providing a feasible imaging method for the characterization of microcirculation status and the diagnosis and treatment of acute and severe diseases.