Predicted effects of image acquisition and analysis conditions on DTMRI tractography-based muscle architecture estimates.

PURPOSE: To quantify the effects of the intrinsic signal pattern, image acquisition conditions, and data analysis conditions on diffusion-tensor MRI (DTMRI) tractography-based muscle architecture estimates using a sampling-reconstruction assessment framework. METHODS: Numerical models of muscles were constructed with realistic architectural properties. DTMRI signals were computed at signal-to-noise ratio (SNR) of 24-96 and common voxel sizes. Fiber tracking was performed, and the results were compared with the known architectural properties. RESULTS: SNR exerted the most significant impact on the outcome. The outcome variables approached asymptotes at SNR ≈ 54. Large in-plane voxel dimensions reduced the similarity between reconstructed fibers and the known architectural properties. Higher order polynomials helped reconstruct fibers with more complicated geometry but overfit noise for less complex geometries. The intrinsic fiber curvature also affected the robustness of polynomial smoothing to SNR. Other conditions, such as the fiber dimensionality, voxel aspect ratio, and slice thickness, did not affect the outcomes. CONCLUSION: SNR ≥ 54 is recommended for accurate muscle architecture characterization using DTMRI. Averaged across all simulated conditions, the greatest percent errors under SNR = 54 were -5.6% and -4.0% for the pennation angle and fiber-tract length estimates, respectively. For fiber tracts with intermediate intrinsic curvature, the greatest percent error for the curvature estimate was 9.8% for SNR = 54. Smaller in-plane voxel size (≤1.5 mm) is preferred to minimize the estimation error in architectural properties. If necessary, slice thickness may be adjusted within typical ranges to achieve sufficient SNR when slices are aligned near the fiber direction. Third-order polynomial fitting is appropriate for smoothing fiber tracts.

The impact of diffusion tensor imaging tractography settings on muscle fascicle architecture and diffusion parameter estimates: Tract length, completion, and curvature are most sensitive to tractography settings.

Diffusion-tensor (DT)-MRI tractography provides information about properties relevant to muscle health and function, including estimates of architectural properties such as fascicle length, pennation angle, and curvature and diffusion properties such as mean diffusivity (MD) and fractional anisotropy (FA). Tractography settings, including integration algorithms, thresholds for early tract termination, and tract smoothing approaches, impact the accuracy of the muscle property estimates. However, muscle DT-MRI tractography is performed using a variety of these settings, complicating comparisons between different studies. The effects of different tractography settings on muscle architecture estimates have not been fully explored, and optimized settings for muscle tractography have not yet been determined. We examined the influence of integration algorithm and termination check settings combined with a range of step sizes, termination criteria, and smoothing polynomial orders on tract characteristics, completion/reason for termination, and goodness of fit between fiber tracts and smoothing polynomials using 3-T DT-MR images of the lower leg muscles of seven healthy adults. We found that tract length and completion were highly sensitive to strict FA and intersegment angle thresholds (25%-69% reduction in complete fiber tracts from lowest to highest minimum FA threshold and 11%-36% reduction from highest to lowest intersegment angle threshold). Higher order polynomials (third and fourth order vs. second order) better fit the muscle fiber trajectories, but curvature estimates were highly sensitive to smoothing polynomial order (3.9-6.6 m-1 increase for second- vs. fourth-order fitting polynomials). Step size impacted curvature estimates, albeit to a lesser degree. Integration algorithm had little impact, and mean pennation angle, and tract-based FA and MD, were relatively insensitive to all parameters. The results demonstrate which muscle diffusion measures and architectural estimates are most sensitive to varying tractography settings and support the need for consistent reporting of tractography details to aid interpretation and comparison of results between studies.

Muscle fiber strain rates in the lower leg during ankle dorsi-/plantarflexion exercise.

