综述
磁共振脂肪测量技术在肌肉病变中的应用进展
磁共振成像, 2019,10(6) : 474-478. DOI: 10.12015/issn.1674-8034.2019.06.017
摘要

肌肉脂肪变性是多种肌肉疾病的主要病理改变,且病变的严重程度与肌肉脂肪含量密切相关。磁共振肌肉脂肪测量技术不但能监测疾病的进展,还可以指导临床合理地选择治疗方案并准确地估评治疗效果。现将近年来常见的磁共振脂肪测量技术及其在肌肉病变中的应用进行综述。

引用本文: 张旭霞, 张皓, 南江, 等.  磁共振脂肪测量技术在肌肉病变中的应用进展 [J] . 磁共振成像, 2019, 10(6) : 474-478. DOI: 10.12015/issn.1674-8034.2019.06.017.
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肌肉脂肪变性是多种肌肉相关病变的主要病理特征,如杜氏型肌营养不良症(duchenne muscular dystrophy,DMD)、2型糖尿病胰岛素抵抗、肌肉退行性病变等,且肌肉内脂肪含量越高,患者的病情越严重[1,2,3,4]。因MRI具有良好的软组织对比度、多参数及多方位成像的优势,不但能较准确地显示肌肉的形态和解剖结构,还可以评估肌肉的脂肪化、水肿、肥大、萎缩等改变,并且能监测肌肉受累的顺序和程度,所以在肌肉疾病的诊断中发挥着重要作用。近年来,磁共振脂肪测量技术已广泛应用于临床研究中[5,6,7],在肌肉疾病中的应用亦是目前的研究热点。

1 磁共振脂肪测量技术

目前用于科研及临床的磁共振肌肉脂肪测量技术主要包括视觉评估分级法、磁共振波谱(magnetic resonance spectroscopy,MRS)、Dixon技术及T2 mapping等。

1.1 视觉评估分级法

视觉评估分级法是根据T1WI或T2WI图像上肌肉中高信号的程度及范围进行分级,来代表肌肉的脂肪浸润程度[8,9,10],是一种半定量的脂肪测量方法。在国内外应用广泛的Goutallier分级就是使用此种方法来测量肩袖脂肪含量。改良版的Goutallier分级是根据T2WI图像中异常高信号的范围将肩袖脂肪浸润程度分为5级:0级:肩袖内无脂肪信号;1级:肩袖内有条状的脂肪信号;2级:脂肪信号较1级范围大,但肌肉信号多于脂肪信号;3级:肌肉信号与脂肪信号的范围相等;4级:肌肉信号范围少于脂肪信号[8]

视觉评估分级法测量方法简单、快速,且可行性高,故广泛应用于椎旁肌、下肢肌肉及肩袖肌肉等脂肪含量的测量[8,9,10]。但研究表明[9,11],这种依赖于视觉评估的方法对于肌肉的轻度脂肪变性不太敏感,且易受主观因素影响。

1.2 磁共振波谱

MRS是目前应用最普遍的磁共振脂肪测量技术。因不同物质的进动频率不同,通过测量它们进动的频率值,就可以区分不同的化学物质;再测量相应频率处的谱线下面积,就可以得到化学物质的含量[13]1H-MRS技术测量脂肪准确度高、可重复性好,是肝脏脂肪含量测定的金标准[14],在肌肉脂肪含量测量中也被广泛应用[15,16,17]1H-MRS可以分别对肌肉细胞内及细胞外脂肪进行量化[14],但MRS对扫描设备及条件要求较高,且成像时间较长,图像处理较繁琐。

1.3 Dixon技术与IDEAL-CPMG技术

Dixon技术基于水和脂肪之间的化学位移不同的原理来获得水脂分离图像。因脂肪和水中质子的共振频率存在差异,通过改进扫描时的回波时间(echo time,TE),使脂肪和水中的质子分别处于同相位和反相位状态,按照公式FF=SI脂肪/(SI脂肪+SI)可测得脂肪百分比,其中SI脂肪是脂肪图像中的信号强度,SI是水图像的信号强度[18]。研究表明[15,19],Dixon技术测得的脂肪分数与MRS测得的脂肪含量具有一致性,且与1H-MRS相比,Dixon技术不但能定量测量脂肪含量,还可以覆盖较大的空间面积,故该技术发展较快,目前广泛应用于肌肉组织的脂肪含量的测量中[18,19,20]。IDEAL-CPMG (iterative decomposition of water and fat with echo asymmetry and least-squares)技术是基于Dixon技术发展而来的,在一次采集中可同时获得水像、脂像及同相位与反相位图像,使用非对称采集技术与迭代最小二乘水脂分离的算法,使得任意的水脂比例都可以进行精确的水脂分离,进而可对肌肉内脂肪进行量化[21]

