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光相干斷層成像技術(shù)測(cè)定纖維蛋白原對(duì)血液凝固過程光學(xué)性質(zhì)的影響

發(fā)布時(shí)間:2018-08-20 12:54
【摘要】:血液凝固是一系列酶促反應(yīng)的綜合過程,對(duì)人體進(jìn)行正常生理活動(dòng)具有重要的作用。正常情況下血液凝固能夠防止機(jī)體意外出血,然而,不正常凝血可能導(dǎo)致血栓或者凝血功能障礙。纖維蛋白原是參與血液凝固過程的重要凝血因子,對(duì)于實(shí)現(xiàn)血液凝固過程的生理作用具有重要意義。因此,將血液凝固與纖維蛋白原聯(lián)系,實(shí)現(xiàn)對(duì)不同纖維蛋白原濃度下的血液凝固檢測(cè)具有重要的臨床意義。光相干斷層成像技術(shù)(optical coherence tomography,OCT)基于低相干光邁克爾遜干涉原理,利用背向散射光攜帶的深度信息實(shí)現(xiàn)對(duì)生物組織內(nèi)部層次、結(jié)構(gòu)及尺寸的解析,具有無創(chuàng)、安全和實(shí)時(shí)監(jiān)測(cè)的優(yōu)點(diǎn)。而且,關(guān)于OCT檢測(cè)血液凝固過程的研究已經(jīng)取得重大進(jìn)展。因而,利用OCT技術(shù)檢測(cè)不同纖維蛋白原濃度下血液凝固過程成為可能。本研究采用OCT光學(xué)參數(shù)—背向散射光強(qiáng)度1/e處的有效透射深度(1/e light penetration depth,d1/e)從光透射深度的變化來反映靜止及流動(dòng)狀態(tài)下的血液凝固過程中的光強(qiáng)度變化,進(jìn)而研究在不同纖維蛋白原水平下血液凝固過程的變化。實(shí)驗(yàn)分別在靜態(tài)及動(dòng)態(tài)條件下,分別研究纖維蛋白原濃度對(duì)血液凝固的影響,期間又分別研究了可能影響血液凝固的因素諸如促凝劑(Ca Cl2)濃度、血細(xì)胞比容(HCT)、以及血流速度。實(shí)驗(yàn)結(jié)果表明d1e可以有效的區(qū)分不同纖維蛋白原濃度下的血液凝固過程。血液凝固過程中d1e變化曲線呈現(xiàn)先增加后基本保持不變的特點(diǎn)。靜態(tài)凝固實(shí)驗(yàn)時(shí),在HCT為35%時(shí),外源纖維蛋白原濃度水平在0、2、4、6、8、10 g/L時(shí)對(duì)應(yīng)的血液凝固時(shí)間分別為588±13.86s、448±13.61s、364±2.65s、314.3±8.14s、266±10.44s、237.3±9.71s。在HCT為45%時(shí),不同外源纖維蛋白原濃度水平(0、2、4、6、8、10 g/L)對(duì)應(yīng)的血液凝固時(shí)間分別為665.3±12.66s、564±7.21s、513.3±7.23s、453±8.89s、395±5s、325.7±4.51s。當(dāng)HCT為55%時(shí),外加纖維蛋白原濃度為0、2、4、6、8 g/L時(shí)對(duì)應(yīng)的血液凝固時(shí)間分別為901±6.56s、812.3±26.31s、592±14.42s、536±32.14s、506.7±4.73s。在實(shí)驗(yàn)中采用的任一HCT下,纖維蛋白原濃度始終與血液凝固時(shí)間呈負(fù)相關(guān),即當(dāng)纖維蛋白原濃度增大時(shí),血液凝固時(shí)間隨之減小。利用凍融法處理血漿去除原有纖維蛋白原后,也能得到相同的結(jié)論;促凝劑的濃度對(duì)血液凝固固過程也有一定的影響,促凝劑Ca2+濃度為0.25mol/L、0.15mol/L、0.05mol/L時(shí)對(duì)應(yīng)的凝固時(shí)間分別為419.7±14.67s、559.3±15.14s、714.7±6.03s,在實(shí)驗(yàn)范圍內(nèi)血液凝固時(shí)間隨著促凝劑濃度的增大而降低;HCT為35%、45%及55%時(shí)對(duì)應(yīng)的血液凝固時(shí)間分別為743.7±11s、811.7±11.6s、901±6.56s,血液凝固時(shí)間與HCT呈正相關(guān),而且在不同纖維蛋白原濃度下HCT對(duì)血液凝固的影響均與上結(jié)論相符。為了更好模擬血液的生理狀態(tài),進(jìn)一步研究了流動(dòng)血液的凝固狀況。動(dòng)態(tài)凝固實(shí)驗(yàn)時(shí),纖維蛋白原濃度對(duì)血液凝固時(shí)間的影響趨勢(shì)同靜態(tài)時(shí)一致,按照外源纖維蛋白原濃度為0、2、4、6、8g/L的遞增順序測(cè)定不同流速下的血液凝固時(shí)間。血流速度為0mm/s時(shí),即靜態(tài)條件下的血液凝固時(shí)間分別為714±11.93s,621.7±19.86s,508±11.53s,468±8.02s,411.7±7.51s。而當(dāng)血流速度為5mm/s時(shí),血液凝固時(shí)間分別為863.7±12.1s,751±19.52s,629±11.36s,544.7±7.09s,503.7±14.5s,440.7±8.62s。血流速度增大到10mm/s時(shí),相應(yīng)的血液凝固時(shí)間依次為1050.7±13.5s、988±9.64s、887.7±11.5s、831.7±5.51s、751±5.03s。最后將血流速度設(shè)置為15mm/s時(shí),其血液凝固時(shí)間分別為1153.7±6.11s、1045±8.33s、967.3±7.02s、898±10.14s、830.3±9.29s。在HCT35%的重組血樣在不同纖維蛋白原濃度水平(0、2、4、6、8、10 g/L)下凝固時(shí)間為735±10s、634.7±4.16s、538.7±18.5s、439.3±16.04s、389±5s、339.3±5.69s。