Muscle Magnetic Resonance Imaging: A New Diagnostic Tool with Promising Avenues in Therapeutic Trials^[*]

Muscle Magnetic Resonance Imaging of the Lower Limbs: Valuable Diagnostic Tool in the Investigation of Childhood Neuromuscular Disorders

Muscle imaging has extraordinarily developed in the past decade. Over the past years, the use of magnetic resonance imaging (MRI) to identify particular involvement of the muscles of the body is becoming a fundamental diagnostic tool. Compared with computed tomography, MRI is a nonradiating technique and offers better tissue contrast for muscle disorders. Different patterns of involvement in T1 turbo spin echo (TSE) sequences have been described in several hereditary myopathies,[1] [2] with additional interest of short tau inversion recovery (STIR) or T2 fat saturation techniques in several of them (p.e. facio-scapulo-humeral (FSH),[3] dysferlin[4]) or in inflammatory myopathies.[5] The particular combination of signal and volume abnormalities, the distribution of fatty infiltration inside a muscle, or the “texture” may give highly informative data to guide the genetic studies to perform in a patient. As a result of these developments, muscle MRI is being increasingly used in clinical practice to approach the diagnosis of hereditary myopathies, sometimes sparing the need for a muscle biopsy or guiding the muscle to sample. In the pediatric patient, MRI has shown great interest in children with suspicion of early-onset myopathy, in particular when they present certain features such as rigid spine stiffness, hyperlaxity, or limb joint contractures.[6] [7] In the study on 28 children by Kana et al,[8] the integration of this new tool in the diagnostic processes of the everyday neuromuscular clinic is nicely shown. In a series of children with suspected congenital myopathy or muscular dystrophy, MRI was contributory to the diagnosis in one-third, and in one-fourth, it led directly to genetic confirmation. In several patients, MRI revealed crucial information, not identified by other classical tests. Very remarkably, MRI not only allowed exploring the possibility of muscle diseases but also showed consistency with neurogenic disorders as spinal muscular atrophy, or pointed to the possibility of a myasthenic syndrome in children with no significant signal abnormalities who still were markedly weak. As shown in this series, imaging may be essential to investigate the implication of large genes difficult to analyze by standard techniques (RYR1, NEB), to target gene sequencing in disorders genetically heterogeneous (three COL6 genes in Ullrich CMD/Bethlem myopathy, nemaline myopathy, centronuclear myopathy, limb girdle muscular dystrophies), or in those with low specificity of atomopathology or immunostaining studies (LMNA, SEPN1). Moreover, MRI shows sometimes a higher diagnostic impact in patients affected with myopathies usually diagnosed by specific biopsy findings (RYR1, calpain) but in whom the muscle specimen remained noninformative or nonconclusive.

Limitations of muscle MRI may be diverse. Time of scanning, need of sedation (young children, noncooperative patients), technical settings and logistic difficulties, metallic implants, ventilation during the procedure, and severe limb contractures may interfere or even prevent the examination. In our experience, these difficulties may be often solved, provided an adapted setting is defined and solutions anticipated. Therefore, close interaction between clinicians and radiologists is mandatory, with bidirectional exchanges. Later on, a supplementary limitation is linked to the complexity for image interpretation, not only related with the quality of images but also of the availability of data in literature. Although it is true that several publications report relatively distinct patterns of involvement in different myopathies, most of them concern a small number of patients and are limited to lower limbs,[7] [8] [9] which may not be informative enough or not concern to the whole spectrum of severities, ages, or phenotypes associated to a gene defect. Certain diseases are not yet described (new genes) or there is not a consistent pattern described. One of the possibilities to increase the diagnostic impact of muscle imaging is spreading the regions scanned. We described in 2012 a relatively short protocol with use in children and adults which has allowed scanning now for more than a decade numerous patients with a large spectrum of ages, phenotypes, severities, and diagnosis.[6] [10] [11] Whole-body MRI (WBMRI) visualizes muscles of the body from head to toes and adds the possibility to obtain frontal views to the standard axial views of sequential MRI techniques. This is particularly useful for scanning certain muscles that follow the body-axis (masticator, psoas, gluteal, neck, trapezius, etc.) or those difficult to explore in axial views (tongue, intercostals).[6] [10] Overall, WBMRI allows not only a muscle-by-muscle approach but also a comparative region-to-region analysis of muscle involvement within the global view of the body, which may offer additional information with diagnostic impact.

As a clinicoradiological experienced team, we are often consulted about patients in whom imaging has been performed before directing targeted sequencing. In the very last years, there is an increasing demand derived from the use of modern genetic techniques such as whole-genome or exome sequencing and SNP-CGH array. These techniques provide a large amount of information but interpretation remains often complex due to the detection of multiple genetic variants and abnormalities of unknown significance. Muscle imaging may help confirming or ruling out multiple genetic variants and abnormalities of unknown significance. Therefore, a great development of these noninvasive techniques is expected in the next future, provided muscle imaging signatures of different myopathies are described in large series of patients. At term, disposing of an atlas of different diseases with their graphical representation by sorts of “WBMRI fingerprints” would offer a potential powerful tool of great interest not only for clinicians but also for basic scientists and molecular researchers.

Other than the use of muscle imaging for diagnostic purposes, active research is currently undergoing to identify sequences and techniques useful in the follow-up of patients and as an outcome measure in therapeutic trials (Dixon, T2 mapping).[12] [13]

Although a lot needs still to be done to improve our knowledge in pattern recognition, scoring, graphical representation, and new quantitative techniques, muscle imaging by MRI techniques appears as a potentially powerful tool for the diagnosis and follow-up of neuromuscular patients, and is called to become an essential element for future therapeutic trials. Given the rarity and large spectrum of hereditary myopathies, the establishment of collaborative efforts and international networking seems critical. In this context, it appears urgent to achieve international consensus in technical settings and image analysis to allow sharing data collection and analysis of large series of patients and optimizing further research.

^* This article is an editorial on “Muscle magnetic resonance imaging of the lower limbs: valuable diagnostic tool in the investigation of childhood neuromuscular disorders” by Kana et al (Neuropediatrics 2014;45(5):278—288, doi: 10.1055/s-0034-1381954).

^§ The authors were part of Working group 1 (WG1) “Improve diagnosis and understanding of muscle pathology,” MYO-MRI COST-Action (BM1304), “Applications of MR imaging and spectroscopy techniques in neuromuscular disease: collaboration on outcome measures and pattern recognition for diagnostics and therapy development,” European Cooperation in Science and Technology (COST).

• References

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