Muscle diffusion tensor imaging in facioscapulohumeral muscular dystrophy.

INTRODUCTION/AIMS: Muscle diffusion tensor imaging has not yet been explored in facioscapulohumeral muscular dystrophy (FSHD). We assessed diffusivity parameters in FSHD subjects compared with healthy controls (HCs), with regard to their ability to precede any fat replacement or edema. METHODS: Fat fraction (FF), water T2 (wT2), mean, radial, axial diffusivity (MD, RD, AD), and fractional anisotropy (FA) of thigh muscles were calculated in 10 FSHD subjects and 15 HCs. All parameters were compared between FSHD and controls, also exploring their gradient along the main axis of the muscle. Diffusivity parameters were tested in a subgroup analysis as predictors of disease involvement in muscle compartments with different degrees of FF and wT2 and were also correlated with clinical severity scores. RESULTS: We found that MD, RD, and AD were significantly lower in FSHD subjects than in controls, whereas we failed to find a difference for FA. In contrast, we found a significant positive correlation between FF and FA and a negative correlation between MD, RD, and AD and FF. No correlation was found with wT2. In our subgroup analysis we found that muscle compartments with no significant fat replacement or edema (FF < 10% and wT2 < 41 ms) showed a reduced AD and FA compared with controls. Less involved compartments showed different diffusivity parameters than more involved compartments. DISCUSSION: Our exploratory study was able to demonstrate diffusivity parameter abnormalities even in muscles with no significant fat replacement or edema. Larger cohorts are needed to confirm these preliminary findings.

Transverse Relaxation Anisotropy of the Achilles and Patellar Tendon Studied by MR Microscopy.

BACKGROUND: T2 * anisotropy affects the clinical assessment of tendons (magic-angle artifact) and may be a source of T2 *-misinterpretation. PURPOSE: To analyze T2 *-anisotropy and T2 *-decay of Achilles and patellar tendons in vitro at microscopic resolution using a variable-echo-time (vTE) sequence. STUDY TYPE: Prospective. SPECIMEN: Four human Achilles and four patellar tendons. FIELD STRENGTH/SEQUENCE: A 7 T MR-microscopy; 3D-vTE spoiled-gradient-echo-sequence (T2 *-mapping). ASSESSMENT: All tendons were measured at 0° and 55° relative to B0 . Additional angles were measured for one Achilles and one patellar tendon for a total of 11 angles ranging from 0° to 90°. T2 *-decay was analyzed with mono- and bi-exponential signal fitting. Mono-exponential T2 *-values (T2 *m ), short and long T2 *-components (T2 *s , T2 *l ), and the fraction of the short component Fs of the bi-exponential T2 *-fit were calculated. T2 *-decay characteristics were compared with morphological MRI and histologic findings based on a region-of-interest analysis. STATISTICAL TESTS: Akaike information criterion (AICC ), F-test, and paired t-test. A P value smaller than the α-level of 0.05 was considered statistically significant. RESULTS: T2 *m -values between fiber-to-field angles of 0° and 55° were increased on average from T2 *m (0°) = 1.92 msec to T2 *m (55°) = 29.86 msec (15.5-fold) in the Achilles and T2 *m (0°) = 1.46 msec to T2 *m (55°) = 23.33 msec (16.0-fold) in the patellar tendons. The changes in T2 *m -values were statistically significant. For the whole tendon, according to F-test and AICC , a bi-exponential model was preferred for angles close to 0°, while the mono-exponential model tended to be preferred at angles close to 55°. CONCLUSION: MR-microscopy provides a deeper insight into the relationship between T2 *-decay (mono- vs. bi-exponential model) and tendon heterogeneity. Changes in fiber-to-field angle result in significant changes in T2 *-values. Thus, we conclude that awareness of T2 *-anisotropy should be noted in quantitative T2 *-mapping of tendons to avoid T2 *-misinterpretation such as a false positive detection of degeneration due to large fiber-to-field angles. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Deep learning for automatic segmentation of thigh and leg muscles.

