Muscle sodium content in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Background: Muscle fatigue and pain are key symptoms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Although the pathophysiology is not yet fully understood, there is ample evidence for hypoperfusion which may result in electrolyte imbalance and sodium overload in muscles. Therefore, the aim of this study was to assess levels of sodium content in muscles of patients with ME/CFS and to compare these to healthy controls. Methods: Six female patients with ME/CFS and six age, BMI and sex matched controls underwent Na-23-MRI of the left lower leg using a clinical 3T MR scanner before and after 3 min of plantar flexion exercise. Sodium reference phantoms with solutions of 10, 20, 30 and 40 mmol/L NaCl were used for quantification. Muscle sodium content over 40 min was measured using a dedicated plugin in the open-source DICOM viewer Horos. Handgrip strength was measured and correlated with sodium content. Results: Baseline tissue sodium content was higher in all 5 lower leg muscle compartments in ME/CFS compared to controls. Within the anterior extensor muscle compartment, the highest difference in baseline muscle sodium content between ME/CFS and controls was found (mean ± SD; 12.20 ± 1.66 mM in ME/CFS versus 9.38 ± 0.71 mM in controls, p = 0.0034). Directly after exercise, tissue sodium content increased in gastrocnemius and triceps surae muscles with + 30% in ME/CFS (p = 0.0005) and + 24% in controls (p = 0.0007) in the medial gastrocnemius muscle but not in the extensor muscles which were not exercised. Compared to baseline, the increase of sodium content in medial gastrocnemius muscle was stronger in ME/CFS than in controls with + 30% versus + 17% to baseline at 12 min (p = 0.0326) and + 29% versus + 16% to baseline at 15 min (p = 0.0265). Patients had reduced average handgrip strength which was associated with increased average muscle tissue sodium content (p = 0.0319, R-2 = 0.3832). Conclusion: Muscle sodium content before and after exercise was higher in ME/CFS than in healthy controls. Furthermore, our findings indicate an inverse correlation between muscle sodium content and handgrip strength. These findings provide evidence that sodium overload may play a role in the pathophysiology of ME/CFS and may allow for potential therapeutic targeting

Reproducibility of three different cardiac T2-mapping sequences at 1.5T and impact of cofactors on T2-relaxation times

Background: The high interindividual variability of myocardial T2 relaxation times appears to be one of the main challenges for the clinical application of cardiac T2-mapping. This study therefore aimed to evaluate potential underlying causes for this variability, analyzing the reproducibility of three different cardiac T2-mapping sequences and evaluating the influence of cofactors on T2 relaxation times. Methods: 30 healthy volunteers were examined three times on a clinical 1.5T scanner (scan 1: in the morning; scan 2: in the evening of the same day; scan 3: in the evening 2-3 weeks later). In each examination three different T2-mapping sequences were acquired at three slices in short axis view: Multi Echo Spin Echo (MESE), T2-prepared balanced Steady State Free Precession (T2prep; [1]) and Gradient Spin Echo (GraSE). Repeated measurements were performed for T2prep and GraSE. Segmented T2-maps were generated for each slice according to the AHA 17-segment model. Intra- and inter-observer reproducibility was tested in a subgroup of 10 randomly selected subjects, where manual ROIs were drawn independently to measure T2 values of each segment blinded to the other results. Results: Overall, we observed no systematic difference of T2 times due to diurnal effects and on long-term analysis. Differentiated analysis of variance components for all sequences, however, revealed a greater variance of T2 times over multiple time points than for repeated measurements within the same scan. Our study revealed a low intra-observer and inter-observer variability of manual ROI-definition and the acquired T2 times for each sequence. The coefficients of variation and intraclass correlation coefficients for intra-observer variability were: 1.3% and 0.89 for T2prep, 1.5% and 0.93 for GraSE, 3.1% and 0.83 for MESE; and for inter-observer variability: 3.3% and 0.66 for T2prep, 2.0% and 0.83 for GraSE, 3.6% and 0.77 for MESE. With respect to the influence of potential cofactors on T2 times, we observed a negative effect of the cofactor heart rate on mean T2 values, yet this effect proved to be not significant. Conversely, we found significant and positive relation between mean T2 times and the cofactors age, weight and height (p < 0.005, p < 0.05 and p < 0.05) in single linear regression models. Using multiple regression models, we observed significant relations between mean T2 times and age (p < 0.005), gender (p < 0.01), and either weight or height (p < 0.005), for given values of the remaining cofactors. Conclusions: Intra- and inter-observer reproducibility of all tested T2-mapping sequnces is high, thereby confirming previous studies. According to our study, the high interindividual variability of myocardial T2 relaxation times is most likely due to proband-related effects such as age, gender, weight and height and other cofactors intraindividually varying with time

A novel multiparametric imaging approach to acute myocarditis using T2-mapping and CMR feature tracking

