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临床研究
心脏磁共振四维血流成像评价肥厚型心肌病患者左心室舒张功能的可行性研究
刘宇豪 李薇 梁文瑛 欧阳丽娜 孙潇 王一帆 朱力

Cite this article as: Liu YH, Li W, Liang WY, et al. Feasibility study of cardiac magnetic resonance four-dimensional flow imaging in evaluating left ventricular diastolic function in patients with hypertrophic cardiomyopathy[J]. Chin J Magn Reson Imaging, 2022, 13(10): 127-131.本文引用格式:刘宇豪, 李薇, 梁文瑛, 等. 心脏磁共振四维血流成像评价肥厚型心肌病患者左心室舒张功能的可行性研究[J]. 磁共振成像, 2022, 13(10): 127-131. DOI:10.12015/issn.1674-8034.2022.10.019.


[摘要] 目的 采用心脏磁共振四维血流(cardiac magnetic resonance four-dimensional flow, CMR 4D Flow)序列对舒张功能障碍的肥厚型心肌病(hypertrophic cardiomyopathy, HCM)患者左心室血流进行测量,探究采用左心室血流动力学特点评价舒张功能的可行性。材料与方法 前瞻性纳入45例HCM患者和31例健康对照者,两组人群均进行了3.0 T磁共振稳态自由进动序列及CMR 4D Flow序列扫描。采用CVI42后处理软件测量两组人群左心室基本功能参数及左心室流入流出道层面舒张早期(左心室抽吸)及晚期(左心房主动收缩)的二尖瓣水平平均血流速度(cm/s)。采用独立样本t检验或Mann-Whitney U检验对两组受试者临床资料及影像学参数进行比较;并对舒张早期平均血流速度(E)与左心室质量(left ventricular mass, LVmass)、舒张期整体室壁峰值厚度(global peak wall thickness, GPWT)进行Spearman相关性分析。结果 HCM组LVmass及GPWT相较健康对照组明显增大[LVmass:(163.70±52.18)vs.(87.27±21.01),单位:g;GPWT:(19.64±3.85)vs.(9.99±2.00),单位:mm;HCM组 vs. 健康对照组,P<0.001];对于二尖瓣水平舒张期平均血流速度:HCM组舒张早期平均血流速度峰值(E峰)小于健康对照组[29.70(17.90)vs. 50.50(16.90),单位:cm/s;HCM组 vs. 健康对照组,P<0.001];HCM组舒张晚期平均血流速度峰值(A峰)与健康对照组差异无统计学意义;HCM组E/A值较健康对照组明显减低[(1.26±0.70)vs.(1.80±0.85),P=0.003]。结论 采用CMR 4D Flow序列能够对左心室内血流进行可视化,能够准确区分心脏在舒张早期及晚期心室内血流运动轨迹,并且二尖瓣水平舒张早期平均血流速度峰值(E峰)及E/A值降低有助于定量评价HCM患者左心室舒张功能障碍,为患者制订个体化治疗方案提供参考依据。
[Abstract] Objective Cardiac magnetic resonance four-dimensional flow (CMR 4D Flow) was used to measure left ventricular blood flow in patients with hypertrophic cardiomyopathy (HCM) with impaired diastolic function relaxation and to explore the feasibility of using left ventricular hemodynamic characteristics to evaluate diastolic function.Materials and Methods A total of 45 HCM patients and 31 healthy controls were retrospectively collected. All subjects in both groups underwent a 3.0 T magnetic resonance steady-state free entry sequence and CMR 4D Flow sequence scan. The CVI42 post-processing software was used to measure the basic functional parameters of the left ventricle and the average blood flow velocity (cm/s) at the mitral valve level in the early (left ventricular aspiration) and late (left active atrial contraction) levels of the left ventricular inflow and outflow tract in the two groups. The independent samples t-test or Mann-Whitney U test were used to compare the clinical data and imaging parameters of the two groups; and Spearman correlation analysis was performed on the average blood flow velocity in early diastole, left ventricular myocardial mass, and peak diastolic thickness of the left ventricular wall.Results The left ventricular mass (LVmass) and the global peak wall thickness (GPWT) in the HCM group were significantly higher than those in the healthy control group [LVmass: (163.70±52.18) vs. (87.27±21.01), unit: g; GPWT: (19.64±3.85) vs. (9.99±2.00), unit: mm; HCM group vs. healthy control group, P<0.001]; for the average diastolic blood flow velocity at the level of the mitral valve, the average blood flow velocity in the early diastole of the HCM group was lower than that of the healthy control group [29.70 (17.90) vs. 50.50 (16.90), unit: cm/s; HCM group vs. healthy control group, P<0.001]; the mean blood flow velocity in late diastole between HCM patients and the control group was not statistically different; the E/A value of the HCM group was significantly lower than that of the healthy control group [(1.26±0.70) vs. (1.80±0.85), HCM group vs. healthy control group, P=0.003].Conclusions The use of CMR 4D Flow can visualize the blood flow in the left ventricle, accurately distinguish the intraventricular blood flow trajectory of the heart in the early and late diastole. In addition, the decrease of mean flow velocity in the early diastolic stage of mitral valve level (E peak) and E/A value is helpful for quantitative evaluation of left ventricular diastolic dysfunction in patients with hypertrophic cardiomyopathy, and provides a reference for patients to formulate individualized treatment plans.
[关键词] 肥厚型心肌病;舒张功能;四维血流;左心室;心脏磁共振;磁共振成像
[Keywords] hypertrophic cardiomyopathy;diastolic function;four-dimensional blood flow;left ventricle;cardiac magnetic resonance;magnetic resonance imaging