OBJECTIVE: In this study we address the automatic segmentation of selected muscles of the thigh and leg through a supervised deep learning approach. MATERIAL AND METHODS: The application of quantitative imaging in neuromuscular diseases requires the availability of regions of interest (ROI) drawn on muscles to extract quantitative parameters. Up to now, manual drawing of ROIs has been considered the gold standard in clinical studies, with no clear and universally accepted standardized procedure for segmentation. Several automatic methods, based mainly on machine learning and deep learning algorithms, have recently been proposed to discriminate between skeletal muscle, bone, subcutaneous and intermuscular adipose tissue. We develop a supervised deep learning approach based on a unified framework for ROI segmentation. RESULTS: The proposed network generates segmentation maps with high accuracy, consisting in Dice Scores ranging from 0.89 to 0.95, with respect to "ground truth" manually segmented labelled images, also showing high average performance in both mild and severe cases of disease involvement (i.e. entity of fatty replacement). DISCUSSION: The presented results are promising and potentially translatable to different skeletal muscle groups and other MRI sequences with different contrast and resolution.

Variable echo time imaging for detecting the short T2* components of the sciatic nerve: a validation study.

OBJECTIVE: The aim of this study was to develop and validate an MRI protocol based on a variable echo time (vTE) sensitive to the short T2* components of the sciatic nerve. MATERIALS AND METHODS: 15 healthy subjects (M/F: 9/6; age: 21-62) were scanned at 3T targeting the sciatic nerve at the thigh bilaterally, using a dual echo variable echo time (vTE) sequence (based on a spoiled gradient echo acquisition) with echo times of 0.98/5.37 ms. Apparent T2* (aT2*) values of the sciatic nerves were calculated with a mono-exponential fit and used for data comparison. RESULTS: There were no significant differences in aT2* related to side, sex, age, and BMI, even though small differences for side were reported. Good-to-excellent repeatability and reproducibility were found for geometry of ROIs (Dice indices: intra-rater 0.68-0.7; inter-rater 0.70-0.72) and the related aT2* measures (intra-inter reader ICC 0.95-0.97; 0.66-0.85) from two different operators. Side-related signal-to-noise-ratio non-significant differences were reported, while contrast-to-noise-ratio measures were excellent both for side and echo. DISCUSSION: Our study introduces a novel MR sequence sensitive to the short T2* components of the sciatic nerve and may be used for the study of peripheral nerve disorders.

Dynamic MR imaging of the skeletal muscle in young and senior volunteers during synchronized minimal neuromuscular electrical stimulation.

OBJECTIVE: Neuromuscular electrical stimulation (NMES)-induced isometric contraction is feasible during MRI and can be combined with acquisition of volumetric dynamic MR data, in a synchronous and controlled way. Since NMES is a potent resource for rehabilitation, MRI synchronized with NMES presents a valuable validation tool. Our aim was to show how minimal NMES-induced muscle contraction characterization, as evaluated through phase-contrast MRI, differs between senior and young volunteers. MATERIALS AND METHODS: Simultaneous NMES of the quadriceps muscle and phase-contrast imaging were applied at 3 T to 11 senior (75 ± 3 years) and 12 young volunteers (29 ± 7 years). A current sufficient to induce muscle twitch without knee extension was applied to both groups. RESULTS: Strain vectors were extracted from the velocity fields and strain datasets were compared with non-parametric tests and descriptive statistics. Strain values were noticeably different between both groups at both current intensities and significant differences were observed for similar current level. DISCUSSION: In conclusion, NMES-synchronized MRI could be successfully applied in senior volunteers with strain results clearly different from the younger volunteers. Also, differences within the senior group were detected both in the magnitude of strain and in the position of maximum strain pixels.

Design and construction of an innovative brain phantom prototype for MRI.

PURPOSE: The purpose of this project was to construct a physical brain phantom for MRI, mimicking structure and T1 relaxation properties of white matter (WM) and gray matter (GM). METHODS: The phantom design comprised 2 compartments, 1 resembling the WM and 1 resembling the GM. Their T1 relaxation times, as assessed using an inversion recovery turbo spin echo sequence, were reproduced using an agar gel doped with contrast agent (CA) and their folding patterns were simulated through a molding-casting procedure using 3D-printed casts and flexible silicone molds. Three versions of the assembling procedure were adopted to build: Phantom1 without any separation; Phantom2 with a varnish layer; and Phantom3 with a thin wax layer between the compartments. RESULTS: Phantom1 was characterized by an immediate diffusion of CA between the 2 compartments. Phantom2 and Phantom3, instead, showed relaxation times and shape comparable with the target ones identified in a healthy control subject (WM: 754 ± 40 ms; GM: 1277 ± 96 ms). Moreover, both compartments revealed intact gyri and sulci. However, the diffusion of CA made Phantom2 stable only for a short period of time. Phantom3 showed stability within a time window of several days but the wax layer between the WM and GM was visible in the MRI. CONCLUSION: Structural and intensity properties of the constructed phantoms are useful in evaluating and validating steps from image acquisition to image processing. Moreover, the described constructing procedure and its modular design make it adjustable to a variety of applications.