Static quantitative magnetic resonance imaging (MRI) provides readouts of structural changes in diseased muscle, but current approaches lack the ability to fully explain the loss of contractile function. Muscle contractile function can be assessed using various techniques including phase-contrast MRI (PC-MRI), where strain rates are quantified. However, current two-dimensional implementations are limited in capturing the complex motion of contracting muscle in the context of its three-dimensional (3D) fiber architecture. The MR acquisitions (chemical shift-encoded water-fat separation scan, spin echo-echoplanar imaging with diffusion weighting, and two time-resolved 3D PC-MRI) wereperformed at 3 T. PC-MRI acquisitions and performed with and without load at 7.5% of the maximum voluntary dorsiflexion contraction force. Acquisitions (3 T, chemical shift-encoded water-fat separation scan, spin echo-echo planar imaging with diffusion weighting, and two time-resolved 3D PC-MRI) were performed with and without load at 7.5% of the maximum voluntary dorsiflexion contraction force. Strain rates and diffusion tensors were calculated and combined to obtain strain rates along and perpendicular to the muscle fibers in seven lower leg muscles during the dynamic dorsi-/plantarflexion movement cycle. To evaluate strain rates along the proximodistal muscle axis, muscles were divided into five equal segments. t-tests were used to test if cyclic strain rate patterns (amplitude > 0) were present along and perpendicular to the muscle fibers. The effects of proximal-distal location and load were evaluated using repeated measures ANOVAs. Cyclic temporal strain rate patterns along and perpendicular to the fiber were found in all muscles involved in dorsi-/plantarflexion movement (p < 0.0017). Strain rates along and perpendicular to the fiber were heterogeneously distributed over the length of most muscles (p < 0.003). Additional loading reduced strain rates of the extensor digitorum longus and gastrocnemius lateralis muscle (p < 0.001). In conclusion, the lower leg muscles involved in cyclic dorsi-/plantarflexion exercise showed cyclic fiber strain rate patterns with amplitudes that varied between muscles and between the proximodistal segments within the majority of muscles.

Exercise MR of Skeletal Muscles, the Heart, and the Brain.

Magnetic resonance (MR) imaging (MRI) is routinely used to evaluate organ morphology and pathology in the human body at rest or in combination with pharmacological stress as an exercise surrogate. With MR during actual physical exercise, we can assess functional characteristics of tissues and organs under real-life stress conditions. This is particularly relevant in patients with limited exercise capacity or exercise intolerance, and where complaints typically present only during physical activity, such as in neuromuscular disorders, inherited metabolic diseases, and heart failure. This review describes practical and physiological aspects of exercise MR of skeletal muscles, the heart, and the brain. The acute effects of physical exercise on these organs are addressed in the light of various dynamic quantitative MR readouts, including phosphorus-31 MR spectroscopy (31P-MRS) of tissue energy metabolism, phase-contrast MRI of blood flow and muscle contraction, real-time cine MRI of cardiac performance, and arterial spin labeling MRI of muscle and brain perfusion. Exercise MR will help advancing our understanding of underlying mechanisms that contribute to exercise intolerance, which often proceed structural and anatomical changes in disease. Its potential to detect disease-driven alterations in organ function, perfusion, and metabolism under physiological stress renders exercise MR stress testing a powerful noninvasive imaging modality to aid in disease diagnosis and risk stratification. Although not yet integrated in most clinical workflows, and while some applications still require thorough validation, exercise MR has established itself as a comprehensive and versatile modality for characterizing physiology in health and disease in a noninvasive and quantitative way. EVIDENCE LEVEL: 5 TECHNICAL EFFICACY: Stage 1.

Diffusion tensor imaging and quantitative T2 mapping to monitor muscle recovery following hamstring injury.

