微血管激光散斑成像及在血管靶向光动力疗法中的应用

发布时间：2018-04-26 17:55

本文选题：血管靶向光动力疗法 + 微血管　；参考：《中国人民解放军医学院》2014年博士论文

【摘要】：目的探索采用激光散斑成像（LSI）技术对微血管管径和流速进行测量，以建立在体、实时、无创的方法监测血管靶向光动力疗法（V-PDT）术中、术后的微血管生物学响应情况，为V-PDT的微血管损伤效应研究及疗效评价提供实验依据和技术方法。方法（1）利用显微LSI获取大鼠隐动脉和兔耳微血管的管径数据并与光学相干层析成像（OCT）和病理切片进行对比；利用显微LSI获取小鼠皮窗（WCM）的流速数据，比较微动静脉及不同管径血管的流速差异；利用大视场LSI获取鲜红斑痣（PWS）病变的流速数据，并与正常皮肤对比。（2）利用显微LSI对V-PDT组和对照组（单纯光敏剂注射、单纯激光照射）WCM的微血管管径和流速进行在体实时检测，分析V-PDT对分支状血管的损伤效应；利用显微LSI对WCM中49根微血管进行检测，计算灌注率并分析不同灌注率的微血管封闭时所需的V-PDT剂量。（3）利用大视场LSI对17名鲜红斑痣（PWS）患者共26个治疗区进行V-PDT术中的流速监测，术后3-6个月由临床医师判定疗效，研究和分析术中治疗区的流速变化与疗效的关系。（4）利用大视场LSI对V-PDT术前和随访时17名PWS患者共40个治疗区进行流速检测，分析随访时治疗区的流速改变与疗效的关系。结果（1）显微LSI所测大鼠隐动脉、兔耳微血管管径与OCT、病理切片一致；显微LSI检测WCM的微动脉流速大于微静脉，流速随管径减小而降低；大视场LSI检测PWS病变的流速大于正常皮肤。（2）V-PDT处理过程中，WCM的微血管管径减小、流速降低，部分微血管完全封闭；灌注率与微血管封闭所需的V-PDT剂量正相关（r=0.89, P0.01），灌注率越小，微血管封闭所需的V-PDT剂量越小。（3）V-PDT术后即刻，26个PWS治疗区的流速均值低于术前（1161±381vs1329±475PU，P0.01），术中治疗区的流速变化与疗效正相关（r=0.77,P0.01）。（4）V-PDT术后随访时，40个PWS治疗区的流速均值低于术前（1282±460vs1421±463PU，P0.01），随访时治疗区的流速改变与疗效正相关（r=0.73,P0.01）。结论（1）显微LSI可对微血管进行清晰成像并获取管径、流速数据；显微LSI可区分微动静脉流速差异；显微LSI管径测量准确、可靠；大视场LSI可在体检测PWS病变的流速，并可区分PWS与正常皮肤的流速差异。（2）显微LSI可在体、实时监测V-PDT过程中分支状微血管管径、流速的动态变化；灌注率可反映V-PDT对微血管作用的敏感性，，灌注率越小，V-PDT越容易致其封闭。（3）大视场LSI可对V-PDT术中PWS病变进行在体、实时、无创成像，并得到空间、时间上的流速信息；V-PDT术中PWS治疗区的流速变化可反映V-PDT的作用效果。（4）V-PDT术后随访时，PWS治疗区的流速下降率可作为疗效评价的一种指标。
[Abstract]:Purpose To investigate the measurement of microvascular diameter and flow velocity by laser speckle imaging (LSI) technique in order to establish a in vivo, real-time and noninvasive method to monitor the microvascular biological response during the operation of targeted photodynamic therapy (PDT). To provide experimental basis and technical method for the study and evaluation of microvascular injury in V-PDT. Method 1) the diameter data of rat saphenous artery and rabbit ear microvessel were obtained by microscopic LSI and compared with optical coherence tomography (Oct) and pathological section. To compare the velocity difference between microarteriovenous vessel and vessel with different diameter, and to obtain the velocity data of the lesions of nevus chrysalis by large field of view (LSI), and to compare them with the normal skin. (2) the microvascular diameter and flow velocity of V-PDT group and control group (single Guang Min injection and laser irradiation) were measured in vivo by microscopic LSI, and the injury effect of V-PDT on branched vessels was analyzed. 49 microvessels in WCM were detected by microscopic LSI, the perfusion rate was calculated and the V-PDT dose was analyzed when the microvessels with different perfusion rates were closed. (3) using large field of view (LSI), 26 treatment areas of 17 patients with nevus chrysalis were used to monitor the flow velocity during V-PDT operation. The effect was determined by clinicians 3-6 months after operation. The relationship between the changes of flow velocity in the treatment area and the curative effect was studied and analyzed. (4) using large field of view (LSI) to detect the flow velocity of 17 patients with PWS before and after V-PDT, and to analyze the relationship between the change of flow velocity and the curative effect. Result 1) the microvascular diameter of rabbit ear was the same as that of Oct and pathological section in saphenous artery measured by microscopic LSI, the velocity of microartery in detecting WCM by microscopic LSI was larger than that in venule, and the velocity of microartery decreased with the decrease of vessel diameter, and the velocity of PWS in large field of view LSI was higher than that in normal skin. During VPDT treatment, the microvascular diameter decreased, the flow velocity decreased and some of the microvessels were completely closed, and the perfusion rate was positively correlated with the V-PDT dose of 0.89, P0.01, the smaller the perfusion rate, the smaller the V-PDT dose required for microvascular closure. Immediately after operation, the mean flow velocity in 26 PWS treatment areas was lower than that in pre-operation (1161 卤381vs1329 卤475PUP 0.01g). There was a positive correlation between the change of flow velocity and the curative effect. The mean flow velocity in 40 PWS treatment areas was lower than that in pre-operation (1282 卤460vs1421 卤463 PUP 0.01g), and there was a positive correlation between the change of flow velocity and the curative effect. Conclusion Microscopic LSI can clearly image the microvessel and obtain the diameter and velocity data; microscopic LSI can distinguish the difference of microarteriovenous velocity; microscopic LSI diameter measurement is accurate and reliable; large field of view LSI can detect the flow velocity of PWS lesion in vivo. The velocity difference between PWS and normal skin can be distinguished. (2) microscopic LSI can be used in vivo to monitor the dynamic changes of branched microvascular diameter and flow velocity in the process of V-PDT, and the perfusion rate can reflect the sensitivity of V-PDT to microvasculature, and the smaller the perfusion rate is, the easier it is to block it. 3) in vivo, real-time and noninvasive imaging of PWS lesions during V-PDT operation with large field of view LSI, the flow velocity information in space and time can be obtained. The change of flow velocity in PWS treatment area during V-PDT operation can reflect the effect of V-PDT. The decrease rate of flow velocity in PWS treatment area during the follow-up of V-PDT can be used as an index to evaluate the curative effect.
【学位授予单位】：中国人民解放军医学院
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R454.2

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