Orientation dependence and decay characteristics of T2 * relaxation in the human meniscus studied with 7 Tesla MR microscopy and compared to histology.

PURPOSE: To evaluate: (1) the feasibility of MR microscopy T2 * mapping by performing a zonal analysis of spatially matched T2 * maps and histological images using microscopic in-plane pixel resolution; (2) the orientational dependence of T2 * relaxation of the meniscus; and (3) the T2 * decay characteristics of the meniscus by statistically evaluating the quality of mono- and biexponential model. METHODS: Ultrahigh resolution T2 * mapping was performed with ultrashort echo time using a 7 Tesla MR microscopy system. Measurement of one meniscus was performed at three orientations to the main magnetic field (0, 55, and 90°). Histological assessment was performed with picrosirius red staining and polarized light microscopy. Quality of mono- and biexponential model fitting was tested using Akaike Information Criteria and F-test. RESULTS: (1) The outer laminar layer, connective tissue fibers from the joint capsule, and the highly organized tendon-like structures were identified using ultra-highly resolved MRI. (2) Highly organized structures of the meniscus showed considerable changes in T2 * values with orientation. (3) No significant biexponential decay was found on a voxel-by-voxel-based evaluation. On a region-of-interest-averaged basis, significant biexponential decay was found for the tendon-like region in a fiber-to-field angle of 0°. CONCLUSION: The MR microscopy approach used in this study allows the identification of meniscus substructures and to quantify T2 * with a voxel resolution approximately 100 times higher than previously reported. T2 * decay showed a strong fiber-to-field angle dependence reflecting the anisotropic properties of the meniscal collagen fibers. No clear biexponential decay behavior was found for the meniscus substructures.

Synchronous MRI of muscle motion induced by electrical stimulation.

PURPOSE: Assessing the functionality of muscle fibers is essential to monitor both pathological and physiological processes. Here, we present a new method for accurate, quantitative measurement of muscle contraction with magnetic resonance imaging (MRI) using an electrical muscle stimulator (EMS), hence allowing the direct assessment of muscle kinematics. METHODS: A commercially available EMS device was used to induce involuntary periodic muscle contraction of the vastus lateralis muscle (VL) synchronized with high-temporal-resolution cine phase contrast MRI acquisition at 3T. The proposed method was evaluated in ten male volunteers at varying levels of stimulation (10-18 mA) and maximum velocity, strain, and strain rate were calculated offline. RESULTS: Artifact-free velocity, strain and strain rate maps were produced and were consistent across the volunteers. Quantitatively, all parameters varied significantly at different levels of stimulation, in an approximately power-law dependence on the stimulation current. At 18 mA maximum contraction speeds at the beginning of the contraction were 4.28 ± 2.64 cm/s; principal strain was 0.30 ± 0.12; and positive in-plane strain rate was 0.25 ± 0.14 s-1 . CONCLUSION: MRI of EMS-controlled involuntary muscle contraction is feasible and allows offline calculation of velocity, strain and strain rate maps, which appear to depend significantly on the stimulation current used. Magn Reson Med 77:664-672, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Combining phase images from array coils using a short echo time reference scan (COMPOSER).

PURPOSE: To develop a simple method for combining phase images from multichannel coils that does not require a reference coil and does not entail phase unwrapping, fitting or iterative procedures. THEORY AND METHODS: At very short echo time, the phase measured with each coil of an array approximates to the phase offset to which the image from that coil is subject. Subtracting this information from the phase of the scan of interest matches the phases from the coils, allowing them to be combined. The effectiveness of this approach is quantified in the brain, calf and breast with coils of diverse designs. RESULTS: The quality of phase matching between coil elements was close to 100% with all coils assessed even in regions of low signal. This method of phase combination was similar in effectiveness to the Roemer method (which needs a reference coil) and was superior to the rival reference-coil-free approaches tested. CONCLUSION: The proposed approach-COMbining Phase data using a Short Echo-time Reference scan (COMPOSER)-is a simple and effective approach to reconstructing phase images from multichannel coils. It requires little additional scan time, is compatible with parallel imaging and is applicable to all coils, independent of configuration. Magn Reson Med 77:318-327, 2017. © 2015 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.

