Effect of a graded running race on lower limb muscle damage, jump performance and muscle soreness in men and women.

PURPOSE: Delayed structural and functional recovery after a 20 km graded running race was analyzed with respect to the sex effect. METHODS: Thirteen female and 14 male recreational runners completed the race and three test sessions: one before (PRE) and two after, once on Day 1 or 2 (D1-2) and then on Day 3 or 4 (D3-4). Muscle damage was assessed indirectly using ultrasonography to quantify changes in cross-sectional area (CSA) of 10 lower-limb muscles. Delayed onset of muscle soreness (DOMS) was assessed for three muscle groups. Functional recovery was quantified by kinetic analysis of a squat jump (SJ) and a drop jump (DJ) test performed on a sledge ergometer. Linear mixed models were used to assess control group reproducibility and recovery patterns according to sex. RESULTS: Regardless of sex, DOMS peaked at D1-2 for all muscle groups and resolved at D3-4. CSA was increased in each muscle group until D3-4, especially in the semimembranosus muscle. A specific increase was found in the short head of the biceps femoris in women. Regardless of sex, SJ and DJ performances declined up to D3-4. Depending on the muscle, positive and/or negative correlations were found between structural and functional changes. Some of these were sex-specific. CONCLUSION: Structural and functional recovery was incomplete in both sexes up to D3-4, although DOMS had disappeared. More emphasis should be placed on hamstring muscle recovery. Highlighting the intermuscular compensations that can occur during multi-joint testing tasks, the structural-functional relationships were either positive or negative, muscle- and sex-dependent.

One-Year Longitudinal Assessment of Patients With CMT1A Using Quantitative MRI.

BACKGROUND AND OBJECTIVES: Intramuscular fat fraction (FF) assessed using quantitative MRI (qMRI) has emerged as one of the few responsive outcome measures in CMT1A suitable for future clinical trials. This study aimed to identify the relevance of multiple qMRI biomarkers for tracking longitudinal changes in CMT1A and to assess correlations between MRI metrics and clinical parameters. METHODS: qMRI was performed in CMT1A patients at 2 time points, a year apart, and various metrics were extracted from 3-dimensional volumes of interest at thigh and leg levels. A semiautomated segmentation technique was used, enabling the analysis of central slices and a larger 3D muscle volume. Metrics included proton density (PD), magnetization transfer ratio (MTR), and intramuscular FF. The sciatic and tibial nerves were also assessed. Disease severity was gauged using Charcot Marie Tooth Neurologic Score (CMTNSv2), Charcot Marie Tooth Examination Score, Overall Neuropathy Limitation Scale scores, and Medical Research Council (MRC) muscle strength. RESULTS: Twenty-four patients were included. FF significantly rose in the 3D volume at both thigh (+1.04% ± 2.19%, p = 0.041) and leg (+1.36% ± 1.87%, p = 0.045) levels. The 3D analyses unveiled a length-dependent gradient in FF, ranging from 22.61% ± 10.17% to 26.17% ± 10.79% at the leg level. There was noticeable variance in longitudinal changes between muscles: +3.17% ± 6.86% (p = 0.028) in the tibialis anterior compared with 0.37% ± 4.97% (p = 0.893) in the gastrocnemius medialis. MTR across the entire thigh volume showed a significant decline between the 2 time points -2.75 ± 6.58 (p = 0.049), whereas no significant differences were noted for the 3D muscle volume and PD. No longitudinal changes were observed in any nerve metric. Potent correlations were identified between FF and primary clinical measures: CMTNSv2 (ρ = 0.656; p = 0.001) and MRC in the lower limbs (ρ = -0.877; p < 0.001). DISCUSSION: Our results further support that qMRI is a promising tool for following up longitudinal changes in CMT1A patients, FF being the paramount MRI metric for both thigh and leg regions. It is crucial to scrutinize the postimaging data extraction methods considering that annual changes are minimal (around +1.5%). Given the varied FF distribution, the existence of a length-dependent gradient, and the differential fatty involution across muscles, 3D volume analysis appeared more suitable than single slice analysis.

Endurance training and hydroxyurea have synergistic effects on muscle function and energetics in sickle cell disease mice.

Sickle cell disease (SCD) is an hemoglobinopathy resulting in the production of an abnormal Hb (HbS) which can polymerize in deoxygenated conditions, leading to the sickling of red blood cells (RBC). These alterations can decrease the oxygen-carrying capacity leading to impaired function and energetics of skeletal muscle. Any strategy which could reverse the corresponding defects could be of interest. In SCD, endurance training is known to improve multiples muscle properties which restores patient's exercise capacity but present reduced effects in anemic patients. Hydroxyurea (HU) can increase fetal hemoglobin production which can reduce anemia in patients. The present study was conducted to determine whether HU can improve the effects of endurance training to improve muscle function and energetics. Twenty SCD Townes mice have been trained for 8 weeks with (n = 11) or without (n = 9) HU. SCD mice muscle function and energetics were analyzed during a standardized rest-exercise-recovery protocol, using Phosphorus-31 Magnetic resonance spectroscopy (31P-MRS) and transcutaneous stimulation. The combination of training and HU specifically decreased fatigue index and PCr consumption while muscle oxidative capacity was improved. These results illustrate the potential synergistic effects of endurance training and HU on muscle function and energetics in sickle cell disease.

