Whole-body Muscle Magnetic Resonance Imaging Research Articles

Whole-body muscle magnetic resonance imaging in inflammatory myopathy with mitochondrial pathology.

Inflammatory myopathy with mitochondrial pathology (IM-Mito) is a rare condition described in a few case series, and it is not clear whether it is a specific disease or a variant of Inclusion Body Myositis (IBM). Radiological data of IM-Mito patients has only been evaluated in one study. To analyze whole-body muscle magnetic resonance imaging (MRI) features in patients with IM-Mito compared with individuals with IBM. Fourteen IM-Mito and ten IBM patients were included. IM-Mito was defined by endomysial inflammatory infiltrate, presence of at least 1% of Cytochrome C Oxidase negative fibers, and absence of rimmed vacuoles in muscle biopsy; and IBM was defined by the presence of dystrophic muscular abnormalities, endomysial inflammatory infiltrate, and rimmed vacuoles. Patients underwent clinical evaluation and whole-body muscle MRI to determine the presence of edema, and fatty infiltration in various muscles. Muscle imaging abnormalities were asymmetric in most patients with IM-Mito and IBM. Muscles with the highest average degree of fatty infiltration in both conditions were the quadriceps and medial gastrocnemius. Most patients with IM-Mito and IBM showed imaging patterns of rectus femoris relatively spared compared to other quadriceps muscles. The flexor digitorum profundus was the most affected muscle of the upper limbs in both IBM and IM-Mito. Although the results suggest some similarities in muscle imaging features between IM-Mito and IBM, there remains uncertainty whether these two conditions are part of the same clinical spectrum.

The central pattern of weakness of ALS: Morphological correlates in whole-body muscle MRI.

Monosynaptically cortically innervated α-motoneurons are early and strongly involved in amyotrophic lateral sclerosis (ALS). Consequently, the muscles that receive the strongest direct corticomotoneuronal input are the clinically most affected. To objectify this concept in vivo through morphological image correlates, whole-body magnetic resonance imaging (MRI) with muscle signal analysis was performed in patients with ALS compared to healthy controls. Modified Dixon-based whole-body MRI was acquired in patients with ALS (n = 33) and matched healthy controls (n = 30). Manual labeling of limb muscle MRI was performed, and a specific subset of nine muscles, selected as pairs of muscle groups with different corticomotoneuronal input, was analyzed per subject based on their volume, fat fraction, and functional remaining muscle area (fRMA). Statistical analysis of 978 muscles in total revealed significantly decreased volumes, decreased fRMA, and increased fat fraction in the muscles of patients with ALS compared to controls. The clinical degree of pareses of directly innervated muscles was significantly worse than that of less directly innervated muscles in each comparison. The muscles receiving stronger direct corticomotoneuronal input showed more pronounced morphological involvement compared to those with less monosynaptic corticomotoneuronal input (fRMA, significant in three pairwise comparisons). In conclusion, whole-body MRI-based muscle analysis provided additional evidence for a characteristic pattern of pareses in ALS. This technical approach (parameterization and quantification of muscle alterations from MRI) to patients with ALS could pave the way for the future establishment of a diagnostic algorithm of muscle MRI for ALS and may serve as a biomarker.

Contractile properties and magnetic resonance imaging-assessed fat replacement of muscles in myotonia congenita.