Water-selective excitation of short T2 species with binomial pulses.

PURPOSE: For imaging of fibrous musculoskeletal components, ultra-short echo time methods are often combined with fat suppression. Due to the increased chemical shift, spectral excitation of water might become a favorable option at ultra-high fields. Thus, this study aims to compare and explore short binomial excitation schemes for spectrally selective imaging of fibrous tissue components with short transverse relaxation time (T2 ). METHODS: Water selective 1-1-binomial excitation is compared with nonselective imaging using a sub-millisecond spoiled gradient echo technique for in vivo imaging of fibrous tissue at 3T and 7T. RESULTS: Simulations indicate a maximum signal loss from binomial excitation of approximately 30% in the limit of very short T2 (0.1 ms), as compared to nonselective imaging; decreasing rapidly with increasing field strength and increasing T2 , e.g., to 19% at 3T and 10% at 7T for T2 of 1 ms. In agreement with simulations, a binomial phase close to 90° yielded minimum signal loss: approximately 6% at 3T and close to 0% at 7T for menisci, and for ligaments 9% and 13%, respectively. CONCLUSION: Overall, for imaging of short-lived T2 components, short 1-1 binomial excitation schemes prove to offer marginal signal loss especially at ultra-high fields with overall improved scanning efficiency.

Quantitative MRI analysis of menisci using biexponential T2* fitting with a variable echo time sequence.

PURPOSE: The goal of this study was to differentiate between normal, degenerative meniscus, and meniscal tears using monoexponentially and biexponentially calculated T2*. Meniscal disease, characterized by an altered collagen fiber matrix, might be detectable in vivo using quantitative T2* mapping. METHODS: A 3D Cartesian spoiled gradient echo technique was adapted to enable the use of a variable echo time approach in combination with a highly asymmetric readout. T2* was calculated monoexponentially and biexponentially using three- and five-parametric non-linear fits, respectively. RESULTS: From a total of 68 evaluated menisci, 48 were normal, 12 were degenerated, and eight had tears. Mean values for the short (T2*s) and long (T2*l) T2* components were as follows: in normal menisci, 0.82 ± 0.38/15.0 ± 5.4 ms, respectively; in degenerated menisci, 1.29 ± 0.53/19.97 ± 5.59 ms, respectively; and, in meniscal tears, 2.05 ± 0.73 and 26.83 ± 7.72 ms, respectively. Biexponentially fitted T2* demonstrated a greater ability to distinguish normal and degenerated menisci using receiver operating characteristic (ROC) analysis (higher area under curve as well as higher specificity and sensitivity). CONCLUSION: This study suggests that biexponential fitting, used for T2* calculation in the menisci, provides better results compared to monoexponential fitting. Observed changes in T2* result from the matrix reorganization in degenerative processes in the menisci, which affects the collagen fiber orientation, as well as content.

In vivo sodium (23Na) imaging of the human kidneys at 7 T: preliminary results.

