背景:寻找敏感的临床结果指标在神经肌肉疾病的自然史研究和治疗试验中变得至关重要。这里,在西罗莫司用于包涵体肌炎(IBM)的安慰剂对照研究中,我们关注定量磁共振成像(MRI)和磷磁共振波谱(31PMRS)的1年纵向数据,还检查它们与功能的联系,力量,和下肢肌肉的临床参数。
方法:定量MRI和31PMRS数据在3T时从单个部位收集,涉及44名患者(22名服用安慰剂,西罗莫司22)在基线和第1年,以及21名健康对照。评估包括脂肪分数(FF),收缩横截面积(cCSA),以及全球腿部和大腿部分的水T2,肌肉群,个体肌肉,以及股四头肌或肱三头肌的31PMRS指数。分析涵盖了患者-对照比较,通过标准t检验和线性混合模型进行年度变化评估,标准化响应平均值(SRM)的计算,并探索MRI之间的相关性,31PMRS,功能,力量,和临床参数。
结果:股四头肌和腓肠肌的FF值最高,表现出显著的异质性和不对称性,尤其是股四头肌.在安慰剂组中,股四头肌的平均1年FF增加为3.2%(P<0.001),而在西罗莫司组中,为0.7%(P=0.033)。1年后,两组股四头肌中的cCSA显着降低(P<0.001),安慰剂组的中位数变化为12.6%,西罗莫司组为5.5%。两组间FF和cCSA变化差异有统计学意义(P<0.001)。安慰剂组的FF和cCSA的SRM值分别为1.3和1.4,西罗莫司组为0.5和0.8,分别。两组股四头肌的水T2值最高,两组均显著超过对照值(P<0.001),且安慰剂组高于西罗莫司组.治疗后,仅西罗莫司组股四头肌的水T2显着增加(P<0.01)。与对照组相比,患者的多个31PMRS指数异常,治疗后保持不变。在基线水T2和FF与FF的变化之间确定了显着的相关性(P<0.001)。此外,在FF之间观察到显著的相关性,cCSA,水T2,以及功能和强度结果测量。
结论:这项研究表明,定量MRI/31PMRS可以辨别安慰剂和西罗莫司治疗的IBM患者之间的可测量差异,为IBM等特发性炎症性肌病的未来治疗试验提供了希望。
BACKGROUND: Finding sensitive clinical outcome measures has become crucial in natural history studies and therapeutic trials of neuromuscular disorders. Here, we focus on 1-year longitudinal data from quantitative magnetic resonance imaging (MRI) and phosphorus magnetic resonance spectroscopy (31P MRS) in a placebo-controlled study of sirolimus for inclusion body myositis (IBM), also examining their links to functional, strength, and clinical parameters in lower limb muscles.
METHODS: Quantitative MRI and 31P MRS data were collected at 3 T from a single site, involving 44 patients (22 on placebo, 22 on sirolimus) at baseline and year-1, and 21 healthy controls. Assessments included fat fraction (FF), contractile cross-sectional area (cCSA), and water T2 in global leg and thigh segments, muscle groups, individual muscles, as well as 31P MRS indices in quadriceps or triceps surae. Analyses covered patient-control comparisons, annual change assessments via standard t-tests and linear mixed models, calculation of standardized response means (SRM), and exploration of correlations between MRI, 31P MRS, functional, strength, and clinical parameters.
RESULTS: The quadriceps and gastrocnemius medialis muscles had the highest FF values, displaying notable heterogeneity and asymmetry, particularly in the quadriceps. In the placebo group, the median 1-year FF increase in the quadriceps was 3.2% (P < 0.001), whereas in the sirolimus group, it was 0.7% (P = 0.033). Both groups experienced a significant decrease in cCSA in the quadriceps after 1 year (P < 0.001), with median changes of 12.6% for the placebo group and 5.5% for the sirolimus group. Differences in FF and cCSA changes between the two groups were significant (P < 0.001). SRM values for FF and cCSA were 1.3 and 1.4 in the placebo group and 0.5 and 0.8 in the sirolimus group, respectively. Water T2 values were highest in the quadriceps muscles of both groups, significantly exceeding control values in both groups (P < 0.001) and were higher in the placebo group than in the sirolimus group. After treatment, water T2 increased significantly only in the sirolimus group\'s quadriceps (P < 0.01). Multiple 31P MRS indices were abnormal in patients compared to controls and remained unchanged after treatment. Significant correlations were identified between baseline water T2 and FF at baseline and the change in FF (P < 0.001). Additionally, significant correlations were observed between FF, cCSA, water T2, and functional and strength outcome measures.
CONCLUSIONS: This study has demonstrated that quantitative MRI/31P MRS can discern measurable differences between placebo and sirolimus-treated IBM patients, offering promise for future therapeutic trials in idiopathic inflammatory myopathies such as IBM.