MRI examinations are accurate for diagnosing sports-related acute hamstring injuries. However, sensitive imaging methods for assessing recovery of these injuries are lacking. Diffusion tensor imaging (DTI) and quantitative T2 (qT2) mapping have both shown promise for assessing recovery of muscle micro trauma and exercise effects. The purpose of this study was to explore the potential of DTI and qT2 mapping for monitoring the muscle recovery processes after acute hamstring injury. In this prospective study, athletes with an acute hamstring injury underwent a 3-T MRI examination of the injured and contralateral hamstrings including DTI and qT2 measurements at three time points: (1) within 1 week after sustaining the injury, (2) 2 weeks after time point 1, and (3) return to play (RTP). A linear mixed model was used for time-effect analysis and paired t-tests for the detection of differences between injured and uninjured muscles. Forty-one athletes (age 27.8 ± 7 years; two females and 39 males) were included. Mean RTP time was 50 (range 12-169) days. A significant time effect was found for mean diffusivity, radial diffusivity, and the second and third eigenvalues (p ≤ 0.001) in the injured muscles. Fractional anisotropy (p = 0.40), first eigenvalue (p = 0.02), and qT2 (p = 0.61) showed no significant time effect. All DTI indices, except for fractional anisotropy, were significantly elevated compared with control muscles right after the injury (p < 0.001). Values normalized during the recovery period, with no significant differences between control and injured muscles at RTP (p values ranged from 0.08 to 0.51). Mean qT2 relaxation times in injured muscles were not significantly elevated compared with control muscles at any time point (p > 0.04). In conclusion, DTI can be used to monitor recovery after an acute hamstring injury. Future work should explore the potential of DTI indices to predict RTP and recovery times in athletes after an acute strain injury.

Model-based reconstructions for intravoxel incoherent motion and diffusion tensor imaging parameter map estimations.

Intravoxel incoherent motion (IVIM) imaging and diffusion tensor imaging (DTI) facilitate noninvasive quantification of tissue perfusion and diffusion. Both are promising biomarkers in various diseases and a combined acquisition is therefore desirable. This comes with challenges, including noisy parameter maps and long scan times, especially for the perfusion fraction f and pseudo-diffusion coefficient D*. A model-based reconstruction has the potential to overcome these challenges. As a first step, our goal was to develop a model-based reconstruction framework for IVIM and combined IVIM-DTI parameter estimation. The IVIM and IVIM-DTI models were implemented in the PyQMRI model-based reconstruction framework and validated with simulations and in vivo data. Commonly used voxel-wise nonlinear least-squares fitting was used as the reference. Simulations with the IVIM and IVIM-DTI models were performed with 100 noise realizations to assess accuracy and precision. Diffusion-weighted data were acquired for IVIM reconstruction in the liver (n = 5), as well as for IVIM-DTI in the kidneys (n = 5) and lower-leg muscles (n = 6) of healthy volunteers. The median and interquartile range (IQR) values of the IVIM and IVIM-DTI parameters were compared to assess bias and precision. With model-based reconstruction, the parameter maps exhibited less noise, which was most pronounced in the f and D* maps, both in the simulations and in vivo. The bias values in the simulations were comparable between model-based reconstruction and the reference method. The IQR was lower with model-based reconstruction compared with the reference for all parameters. In conclusion, model-based reconstruction is feasible for IVIM and IVIM-DTI and improves the precision of the parameter estimates, particularly for f and D* maps.

Compositional and Functional MRI of Skeletal Muscle: A Review.

Due to its exceptional sensitivity to soft tissues, MRI has been extensively utilized to assess anatomical muscle parameters such as muscle volume and cross-sectional area. Quantitative Magnetic Resonance Imaging (qMRI) adds to the capabilities of MRI, by providing information on muscle composition such as fat content, water content, microstructure, hypertrophy, atrophy, as well as muscle architecture. In addition to compositional changes, qMRI can also be used to assess function for example by measuring muscle quality or through characterization of muscle deformation during passive lengthening/shortening and active contractions. The overall aim of this review is to provide an updated overview of qMRI techniques that can quantitatively evaluate muscle structure and composition, provide insights into the underlying biological basis of the qMRI signal, and illustrate how qMRI biomarkers of muscle health relate to function in healthy and diseased/injured muscles. While some applications still require systematic clinical validation, qMRI is now established as a comprehensive technique, that can be used to characterize a wide variety of structural and compositional changes in healthy and diseased skeletal muscle. Taken together, multiparametric muscle MRI holds great potential in the diagnosis and monitoring of muscle conditions in research and clinical applications. EVIDENCE LEVEL: 5 TECHNICAL EFFICACY: Stage 2.

