Longitudinal Follow-Up of Patients With Duchenne Muscular Dystrophy Using Quantitative 23Na and 1H MRI

IF 9.4 1区医学 Q1 GERIATRICS & GERONTOLOGY

Journal of Cachexia Sarcopenia and Muscle Pub Date : 2025-04-20 DOI:10.1002/jcsm.13812

Teresa Gerhalter, Benjamin Marty, Lena V. Gast, Frank Roemer, Pierre-Yves Baudin, Regina Trollmann, Michael Uder, Pierre G. Carlier, Armin M. Nagel

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Abstract

Background

Quantitative muscle MRI commonly evaluates disease activity and muscle wasting in Duchenne muscular dystrophy (DMD). Disturbances in ion homeostasis contribute to DMD pathophysiology, but their relationships with disease progression is unclear. ²³Na MRI may provide insights into the disease course and treatment response. This longitudinal study assessed whether sodium levels are elevated in DMD patients regardless of fat fraction (FF) and whether baseline sodium levels influence FF changes over time. Additionally, we quantified the effect of slice selection on measured sodium values.

Methods

Thirteen DMD boys (age 7.8 ± 2.4 years) underwent MRI of lower leg muscles at 3T at three visits, spaced 6 months apart. We assessed FF for disease progression and water T₂, pH, apparent tissue sodium concentration (aTSC), and intracellular-weighted ²³Na signal (ICwS) for disease activity. Fourteen healthy boys (age 9.5 ± 1.7 years) underwent the same MRI protocol once. Linear regression and mixed-effect modelling were used to examine sodium level increases and their impact on FF changes.

Results

In DMD, muscles with FF < 10% exhibited significantly elevated aTSC (24.8 ± 4.6 mM vs. 14.5 ± 2.1 mM in controls, p < 0.001) and higher ICwS (23.6 ± 2.5 a.u. vs. 14.1 ± 2.1 a.u., p < 0.001). At Visit 1, FF values showed a significant negative association with aTSC (β = −17.30, p = 0.016) and ICwS (β = −21.02, p < 0.001).

The first mixed-effect model, which assessed aTSC alone, showed no significant effect on FF progression but indicated a weak trend (p = 0.098). The second, more comprehensive model—incorporating also ICwS and water T₂—revealed that FF changes were positively associated with aTSC (p = 0.0023) and negatively associated with ICwS and wT₂ (p < 0.001 and p = 0.025, respectively), with ICwS showing a significant interaction with time (p = 0.0033).

Varying slice positioning and slice number demonstrated minimal impact on aTSC and ICwS, with low CV (2%–4%) in the mid-belly region.

Conclusions

The study demonstrates significant MRI-based changes related to dystrophic alterations in DMD. We identified early alterations in sodium homeostasis, independent of FF. Our findings suggest that the relationship between sodium levels and FF progression is complex and may not be fully explained by total sodium measurements alone. Given the small sample size, further validation in larger cohorts is needed. Combined ¹H and ²³Na-MRI may offer deeper insights into how metabolic and ionic changes interact with FF progression and overall disease activity.

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利用 23Na 和 1H 磁共振成像定量对杜氏肌营养不良症患者进行纵向随访

定量肌肉MRI通常评估杜氏肌营养不良症（DMD）的疾病活动性和肌肉萎缩。离子稳态紊乱有助于DMD病理生理，但它们与疾病进展的关系尚不清楚。23Na核磁共振成像可以深入了解疾病的病程和治疗反应。这项纵向研究评估了DMD患者的钠水平是否会升高，而不考虑脂肪分数（FF），以及基线钠水平是否会影响FF随时间的变化。此外，我们量化了切片选择对测量钠值的影响。方法13例DMD男孩（年龄7.8±2.4岁），每隔6个月进行3次3T下肢肌肉MRI检查。我们评估了FF的疾病进展和水T2、pH、表观组织钠浓度（aTSC）和细胞内加权23Na信号（ICwS）的疾病活动性。14名健康男孩（年龄9.5±1.7岁）接受了一次相同的MRI方案。线性回归和混合效应模型用于检验钠水平升高及其对FF变化的影响。结果：在DMD中，加入FF和lt 10%的肌肉表现出显著升高的aTSC（24.8±4.6 mM，对照组为14.5±2.1 mM, p < 0.001）和较高的ICwS（23.6±2.5 a.u）。Vs. 14.1±2.1 a.u.。， p < 0.001)。在访问1时，FF值与aTSC （β = - 17.30, p = 0.016）和ICwS （β = - 21.02, p < 0.001）呈显著负相关。第一个混合效应模型，单独评估aTSC，对FF进展没有显著影响，但显示出微弱的趋势（p = 0.098）。第二个更全面的模型——也纳入了ICwS和水t2——显示FF变化与aTSC呈正相关（p = 0.0023），与ICwS和wT2负相关（p <； 0.001和p = 0.025）， ICwS与时间有显著的相互作用（p = 0.0033）。不同的切片位置和切片数量对aTSC和ICwS的影响最小，腹部中部的CV较低（2%-4%）。结论：该研究显示了与DMD营养不良改变相关的显著mri变化。我们发现了独立于FF的钠稳态的早期改变。我们的研究结果表明，钠水平与FF进展之间的关系是复杂的，可能不能仅通过总钠测量来完全解释。由于样本量小，需要在更大的队列中进一步验证。结合1H和23Na-MRI可以更深入地了解代谢和离子变化如何与FF进展和整体疾病活动相互作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Cachexia Sarcopenia and Muscle MEDICINE, GENERAL & INTERNAL-

CiteScore

13.30

自引率

12.40%

发文量

234

审稿时长

16 weeks

期刊介绍： The Journal of Cachexia, Sarcopenia and Muscle is a peer-reviewed international journal dedicated to publishing materials related to cachexia and sarcopenia, as well as body composition and its physiological and pathophysiological changes across the lifespan and in response to various illnesses from all fields of life sciences. The journal aims to provide a reliable resource for professionals interested in related research or involved in the clinical care of affected patients, such as those suffering from AIDS, cancer, chronic heart failure, chronic lung disease, liver cirrhosis, chronic kidney failure, rheumatoid arthritis, or sepsis.