刘宇豪 1, 2   李薇 1   梁文瑛 2   欧阳丽娜 2   孙潇 3   王一帆 3   朱力 3*  

1 宝鸡市中心医院医学影像科,宝鸡 721000

2 宁夏医科大学,银川 750000

3 宁夏医科大学总医院放射科,银川 750000

朱力,E-mail:zhuli72@163.com

作者利益冲突声明:全部作者均声明无利益冲突。


基金项目: 国家重点研发计划项目 2022YFC2010000 国家自然科学基金 82160333 宁夏自然科学基金 2020AAC03420
收稿日期:2022-05-24
接受日期:2022-10-09
中图分类号:R445.2  R542.2 
文献标识码:A
DOI: 10.12015/issn.1674-8034.2022.10.019
本文引用格式:刘宇豪, 李薇, 梁文瑛, 等. 心脏磁共振四维血流成像评价肥厚型心肌病患者左心室舒张功能的可行性研究[J]. 磁共振成像, 2022, 13(10): 127-131. DOI:10.12015/issn.1674-8034.2022.10.019

       肥厚型心肌病(hypertrophic cardiomyopathy, HCM)是最常见的遗传性心肌病,主要表现为左心室壁非对称性增厚[1]。HCM患者临床症状差异性大,最常见的症状是劳力性呼吸困难、胸痛、心悸等,但是有些患者首发症状即为猝死[2]。相较于收缩功能异常,HCM患者左心室舒张功能障碍更为常见。由于心肌肥厚导致血流动力学紊乱从而继发舒张功能障碍,主要原因包括心肌舒张运动协调性和顺应性降低、心室虹吸作用减弱和细胞内钙摄取异常[3]。当舒张功能进一步损害时,HCM患者左心房压力升高并导致肺动脉高压,严重影响患者预后[4]。因此,如果能够对HCM患者左心室舒张功能进行定量评估,早期进行积极的临床干预,则会有效防止心脏不良事件的发生,改善HCM患者预后水平。

