本文選題：血管靶向光動力療法 + 微血管�。� 參考：《中國人民解放軍醫(yī)學院》2014年博士論文

【摘要】：目的 探索采用激光散斑成像（LSI）技術對微血管管徑和流速進行測量，以建立在體、實時、無創(chuàng)的方法監(jiān)測血管靶向光動力療法（V-PDT）術中、術后的微血管生物學響應情況，為V-PDT的微血管損傷效應研究及療效評價提供實驗依據(jù)和技術方法。 方法 （1）利用顯微LSI獲取大鼠隱動脈和兔耳微血管的管徑數(shù)據(jù)并與光學相干層析成像（OCT）和病理切片進行對比；利用顯微LSI獲取小鼠皮窗（WCM）的流速數(shù)據(jù)，比較微動靜脈及不同管徑血管的流速差異；利用大視場LSI獲取鮮紅斑痣（PWS）病變的流速數(shù)據(jù)，并與正常皮膚對比。 （2）利用顯微LSI對V-PDT組和對照組（單純光敏劑注射、單純激光照射）WCM的微血管管徑和流速進行在體實時檢測，分析V-PDT對分支狀血管的損傷效應；利用顯微LSI對WCM中49根微血管進行檢測，計算灌注率并分析不同灌注率的微血管封閉時所需的V-PDT劑量。 （3）利用大視場LSI對17名鮮紅斑痣（PWS）患者共26個治療區(qū)進行V-PDT術中的流速監(jiān)測，術后3-6個月由臨床醫(yī)師判定療效，研究和分析術中治療區(qū)的流速變化與療效的關系。 （4）利用大視場LSI對V-PDT術前和隨訪時17名PWS患者共40個治療區(qū)進行流速檢測，分析隨訪時治療區(qū)的流速改變與療效的關系。 結果 （1）顯微LSI所測大鼠隱動脈、兔耳微血管管徑與OCT、病理切片一致；顯微LSI檢測WCM的微動脈流速大于微靜脈，流速隨管徑減小而降低；大視場LSI檢測PWS病變的流速大于正常皮膚。 （2）V-PDT處理過程中，WCM的微血管管徑減小、流速降低，部分微血管完全封閉；灌注率與微血管封閉所需的V-PDT劑量正相關（r=0.89, P0.01），灌注率越小，微血管封閉所需的V-PDT劑量越小。 （3）V-PDT術后即刻，26個PWS治療區(qū)的流速均值低于術前（1161±381vs1329±475PU，P0.01），術中治療區(qū)的流速變化與療效正相關（r=0.77,P0.01）。 （4）V-PDT術后隨訪時，40個PWS治療區(qū)的流速均值低于術前（1282±460vs1421±463PU，P0.01），隨訪時治療區(qū)的流速改變與療效正相關（r=0.73,P0.01）。 結論 （1）顯微LSI可對微血管進行清晰成像并獲取管徑、流速數(shù)據(jù)；顯微LSI可區(qū)分微動靜脈流速差異；顯微LSI管徑測量準確、可靠；大視場LSI可在體檢測PWS病變的流速，并可區(qū)分PWS與正常皮膚的流速差異。 （2）顯微LSI可在體、實時監(jiān)測V-PDT過程中分支狀微血管管徑、流速的動態(tài)變化；灌注率可反映V-PDT對微血管作用的敏感性，，灌注率越小，V-PDT越容易致其封閉。 （3）大視場LSI可對V-PDT術中PWS病變進行在體、實時、無創(chuàng)成像，并得到空間、時間上的流速信息；V-PDT術中PWS治療區(qū)的流速變化可反映V-PDT的作用效果。 （4）V-PDT術后隨訪時，PWS治療區(qū)的流速下降率可作為療效評價的一種指標。
[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 鹵381vs1329 鹵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 鹵460vs1421 鹵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.
【學位授予單位】：中國人民解放軍醫(yī)學院
【學位級別】：博士
【學位授予年份】：2014
【分類號】：R454.2

【參考文獻】

相關期刊論文 前10條

1 顧瑛,李峻亨,郭中和,崔效杰,梁潔;光動力學療法治療鮮紅斑痣[J];北京醫(yī)學;1991年05期

2 王雷;顧瑛;李曉松;劉凡光;于常青;;鮮紅斑痣光動力治療的熒光光譜監(jiān)測[J];光譜學與光譜分析;2007年09期

3 趙士勇;俞信;邱海霞;黃乃艷;王天時;薛平;顧瑛;;光學相干層析術用于鮮紅斑痣診斷[J];光譜學與光譜分析;2010年12期

4 王穎;廖小華;顧瑛;陳榮;曾晶;;漫反射光譜用于光動力治療中鮮紅斑痣皮膚氧含量監(jiān)測的初步研究[J];光譜學與光譜分析;2010年12期

5 邱建軍;張紅艷;駱衛(wèi)華;李鵬程;駱清銘;;像面散斑平均尺寸對激光散斑成像的影響[J];光學學報;2009年07期

6 程海英,朱

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