Myotonia congenita (MC) is a muscle channelopathy in which pathogenic variants in a key sarcolemmal chloride channel Gene (CLCN1) cause myotonia. This study used muscle magnetic resonance imaging (MRI) to quantify contractile properties and fat replacement of muscles in a Danish cohort of MC patients. Individuals with the Thomsen (dominant) and Becker (recessive) variants of MC were studied. Isometric muscle strength, whole-body MRI, and clinical data were collected. The degree of muscle fat replacement of thigh, calf, and forearm muscles was quantitively calculated on Dixon MRI as fat fractions (FFs). Contractility was evaluated as the muscle strength per contractile muscle cross-sectional area (PT/CCSA). Muscle contractility was compared with clinical data. Intramuscular FF was increased and contractility reduced in calf and in forearm muscles compared with controls (FF = 7.0-14.3% vs. 5.3-9.6%, PT/CCSA = 1.1-4.9 Nm/cm2 vs. 1.9-5.8 Nm/cm2 [p < 0.05]). Becker individuals also showed increased intramuscular FF and reduced contractility of thigh muscles (FF = 11.9% vs. 9.2%, PT/CCSA = 1.9 Nm/cm2 vs. 3.2 Nm/cm2 [p < 0.05]). Individual muscle analysis showed that increased FF was limited to seven of 18 examined muscles (p < 0.05). There was a weak correlation between reduced contractility and severity of symptoms. Individuals with MC have increased fat replacement and reduced contractile properties of muscles. Nonetheless, changes were small and likely did not impact clinically on their myotonic symptoms.

Whole-Body Muscle Magnetic Resonance Imaging in 81 Patients with Spinal and Bulbar Muscular Atrophy: A Prospective Study.

Spinal and bulbar muscular atrophy (SBMA) is characterized by slow, progressive bulbar and limb muscle weakness; however, the pattern of progression of muscle fat infiltration remains unclear. We assessed the progression of muscle involvement in 81 patients with SBMA using whole-body muscle magnetic resonance imaging (MRI), alongside clinical and laboratory findings. This prospective study included patients with genetically confirmed SBMA who underwent whole-body muscle MRI. We analyzed muscle fat infiltration and the pattern of involved muscles using cluster analysis, visualizing the sequential progression of fat infiltration. Muscle clusters demonstrated correlation with clinical scales and laboratory findings. Additionally, linear regression analysis was performed to identify the MRI section most strongly associated with 6-minute walk test (6MWT). We included 81 patients with SBMA (age = 54.3 years). After categorizing the patients into 6 clusters based on the pattern of muscle fat infiltration, we observed that muscle involvement began in the posterior calf and progressed to the posterior thigh, pelvis, trunk, anterior thigh, medial thigh, anterior calf, and upper extremity muscles. These muscle clusters correlated significantly with disease duration (τ = 0.47, p < 0.001), 6MWT (τ = -0.49, p < 0.001), and serum creatinine level (τ = -0.46, p < 0.001). The whole-body MRI indicated the thigh as the section most significantly correlated with 6MWT. We used whole-body muscle MRI to determine the sequential progression of the fat infiltration in SBMA. Our findings may enable the identification of objective and reliable imaging outcome measures in the study of the natural history or future clinical trials of SBMA. ANN NEUROL 2024;95:596-606.

A deep learning tool without muscle-by-muscle grading to differentiate myositis from facio-scapulo-humeral dystrophy using MRI

PurposeThe purpose of this study was to assess the capabilities of a deep learning (DL) tool to discriminate between type 1 facioscapulo-humeral dystrophy (FSHD1) and myositis using whole-body muscle magnetic resonance imaging (MRI) examination without the need for visual grading of muscle signal changes. Materials and methodsA total of 40 patients who underwent whole-body MRI examination that included T1-weighted and STIR sequences were included. There were 19 patients with proven FSHD1 (9 men, 10 women; mean age, 47.7 ± 18.0 [SD] years; age range: 20–72 years) and 21 patients with myositis fulfilling European Neuromuscular Centre criteria and European League Against Rheumatism and American College of Rheumatology criteria (11 men, 10 women; mean age, 59.3 ± 17.0 [SD]; age range: 19–78 years). Based on thigh, calf, and shoulder sections a supervised training of a neural network was performed and its diagnostic performance was studied using a 5-fold cross validation method and compared to the results obtained by two radiologists specialized in musculoskeletal imaging. ResultsThe DL tool was able to differentiate FSHD1 from myositis with a correct classification percentage respectively of 69 % (95% CI: 39–99), 75% (95% CI: 48–100) and 77% (95% CI: 60–94) when thigh only, thigh and calf or the thigh, calf, and shoulder MR images were analyzed. The percentages of correct classification of the two radiologists for these later MR images were 38/40 (95%) and 35/40 (87.5%), respectively; with no differences with DL tool correct classification (P = 0.41 and P > 0.99, respectively). Among the seven patients who were misclassified by the radiologists, the DL tool correctly classified six of them. ConclusionA DL tool was developed to discriminate between FSHD1 and myositis using whole-body MRI with performances equivalent to those achieved by two radiologists. This study provides a proof of concept of the effectiveness of a DL approach to distinguish between two myopathies using MRI with a small amount of data, and no prior muscle signal changes grading.

