Background loss of skeletal muscle function, strength and mass is common in older adults, with important socioeconomic impacts. Subclinical hypothyroidism is common with increasing age and has been... Show moreBackground loss of skeletal muscle function, strength and mass is common in older adults, with important socioeconomic impacts. Subclinical hypothyroidism is common with increasing age and has been associated with reduced muscle strength. Yet, no randomized placebo-controlled trial (RCT) has investigated whether treatment of subclinical hypothyroidism affects muscle function and mass. Methods this is an ancillary study within two RCTs conducted among adults aged >= 65 years with persistent subclinical hypothyroidism (thyrotropin (TSH) 4.60-19.99 mIU/l, normal free thyroxine). Participants received daily levothyroxine with TSH-guided dose adjustment or placebo and mock titration. Primary outcome was gait speed at final visit (median 18 months). Secondary outcomes were handgrip strength at 1-year follow-up and yearly change in muscle mass. Results we included 267 participants from Switzerland and the Netherlands. Mean age was 77.5 years (range 65.1-97.1), 129 (48.3%) were women, and their mean baseline TSH was 6.36 mIU/l (standard deviation [SD] 1.9). At final visit, mean TSH was 3.8 mIU/l (SD 2.3) in the levothyroxine group and 5.1 mIU/l (SD 1.8, P < 0.05) in the placebo group. Compared to placebo, participants in the levothyroxine group had similar gait speed at final visit (adjusted between-group mean difference [MD] 0.01 m/s, 95% confidence interval [CI] -0.06 to 0.09), similar handgrip strength at one year (MD -1.22 kg, 95% CI -2.60 to 0.15) and similar yearly change in muscle mass (MD -0.15 m(2), 95% CI -0.49 to 0.18). Conclusions in this ancillary analysis of two RCTs, treatment of subclinical hypothyroidism did not affect muscle function, strength and mass in individuals 65 years and older. Show less
Microvascular function is an important component in the physiology of muscle. One of the major parameters, blood perfusion, can be measured noninvasively and quantitatively by arterial spin... Show moreMicrovascular function is an important component in the physiology of muscle. One of the major parameters, blood perfusion, can be measured noninvasively and quantitatively by arterial spin labeling (ASL) MRI. Most studies using ASL in muscle have only reported data from a single slice, thereby assuming that muscle perfusion is homogeneous within muscle, whereas recent literature has reported proximodistal differences in oxidative capacity and perfusion. Here, we acquired pulsed ASL data in 12 healthy volunteers after dorsiflexion exercise in two slices separated distally by 7 cm. We combined this with a Look-Locker scheme to acquire images at multiple postlabeling delays (PLDs) and with a multiecho readout to measure T-2*. This enabled the simultaneous evaluation of quantitative muscle blood flow (MBF), arterial transit time (ATT), and T-2* relaxation time in the tibialis anterior muscle during recovery. Using repeated measures analyses of variance we tested the effect of time, slice location, and their interaction on MBF, ATT, and T-2*. Our results showed a significant difference as a function of time postexercise for all three parameters (MBF: F = 34.0, p < .0001; T-2*: F = 73.7, p < .0001; ATT: F = 13.6, p < .001) and no average differences between slices over the total time postexercise were observed. The interaction effect between time postexercise and slice location was significant for MBF and T-2* (F = 5.5, p = 0.02, F = 6.1, p = 0.02, respectively), but not for ATT (F = 2.2, p = .16). The proximal slice showed a higher MBF and a lower ATT than the distal slice during the first 2 min of recovery, and T-2* showed a delayed response in the distal slice. These results imply a higher perfusion and faster microvascular response to exercise in the proximal slice, in line with previous literature. Moreover, the differences in ATT indicate that it is difficult to correctly determine perfusion based on a single PLD as is commonly performed in the muscle literature. Show less