Magnetic resonance reveals mitochondrial dysfunction and muscle remodelling in spinal muscular atrophy.

Genetic therapy has changed the prognosis of hereditary proximal spinal muscular atrophy, although treatment efficacy has been variable. There is a clear need for deeper understanding of underlying causes of muscle weakness and exercise intolerance in patients with this disease to further optimize treatment strategies. Animal models suggest that in addition to motor neuron and associated musculature degeneration, intrinsic abnormalities of muscle itself including mitochondrial dysfunction contribute to the disease aetiology. To test this hypothesis in patients, we conducted the first in vivo clinical investigation of muscle bioenergetics. We recruited 15 patients and 15 healthy age and gender-matched control subjects in this cross-sectional clinico-radiological study. MRI and 31P magnetic resonance spectroscopy, the modality of choice to interrogate muscle energetics and phenotypic fibre-type makeup, was performed of the proximal arm musculature in combination with fatiguing arm-cycling exercise and blood lactate testing. We derived bioenergetic parameter estimates including: blood lactate, intramuscular pH and inorganic phosphate accumulation during exercise, and muscle dynamic recovery constants. A linear correlation was used to test for associations between muscle morphological and bioenergetic parameters and clinico-functional measures of muscle weakness. MRI showed significant atrophy of triceps but not biceps muscles in patients. Maximal voluntary contraction force normalized to muscle cross-sectional area for both arm muscles was 1.4-fold lower in patients than in controls, indicating altered intrinsic muscle properties other than atrophy contributed to muscle weakness in this cohort. In vivo31P magnetic resonance spectroscopy identified white-to-red remodelling of residual proximal arm musculature in patients on the basis of altered intramuscular inorganic phosphate accumulation during arm-cycling in red versus white and intermediate myofibres. Blood lactate rise during arm-cycling was blunted in patients and correlated with muscle weakness and phenotypic muscle makeup. Post-exercise metabolic recovery was slower in residual intramuscular white myofibres in patients demonstrating mitochondrial ATP synthetic dysfunction in this particular fibre type. This study provides the first in vivo evidence in patients that degeneration of motor neurons and associated musculature causing atrophy and muscle weakness in 5q spinal muscular atrophy type 3 and 4 is aggravated by disproportionate depletion of myofibres that contract fastest and strongest. Our finding of decreased mitochondrial ATP synthetic function selectively in residual white myofibres provides both a possible clue to understanding the apparent vulnerability of this particular fibre type in 5q spinal muscular atrophy types 3 and 4 as well as a new biomarker and target for therapy.

Effect of two eccentric hamstring exercises on muscle architectural characteristics assessed with diffusion tensor MRI.

OBJECTIVES: To evaluate the effect of a Nordic hamstring exercise or Diver hamstring exercise intervention on biceps femoris long head, semitendinosus and semimembranosus muscle's fascicle length and orientation through diffusion tensor imaging (DTI) with magnetic resonance imaging. METHODS: In this three-arm, single-center, randomized controlled trial, injury-free male basketball players were randomly assigned to a Nordic, Diver hamstring exercise intervention or control group. The primary outcome was the DTI-derived fascicle length and orientation of muscles over 12 weeks. RESULTS: Fifty-three participants were included for analysis (mean age 22 ± 7 years). Fascicle length in the semitendinosus over 12 weeks significantly increased in the Nordic-group (mean [M]: 20.8 mm, 95% confidence interval [95% CI]: 7.8 to 33.8) compared with the Control-group (M: 0.9 mm, 95% CI: -7.1 to 8.9), mean between-groups difference: 19.9 mm, 95% CI: 1.9 to 37.9, p = 0.026. Fascicle orientation in the biceps femoris long head over 12 weeks significantly decreased in the Diver-group (mean: -2.6°, 95% CI: -4.1 to -1.0) compared with the Control-group (mean: -0.2°, 95% CI: -1.4 to 1.0), mean between-groups difference: -2.4°, 95% CI: -4.7 to -0.1, p = 0.039. CONCLUSION: The Nordic hamstring exercise intervention did significantly increase the fascicle length of the semitendinosus and the Diver hamstring exercise intervention did significantly change the orientation of fascicles of the biceps femoris long head. As both exercises are complementary to each other, the combination is relevant for preventing hamstring injuries.

