【作者】 刘秋颖；

【导师】 任卫东；

【作者基本信息】 中国医科大学 ， 影像医学与核医学， 2009， 博士

【摘要】 前言目前临床上常用的外周动脉检查手段包括多普勒超声、CT血管造影、磁共振血管造影和有创的数字减影血管造影（DSA）、血管内超声等,其中CT和磁共振均为重建图像,分辨力受到较大影响,所得狭窄率与病理和DSA的相关性较低,DSA虽为金标准,但只有拟行介入治疗的患者才愿意接受。多普勒超声因操作简便、价格低廉而应用广泛,但受仪器调节、患者自身条件及检查者操作技术影响很大。因此,临床上迫切需要一种无创、低价而又准确度高的影像学方法来观察外周动脉疾病的严重程度、病变进展情况或进行疗效判定。近年来随着各种血管腔内介入治疗手术的广泛开展,术后动脉再次狭窄的发生率越来越高,但由于透声条件所限,再次狭窄时狭窄程度和病变范围的判定变得更加困难。大多数再狭窄的实验研究仍以DSA为金标准,由于其有创、需要使用价格昂贵的导管导丝,动物实验时操作难度大,短时间内反复检查还会显著增加实验动物死亡率,因此不适于定期随访。超声造影采用经外周静脉注入声学微泡的方法增加散射强度,能将动脉管腔与周围组织进行明显区分,这给超声诊断血管疾病带来了新的希望。本研究对比了超声造影与常规超声在评价不同程度动脉狭窄时的准确度和重复性,记录了造影前后彩色多普勒和频谱多普勒的变化,观察了不同程度球囊损伤后动脉狭窄的发生和演变过程,对比不同超声学方法在随访过程中的应用价值。材料与方法30只兔腹主动脉采用针控线栓法,用1-0号丝线分别将不同粗细的针头（23G,20G,18G）与腹主动脉并行缠绕结扎,然后拔出针头,将腹主动脉制作成不同程度环形缩窄,每只兔在制作完1种狭窄程度后即刻DSA检查,并由两名医师分别进行常规超声和超声造影（CEUS,包括谐波造影和彩超造影）,二维（2D）、彩色多普勒（CDFI）和CEUS分别测量直径狭窄率,记录造影前后血流动力学参数,如峰值流速（PSV）、搏动指数（PI）和阻力指数（RI）并计算峰值流速比值（SVR）,计算各种超声方法狭窄率测定的准确度,判断其与DSA狭窄率的一致性,最后计算观察者间一致性系数。另取30只月龄均为6个月的雄性日本大耳白兔随机入选至轻度损伤组（普通球囊）和重度损伤组（金属丝缠绕球囊）,经右髂外动脉将球囊导管送至腹主动脉中段,注入生理盐水后回撤球囊至腹主动脉分叉处,吸出盐水,送球囊至原来位置,重复上述过程3次。术后3、7、14、28天时常规超声和CEUS观察损伤动脉的直径变化、CDFI和血流动力学参数变化,测量造影剂时间—强度曲线上的造影剂达峰时间（Tp）、减半时间(T_1/2)、峰值强度（Ip）和曲线下面积（AUC）。术后28天取损伤节段动脉进行病理形态学分析,以狭窄指数（面积狭窄率）反映狭窄程度。结果1、狭窄率判定的准确度由高到低依次为超声造影＞频谱＞CDFI＞2D;四种方法与DSA的一致性系数（k值）分别为0.933、0.866、0.783和0.548;超声造影的观察者间一致性系数高于其它超声方法,尤其在中、重度狭窄组。2、不同狭窄程度时注入造影剂后狭窄处与上游PSV、PI均较造影前加快,其余血流动力学参数造影前后无差异。彩超造影在中、重度狭窄组出现“Blooming”伪像。3、轻度损伤组术后3、7、14天时常规超声显示内膜光滑,内径与上游相比无差异,血流信号均匀,SVR小于2。28天损伤处直径小于上游（P=0.027）,狭窄率25.28%。彩超造影于术后3、7天时显示损伤处血流轻度紊乱,14和28天时呈五彩镶嵌样。超声造影于术后14天发现损伤部位管腔减小（P=0.013）,早于常规超声,狭窄率30.58%,28天时狭窄率为33.92%。4、重度损伤组常规超声显示3、7天时损伤处内膜欠光滑,内径与上游相比无差异,彩色血流均匀;14天时内膜增厚、管径变细,狭窄率29.31%,彩色血流轻度紊乱,PSV轻度加快,SVR小于2;28天时内膜面显示欠清,管腔显著缩小,狭窄率47.39%,CDFI呈五彩镶嵌样,PSV大于150cm/s,SVR大于2,估计狭窄率大于50%。彩超造影术后3天时显示损伤处色彩反转,7天时五色镶嵌样,14天和28天时均出现“Blooming”伪像。超声造影显示7、14、28天时损伤处直径均小于上游,狭窄率分别为31.78%、50.39%、63.25%,呈递增趋势。5、术后3天造影剂时间—强度曲线分析表明轻度组损伤处Tp、T_1/2、Ip和AUC与上游相比均无统计学差异;重度组损伤处Tp和T_1/2显著长于上游且长于轻度组,Ip和AUC大于上游,但与轻度组相比无差异。6、损伤后28天轻度损伤组病理学狭窄指数为38.55%,重度组为75.37%。常规超声和谐波造影直径狭窄率与狭窄指数的相关系数在轻度组分别为0.68和0.81,在重度组分别为0.60和0.88。结论1、谐波造影能清晰显示流道轮廓,易于识别内膜面,狭窄率测定的准确度和观察者间重复性高于其它超声学方法。2、彩超造影将血流紊乱放大显示,中、重度狭窄时出现“Blooming”伪像。注入造影剂后PSV和PI较造影前增加,其余血流动力学参数未发生改变。3、普通球囊损伤未引起导致血流动力学改变的狭窄程度,金属丝缠绕的球囊能明显加重损伤程度,所致狭窄程度大于50%。4、随访球囊损伤后动脉狭窄时超声造影可早期发现管腔直径的轻微变化,狭窄率判定的准确度优于常规超声。彩超造影比CDFI更易发现轻微血流紊乱,在损伤后早期内径和血流动力学参数无改变时可用于定位损伤部位。5、损伤部位造影剂时间—强度曲线上的时间参数间接反映损伤程度,可在一定程度上预测损伤动脉的狭窄程度。更多还原

【Abstract】 The phyisical examinations of vascular disease include Doppler ultrasonography, CT angiography（CYA）,magnetic resonance angiography（MRA）,digital substract angiography（DSA）,and intravascular ultrasonography.CTA and MRA obtain images by reconstruction,so the image definition is bad and the stenosis rate measured by them are not well related with DSA and pathology.Although DSA is the golden standard, few people choose it only when have they had to accept intervention.Doppler ultrasonography has been adopted widely because of its convenience and low-cost,but the quality