       超声心动是目前无创评价左心室舒张功能的最常用的方法,测量二尖瓣血流频谱因其操作简单、可重复性高,是最常用的评价舒张功能的参数之一[5, 6]。然而,随着MRI技术的发展,心脏磁共振(cardiac magnetic resonance, CMR)检查凭借多参数成像、大视野、无辐射等优点,并且能提供心脏形态学和功能学信息,成为心脏大血管结构测量和功能评价的金标准[7]。心脏磁共振四维血流(CMR four-dimensional flow, CMR 4D Flow)的应用不仅可以观察到心脏内复杂的血流运动轨迹,还可以提供血流动力学信息[8, 9]。Pruijssen等[10]发现HCM患者收缩期量较健康人群明显增多,并且与流出道直径及心肌质量有一定相关性。Suwa等[11]通过对梗阻性HCM患者实行酒精间隔消融术前后对比发现,术后患者升主动脉内涡流发生率的综合评分显著低于术前,涡流持续时间也明显减少。虽然国外已有CMR 4D Flow对HCM的应用研究,但是评价HCM患者左心室舒张功能尚存在一定空白。

       本研究旨在采用CMR 4D Flow序列,测量二尖瓣水平舒张期血流动力学参数,对HCM患者的左心室舒张功能进行定量评估,并与健康对照组进行差异分析,探讨CMR 4D Flow定量评价HCM患者左心室舒张功能的价值。

1 材料与方法

1.1 研究对象

       本研究为前瞻性研究,遵守《赫尔辛基宣言》,经过宁夏医科大学总医院科研伦理委员会批准(批准文号:2020-185),受试者均签署知情同意书。本研究纳入在宁夏医科大学总医院2020年6月1日至2021年12月31日符合纳入及排除标准的HCM患者及健康对照者。

       HCM组纳入标准:(1)符合欧洲心脏病协会制定的HCM的临床诊断标准[12];(2)左室射血分数(left ventricular ejection fraction, LVEF)≥50%;(3)患者在CMR检查前后两周内行超声心动检查并且综合评估认定为舒张功能障碍[13];(4)CMR 4D Flow图像能够完成后处理,并且能清晰显示标准三腔心层面,包括左心房、左心室、流入流出道、二尖瓣及主动脉瓣。排除标准:(1)合并其他心源性或全身性疾病;(2)患有幽闭恐惧症无法完成检查者。健康对照组纳入标准:(1)经CMR、超声心动检查、心电图检查未见异常;(2)临床检查除外严重心律失常、原发或继发高血压、瓣膜心脏病、糖尿病、恶性肿瘤等疾病。

1.2 扫描方法

       采用飞利浦公司Ingenia 3.0 T超导磁共振仪进行心脏扫描。受试者扫描前准备:去除随身携带金属类物品,采取仰卧位,8通道心脏专用阵列线圈置于前胸部及背部,进行呼气末屏气训练,同时监测心电门控和呼吸门控。心脏定位:在常规轴位、矢状位、冠状位确定心脏位置。稳态自由进动序列:标准化选取短轴两腔心、左室长轴两腔心、长轴四腔心、三腔心切面;扫描参数为TE 1.28 ms,TR 2.6 ms,翻转时间200 ms,FA 45°,FOV 350 mm×350 mm,重建矩阵256×192,层厚为8 mm;4D Flow序列:标准化选取三腔心切面,扫描参数为TE shortest,TR shortest,FA 8°,平均采集次数为1次,FOV 300 mm×300 mm,重建矩阵120×120,层厚为10 mm,层间距为0 mm,时间分辨率为每个心动周期采集20帧图像。采用膈肌导航降低运动伪影。结合文献[14]和本研究情况,流速编码Venc值选取200 cm/s。

