建模杜氏肌营养不良症的疾病进程。
Modeling disease trajectory in Duchenne muscular dystrophy.
机构信息
From the Advanced Imaging Research Center (W.D.R., Y.A.B., I.A., E.O., B.M.), Department of Neurology (W.D.R., I.A., B.S.R., E.L.F.), Department of Biomedical Engineering (W.D.R.), Department of Behavioral Neuroscience (W.D.R., Y.A.B.), and Department of Pediatrics (B.S.R., E.L.F.), Oregon Health & Science University, Portland; Departments of Physical Therapy (W.T.T., S.C.F., R.J.W., H.A., C.S., D.J.L., K.V.), Statistics (S.C., M.J.D.), Physiology and Functional Genomics (A.B., G.A.W.), and Pharmacology & Therapeutics (H.L.S.), University of Florida, Gainesville; Department of Radiology (D.-J.W.) and Division of Neurology (G.T.), Children's Hospital of Philadelphia, PA; Department of Pediatrics (R.F.), Nemours Children's Hospital, Orlando, FL; and Shriners Hospital (B.S.R., E.L.F.), Portland, OR.
出版信息
Neurology. 2020 Apr 14;94(15):e1622-e1633. doi: 10.1212/WNL.0000000000009244. Epub 2020 Mar 17.
OBJECTIVE
To quantify disease progression in individuals with Duchenne muscular dystrophy (DMD) using magnetic resonance biomarkers of leg muscles.
METHODS
MRI and magnetic resonance spectroscopy (MRS) biomarkers were acquired from 104 participants with DMD and 51 healthy controls using a prospective observational study design with patients with DMD followed up yearly for up to 6 years. Fat fractions (FFs) in vastus lateralis and soleus muscles were determined with H MRS. MRI quantitative T (qT) values were measured for 3 muscles of the upper leg and 5 muscles of the lower leg. Longitudinal changes in biomarkers were modeled with a cumulative distribution function using a nonlinear mixed-effects approach.
RESULTS
MRS FF and MRI qT increased with DMD disease duration, with the progression time constants differing markedly between individuals and across muscles. The average age at half-maximal muscle involvement (μ) occurred 4.8 years earlier in vastus lateralis than soleus, and these measures were strongly associated with loss-of-ambulation age. Corticosteroid treatment was found to delay μ by 2.5 years on average across muscles, although there were marked differences between muscles with more slowly progressing muscles showing larger delay.
CONCLUSIONS
MRS FF and MRI qT provide sensitive noninvasive measures of DMD progression. Modeling changes in these biomarkers across multiple muscles can be used to detect and monitor the therapeutic effects of corticosteroids on disease progression and to provide prognostic information on functional outcomes. This modeling approach provides a method to transform these MRI biomarkers into well-understood metrics, allowing concise summaries of DMD disease progression at individual and population levels.
CLINICALTRIALSGOV IDENTIFIER
NCT01484678.
目的
利用腿部肌肉的磁共振生物标志物来量化杜氏肌营养不良症（DMD）患者的疾病进展。
方法
采用前瞻性观察性研究设计，对 104 名 DMD 患者和 51 名健康对照者进行 MRI 和磁共振波谱（MRS）生物标志物检测，DMD 患者每年随访一次，最长随访 6 年。采用 H MRS 测定股外侧肌和比目鱼肌的脂肪分数（FF）。测量大腿 3 块肌肉和小腿 5 块肌肉的 MRI 定量 T（qT）值。采用非线性混合效应方法，使用累积分布函数对生物标志物的纵向变化进行建模。
结果
MRS FF 和 MRI qT 随 DMD 病程增加而增加，个体间和肌肉间的进展时间常数差异显著。半最大肌肉受累年龄（μ）平均在股外侧肌比比目鱼肌早 4.8 年，这些指标与丧失行走能力的年龄密切相关。发现皮质类固醇治疗可使平均肌肉μ值平均延迟 2.5 年，但肌肉之间存在显著差异，进展较慢的肌肉延迟较大。
结论
MRS FF 和 MRI qT 提供了 DMD 进展的敏感无创测量方法。对多个肌肉的这些生物标志物的变化进行建模，可用于检测和监测皮质类固醇对疾病进展的治疗效果，并提供功能结局的预后信息。这种建模方法提供了一种将这些 MRI 生物标志物转化为理解透彻的指标的方法，从而可以在个体和人群水平上对 DMD 疾病进展进行简明总结。
临床试验.gov 标识符：NCT01484678。
Zotero 插件