Detecting myositis as a cause of unexplained dysphagia: Proposal for a diagnostic algorithm.

Idiopathic inflammatory myopathy (IIM) can present with dysphagia as a leading or only symptom. In such cases, diagnostic evaluation may be difficult, especially if serological and electromyographical findings are unsuspicious. In this observational study we propose and evaluate a diagnostic algorithm to identify IIM as a cause of unexplained dysphagia. Over a period of 4years, patients with unexplained dysphagia were offered diagnostic evaluation according to a specific algorithm: The pattern of dysphagia was characterized by instrumental assessment (swallowing endoscopy, videofluoroscopy, high-resolution manometry). Patients with an IIM-compatible dysphagia pattern were subjected to further IIM-focused diagnostic procedures, including whole-body muscle magnetic resonance imaging, electromyography, creatine kinase blood level, IIM antibody panel and, as a final diagnostic step, muscle biopsy. Muscle biopsies were taken from affected muscles. In cases where no other muscles showed abnormalities, the cricopharyngeal muscle was targeted. Seventy-two patients presented with IIM-compatible dysphagia as a leading or only symptom. As a result of the specific diagnostic approach, 19 of these patients were diagnosed with IIM according to the European League Against Rheumatism (EULAR) criteria. Eighteen patients received immunomodulatory therapy as a result of the diagnosis. Of 10 patients with follow-up swallowing examination, dysphagia improved in three patients after therapy, while it remained at least stable in six patients. Idiopathic inflammatory myopathy constitutes a potentially treatable etiology in patients with unexplained dysphagia. The diagnostic algorithm presented in this study helps to identify patients with an IIM-compatible dysphagia pattern and to assign those patients for further IIM-focused diagnostic and therapeutic procedures.

Whole-body muscle magnetic resonance imaging in patients with muscle symptoms: incidental findings and outcomes.

Whole-body muscle magnetic resonance imaging (MRI) has become widely used for diagnostic workup in patients with muscle diseases. The prevalence of incidental findings in diagnostic whole-body muscle MRI is unknown. Here, the prevalence and outcomes of incidentalomas in whole-body muscle MRI in a large cohort of patients with muscle symptoms were studied. Two hundred and six patients who consulted at our neuromuscular clinic with muscle weakness and/or myalgia and/or increased serum creatine kinase and in whom a whole-body muscle MRI was performed between January 2016 and March 2020 were included. Whole-body muscle MRI revealed at least one incidentaloma in 132 patients (64.1%), with mean age at MRI examination 50.4years (19-74years). Most of the incidental findings were benign. However, diagnostic examinations were indicated in 16.3% of the incidentalomas, treatment was needed in 4.7% and, in retrospect, symptoms related to the incidental findings were identified in 14.3%. Three malignant (glioblastoma multiforme, renal cell carcinoma and hepato-splenomegaly related to a lymphoma) and one precancerous (low-grade appendiceal mucinous neoplasm) incidental findings were identified. In one patient an abdominal aortic aneurysm was detected and in another a large cerebral arteriovenous malformation. In 1.2% of the incidentalomas, i.e. periventricular white matter lesions (LAMA2 mutations) and fibrous dysplasia (ANO5 mutations), an indirect link with the muscle disease could be established. It is concluded that incidental findings in diagnostic whole-body muscle MRI in patients with muscle symptoms occur frequently. Most of them are benign, but in some timely detecting the incidentaloma leads to early treatment and can thus impact prognosis.

