A split-label design for simultaneous measurements of perfusion in distant slices by pulsed arterial spin labeling

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 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.Cardiovascular Aspects of RadiologyNeuro Imaging Researc

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 x 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.Neuro Imaging Researc

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 (Delta FF). 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 spinecho MRI and 7-T P-31 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 T-2 (stdT(2)) and the phosphodiester (PDE) over ATP ratio at baseline had additional value to FFbase for predicting Delta FF. The association between FFbase and Delta FF was described by the derivative of a sigmoid function and resulted in a peak Delta FF around 0.45 FFbase (fourth-order polynomial term: t = 3.7, p < .001). StdT(2) and PDE/ATP were not significantly associated with Delta FF if FFbase was included in the model. The relationship between FFbase and Delta 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.Orthopaedics, Trauma Surgery and Rehabilitatio

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 p p Radiolog

Preserved thenar muscles in non-ambulant Duchenne muscular dystrophy patients

Background Clinical trials in Duchenne muscular dystrophy (DMD) focus primarily on ambulant patients. Results cannot be extrapolated to later disease stages due to a decline in targeted muscle tissue. In non-ambulant DMD patients, hand function is relatively preserved and crucial for daily-life activities. We used quantitative MRI (qMRI) to establish whether the thenar muscles could be valuable to monitor treatment effects in non-ambulant DMD patients.Methods Seventeen non-ambulant DMD patients (range 10.2-24.1 years) and 13 healthy controls (range 9.5-25.4 years) underwent qMRI of the right hand at 3 T at baseline. Thenar fat fraction (FF), total volume (TV), and contractile volume (CV) were determined using 4-point Dixon, and T2(water) was determined using multiecho spin-echo. Clinical assessments at baseline (n = 17) and 12 months (n = 13) included pinch strength (kg), performance of the upper limb (PUL) 2.0, DMD upper limb patient reported outcome measure (PROM), and playing a video game for 10 min using a game controller. Group differences and correlations were assessed with non-parametric tests.Results Total volume was lower in patients compared with healthy controls (6.9 cm(3), 5.3-9.0 cm(3) vs. 13.0 cm(3), 7.6-15.8 cm(3), P = 0.010). CV was also lower in patients (6.3 cm(3), 4.6-8.3 cm(3) vs. 11.9 cm(3), 6.9-14.6 cm(3), P = 0.010). FF was slightly elevated (9.7%, 7.3-11.4% vs. 7.7%, 6.6-8.4%, P = 0.043), while T2(water) was higher (31.5 ms, 30.0-32.6 ms vs. 28.1 ms, 27.8-29.4 ms, P < 0.001). Pinch strength and PUL decreased over 12 months (2.857 kg, 2.137-4.010 to 2.243 kg, 1.930-3.339 kg, and 29 points, 20-36 to 23 points, 17-30, both P < 0.001), while PROM did not (49 points, 36-57 to 44 points, 30-54, P = 0.041). All patients were able to play for 10 min at baseline or follow-up, but some did not comply with the study procedures regarding this endpoint. Pinch strength correlated with TV and CV in patients (rho = 0.72 and rho = 0.68) and controls (both rho = 0.89). PUL correlated with TV, CV, and T2(water) (rho = 0.57, rho = 0.51, and rho = -0.59).Conclusions Low thenar FF, increased T2(water), correlation of muscle size with strength and function, and the decrease in strength and function over 1 year indicate that the thenar muscles are a valuable and quantifiable target for therapy in later stages of DMD. Further studies are needed to relate these data to the loss of a clinically meaningful milestone.Neuro Imaging Researc

Selection approach to identify the optimal biomarker using quantitative muscle MRI and functional assessments in Becker muscular dystrophy

Objective To identify the best quantitative fat-water MRI biomarker for disease progression of leg muscles in Becker muscular dystrophy (BMD) by applying a stepwise approach based on standardized response mean (SRM) over 24 months, correlations with baseline ambulatory tests, and reproducibility. Methods Dixon fat-water imaging was performed at baseline (n = 24) and 24 months (n = 20). Fat fractions (FF) were calculated for 3 center slices and the whole muscles for 19 muscles and 6 muscle groups. Contractile cross-sectional area (cCSA) was obtained from the center slice. Functional assessments included knee extension and flexion force and 3 ambulatory tests (North Star Ambulatory Assessment [NSAA], 10-meter run, 6-minute walking test). MRI measures were selected using SRM (>= 0.8) and correlation with all ambulatory tests (rho = 0.999) and similar SD of the interrater difference. Whole thigh 3 center slices FF was the best biomarker (SRM 1.04, correlations rho <= -0.81, ICC 1.00, SD 0.23%, sample size 59) based on low SD and acquisition and analysis time. Conclusion In BMD, median FF of all muscles increased over 24 months. Whole thigh 3 center slices FF reduced the sample size by approximately 40% compared to NSAA.Neuro Imaging Researc

The effects of shoulder load and pinch force on electromyographic activity and blood flow in the forearm during a pinch task

The object of the current study was to determine whether static contraction of proximal musculature has an effect on the blood flow more distally in the upper extremity. Static contractions of muscles in the neck shoulder region at three levels (relaxed, shoulders elevated and shoulders elevated loaded with 4.95 kg each) were combined with intermittent pinch forces at 0, 10 and 25% of the maximum voluntary contraction (MVC). Blood flow to the forearm was measured with Doppler ultrasound. Myoelectric activity of the forearm and neck-shoulder muscles was recorded to check for the workload levels. Across all levels of shoulder load, blood flow increased significantly with increasing pinch force (21% at 10% MVC and by 44% at 25% MVC). Blood flow was significantly affected by shoulder load, with the lowest blood flow at the highest shoulder load. Interactions of pinch force and shoulder load were not significant. The myoelectric activity of forearm muscles increased with increasing pinch force. The activation of the trapezius muscle decreased with increasing pinch force and increased with increasing shoulder load. The precise mechanisms accounting for the influence of shoulder load remains unclear. The results of this study indicate that shoulder load might influence blood flow to the forearm

Water–fat separation in spiral magnetic resonance fingerprinting for high temporal resolution tissue relaxation time quantification in muscle

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. 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.Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

Water-fat separation in spiral magnetic resonance fingerprinting for high temporal resolution tissue relaxation time quantification in muscle

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. 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.Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

Microvascular response to exercise varies along the length of the tibialis anterior muscle

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 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.Pathofysiological analysis of movement disorders in relation to functio