Baseline fat fraction is a strong predictor of disease progression in Becker muscular dystrophy.

In Becker muscular dystrophy (BMD), muscle weakness progresses relatively slowly, with a highly variable rate among patients. This complicates clinical trials, as clinically relevant changes are difficult to capture within the typical duration of a trial. Therefore, predictors for disease progression are needed. We assessed if temporal increase of fat fraction (FF) in BMD follows a sigmoidal trajectory and whether fat fraction at baseline (FFbase) could therefore predict FF increase after 2 years (ΔFF). Thereafter, for two different MR-based parameters, we tested the additional predictive value to FFbase. We used 3-T Dixon data from the upper and lower leg, and multiecho spin-echo MRI and 7-T 31 P MRS datasets from the lower leg, acquired in 24 BMD patients (age: 41.4 [SD 12.8] years). We assessed the pattern of increase in FF using mixed-effects modelling. Subsequently, we tested if indicators of muscle damage like standard deviation in water T2 (stdT2 ) and the phosphodiester (PDE) over ATP ratio at baseline had additional value to FFbase for predicting ∆FF. The association between FFbase and ΔFF was described by the derivative of a sigmoid function and resulted in a peak ΔFF around 0.45 FFbase (fourth-order polynomial term: t = 3.7, p < .001). StdT2 and PDE/ATP were not significantly associated with ∆FF if FFbase was included in the model. The relationship between FFbase and ∆FF suggests a sigmoidal trajectory of the increase in FF over time in BMD, similar to that described for Duchenne muscular dystrophy. Our results can be used to identify muscles (or patients) that are in the fast progressing stage of the disease, thereby facilitating the conduct of clinical trials.

Multi-parametric quantitative magnetic resonance imaging of the upper arm muscles of patients with spinal muscular atrophy.

Quantitative magnetic resonance imaging (qMRI) is frequently used to map the disease state and disease progression in the lower extremity muscles of patients with spinal muscular atrophy (SMA). This is in stark contrast to the almost complete lack of data on the upper extremity muscles, which are essential for carrying out daily activities. The aim of this study was therefore to assess the disease state in the upper arm muscles of patients with SMA in comparison with healthy controls by quantitative assessment of fat fraction, diffusion indices, and water T2 relaxation times, and to relate these measures to muscle force. We evaluated 13 patients with SMA and 15 healthy controls with a 3-T MRI protocol consisting of DIXON, diffusion tensor imaging, and T2 sequences. qMRI measures were compared between groups and related to muscle force measured with quantitative myometry. Fat fraction was significantly increased in all upper arm muscles of the patients with SMA compared with healthy controls and correlated negatively with muscle force. Additionally, fat fraction was heterogeneously distributed within the triceps brachii (TB) and brachialis muscle, but not in the biceps brachii muscle. Diffusion indices and water T2 relaxation times were similar between patients with SMA and healthy controls, but we did find a slightly reduced mean diffusivity (MD), λ1, and λ3 in the TB of patients with SMA. Furthermore, MD was positively correlated with muscle force in the TB of patients with SMA. The variation in fat fraction further substantiates the selective vulnerability of muscles. The reduced diffusion tensor imaging indices, along with the positive correlation of MD with muscle force, point to myofiber atrophy. Our results show the feasibility of qMRI to map the disease state in the upper arm muscles of patients with SMA. Longitudinal data in a larger cohort are needed to further explore qMRI to map disease progression and to capture the possible effects of therapeutic interventions.

Supervised segmentation framework for evaluation of diffusion tensor imaging indices in skeletal muscle.