Purpose Low-field (B-0 < 0.1 T) MRI has generated much interest as a means of increased accessibility via reduced cost and improved portability compared to conventional clinical systems (B-0 >... Show morePurpose Low-field (B-0 < 0.1 T) MRI has generated much interest as a means of increased accessibility via reduced cost and improved portability compared to conventional clinical systems (B-0 >= 1.5 Tesla). Here we measure MR relaxation times at 50 mT and compare results with commonly used models based on both in vivo and ex vivo measurements. Methods Using 3D turbo spin echo readouts, T-1 and T-2 maps of the human brain and lower leg were acquired on a custom-built 50 mT MRI scanner using inversion-recovery and multi-echo-based sequences, respectively. Image segmentation was performed based on a histogram analysis of the relaxation times. Results The average T-1 times of gray matter, white matter, and cerebrospinal fluid (CSF) were 327 +/- 10 ms, 275 +/- 5 ms, and 3695 +/- 287 ms, respectively. Corresponding values of T-2 were 102 +/- 6 ms, 102 +/- 6 ms, and 1584 +/- 124 ms. T-1 times in the calf muscle were measured to be 171 +/- 11 ms and were 130 +/- 5 ms in subcutaneous and bone marrow lipid. Corresponding T-2 times were 39 +/- 2 ms in muscle and 90 +/- 13 ms in lipid. Conclusions For tissues except for CSF, the measured T-1 times are much shorter than reported at higher fields and generally lie within the range of different models in the literature. As expected, T-2 times are similar to those seen at typical clinical field strengths. Analysis of the relaxation maps indicates that segmentation of white and gray matter based purely on T-1 or T-2 will be quite challenging at low field given the relatively small difference in relaxation times. Show less
Purpose Multislice arterial spin labeling (ASL) MRI acquisitions are currently challenging in skeletal muscle because of long transit times, translating into low-perfusion SNR in distal slices when... Show morePurpose Multislice arterial spin labeling (ASL) MRI acquisitions are currently challenging in skeletal muscle because of long transit times, translating into low-perfusion SNR in distal slices when large spatial coverage is required. However, fiber type and oxidative capacity vary along the length of healthy muscles, calling for multislice acquisitions in clinical studies. We propose a new variant of flow alternating inversion recovery (FAIR) that generates sufficient ASL signal to monitor exercise-induced perfusion changes in muscle in two distant slices.Methods Label around and between two 7-cm distant slices was created by applying the presaturation/postsaturation and selective inversion modules selectively to each slice (split-label multislice FAIR). Images were acquired using simultaneous multislice EPI. We validated our approach in the brain to take advantage of the high resting-state perfusion, and applied it in the lower leg muscle during and after exercise, interleaved with a single-slice FAIR as a reference.Results We show that standard multislice FAIR leads to an underestimation of perfusion, while the proposed split-label multislice approach shows good agreement with separate single-slice FAIR acquisitions in brain, as well as in muscle following exercise.Conclusion Split-label FAIR allows measuring muscle perfusion in two distant slices simultaneously without losing sensitivity in the distal slice. Show less
The role of neuromuscular imaging in the diagnosis of inherited and acquired muscle diseases has gained clinical relevance. In particular, magnetic resonance imaging (MRI), especially whole-body... Show moreThe role of neuromuscular imaging in the diagnosis of inherited and acquired muscle diseases has gained clinical relevance. In particular, magnetic resonance imaging (MRI), especially whole-body applications, is increasingly being used for the diagnosis and monitoring of disease progression. In addition, they are considered as a powerful outcome measure in clinical trials. Because many muscle diseases have a distinct muscle involvement pattern, whole-body imaging can be of diagnostic value by identifying this pattern and thus narrowing the differential diagnosis and supporting the clinical diagnosis. In addition, more advanced MRI applications including non-proton MRI, diffusion tensor imaging, perfusion MRI, T2 mapping, and magnetic resonance spectroscopy provide deeper insights into muscle pathophysiology beyond the mere detection of fatty degeneration and/or muscle edema. In this review article, we present and discuss recent data on these quantitative MRI techniques in muscle diseases, with a particular focus on non-proton imaging techniques. Show less
Raz, Y.; Akker, E.B. van den; Roest, T.; Riaz, M.; Rest, O. van de; Suchiman, H.E.D.; ... ; Slagboom, P.E. 2020