1.4 T2 mapping

RF脉冲中止后,原子核从高能级激发状态释放能量恢复到低能级平衡状态的过程称为弛豫,该过程所需要的时间称为弛豫时间。横向弛豫时间即T2弛豫时间,为横向磁化矢量衰减至其37%的所需时间。T2 mapping技术是近年来出现的新兴MRI定量技术,通过测量组织T2值来定量分析组织内部成分变化[22],该成像方法是近年来国内外研究关节软骨成像最常用的技术[23,24],在骨骼肌疾病中亦有应用[25]。在不同状态下肌肉的T2弛豫时间不同,肌肉组织处于脂肪浸润状态时,可出现T2弛豫时间延长[26],通过对T2值进行定量测量就可以获得肌肉脂肪浸润程度[27]。T2 mapping成像回波次数越多,对组织T2值的测量会越准确,但扫描时间会延长[28]

2 磁共振脂肪测量技术在肌肉病变中的应用

目前磁共振脂肪测量技术主要应用于杜氏型肌营养不良症、2型糖尿病胰岛素抵抗及肌肉退行性病变等。

2.1 磁共振脂肪测量技术在DMD中的应用

DMD是一种X连锁隐性遗传的致命性疾病,由于抗肌萎缩蛋白的突变或缺失,导致肌膜不稳定,在肌肉收缩的过程中肌膜破裂。早期的主要病理改变是肌肉变性、纤维化、坏死,肌膜破裂,进一步发展则可出现不可逆的肌肉脂肪变性。多数患者通常于10~15岁丧失行走能力,在二十几岁因进行性肌无力和心肺功能障碍而死亡[29]。糖皮质激素可降低肌细胞凋亡率,并可减缓肌纤维坏死过程,改善肌肉功能[19]。临床功能评分系统常用来评估患儿的肌肉力量,但无法对单个肌肉的功能进行评估,且此类患儿往往难以配合该项检查[19]。研究表明,肌肉脂肪浸润程度是影响DMD患儿预后的重要因素[12,30],故测量DMD患者肌肉的脂肪含量来评估患者病情是非常有必要的。目前测定肌肉脂肪浸润程度的金标准是肌肉活检,但因该方法是有创的,重复肌肉活检来监测疾病的进展程度及治疗效果是不切实际的。多种MRI脂肪测量技术已应用于该疾病中,并为疾病的严重程度进行较准确的评估。Wren等[19]使用Dixon技术对9例DMD男性患儿的下肢肌肉中的脂肪含量进行测量,并对其进行临床功能等级评分,结果显示,患儿肌肉的临床功能等级与用Dixon技术测量得到的肌肉脂肪含量呈明显的负相关,得出Dixon技术测得的肌肉脂肪含量可以准确评估DMD患者严重程度的结论。同样,郁伟斌等[12]使用T2 mapping及视觉评估分级法对DMD患儿骨盆及大腿部肌肉的脂肪含量进行测量,发现T2 mapping及视觉评估分级法测得的脂肪含量与临床评估等级有着显著的相关性。Forbes等[31]的研究表明,1H-MRS不仅可以测量下肢肌肉脂质含量来对DMD患者疾病现状进行评估,还可监测患者疾病的进展并指导临床在合适的年龄阶段进行干预。Arpan等[32]将15例接受糖皮质激素治疗的DMD患者纳为研究对象,运用T2 mapping及MRS测量下肢肌肉T2值和脂肪含量来评估糖皮质激素治疗效果,发现经糖皮质激素治疗后,DMD患儿肌肉的T2减低、肌肉脂肪沉积减少。MRI脂肪测量技术不但能准确地评估DMD患者病情的进展程度,还可以评估治疗效果进而指导临床及时进行干预。