Diffusion tensor imaging (DTI) is becoming a relevant diagnostic tool to understand muscle disease and map muscle recovery processes following physical activity or after injury. Segmenting all the individual leg muscles, necessary for quantification, is still a time-consuming manual process. The purpose of this study was to evaluate the impact of a supervised semi-automatic segmentation pipeline on the quantification of DTI indices in individual upper leg muscles. Longitudinally acquired MRI datasets (baseline, post-marathon and follow-up) of the upper legs of 11 subjects were used in this study. MR datasets consisted of a DTI and Dixon acquisition. Semi-automatic segmentations for the upper leg muscles were performed using a transversal propagation approach developed by Ogier et al on the out-of-phase Dixon images at baseline. These segmentations were longitudinally propagated for the post-marathon and follow-up time points. Manual segmentations were performed on the water image of the Dixon for each of the time points. Dice similarity coefficients (DSCs) were calculated to compare the manual and semi-automatic segmentations. Bland-Altman and regression analyses were performed, to evaluate the impact of the two segmentation methods on mean diffusivity (MD), fractional anisotropy (FA) and the third eigenvalue (λ3 ). The average DSC for all analyzed muscles over all time points was 0.92 ± 0.01, ranging between 0.48 and 0.99. Bland-Altman analysis showed that the 95% limits of agreement for MD, FA and λ3 ranged between 0.5% and 3.0% for the transversal propagation and between 0.7% and 3.0% for the longitudinal propagations. Similarly, regression analysis showed good correlation for MD, FA and λ3 (r = 0.99, p < 60; 0.0001). In conclusion, the supervised semi-automatic segmentation framework successfully quantified DTI indices in the upper-leg muscles compared with manual segmentation while only requiring manual input of 30% of the slices, resulting in a threefold reduction in segmentation time.

Muscle architecture is associated with muscle fat replacement in Duchenne and Becker muscular dystrophies.

INTRODUCTION/AIMS: Duchenne and Becker muscular dystrophies (DMD and BMD, respectively) are characterized by fat replacement of different skeletal muscles in a specific temporal order. Given the structural role of dystrophin in skeletal muscle mechanics, muscle architecture could be important in the progressive pathophysiology of muscle degeneration. Therefore, the aim of this study was to assess the role of muscle architecture in the progression of fat replacement in DMD and BMD. METHODS: We assessed the association between literature-based leg muscle architectural characteristics and muscle fat fraction from 22 DMD and 24 BMD patients. Dixon-based magnetic resonance imaging estimates of fat fractions at baseline and 12 (only DMD) and 24 months were related to fiber length and physiological cross-sectional area (PCSA) using age-controlled linear mixed modeling. RESULTS: DMD and BMD muscles with long fibers and BMD muscles with large PCSAs were associated with increased fat fraction. The effect of fiber length was stronger in muscles with larger PCSA. DISCUSSION: Muscle architecture may explain the pathophysiology of muscle degeneration in dystrophinopathies, in which proximal muscles with a larger mass (fiber length × PCSA) are more susceptible, confirming the clinical observation of a temporal proximal-to-distal progression. These results give more insight into the mechanical role in the pathophysiology of muscular dystrophies. Ultimately, this new information can be used to help support the selection of current and the development of future therapies.

T2 relaxation-time mapping in healthy and diseased skeletal muscle using extended phase graph algorithms.

PURPOSE: Multi-echo spin-echo (MSE) transverse relaxometry mapping using multi-component models is used to study disease activity in neuromuscular disease by assessing the T2 of the myocytic component (T2water ). Current extended phase graph algorithms are not optimized for fat fractions above 50% and the effects of inaccuracies in the T2fat calibration remain unexplored. Hence, we aimed to improve the performance of extended phase graph fitting methods over a large range of fat fractions, by including the slice-selection flip angle profile, a through-plane chemical-shift displacement correction, and optimized calibration of T2fat . METHODS: Simulation experiments were used to study the influence of the slice flip-angle profile with chemical-shift and T2fat estimations. Next, in vivo data from four neuromuscular disease cohorts were studied for different T2fat calibration methods and T2water estimations. RESULTS: Excluding slice flip-angle profiles or chemical-shift displacement resulted in a bias in T2water up to 10 ms. Furthermore, a wrongly calibrated T2fat caused a bias of up to 4 ms in T2water . For the in vivo data, one-component calibration led to a lower T2fat compared with a two-component method, and T2water decreased with increasing fat fractions. CONCLUSION: In vivo data showed a decline in T2water for increasing fat fractions, which has important implications for clinical studies, especially in multicenter settings. We recommend using an extended phase graph-based model for fitting T2water from MSE sequences with two-component T2fat calibration. Moreover, we recommend including the slice flip-angle profile in the model with correction for through-plane chemical-shift displacements.