of image depends on appropriate modulation of the machine,condition of patients and technique of doctors.People are looking forward to a new method with non-invasion,low-cost and high accuracy to observe the severity of lesion,follow up the entire process,and assess revasculization theraphy.With the developement of intravascular intervention,the incidence of restenosis is higher than before.Due to the limitation of ultrasound condition,the assessment of restenosis is difficult.DSA is regarded as golden standard in a lot of studies on restenosis,but it is high-cost and difficult to practice on animals which can not tolerate again and again within a short period.So,DSA is not suitable to follow up.Contrast-enhanced ultrasonography （CEUS） can distinguish artery lumen by means of enhancing scatter intensity by injection of contrast agent.In my study,I compared the accuracy and reproducibility of CEUS and common ultrasonography（US） in assessment of artery stenosis in different degrees,and recorded the changes of color Doppler and pulse wave Doppler after injection of contrast agent.I also observed the process of abdominal aortic stenosis after different balloon injuries in rabbits and compared the value of CEUS and US in following-up process. Materials and methodsTirty rabbits underwent US,CEUS and DSA by two observers after abdominal aorta was ligated in 3 different degrees（We ligated different diameter needles with abdominal aorta parallelly and then took off the needles）.We measured diameter stenosis rate by 2-dimesion,color Doppler flow imaging（CDFI） and CEUS,and some dynamic parameters,such as peak of systolic velocity（PSV）,pulse index（PI）,resistance index（N）,and calculated ratio of systolic velocity（SVR）.We compared the accuracy and reproducibility of 4 ultrasonic methods and calculated the concordance coefficient between observers.We also recorded changes of CDFI and parameters on pulse wave Doppler（PW） curve.Tirty rabbit’s abdominal aortas were injured by different balloons in order to establish stenosis in different degrees.The light injury group was dealt with a common 3.0mm balloon and the severe injury group was injuried by a special balloon which enveloped with slender wire.They underwent CEUS and US on the 3^rd,7^th,14^th and 28^th days.We measured diameter stenosis rate（R） by CEUS and US,compared them with stenosis index measured by pathology on the 28^th day.At last,we measured peak of intensity（I_P）,time to peak（T_P）,halving time(T_1/2) and area under curve（AUC） on time-intensity curve of contrast agent.Results1、The order of accuracy of stenosis rate from top to bottom was CEUS,PW,CDFI and 2-dimesion.In comparision with DSA,the kappa value of four ultrasonic methods was 0.933,0.866,0.783 and 0.548,respectively.The kappa value between observers of CEUS is higher than other ultrasonic methods.2、PSV and PI increased after we injected contrast media,but RI and SVR did not change.There