Whole-body muscle MRI of patients with MATR3-associated distal myopathy reveals a distinct pattern of muscular involvement and highlights the value of whole-body examination

ObjectiveMATR3-associated distal myopathy is a rare distal myopathy predominantly affecting lower legs as well as wrist- and finger extensors. Whilst most distal myopathies are clinically and genetically well characterized, diagnosis often remains challenging. Pattern-based magnetic resonance imaging (MRI) approaches offer valuable additional information. However, a consistent pattern of muscular affection is missing for most distal myopathies. Thus, the aim of the present study was to establish a disease-specific pattern of muscular involvement in MATR3-associated distal myopathy using whole-body MRI.Methods15 patients (25–79 years of age, 7 female) with MATR3-associated distal myopathy were subjected to whole-body MRI. The grade of fatty involution for individual muscles was determined using Fischer-Grading. Results were compared to established MRI-patterns of other distal myopathies.ResultsThere was a predominant affection of the distal lower extremities. Lower legs showed a severe fatty infiltration, prominently affecting gastrocnemius and soleus muscle. In thighs, a preferential involvement of semimembranous and biceps femoris muscle was observed. Severe affection of gluteus minimus muscle as well as axial musculature, mainly affecting the thoracic segments, was seen. A sufficient discrimination to other forms of distal myopathy based solely on MRI-findings of the lower extremities was not possible. However, the inclusion of additional body parts seemed to yield specificity.InterpretationMuscle MRI of patients with MATR3-associated distal myopathy revealed a distinct pattern of muscular involvement. The usage of whole-body muscle MRI provided valuable additional findings as compared to regular MRI of the lower extremities to improve distinction from other disease entities.

Carnitine palmitoyltransferase type 2 deficiency: novel mutation in a Native South American family with whole-body muscle magnetic resonance imaging findings: two case reports

BackgroundThe myopathic form of carnitine palmitoyltransferase type II deficiency is an inherited autosomal recessive metabolic myopathy usually starting in childhood. Most reports have been on European and Japanese populations, and no Native South American patients have been reported to date. The p.Ser113Leu mutation is the most frequent in the European population. Only lower-leg magnetic resonance imaging findings have been reported, with gluteus maximus involvement in one case and normal imaging in other patients.Case presentationTwo Native South American siblings, a boy and a girl, presented to our neuromuscular clinic with recurrent rhabdomyolysis associated with transient muscle weakness after prolonged exercise. During episodes, their creatine kinase concentrations were markedly increased, up to 148,000 (1.48 × 105) IU/L in the boy and 18,000 (1.8 × 104) IU/L in the girl. The results of electroneuromyography and histopathology suggested a nonspecific myopathy. CPT2 gene sequencing showed two heterozygous mutations: the p.Ser113Leu variant and a novel one (predicted to be deleterious by in silico analysis), the p.Ser373Pro variant. The patients’ parents were asymptomatic carriers. Whole-body magnetic resonance imaging showed mild selective involvement in the thoracic extensors and pelvic girdle in both siblings, and in the thighs and lower legs in one of them. Dietary and bezafibrate treatment was started, and symptomatic relief was observed.ConclusionsTo the best of our knowledge, this is the first reported Native South American family with a CPT2 deficiency carrying a novel mutation and particular features visualized by whole-body magnetic resonance imaging.