重組血樣HCT為55%時(shí)血樣對(duì)應(yīng)的凝固時(shí)間分別為967.3±19.1s、848.7±9.61s、743.7±15.18s、640.3±14.74s、601±3s、521±10.54s。以上結(jié)果表明:纖維蛋白原濃度與血液凝固時(shí)間呈負(fù)相關(guān),纖維蛋白原濃度越大血液凝固時(shí)間越短,其促進(jìn)血液凝固越明顯。同時(shí),血流速度與HCT是影響血液凝固的兩大重要因素。實(shí)驗(yàn)條件下,血細(xì)胞比容與血流速度越大血液凝固時(shí)間也越長。因此,本研究證實(shí)了OCT技術(shù)測(cè)定纖維蛋白原對(duì)血液凝固影響的可行性,OCT技術(shù)有望發(fā)展成可用于臨床檢測(cè)的新技術(shù)。
[Abstract]:Blood coagulation is a comprehensive process of a series of enzymatic reactions and plays an important role in normal physiological activities. Normally, blood coagulation can prevent the body from accidental bleeding. However, abnormal blood coagulation may lead to thrombosis or coagulation dysfunction. Fibrinogen is an important coagulation factor involved in blood coagulation. It is of great significance to realize the physiological function of blood coagulation process. Therefore, it is of great clinical significance to link blood coagulation with fibrinogen and detect blood coagulation at different fibrinogen concentrations. Optical coherence tomography (OCT) is based on the principle of low coherence optical Michelson interferometry. It has the advantages of noninvasive, safe and real-time monitoring by using the depth information carried by backscattering light to analyze the internal layers, structures and sizes of biological tissues. Moreover, great progress has been made in the study of OCT for detecting blood coagulation process. Therefore, OCT technology is used to detect the formation of blood coagulation process at different fibrinogen concentrations. In this study, the optical parameters of OCT-effective light penetration depth (d1/e) at 1/e of backscattered light intensity were used to reflect the changes of light intensity during blood coagulation at rest and flow state, and then the changes of blood coagulation process at different fibrinogen levels were studied. The effects of fibrinogen concentration on blood coagulation were studied under static and dynamic conditions. The possible factors affecting blood coagulation, such as the concentration of coagulant (Ca Cl2), hematocrit (HCT) and blood flow velocity, were also studied. The results showed that d1e could effectively distinguish different fibrinogen concentrations. In static coagulation test, when HCT was 35%, the concentration of foreign fibrinogen at 0, 2, 4, 6, 8, 10 g/L corresponded to the coagulation time of 588, 448, 13.61s, 364, 314.3, 8.14s, 266, 10.44s, 237, 237, respectively. At 45% HCT, the blood coagulation time corresponding to different levels of fibrinogen (0,2,4,6,8,10 