OBJECTIVE: To evaluate the feasibility of in vivo (23)Na imaging of the corticomedullary (23)Na gradient and to measure (23)Na transverse relaxation times (T2*) in human kidneys. METHODS: In this prospective, IRB-approved study, eight healthy volunteers (4 female, 4 male; mean age 29.4 ± 3.6 years) were examined on a 7-T whole-body MR system using a (23)Na-only spine-array coil. For morphological (23)Na-MRI, a 3D gradient echo (GRE) sequence with a variable echo time scheme (vTE) was used. T2* times were calculated using a multiecho 3D vTE-GRE approach. (23)Na signal-to-noise ratios (SNR) were given on a pixel-by-pixel basis for a 20-mm section from the cortex in the direction of the medulla. T2* maps were calculated by fitting the (23)Na signal decay monoexponentially on a pixel-by-pixel basis, using least squares fit. RESULTS: Mean corticomedullary (23)Na-SNR increased from the cortex (32.2 ± 5.6) towards the medulla (85.7 ± 16.0). The SNR increase ranged interindividually from 57.2% to 66.3%. Mean (23)Na-T2* relaxation times differed statistically significantly (P < 0.001) between the cortex (17.9 ± 0.8 ms) and medulla (20.6 ± 1.0 ms). CONCLUSION: The aim of this study was to evaluate the feasibility of in vivo (23)Na MRI of the corticomedullary (23)Na gradient and to measure the (23)Na T2* relaxation times of human kidneys at 7 T. KEY POINTS: • High field MR offers new insights into renal anatomy and physiology. • (23) Na MRI of healthy human kidneys is feasible at ultra-high field. • Renal (23) Na concentration increases from the cortex in the medullary pyramid direction. • In vivo measurements of renal (23) Na-T2* times are demonstrated at 7.0 T.

In vivo visualization of cells labeled with superparamagnetic iron oxides by a sub-millisecond gradient echo sequence.

OBJECT: In vivo magnetic resonance imaging (MRI) of iron-labeled pancreatic islets (PIs) transplanted into the liver is still challenging in humans. The aim of this study was to develop and evaluate a double contrast method for the detection of PIs labeled with superparamagnetic iron oxide (SPIO) nanoparticles. MATERIALS AND METHODS: A double-echo three-dimensional (3D) spoiled gradient echo sequence was adapted to yield a sub-millisecond first echo time using variable echo times and highly asymmetric Cartesian readout. Positive contrast was achieved by conventional and relative image subtraction. Experiments for cell detection efficiency were performed in vitro on gelatin phantoms, in vivo on a Lewis rat and on a patient 6 months after PI transplantation. RESULTS: It was demonstrated that the proposed method can be used for the detection of transplanted PIs with positive contrast in vitro and in vivo. For all experiments, relative subtraction yielded comparable and in some cases better contrast than conventional subtraction. For the first time, positive contrast imaging of transplanted human PIs was performed in vivo in patients. CONCLUSION: The proposed method allows 3D data acquisition within a single breath-hold and yields enhanced contrast-to-noise ratios of transplanted SPIO labeled pancreatic islets relative to negative contrast images, therefore providing improved identification.

Bi-exponential T2 analysis of healthy and diseased Achilles tendons: an in vivo preliminary magnetic resonance study and correlation with clinical score.

OBJECTIVE: To compare mono- and bi-exponential T2 analysis in healthy and degenerated Achilles tendons using a recently introduced magnetic resonance variable-echo-time sequence (vTE) for T2 mapping. METHODS: Ten volunteers and ten patients were included in the study. A variable-echo-time sequence was used with 20 echo times. Images were post-processed with both techniques, mono- and bi-exponential [T2 m, short T2 component (T2 s) and long T2 component (T2 l)]. The number of mono- and bi-exponentially decaying pixels in each region of interest was expressed as a ratio (B/M). Patients were clinically assessed with the Achilles Tendon Rupture Score (ATRS), and these values were correlated with the T2 values. RESULTS: The means for both T2 m and T2 s were statistically significantly different between patients and volunteers; however, for T2 s, the P value was lower. In patients, the Pearson correlation coefficient between ATRS and T2 s was -0.816 (P = 0.007). CONCLUSION: The proposed variable-echo-time sequence can be successfully used as an alternative method to UTE sequences with some added benefits, such as a short imaging time along with relatively high resolution and minimised blurring artefacts, and minimised susceptibility artefacts and chemical shift artefacts. Bi-exponential T2 calculation is superior to mono-exponential in terms of statistical significance for the diagnosis of Achilles tendinopathy. KEY POINTS: • Magnetic resonance imaging offers new insight into healthy and diseased Achilles tendons • Bi-exponential T2 calculation in Achilles tendons is more beneficial than mono-exponential • A short T2 component correlates strongly with clinical score • Variable echo time sequences successfully used instead of ultrashort echo time sequences.

Radiomics and machine learning applied to STIR sequence for prediction of quantitative parameters in facioscapulohumeral disease.