Skeletal muscles control posture, mobility and strength, and influence whole-body metabolism. Muscles are built of different types of myofibers, each having specific metabolic, molecular, and... Show moreSkeletal muscles control posture, mobility and strength, and influence whole-body metabolism. Muscles are built of different types of myofibers, each having specific metabolic, molecular, and contractile properties. Fiber classification is, therefore, regarded the key for understanding muscle biology, (patho-) physiology. The expression of three myosin heavy chain (MyHC) isoforms, MyHC-1, MyHC-2A, and MyHC-2X, marks myofibers in humans. Typically, myofiber classification is performed by an eye-based histological analysis. This classical approach is insufficient to capture complex fiber classes, expressing more than one MyHC-isoform. We, therefore, developed a methodological procedure for high-throughput characterization of myofibers on the basis of multiple isoforms. The mean fluorescence intensity of the three most abundant MyHC isoforms was measured per myofiber in muscle biopsies of 56 healthy elderly adults, and myofiber classes were identified using computational biology tools. Unsupervised clustering revealed the existence of six distinct myofiber clusters. A comparison with the visual assessment of myofibers using the same images showed that some of these myofiber clusters could not be detected or were frequently misclassified. The presence of these six clusters was reinforced by RNA expressions levels of sarcomeric genes. In addition, one of the clusters, expressing all three MyHC isoforms, correlated with histological measures of muscle health. To conclude, this methodological procedure enables deep characterization of the complex muscle heterogeneity. This study opens opportunities to further investigate myofiber composition in comparative studies. Show less
Meyerspeer, M.; Boesch, C.; Cameron, D.; Dezortova, M.; Forbes, S.C.; Heerschap, A.; ... ; Experts Working Grp P MR 2020
Skeletal muscle phosphorus-31 P-31 MRS is the oldest MRS methodology to be applied to in vivo metabolic research. The technical requirements of P-31 MRS in skeletal muscle depend on the research... Show moreSkeletal muscle phosphorus-31 P-31 MRS is the oldest MRS methodology to be applied to in vivo metabolic research. The technical requirements of P-31 MRS in skeletal muscle depend on the research question, and to assess those questions requires understanding both the relevant muscle physiology, and how P-31 MRS methods can probe it. Here we consider basic signal-acquisition parameters related to radio frequency excitation, TR, TE, spectral resolution, shim and localisation. We make specific recommendations for studies of resting and exercising muscle, including magnetisation transfer, and for data processing. We summarise the metabolic information that can be quantitatively assessed with P-31 MRS, either measured directly or derived by calculations that depend on particular metabolic models, and we give advice on potential problems of interpretation. We give expected values and tolerable ranges for some measured quantities, and minimum requirements for reporting acquisition parameters and experimental results in publications. Reliable examination depends on a reproducible setup, standardised preconditioning of the subject, and careful control of potential difficulties, and we summarise some important considerations and potential confounders. Our recommendations include the quantification and standardisation of contraction intensity, and how best to account for heterogeneous muscle recruitment. We highlight some pitfalls in the assessment of mitochondrial function by analysis of phosphocreatine (PCr) recovery kinetics. Finally, we outline how complementary techniques (near-infrared spectroscopy, arterial spin labelling, BOLD and various other MRI and H-1 MRS measurements) can help in the physiological/metabolic interpretation of P-31 MRS studies by providing information about blood flow and oxygen delivery/utilisation. Our recommendations will assist in achieving the fullest possible reliable picture of muscle physiology and pathophysiology. Show less
Purpose To minimize the known biases introduced by fat in rapid T-1 and T-2 quantification in muscle using a single-run magnetic resonance fingerprinting (MRF) water-fat separation sequence.... Show morePurpose To minimize the known biases introduced by fat in rapid T-1 and T-2 quantification in muscle using a single-run magnetic resonance fingerprinting (MRF) water-fat separation sequence. Methods The single-run MRF acquisition uses an alternating in-phase/out-of-phase TE pattern to achieve water-fat separation based on a 2-point DIXON method. Conjugate phase reconstruction and fat deblurring were applied to correct for B-0 inhomogeneities and chemical shift blurring. Water and fat signals were matched to the on-resonance MRF dictionary. The method was first tested in a multicompartment phantom. To test whether the approach is