was no difference in accuracy rate of SVR before and after we injected contrast media.The sign of blooming was found in moderate and serious stenosis group after we injected contrast media.3、In light injury group,there was no difference of diameter between lesion and normal segement and color was well-distributed on the 3^rd,7^th,14^th days.The decrease of diameter on the lesion was detected by common US on the 28^th day and stenosis rate was 25.28%.SVR was lower than 2 in the entire process.Color Doppler CEUS displayed slight turbulence on the 3^rd and 7^th days,the festoon color on the 14^th and 28^th days.CEUS detected slight decrease of diameter on the lesion on the 14^th day.This detection was earlier than common US.The stenosis rate was 33.92%on the 28^th day.4、In severe injury group,thickening of intima and decrease of diameter were detected by common US on the 14^th day.The stenosis rate was 29.31%on the 14^th day, and slight turbulence was detected by CDFI and PSV increased at the same time.On the 28th day,the serious decrease of diameter and festoon color code were observed by common US and PSV increased more than 150cm/s,SVR was higher than 2,so it was confirmed that stenosis rate was higher than 50%.Color Doppler CEUS showed the reverse of color on the lesion on the 3^rd day,festoon color on the 7^th day,and blooming on the 14th and the 28^th days.The stenosis rates measured by CEUS on the 7^th,14^th and 28^th days were 31.78%,50.39%and 63.25%,respectively.5、The comparision of T_P,I_P,AUC and T_1/2 on the 3^rd day indicated that there was no statistical difference between lesion and normal segement in light injury group.In severe injury group,T_P and T_1/2 of the lesion were longer than normal segement and also longer than parameters of the lesion in light injured group.Ip and AUC of the lesion were higher than normal segement but were similar with the lesion in light injured group.Conclusion1、CEUS displayed flow tract more clearly than other ultrasonic methods and made it easy to distinguish the border of intima,so its accuracy and reproducbility were the highest.2、Color Doppler CEUS amplified the turbulance and expressed "blooming" in sever stenosis.PSV and PI increased after contrast agent was injected to rabbits,but SVR,and RI didn’t change.3、Injury by a common balloon didn’t induce stenosis with dynamic change,and injury by the balloon enveloped with wire produced stenosis at the rate of more than 50%.4、In follow-up process of artery stenosis after balloon injury,CEUS detected slight decrease of diameter earlier than common US,and the accuracy of CEUS was higher than common US.Color Doppler CEUS displayed turbulence more clearly and could locate position of injury in the early stage when no difference occurred in diameter and hemodynamics.5、The parameters on time-intensity curve of lesion indirectly implied the degree of injury and should be helpful to adjust stenosis degree.更多还原