2.2 MRI肌肉脂肪测量技术在2型糖尿病胰岛素抵抗中的应用

目前在世界范围内,糖尿病的患病率、发病率急剧上升,是严重威胁人类健康的世界性公共卫生问题[33]。胰岛素抵抗是2型糖尿病的特征,骨骼肌既是胰岛素作用的重要靶细胞,同时也是胰岛素抵抗的重要部位。肌肉细胞内脂肪(intramyocellular lipid,IMCL)的含量异常增高可导致胰岛素作用的敏感性降低[34],进而导致胰岛素抵抗,且IMCL含量与胰岛素抵抗程度呈明显正相关[2]。目前判断胰岛素抵抗的金标准是高胰岛素-正葡萄糖钳夹技术,由于该项检查方式耗时较长,操作过程繁琐,对操作人员要求高,临床开展与推广困难[35]。Jazet等[36]对10例2型糖尿病患者的研究表明,经短期饮食限制和减重治疗后胰岛素抵抗得以改善,同时大腿肌肉活检显示肌肉内脂肪含量也减少。因此,肌肉内脂质含量可以用作早期检测胰岛素抵抗及评估治疗效果的体内生物标志物[13]。Laracastro等[37]将7例2型糖尿病患者及5例非糖尿病肥胖患者作为研究对象,经短期低热量饮食治疗后发现受试者的胰岛素敏感性增加,且用1H-MRS测量得到比目鱼肌的IMCL减少,进一步验证了胰岛素抵抗与IMCL含量相关。Tamura等[38]将14例2型糖尿病患者分成两组,分别采用单纯饮食治疗及饮食加运动治疗,结果显示经饮食加运动治疗后,用1H-MRS测得的胫骨前肌内脂质含量较前下降明显,用高胰岛素-正葡萄糖钳夹技术检测胰岛素敏感性升高,胰岛素抵抗得到改善。同样有研究者[39]对24例2型糖尿病患者进行了研究,发现在患者使用吡格列酮治疗4个月后,高胰岛素-正葡萄糖钳夹技术测得胰岛素抵抗得到改善,同时用1H-MRS测量得到的小腿比目鱼肌的脂肪含量有所下降。由此看出,用1H-MRS测得的IMCL含量不仅可以评估2型糖尿病患者胰岛素抵抗程度,还可通过IMCL含量的变化评估治疗效果。

2.3 MRI脂肪测量技术在肌肉退行性病变中的应用

腰部椎旁肌在维持腰椎功能中发挥着重要作用,椎旁肌退变时主要表现为肌肉萎缩和脂肪浸润[40]。随着年龄增加,脂肪含量也会增加[41],椎旁肌退变的同时,肌肉疲劳性增加,进而更容易发生损伤,致使腰部不适症状加重。Kjaer等[42]用MRI视觉评估分级法对大样本人群的多裂肌进行脂肪定量,结果显示腰椎多裂肌脂肪浸润程度与成人下腰痛强相关。Markus等[43]使用MRI视觉评估分级法对腰椎多裂肌中脂肪浸润程度进行分级,发现腰椎多裂肌中脂肪浸润的严重程度与腰椎前屈功能受限有关。同样有研究表明,MRI Dixon技术可以定量测量椎旁肌的脂肪信号分数,所测得的椎旁肌的脂肪信号分数与年龄呈正相关,Dixon技术可用来监测脊旁肌随年龄增长发生的退行性变[44]1H-MRS也可以测量腰背部椎旁肌群的脂肪含量[45],有研究运用1H-MRS测量多裂肌的脂肪含量,证实慢性下腰痛患者的多裂肌中脂肪含量显著高于无症状志愿者[46]。MRI脂肪测量技术可用来检测及评价椎旁肌的退行性改变,并指导临床及时进行康复训练。

肩袖撕裂是引起慢性肩痛及肩关节功能障碍的常见原因,其患病率随年龄的增加而上升[47]。肩袖撕裂后肌肉退变的主要病理变化是肌肉组织萎缩和脂肪浸润[48],且脂肪浸润程度与治疗效果、治疗方式及患者预后密切相关[48,49,50]。因此,应用影像学检查技术对肩袖损伤后冈上肌退变进行评估具有非常重要的临床指导意义。Goutallier分级[51]是运用影像学方法来测量肩袖肌肉脂肪浸润程度,这种基于视觉评估分级法的脂肪测量方法广泛运用于临床及相关研究中。多个研究表明,MRI脂肪测量技术可评价肩袖肌肉的脂肪变性程度[8,20,26,52,53,54],并发现肩袖肌肉脂肪含量与肩袖的撕裂程度及预后呈正相关[8,20,54]。Kim等[8]对105例行关节镜下肩袖修复的患者进行研究,患者在术前行肩关节MR检查,运用视觉评估分级法对肩袖肌肉进行脂肪浸润程度进行判断,结果显示,冈下肌脂肪浸润程度是预测肩袖可修复性的有效指标。Nozaki等[20]对50例肩袖撕裂患者通过使用Dixon技术来量化术前和术后肩袖脂肪变性的程度,发现手术失败修复组术前肩袖肌肉的脂肪含量明显高于完全整修复组。总之,MRI脂肪测量技术不仅可以协助诊断肩袖撕裂、评估肩袖撕裂的程度,还可以指导临床制订治疗方案及合理判断预后。

3 总结与展望

评估肌肉脂肪化的磁共振脂肪测量技术主要包括视觉评估分级法、T2 mapping、Dixon技术及MRS等,MRI脂肪评估测量技术是一种无创性的检查方法,但还存在几点不足:(1)成像时间长,后处理繁琐;(2)目前尚无公认的最优化测量方式;(3) MRI脂肪评估测量技术还处于研究阶段,还未被广泛应用到临床工作中。尽管如此,不论作为科研项目还是临床检查项目,MRI脂肪测量技术在评估患者病情、指导临床选择治疗方案、评估临床治疗效果方面都有着十分乐观的应用前景。

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