capable of measuring small in vivo dynamic changes in relaxation times, experiments were run in 9 healthy volunteers; parameter values were compared with and without water-fat separation during muscle recovery after plantar flexion exercise. Results Phantom results show the robustness of the water-fat resolving MRF approach to undersampling. Parameter maps in volunteers show a significant (P < .01) increase in T-1 (105 +/- 94 ms) and decrease in T-2 (14 +/- 6 ms) when using water-fat-separated MRF, suggesting improved parameter quantification by reducing the well-known biases introduced by fat. Exercise results showed smooth T-1 and T-2 recovery curves. Conclusion Water-fat separation using conjugate phase reconstruction is possible within a single-run MRF scan. This technique can be used to rapidly map relaxation times in studies requiring dynamic scanning, in which the presence of fat is problematic. Show less
Schlaffke, L.; Rehmann, R.; Rohm, M.; Otto, L.A.M.; Luca, A. de; Burakiewicz, J.; ... ; Froeling, M. 2019
The purpose of this study was to evaluate temporal stability, multi-center reproducibility and the influence of covariates on a multimodal MR protocol for quantitative muscle imaging and to... Show moreThe purpose of this study was to evaluate temporal stability, multi-center reproducibility and the influence of covariates on a multimodal MR protocol for quantitative muscle imaging and to facilitate its use as a standardized protocol for evaluation of pathology in skeletal muscle. Quantitative T2, quantitative diffusion and four-point Dixon acquisitions of the calf muscles of both legs were repeated within one hour. Sixty-five healthy volunteers (31 females) were included in one of eight 3-T MR systems. Five traveling subjects were examined in six MR scanners. Average values over all slices of water-T2 relaxation time, proton density fat fraction (PDFF) and diffusion metrics were determined for seven muscles. Temporal stability was tested with repeated measured ANOVA and two-way random intraclass correlation coefficient (ICC). Multi-center reproducibility of traveling volunteers was assessed by a two-way mixed ICC. The factors age, body mass index, gender and muscle were tested for covariance. ICCs of temporal stability were between 0.963 and 0.999 for all parameters. Water-T2 relaxation decreased significantly (P < 10(-3)) within one hour by similar to 1 ms. Multi-center reproducibility showed ICCs within 0.879-0.917 with the lowest ICC for mean diffusivity. Different muscles showed the highest covariance, explaining 20-40% of variance for observed parameters. Standardized acquisition and processing of quantitative muscle MRI data resulted in high comparability among centers. The imaging protocol exhibited high temporal stability over one hour except for water T2 relaxation times. These results show that data pooling is feasible and enables assembling data from patients with neuromuscular diseases, paving the way towards larger studies of rare muscle disorders. Show less
PurposeTo develop a method of suppressing the multi-resonance fat signal in diffusion-weighted imaging of skeletal muscle. This is particularly important when imaging patients with muscular... Show morePurposeTo develop a method of suppressing the multi-resonance fat signal in diffusion-weighted imaging of skeletal muscle. This is particularly important when imaging patients with muscular dystrophies, a group of diseases which cause gradual replacement of muscle tissue by fat.Theory and MethodsThe signal from the olefinic fat peak at 5.3 ppm can significantly confound diffusion-tensor imaging measurements. Dixon olefinic fat suppression (DOFS), a magnitude-based chemical-shift-based method of suppressing the olefinic peak, is proposed. It is verified in vivo by performing diffusion tensor imaging (DTI)-based quantification in the lower leg of seven healthy volunteers, and compared to two previously described fat-suppression techniques in regions with and without fat contamination.ResultsIn the region without fat contamination, DOFS produces similar results to existing techniques, whereas in muscle contaminated by subcutaneous fat signal moved due to the chemical shift artefact, it consistently showed significantly higher (P=0.018) mean diffusivity (MD). Because fat presence lowers MD, this suggests improved fat suppression.ConclusionDOFS offers superior fat suppression and enhances quantitative measurements in the muscle in the presence of fat. DOFS is an alternative to spectral olefinic fat suppression. Magn Reson Med 79:152-159, 2018. (c) 2017 International Society for Magnetic Resonance in Medicine. Show less