Multi-parametric MR in Becker muscular dystrophy patients.

Quantitative MRI and MRS of muscle are increasingly being used to measure individual pathophysiological processes in Becker muscular dystrophy (BMD). In particular, muscle fat fraction was shown to be highly associated with functional tests in BMD. However, the muscle strength per unit of contractile cross-sectional area is lower in patients with BMD compared with healthy controls. This suggests that the quality of the non-fat-replaced (NFR) muscle tissue is lower than in healthy controls. Consequently, a measure that reflects changes in muscle tissue itself is needed. Here, we explore the potential of water T2 relaxation times, diffusion parameters and phosphorus metabolic indices as early disease markers in patients with BMD. For this purpose, we examined these measures in fat-replaced (FR) and NFR lower leg muscles in patients with BMD and compared these values with those in healthy controls. Quantitative proton MRI (three-point Dixon, multi-spin-echo and diffusion-weighted spin-echo echo planar imaging) and 2D chemical shift imaging 31 P MRS data were acquired in 24 patients with BMD (age 18.8-66.2 years) and 13 healthy controls (age 21.3-63.6 years). Muscle fat fractions, phosphorus metabolic indices, and averages and standard deviations (SDs) of the water T2 relaxation times and diffusion tensor imaging (DTI) parameters were assessed in six individual leg muscles. Phosphodiester levels were increased in the NFR and FR tibialis anterior, FR peroneus and FR gastrocnemius lateralis muscles. No clear pattern was visible for the other metabolic indices. Increased T2 SD was found in the majority of FR muscles compared with NFR and healthy control muscles. No differences in average water T2 relaxation times or DTI indices were found between groups. Overall, our results indicate that primarily muscles that are further along in the disease process showed increases in T2 heterogeneity and changes in some metabolic indices. No clear differences were found for the DTI indices between groups.

Quantitative MRI Reveals Microstructural Changes in the Upper Leg Muscles After Running a Marathon.

BACKGROUND: The majority of sports-related injuries involve skeletal muscle. Unlike acute trauma, which is often caused by a single traumatic event leading to acute symptoms, exercise-induced microtrauma may remain subclinical and difficult to detect. Therefore, novel methods to detect and localize subclinical exercise-induced muscle microtrauma are desirable. PURPOSE: To assess acute and delayed microstructural changes in upper leg muscles with multiparametric quantitative MRI after running a marathon. STUDY TYPE: Longitudinal; 1-week prior, 24-48 hours postmarathon and 2-week follow-up POPULATION: Eleven men participants (age: 47-68 years). FIELD STRENGTH/SEQUENCE: Spin-echo echo planar imaging (SE-EPI) with diffusion weighting, multispin echo, Dixon, and fat-suppressed turbo spin-echo (TSE) sequences at 3T. MR datasets and creatine kinase (CK) concentrations were obtained at three timepoints. ASSESSMENT: Diffusion parameters, perfusion fractions, and quantitative (q)T2 values were determined for hamstring and quadriceps muscles, TSE images were scored for acute injury. The vastus medialis and biceps femoris long head muscles were divided and analyzed in five segments to assess local damage. STATISTICAL TESTS: Differences between timepoints in MR parameters were assessed with a multilevel linear mixed model and in CK concentrations with a Friedman test. Mean diffusivity (MD) and qT2 for whole muscle and muscle segments were compared using a multivariate analysis of covariance (MANCOVA). RESULTS: CK concentrations were elevated (1194 U/L [166-3906], P < 0.001) at 24-48 hours postmarathon and returned to premarathon values (323 U/L [56-2216]) at 2-week follow-up. Most of the MRI diffusion indices in muscles without acute injury changed at 24-48 hours postmarathon and returned to premarathon values at follow-up (MD, RD, and λ3; P < 0.006). qT2 values (P = 0.003) and perfusion fractions (P = 0.003) were higher at baseline compared to follow-up. Local assessments of MD and qT2 revealed more pronounced changes than whole muscle assessment (2-3-fold; P < 0.01). DATA CONCLUSION: Marathon running-induced microtrauma was detected with MRI in individual whole upper leg muscles and even more pronounced on local segments. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 3 J. Magn. Reson. Imaging 2020;52:407-417.