Lower-extremity magnetic resonance imaging in patients with hyperkalemic periodic paralysis carrying the SCN4A mutation T704M: 30-month follow-up of seven patients

Hyperkalemic periodic paralysis (hyperKPP) is a muscle channelopathy characterized by recurrent paralytic attacks. Our previous study, in which we conducted whole-body muscle magnetic resonance imaging (MRI) in patients with hyperKPP, revealed muscle atrophy and fatty change in the lower extremity, especially in older persons. The aim of current study was to identify the progression of myopathy in hyperKPP patients had been assessed in the previous study. We performed lower-extremity muscle MRI in seven hyperKPP patients carrying the T704M mutation in the SCN4A gene at an interval of 30 months. Muscle atrophy, edematous change, fatty change, and fat fraction quantified using the Dixon technique were compared with the previous MRI findings. The lower-extremity MRI scan showed progressive muscle pathologic findings when compared with the previous study. Muscle atrophy, edematous change, and fatty change were prominent in the superficial posterior compartment of the lower leg. The follow-up lower-extremity muscle MRI findings provide evidence for chronic progressive myopathy and suggest the usefulness of MRI for assessing disease progression in patients with hyperKPP. This study is meaningful in terms of providing data showing the longitudinal changes of muscles in patients with periodic paralysis.

Correlation between quantitative whole-body muscle magnetic resonance imaging and clinical muscle weakness in Pompe disease.

Previous examination of whole-body muscle involvement in Pompe disease has been limited to physical examination and/or qualitative magnetic resonance imaging (MRI). In this study we assess the feasibility of quantitative proton-density fat-fraction (PDFF) whole-body MRI in late-onset Pompe disease (LOPD) and compare the results with manual muscle testing. Seven LOPD patients and 11 disease-free controls underwent whole-body PDFF MRI. Quantitative MR muscle group assessments were compared with physical testing of muscle groups. The 95% upper limits of confidence intervals for muscle groups were 4.9-12.6% in controls and 6.8-76.4% in LOPD patients. LOPD patients showed severe and consistent tongue and axial muscle group involvement, with less marked involvement of peripheral musculature. MRI was more sensitive than physical examination for detection of abnormality in multiple muscle groups. This integrated, quantitative approach to muscle assessment provides more detailed data than physical examination and may have clinical utility for monitoring disease progression and treatment response.

Structural and functional cardiac analyses using modern and sensitive myocardial techniques in adult Pompe disease.

The purpose of this study was to analyze comprehensively the heart using modern and sensitive myocardial techniques in order to determine if structural or functional cardiac alterations are present in adult Pompe disease. Twelve patients with adult Pompe disease and a control group of 187 healthy subjects of similar age and gender were included. Structural and functional cardiac characteristics were analyzed by conventional and 2D speckle-tracking echocardiography. In addition, in a subgroup of adult Pompe patients, we analyzed the myocardial and musculoskeletal features by means of cardiac and whole-body muscle magnetic resonance imaging. Patients with Pompe disease had significant structural and functional musculoskeletal alterations such as atrophy with fatty replacement and weakness in trunk and extremities. In contrast, Pompe patients had similar structural and functional myocardial features to healthy subjects (LV strain -20.7 ± 1.9 vs. -21.3 ± 2.1%; RV strain -24.2 ± 5.3 vs. -24.8 ± 3.8%; LA strain 41.5 ± 10.3 vs. 44.8 ± 11.0%; P > 0.05; and no evidence of LV and RV hypertrophy or LA enlargement). In addition, there was no evidence of valvular cardiac alterations, electrocardiographic abnormalities, or myocardial fibrosis in Pompe patients. In the current study analyzing the heart with modern and sensitive myocardial techniques, we evidenced that functional and structural cardiac alterations are not present when Pompe disease begins in adulthood. Therefore, these findings suggest that adult Pompe disease should not be taken into consideration in the differential diagnostic of structural or functional cardiac disorders.

Whole-Body Muscle MRI in Patients with Hyperkalemic Periodic Paralysis Carrying the SCN4A Mutation T704M: Evidence for Chronic Progressive Myopathy with Selective Muscle Involvement.