Purpose: Quantitative Muscle MRI (qMRI) is a valuable and non-invasive tool to assess disease involvement and progression in neuromuscular disorders being able to detect even subtle changes in muscle pathology. The aim of this study is to evaluate the feasibility of using a conventional short-tau inversion recovery (STIR) sequence to predict fat fraction (FF) and water T2 (wT2) in skeletal muscle introducing a radiomic workflow with standardized feature extraction combined with machine learning algorithms. Methods: Twenty-five patients with facioscapulohumeral muscular dystrophy (FSHD) were scanned at calf level using conventional STIR sequence and qMRI techniques. We applied and compared three different radiomics workflows (WF1, WF2, WF3), combined with seven Machine Learning regression algorithms (linear, ridge and lasso regression, tree, random forest, k-nearest neighbor and support vector machine), on conventional STIR images to predict FF and wT2 for six calf muscles. Results: The combination of WF3 and K-nearest neighbor resulted to be the best predictor model of qMRI parameters with a mean absolute error about ± 5 pp for FF and ± 1.8 ms for wT2. Conclusion: This pilot study demonstrated the possibility to predict qMRI parameters in a cohort of FSHD subjects starting from conventional STIR sequence.

Muscle quantitative MRI as a novel biomarker in hereditary transthyretin amyloidosis with polyneuropathy: a cross-sectional study.

BACKGROUND: The development of reproducible and sensitive outcome measures has been challenging in hereditary transthyretin (ATTRv) amyloidosis. Recently, quantification of intramuscular fat by magnetic resonance imaging (MRI) has proven as a sensitive marker in patients with other genetic neuropathies. The aim of this study was to investigate the role of muscle quantitative MRI (qMRI) as an outcome measure in ATTRv. METHODS: Calf- and thigh-centered multi-echo T2-weighted spin-echo and gradient-echo sequences were obtained in patients with ATTRv amyloidosis with polyneuropathy (n = 24) and healthy controls (n = 12). Water T2 (wT2) and fat fraction (FF) were calculated. Neurological assessment was performed in all ATTRv subjects. Quantitative MRI parameters were correlated with clinical and neurophysiological measures of disease severity. RESULTS: Quantitative imaging revealed significantly higher FF in lower limb muscles in patients with ATTRv amyloidosis compared to controls. In addition, wT2 was significantly higher in ATTRv patients. There was prominent involvement of the posterior compartment of the thighs. Noticeably, FF and wT2 did not exhibit a length-dependent pattern in ATTRv patients. MRI biomarkers correlated with previously validated clinical outcome measures, Polyneuropathy Disability scoring system, Neuropathy Impairment Score (NIS) and NIS-lower limb, and neurophysiological parameters of axonal damage regardless of age, sex, treatment and TTR mutation. CONCLUSIONS: Muscle qMRI revealed significant difference between ATTRv and healthy controls. MRI biomarkers showed high correlation with clinical and neurophysiological measures of disease severity making qMRI as a promising tool to be further investigated in longitudinal studies to assess its role at monitoring onset, progression, and therapy efficacy for future clinical trials on this treatable condition.

Integrated active tracking detector for MRI-guided interventions.

We present a fully integrated detector suitable for active tracking of interventional devices in MR-guided interventions. The single-chip microsystem consists of a detection coil, a tuning capacitor, an intermediate frequency downconversion receiver, and a phase-locked-loop-based frequency synthesizer. Thanks to the integrated mixer, the chip output stage delivers an analog frequency-downconverted NMR signal in the frequency range from 0 to 200 kHz. The microchip, realized in a standard complementary metal oxide semiconductor technology, has a size of 1 × 2 × 0.74 mm(3) and operates at a frequency of 63 MHz (i.e., in 1.5 T clinical scanners). Tests in a standard clinical scanner demonstrate the compatibility of the complementary metal oxide semiconductor microchip with clinical MRI systems. Using a solid sample of cis-polyisoprene having a size of 1 × 1.9 × 0.8 mm(3) as internal signal source, the detector achieves a three-dimensional isotropic spatial resolution of 0.15 mm in a measuring time of 100 ms.

Dynamic magnetic resonance imaging of muscle contraction in facioscapulohumeral muscular dystrophy.