1.3 图像处理

       运用CVI42分析软件(Version 5.13.5,Canada Circle Cardiovascular)进行图像后处理及分析。(1)心功能参数测量:在短轴两腔心电影序列上,软件自动根据美国心脏协会(American Heart Asociation, AHA)提出的心肌标准分段法[15]自动勾画左心室心内、外膜边界,统一不勾画乳头肌轮廓,软件自动生成左室舒张末期容积(left ventricular end diastolic volume, LVEDV)、左心室收缩末期容积(left ventricular end-systolic volume, LVESV)、LVEF、左心室质量(left ventricular mass, LVmass)、舒张期整体室壁峰值厚度(global peak wall thickness, GPWT)等参数。(2)血流动力学参数测量:①将CMR 4D Flow数据导入模块后,选取感兴趣区;②图像预处理,首先,手动调节蒙版,常规进行偏移校正,即摒弃静态及气体组织图像数据;然后,根据是否产生混杂信号,适当进行信号混叠校正;③分割图像,采用3D渲染的方式渲染出标准左心室流入流出道层面并保存图像;④分析血流,将取样容积置于二尖瓣瓣口水平,取样框与血流方向保持垂直,软件生成心动周期内血流平均速度-时间曲线图,观察血流迹线图并记录舒张早期及晚期峰值平均血流速度。详见图1、2。

图1  三腔心层面舒张期血流迹线图。1A:舒张早期;1B:舒张晚期。
图2  血流平均速度-时间曲线图。2A:肥厚型心肌病(HCM)患者;2B:健康对照者;舒张早期、晚期产生的平均血流速度峰值分别为E峰、A峰,可以观察到HCM患者E峰明显低于A峰。
Fig. 1  Three-chamber heart level diastolic blood flow traces. 1A: Early diastole; 1B: Late diastole.
Fig. 2  Average blood flow velocity-time curve. 2A: Hypertrophic cardiomyopathy (HCM) patient; 2B: Healthy control; the average blood flow velocity peaks in the early and late diastoles are E peak and A peak, respectively, it can be observed that the E peak of HCM patients is significantly lower than the A peak of the average blood flow velocity in the late diastole.

1.4 统计学方法

       数据分析应用SPSS 26.0统计分析软件,符合正态分布的计量资料用均数±标准差(x¯±s)表示,不符合的用中位数(四分位数间距)[MIQR)]表示,计数资料以频数表示;正态分布的计量资料均数比较采用独立样本t检验,非正态分布的计量资料均数比较采用Mann-Whitney U检验,组间计数资料比较采用χ2检验;舒张早期平均血流速度(E)与LVmass、GPWT作Spearman相关性分析;采用双侧检验,P<0.05为差异有统计学意义。

2 结果

2.1 临床资料及CMR左心室功能参数

       HCM组最终纳入HCM患者45例,年龄21~66岁,其中男29例;健康对照组共纳入31例,年龄27~67岁,其中男20例。

       HCM组与健康对照组基本资料及MRI左心室功能参数详见表1。其中,HCM组LVmass及GPWT均大于健康对照组,差异具有统计学意义(P<0.001),其余心功能参数未见明显差异。

表1  人群基本资料及左心基本功能参数差异
Tab. 1  The basic information of the population and the differences of the basic functional parameters of the left heart

2.2 CMR 4D Flow测量二尖瓣水平舒张期平均血流速度

       HCM组与健康对照组人群的二尖瓣水平舒张早期及晚期平均血流速度参数详见表2。其中,HCM组E峰及E/A值明显低于健康对照组,差异具有统计学意义(P<0.05)。

表2  二尖瓣水平舒张期平均血流速度
Tab. 2  Mean diastolic blood flow velocity at the mitral valve level

2.3 二尖瓣水平舒张早期平均血流速度与心功能参数相关性分析

       本研究中发现二尖瓣水平舒张早期平均血流速度与组LVmass及GPWT均呈负相关(r=-0.360,P=0.001;r=-0.551,P<0.001),详见图3

图3  相关性分析散点图。二尖瓣水平舒张早期平均血流速度与左心室心肌质量(3A)、舒张期整体室壁峰值厚度(3B)均呈负相关。
Fig. 3  Correlation analysis scatter plot. The mean early diastolic blood flow velocity at the mitral valve level was negatively correlated with left ventricular myocardial mass (3A) and overall peak diastolic wall thickness (3B).

