光相干断层成像技术测定纤维蛋白原对血液凝固过程光学性质的影响

发布时间：2018-08-20 12:54

【摘要】：血液凝固是一系列酶促反应的综合过程,对人体进行正常生理活动具有重要的作用。正常情况下血液凝固能够防止机体意外出血,然而,不正常凝血可能导致血栓或者凝血功能障碍。纤维蛋白原是参与血液凝固过程的重要凝血因子,对于实现血液凝固过程的生理作用具有重要意义。因此,将血液凝固与纤维蛋白原联系,实现对不同纤维蛋白原浓度下的血液凝固检测具有重要的临床意义。光相干断层成像技术(optical coherence tomography,OCT)基于低相干光迈克尔逊干涉原理,利用背向散射光携带的深度信息实现对生物组织内部层次、结构及尺寸的解析,具有无创、安全和实时监测的优点。而且,关于OCT检测血液凝固过程的研究已经取得重大进展。因而,利用OCT技术检测不同纤维蛋白原浓度下血液凝固过程成为可能。本研究采用OCT光学参数—背向散射光强度1/e处的有效透射深度(1/e light penetration depth,d1/e)从光透射深度的变化来反映静止及流动状态下的血液凝固过程中的光强度变化,进而研究在不同纤维蛋白原水平下血液凝固过程的变化。实验分别在静态及动态条件下,分别研究纤维蛋白原浓度对血液凝固的影响,期间又分别研究了可能影响血液凝固的因素诸如促凝剂(Ca Cl2)浓度、血细胞比容(HCT)、以及血流速度。实验结果表明d1e可以有效的区分不同纤维蛋白原浓度下的血液凝固过程。血液凝固过程中d1e变化曲线呈现先增加后基本保持不变的特点。静态凝固实验时,在HCT为35%时,外源纤维蛋白原浓度水平在0、2、4、6、8、10 g/L时对应的血液凝固时间分别为588±13.86s、448±13.61s、364±2.65s、314.3±8.14s、266±10.44s、237.3±9.71s。在HCT为45%时,不同外源纤维蛋白原浓度水平(0、2、4、6、8、10 g/L)对应的血液凝固时间分别为665.3±12.66s、564±7.21s、513.3±7.23s、453±8.89s、395±5s、325.7±4.51s。当HCT为55%时,外加纤维蛋白原浓度为0、2、4、6、8 g/L时对应的血液凝固时间分别为901±6.56s、812.3±26.31s、592±14.42s、536±32.14s、506.7±4.73s。在实验中采用的任一HCT下,纤维蛋白原浓度始终与血液凝固时间呈负相关,即当纤维蛋白原浓度增大时,血液凝固时间随之减小。利用冻融法处理血浆去除原有纤维蛋白原后,也能得到相同的结论;促凝剂的浓度对血液凝固固过程也有一定的影响,促凝剂Ca2+浓度为0.25mol/L、0.15mol/L、0.05mol/L时对应的凝固时间分别为419.7±14.67s、559.3±15.14s、714.7±6.03s,在实验范围内血液凝固时间随着促凝剂浓度的增大而降低;HCT为35%、45%及55%时对应的血液凝固时间分别为743.7±11s、811.7±11.6s、901±6.56s,血液凝固时间与HCT呈正相关,而且在不同纤维蛋白原浓度下HCT对血液凝固的影响均与上结论相符。为了更好模拟血液的生理状态,进一步研究了流动血液的凝固状况。动态凝固实验时,纤维蛋白原浓度对血液凝固时间的影响趋势同静态时一致,按照外源纤维蛋白原浓度为0、2、4、6、8g/L的递增顺序测定不同流速下的血液凝固时间。血流速度为0mm/s时,即静态条件下的血液凝固时间分别为714±11.93s,621.7±19.86s,508±11.53s,468±8.02s,411.7±7.51s。而当血流速度为5mm/s时,血液凝固时间分别为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时,相应的血液凝固时间依次为1050.7±13.5s、988±9.64s、887.7±11.5s、831.7±5.51s、751±5.03s。最后将血流速度设置为15mm/s时,其血液凝固时间分别为1153.7±6.11s、1045±8.33s、967.3±7.02s、898±10.14s、830.3±9.29s。在HCT35%的重组血样在不同纤维蛋白原浓度水平(0、2、4、6、8、10 g/L)下凝固时间为735±10s、634.7±4.16s、538.7±18.5s、439.3±16.04s、389±5s、339.3±5.69s。重组血样HCT为55%时血样对应的凝固时间分别为967.3±19.1s、848.7±9.61s、743.7±15.18s、640.3±14.74s、601±3s、521±10.54s。以上结果表明:纤维蛋白原浓度与血液凝固时间呈负相关,纤维蛋白原浓度越大血液凝固时间越短,其促进血液凝固越明显。同时,血流速度与HCT是影响血液凝固的两大重要因素。实验条件下,血细胞比容与血流速度越大血液凝固时间也越长。因此,本研究证实了OCT技术测定纤维蛋白原对血液凝固影响的可行性,OCT技术有望发展成可用于临床检测的新技术。
[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.
【学位授予单位】：浙江理工大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R446.11;O657.3

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