Background: The aim of this study was to evaluate the diagnostic potential of a novel cardiovascular magnetic resonance (CMR) based multiparametric imaging approach in suspected myocarditis and to compare it to traditional Lake Louise criteria (LLC). Methods: CMR data from 67 patients with suspected acute myocarditis were retrospectively analyzed. Seventeen age- and gender-matched healthy subjects served as control. T2-mapping data were acquired using a Gradient-Spin-Echo T2-mapping sequence in short-axis orientation. T2-maps were segmented according to the 16-segments AHA-model and segmental T2 values and pixel-standard deviation (SD) were recorded. Afterwards, the parameters maxT2 (the highest segmental T2 value) and madSD (the mean absolute deviation (MAD) of the pixel-SDs) were calculated for each subject. Cine sequences in three long axes and a stack of short-axis views covering the left and right ventricle were analyzed using a dedicated feature tracking algorithm. Results: A multiparametric imaging model containing madSD and LV global circumferential strain (GCSLV) resulted in the highest diagnostic performance in receiver operating curve analyses (area under the curve [AUC] 0.84) when compared to any model containing a single imaging parameter or to LLC (AUC 0.79). Adding late gadolinium enhancement (LGE) to the model resulted in a further increased diagnostic performance (AUC 0.93) and yielded the highest diagnostic sensitivity of 97% and specificity of 77%. Conclusions: A multiparametric CMR imaging model including the novel T2-mapping derived parameter madSD, the feature tracking derived strain parameter GCSLV and LGE yields superior diagnostic sensitivity in suspected acute myocarditis when compared to any imaging parameter alone and to LLC. © 2017 The Author(s)

CMR in Patients With Severe Myocarditis Diagnostic Value of Quantitative Tissue Markers Including Extracellular Volume Imaging

AbstractObjectivesThis study evaluated the accuracy of T2, T1, and extracellular volume (ECV) quantification as novel quantitative tissue markers in comparison with standard “Lake-Louise” cardiac magnetic resonance (CMR) criteria to diagnose myocarditis.BackgroundNovel approaches using T2 and T1 mapping may overcome the limitations of signal intensity-based parameters, which would potentially result in a better diagnostic accuracy compared with standard CMR techniques in suspected myocarditis.MethodsCMR was performed in 104 patients with myocarditis and 21 control subjects at 1.5-T. Patients with myocarditis underwent CMR 2 weeks (interquartile range: 1 to 7 weeks) after presentation with new-onset heart failure (n = 66) or acute chest pain (n = 38). T2 and T1 mapping were implemented into a standard protocol including T2-weighted (T2w), early gadolinium enhancement (EGE) CMR, and late gadolinium enhancement (LGE) CMR. T2 quantification was performed using a free-breathing, navigator-gated multiecho sequence. T1 quantification was performed using the modified Look-Locker inversion recovery sequence before and after administration of 0.075 mmol/kg gadobenate dimeglumine. T2, T1, and ECV maps were generated using a plug-in for the OsiriX software (Pixmeo, Bernex, Switzerland) to calculate mean global myocardial T2, T1, and ECV values.ResultsThe diagnostic accuracies of conventional CMR were 70% (95% confidence interval [CI]: 61% to 77%) for T2w CMR, 59% (95% CI: 56% to 73%) for EGE, and 67% (95% CI: 59% to 75%) for LGE. The diagnostic accuracies of mapping techniques were 63% (95% CI: 53% to 73%) for myocardial T2, 69% (95% CI: 60% to 76%) for native myocardial T1, and 76% (95% CI: 68% to 82%) for global myocardial ECV. The diagnostic accuracy of CMR was significantly improved to 90% (95% CI: 84% to 95%) by a stepwise approach, using the presence of LGE and myocardial ECV ≥27% as diagnostic criteria, compared with 79% (95% CI: 71% to 85%; p = 0.0043) for the Lake-Louise criteria.ConclusionsIn patients with clinical evidence for subacute, severe myocarditis, ECV quantification with LGE imaging significantly improved the diagnostic accuracy of CMR compared with standard Lake-Louise criteria

Assessment of Global Longitudinal and Circumferential Strain Using Computed Tomography Feature Tracking: Intra-Individual Comparison with CMR Feature Tracking and Myocardial Tagging in Patients with Severe Aortic Stenosis

In this study, we used a single commercially available software solution to assess global longitudinal (GLS) and global circumferential strain (GCS) using cardiac computed tomography (CT) and cardiac magnetic resonance (CMR) feature tracking (FT). We compared agreement and reproducibility between these two methods and the reference standard, CMR tagging (TAG). Twenty-seven patients with severe aortic stenosis underwent CMR and cardiac CT examinations. FT analysis was performed using Medis suite version 3.0 (Leiden, The Netherlands) software. Segment (Medviso) software was used for GCS assessment from tagged images. There was a trend towards the underestimation of GLS by CT-FT when compared to CMR-FT (19.4 +/- 5.04 vs. 22.40 +/- 5.69, respectively; p = 0.065). GCS values between TAG, CT-FT, and CMR-FT were similar (p = 0.233). CMR-FT and CT-FT correlated closely for GLS (r = 0.686, p < 0.001) and GCS (r = 0.707, p < 0.001), while both of these methods correlated moderately with TAG for GCS (r = 0.479, p < 0.001 for CMR-FT vs. TAG; r = 0.548 for CT-FT vs. TAG). Intraobserver and interobserver agreement was excellent in all techniques. Our findings show that, in elderly patients with severe aortic stenosis (AS), the FT algorithm performs equally well in CMR and cardiac CT datasets for the assessment of GLS and GCS, both in terms of reproducibility and agreement with the gold standard, TAG