3 讨论

       本研究通过CMR 4D Flow对舒张功能障碍的HCM患者左心内血流进行可视化,能够准确区分心脏在不同时期心室内血流运动轨迹,并且对二尖瓣水平舒张期血流进行定量分析,发现舒张早期平均血流速度较健康对照组明显减低,舒张晚期平均血流速度无明显差异;LVmass、GPWT与二尖瓣水平舒张早期平均血流存在负相关,其中与GPWT相关性较大。

3.1 HCM患者左心室舒张功能障碍的机制

       本研究中,HCM组左心室LVmass、GPWT均明显增大,这与以往研究结果相同[16],也与HCM诊断指南中影像表现相符合[17]。HCM通常表现为左心室非对称肥厚,受累节段心肌细胞肥大,纤维排列紊乱[18, 19]。相较于健康人群,笔者认为心肌非对称肥厚导致心肌顺应性的降低,心脏在舒张期无法形成幅度较大、速度较快的舒张运动。笔者在先前研究中通过心肌特征追踪技术也证实了舒张期心肌运动幅度及速度均明显减低[20]。因此左室心肌在舒张早期虹吸作用减弱,进而血液无法有效充盈心室,导致舒张功能障碍。

3.2 CMR 4D Flow序列对HCM患者舒张期血流定量分析

       本研究通过CMR 4D Flow序列能够准确区分心脏在舒张早期及晚期心室内血流运动轨迹,并且对二尖瓣下血流动力学参数进行测量,发现HCM患者二尖瓣下舒张早期平均血流速度峰值(E峰)及E/A 值较健康对照组明显减低,而舒张晚期平均血流速度峰值(A峰)未见明显差异,HCM患者心脏舒张功能障碍。相较于传统2D相位对比血流成像,4D Flow序列扫描定位较为简便,可以对心腔内不同心动周期运动复杂的血液流向进行可视化分析及定量参数评价[21, 22]。4D Flow序列的加入填补了“一站式”磁共振评价心脏运动中血流动力学的空白。心脏舒张早期血流主要是通过左心室主动舒张,房室之间形成压力差导致二尖瓣开放产生,压力差越大,产生血流平均速度越快[23]。因此,舒张早期平均血流速度一定程度上间接反映了左心室松弛运动状态[24]。舒张晚期血流即左心房主动收缩产生,血流速度受左心室顺应性和左房收缩功能的影响。本研究发现HCM组患者E峰相较于健康人群明显减低,笔者认为这是由于心肌肥厚导致心肌顺应性的降低,虹吸作用减弱,压力差减小导致血液运动速度的减慢。以往研究[25]提出对于舒张功能障碍Ⅰ级患者二尖瓣水平峰值血流速度E/A<1,与本研究通过CMR 4D Flow测量的E/A值(1.26±0.70)存在差异,笔者认为可能是由于舒张功能假性正常化导致,即部分HCM患者左房充盈压轻中度增高,使得舒张晚期血流减慢,导致E/A值升高[26]。但是,舒张早期平均血流速峰值(E峰)和E/A值小于健康对照组,对于评价左心舒张功能仍存在一定意义。本研究进一步发现LVmass、GPWT与二尖瓣水平舒张早期平均血流速度存在负相关,其中GPWT相关性较大。

3.3 不足与展望

       本研究存在一定的局限性:(1)样本量较小,无法针对不同程度舒张功能障碍患者进行血流探究;(2)由于左心导管漂浮实验测定舒张压属于有创检查,无法对HCM及健康人群常规测定;(3)对于梗阻性及非梗阻性HCM舒张功能须进一步探究。

       综上所述,采用CMR 4D Flow 对能够对左心室内血流进行可视化,能够准确区分心脏在舒张早期及晚期心室内血流运动轨迹,并且二尖瓣水平舒张早期平均血流速峰值(E峰)及E/A值降低有助于定量评价HCM患者左心室舒张功能障碍,为患者制订个体化治疗方案提供参考依据。

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