The repeatability of bilateral diffusion tensor imaging (DTI) in the upper leg muscles of healthy adults.

OBJECTIVES: Assessment of the repeatability of diffusion parameter estimations in the upper leg muscles of healthy adults over the time course of 2 weeks, from a simultaneous bilateral upper leg DTI measurement. METHODS: SE-EPI DTI datasets were acquired at 3 T in the upper legs of 15 active adults at a time interval of 2 weeks. ROIs were manually drawn for four quadriceps and three hamstring muscles of both legs. The following DTI parameters were analyzed: 1st, 2nd, and 3rd eigenvalue (λ1, λ2, and λ3), mean diffusivity (MD), and fractional anisotropy (FA). DTI parameters per muscle were calculated with and without intravoxel incoherent motion (IVIM) correction together with SNR levels per muscle. Bland-Altman plots and within-subject coefficient of variation (wsCV) were calculated. Left-right differences between muscles were assessed. RESULTS: The Bland-Altman analysis showed good repeatability of all DTI parameters except FA for both the IVIM-corrected and standard data. wsCV values show that MD has the highest repeatability (4.5% IVIM; 5.6% standard), followed by λ2 (4.9% IVIM; 5.5% standard), λ1 (5.3% IVIM; 7.5% standard), and λ3 (5.7% IVIM; 5.7% standard). wsCV values of FA were 15.2% for the IVIM-corrected data and 13.9% for the standard analysis. The SNR (41.8 ± 16.0 right leg, 41.7 ± 17.1 left leg) and wsCV values were similar for the left and right leg and no left-right bias was detected. CONCLUSIONS: Repeatability was good for standard DTI data and slightly better for IVIM-corrected DTI data. Our protocol is suitable for DTI of the upper legs with overall good SNR. KEY POINTS: • The presented DTI protocol is repeatable and therefore suitable for bilateral DT imaging of the upper legs. • Additional B1+calibrations improve SNR and repeatability. • Correcting for perfusion effects improves repeatability.

Multi-center evaluation of stability and reproducibility of quantitative MRI measures in healthy calf muscles.

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 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 ~ 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.

Improved olefinic fat suppression in skeletal muscle DTI using a magnitude-based dixon method.

PURPOSE: To 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 METHODS: The 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. RESULTS: In 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. CONCLUSION: DOFS 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. © 2017 International Society for Magnetic Resonance in Medicine.

T2 relaxation times are increased in Skeletal muscle of DMD but not BMD patients.

INTRODUCTION: Exon-skipping drugs in Duchenne muscular dystrophy (DMD) aim to restore truncated dystrophin expression, which is present in the milder Becker muscular dystrophy (BMD). MRI skeletal muscle T2 relaxation times as a representation of edema/inflammation could be quantitative outcome parameters for such trials. METHODS: We studied T2 relaxation times, adjusted for muscle fat fraction using Dixon MRI, in lower leg muscles of DMD and BMD patients and healthy controls. RESULTS: T2 relaxation times correlated significantly with fat fractions in patients only (P < 0.001). After adjusting for muscle fat, T2 relaxation times were significantly increased in 6 muscles of DMD patients (P < 0.01), except for the extensor digitorum longus. In BMD, T2 relaxation times were unchanged. CONCLUSIONS: T2 relaxation times could be a useful outcome parameter in exon-skipping trials in DMD but are influenced by fat despite fat suppression. This should be accounted for when using quantitative T2 mapping to investigate edema/inflammation.