Quantitative muscle MRI (water-T2 and fat mapping) is being increasingly used to assess disease involvement in muscle disorders, while imaging techniques for assessment of the dynamic and elastic muscle properties have not yet been translated into clinics. In this exploratory study, we quantitatively characterized muscle deformation (strain) in patients affected by facioscapulohumeral muscular dystrophy (FSHD), a prevalent muscular dystrophy, by applying dynamic MRI synchronized with neuromuscular electrical stimulation (NMES). We evaluated the quadriceps muscles in 34 ambulatory patients and 13 healthy controls, at 6-to 12-month time intervals. While a subgroup of patients behaved similarly to controls, for another subgroup the median strain decreased over time (approximately 57% over 1.5 years). Dynamic MRI parameters did not correlate with quantitative MRI. Our results suggest that the evaluation of muscle contraction by NMES-MRI is feasible and could potentially be used to explore the elastic properties and monitor muscle involvement in FSHD and other neuromuscular disorders.

Combination of Quantitative MRI Fat Fraction and Texture Analysis to Evaluate Spastic Muscles of Children With Cerebral Palsy.

Background: Cerebral palsy (CP) is the most common cause of physical disability in childhood. Muscle pathologies occur due to spasticity and contractures; therefore, diagnostic imaging to detect pathologies is often required. Imaging has been used to assess torsion or estimate muscle volume, but additional methods for characterizing muscle composition have not thoroughly been investigated. MRI fat fraction (FF) measurement can quantify muscle fat and is often a part of standard imaging in neuromuscular dystrophies. To date, FF has been used to quantify muscle fat and assess function in CP. In this study, we aimed to utilize a radiomics and FF analysis along with the combination of both methods to differentiate affected muscles from healthy ones. Materials and Methods: A total of 9 patients (age range 8-15 years) with CP and 12 healthy controls (age range 9-16 years) were prospectively enrolled (2018-2020) after ethics committee approval. Multi-echo Dixon acquisition of the calf muscles was used for FF calculation. The images of the second echo (TE = 2.87 ms) were used for feature extraction from the soleus, gastrocnemius medialis, and gastrocnemius lateralis muscles. The least absolute shrinkage and selection operator (LASSO) regression was employed for feature selection. RM, FF model (FFM), and combined model (CM) were built for each calf muscle. The receiver operating characteristic (ROC) curve and their respective area under the curve (AUC) values were used to evaluate model performance. Results: In total, the affected legs of 9 CP patients and the dominant legs of 12 healthy controls were analyzed. The performance of RM for soleus, gastrocnemius medialis, and gastrocnemius lateralis (AUC 0.92, 0.92, 0.82, respectively) was better than the FFM (AUC 0.88, 0.85, 0.69, respectively). The combination of both models always had a better performance than RM or FFM (AUC 0.95, 0.93, 0.83). FF was higher in the patient group (FFS 9.1%, FFGM 8.5%, and FFGL 10.2%) than control group (FFS 3.3%, FFGM 4.1%, FFGL 6.6%). Conclusion: The combination of MRI quantitative fat fraction analysis and texture analysis of muscles is a promising tool to evaluate muscle pathologies due to CP in a non-invasive manner.

Treatment with L-Citrulline in patients with post-polio syndrome: A single center, randomized, double blind, placebo-controlled trial.

This single-centered, randomized, double-blind, placebo-controlled study reports the results of L-Citrulline treatment for 24 weeks in patients with post-polio syndrome (PPS). Twenty-nine patients were randomized and assigned into receiving a treatment of 15 g L-Citrulline or placebo. The primary endpoint was the change of the 6 min walking distance test. Secondary endpoints included motor function measure, quantitative muscle strength, quantitative MRI and self-reported impairment questionnaires. Patients receiving L-Citrulline walked 17.5 longer in the 6 min walking distance test when compared to placebo group, however not statistically significant (95% CI = -14.69; 49.68, p = 0.298). None of the secondary endpoints showed a statistically significant change in the L-Citrulline group when compared to placebo group. The motor function measure showed a change of -0.78 (95% CI= [-3.39; 1.83] p = 0.563). Muscle degeneration of leg muscles assessed with quantitative MRI indicated no significant change (estimate= -0.01, 95% CI =-0.13; 0.11, p = 0.869). L-Citrulline was safe and well tolerated. In conclusion, administration of 15 g L-Citrulline daily for 24 weeks to patients with PPS showed no beneficial treatment effect in timed muscle function.