Background and PurposeHyperkalemic periodic paralysis (hyperKPP) is a muscle sodium-ion channelopathy characterized by recurrent paralytic attacks. A proportion of affected individuals develop fixed or chronic progressive weakness that results in significant disability. However, little is known about the pathology of hyperKPP-induced fixed weakness, including the pattern of muscle involvement. The aim of this study was to characterize the patterns of muscle involvement in hyperKPP by whole-body magnetic resonance imaging (MRI).MethodsWe performed whole-body muscle MRI in seven hyperKPP patients carrying the T704M mutation in the SCN4A skeletal sodium-channel gene. Muscle fat infiltration, suggestive of chronic progressive myopathy, was analyzed qualitatively using a grading system and was quantified by the two-point Dixon technique.ResultsWhole-body muscle MRI analysis revealed muscle atrophy and fatty infiltration in hyperKPP patients, especially in older individuals. Muscle involvement followed a selective pattern, primarily affecting the posterior compartment of the lower leg and anterior thigh muscles. The muscle fat fraction increased with patient age in the anterior thigh (r=0.669, p=0.009), in the deep posterior compartment of the lower leg (r=0.617, p=0.019), and in the superficial posterior compartment of the lower leg (r=0.777, p=0.001).ConclusionsOur whole-body muscle MRI findings provide evidence for chronic progressive myopathy in hyperKPP patients. The reported data suggest that a selective pattern of muscle involvement-affecting the posterior compartment of the lower leg and the anterior thigh-is characteristic of chronic progressive myopathy in hyperKPP.

Whole-Body muscle MRI in a series of patients with congenital myopathy related to TPM2 gene mutations

Beta-tropomyosin 2 (TPM2) gene mutations are a rare cause of congenital myopathy with variable clinical and histological features. We describe muscle involvement using Whole-Body muscle Magnetic Resonance Imaging (WBMRI) in 8 individuals with genetically proven TPM2 mutations and different clinical and histological features (nemaline myopathy, 'cap disease', Bethlem-like phenotype, arthrogryposis). Most patients shared a recognizable MRI pattern with the involvement of masticatory and distal lower leg muscles. The lower leg showed constant soleus muscle involvement, and often also involvement of peroneus, tibialis anterior, and toe flexor muscles. Pelvic and shoulder girdles, and upper limbs muscles were quite spared. Two adult subjects (a patient and a paucisymptomatic parent) had a more diffuse involvement with striking fat infiltration of the rectus femoris muscle. Two children showed variant findings: one presented with masseter involvement associated with severe axial fat infiltration, the second had masticatory and distal leg muscle involvement (soleus and gastrocnemius muscles). Our study suggests that, independently of the clinical and histological presentation, most patients with TPM2 mutations show a predominant involvement of masticatory and distal leg muscles with the other regions relatively spared. More spread involvement may be observed. This cephalic-distal MRI pattern is not frequent in other known myopathies.

Whole-body high-field MRI shows no skeletal muscle degeneration in young patients with recessive myotonia congenita

Muscle magnetic resonance imaging (MRI) is the most sensitive method in the detection of dystrophic and non-dystrophic abnormalities within striated muscles. We hypothesized that in severe myotonia congenita type Becker muscle stiffness, prolonged transient weakness and muscle hypertrophy might finally result in morphologic skeletal muscle alterations reflected by MRI signal changes. To assess dystrophic and/or non-dystrophic alterations such as fatty or connective tissue replacement and muscle edema in patients with severe recessive myotonia congenita. We studied three seriously affected patients with myotonia congenita type Becker using multisequence whole-body high-field MRI. All patients had molecular genetic testing of the muscle chloride channel gene (CLCN1). Molecular genetic analyses demonstrated recessive CLCN1 mutations in all patients. Two related patients were compound heterozygous for two novel CLCN1 mutations, Q160H and L657P. None of the patients showed skeletal muscle signal changes indicative of fatty muscle degeneration or edema. Two patients showed muscle bulk hypertrophy of thighs and calves in line with the clinical appearance. We conclude that (i) chloride channel dysfunction alone does not result in skeletal muscle morphologic changes even in advanced stages of myotonia congenita, and (ii) MRI skeletal muscle alterations in myotonic dystrophy must be clear consequences of the dystrophic disease process.