g/L) was 665.3 (+ 12.66 s), 564 (+ 7.21 s), 513.3 (+ 7.23 s), 453 (+ 8.89s), 395 (+ 5 s), 325.7 (+ 4.51 s). When HCT was 55%, the fibrinogen concentration was 0,2,4,6,8 g/L, the corresponding blood coagulation time was 901 (+ 6.568 s), respectively. The plasma fibrinogen concentration was negatively correlated with the blood coagulation time at any HCT used in the experiment, that is, when the fibrinogen concentration increased, the blood coagulation time decreased accordingly. The coagulation time of 0.25 mol/L, 0.15 mol/L, 0.05 mol/L of Ca 2+ was 419.7 (+ 14.67 s), 559.3 (+ 15.14 s) and 714.7 (+ 6.03 s), respectively. The coagulation time of blood decreased with the increase of the coagulant concentration in the experimental range, and that of HCT was 35%, 45% and 55% respectively. In order to better simulate the physiological state of blood, the coagulation state of flowing blood was further studied. The effect of plasma fibrinogen concentration on coagulation time was consistent with that of static state. The coagulation time at different flow rates was measured according to the increasing order of fibrinogen concentration at 0,2,4,6,8 g/L. The coagulation time at 0 mm/s was 714 65507 When the blood flow velocity was 5 mm/s, the blood coagulation time was 863.7 (+ 12.1 s), 751 (+ 19.52 s), 629 (+ 11.36 s), 544.7 (+ 7.09s), 503.7 (+ 14.5 s), 440.7 (+ 8.62 s). When the blood flow velocity was increased to 10 mm/s, the corresponding blood coagulation time was 1050.7 (+ 13.5 s), 988 (+ 9.64 s, 887 (+ 11.5 s), 831.7 (+ 5.51s), and 751 (+ 5.035 s). The blood coacoagulation time of 15 15 m/s was 1153.7.7 6.11 s, 1045 5 1 1045 1 1045 1 1045 1 1045 1 1045 1 1045 967.3 7.027 7.02s, 898 1 8 8 8 8 8 8 8 10 14 s, 830.830.0.3 (10.3 0.3 Sample HCT was 55% The coagulation time of blood samples was 967.3+19.1 s, 848.7+9.61 s, 743.7+15.18 s, 640.3+14.74 s, 601+3 s, 521+10.54 s, respectively. The results showed that the plasma fibrinogen concentration was negatively correlated with the coagulation time, and the shorter the coagulation time, the more obvious the coagulation was promoted. Under the experimental conditions, the greater the specific volume of blood cells and the blood flow velocity, the longer the blood coagulation time. Therefore, this study confirmed the feasibility of OCT technology to determine the effect of fibrinogen on blood coagulation, OCT technology is expected to develop into a new technology for clinical detection.
【學(xué)位授予單位】:浙江理工大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2015
【分類號(hào)】:R446.11;O657.3

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