Mitigating slice cross-talk in multi-slice multi-echo spin echo T2 mapping.

PURPOSE: To investigate whether a T2 inter-slice variation could occur when a multi-slice multi-echo spin echo (MESE) sequence is used for image acquisition and to propose an enhanced method for reconstructing T2 maps that can effectively address and correct these variations. METHODS: Bloch simulations were performed accounting for the direct saturation effect to evaluate magnetization changes in multi-slice 2D MESE sequence. Experimental phantom scans were performed to validate these simulations. An improved version of the dictionary-based reconstruction approach was proposed, enabling the creation of a multi-slice dictionary of echo modulation curves (EMC). The corresponding method has been assayed considering inter-slice T2 variation with phantoms and in lower leg. RESULTS: Experimental and numerical study illustrate that direct saturation leads to a bias of EMCs. This bias during the T2 maps reconstructions using original single-slice EMC-dictionary method led to inter-slice T2 variation of 2.03% in average coefficient of variation (CV) in agarose phantoms, and up to 2.8% in vivo (for TR = 2 s, slice gap = 0%). A reduction of CV was observed when increasing the gap up to 100% (0.36% in phantoms, and up to 1.5% in vivo) or increasing TR up to 4 s (0.76% in phantoms, and up to 1.9% in vivo). Matching the multi-slice experimental data with multi-slice dictionaries provided a reduced CV of 0.54% in phantoms and up to 2.3% in vivo. CONCLUSION: T2 values quantified from multi-slice MESE images using single-slice dictionaries are biased. A dedicated multi-slice EMC method providing the appropriate dictionaries can reduce the inter-slice T2 variation.

Robust Strategy for Hit-to-Lead Discovery: NMR for SAR.

Establishing robust structure-activity relationships (SARs) is key to successful drug discovery campaigns, yet it often remains elusive due to screening and hit validation artifacts (false positives and false negatives), which frequently result in unproductive downstream expenditures of time and resources. To address this issue, we developed an integrative biophysics-driven strategy that expedites hit-to-lead discovery, mitigates false positives/negatives and common hit validation errors, and provides a robust approach to obtaining accurate binding and affinity measurements. The advantage of this method is that it vastly improves the clarity and reproducibility for affinity-driven SAR by monitoring and eliminating confounding factors. We demonstrate the ease at which high-quality micromolar binders can be generated from the initial millimolar fragment screening hits against an "undruggable" protein target, HRas.

Quantification of muscle involvement in familial amyloid polyneuropathy using MRI.

BACKGROUND AND PURPOSE: Transthyretin familial amyloid polyneuropathy (TTR-FAP) is a rare genetic disease with autosomal-dominant inheritance. In this study, we aimed to quantify fatty infiltration (fat fraction [FF]) and magnetization transfer ratio (MTR) in individual muscles of patients with symptomatic and asymptomatic TTR-FAP using magnetic resonance imaging. Secondarily, we aimed to assess correlations with clinical and electrophysiological variables. METHODS: A total of 39 patients with a confirmed mutation in the TTR gene (25 symptomatic and 14 asymptomatic) and 14 healthy volunteers were included. A total of 16 muscles were manually delineated in the nondominant lower limb from T1-weighted anatomical images. The corresponding masks were propagated on the MTR and FF maps. Detailed neurological and electrophysiological examinations were conducted in each group. RESULTS: The MTR was decreased (42.6 AU; p = 0.001) and FF was elevated (14%; p = 0.003) in the lower limbs of the symptomatic group, with preferential posterior and lateral involvement. In the asymptomatic group, elevated FF was quantified in the gastrocnemius lateralis muscle (11%; p = 0.021). FF was significantly correlated with disease duration (r = 0.49, p = 0.015), neuropathy impairment score for the lower limb (r = 0.42, p = 0.041), Overall Neuropathy Limitations Scale score (r = 0.49, p = 0.013), polyneuropathy disability score (r = 0.57, p = 0.03) and the sum of compound muscle action potential (r = 0.52, p = 0.009). MTR was strongly correlated to FF (r = 0.78, p < 0.0001), and a few muscles with an FF within the normal range had a reduced MTR. CONCLUSION: These observations suggest that FF and MTR could be interesting biomarkers in TTR-FAP. In asymptomatic patients, FF in the gastrocnemius lateralis muscle could be a good indicator of the transition from an asymptomatic to a symptomatic form of the disease. MTR could be an early biomarker of muscle alterations.

Ultra-high field magnetic resonance imaging of the quadriceps tendon enthesis in healthy subjects.

PURPOSE: Although enthesitis is a hallmark of several rheumatologic conditions, current imaging methods are still unable to characterize entheses changes because of the corresponding short transverse relaxation times (T2). A growing number of MR studies have used Ultra-High Field (UHF) MRI in order to assess low-T2 tissues e.g., tendon but never in humans. The purpose of the present study was to assess in vivo the enthesis of the quadriceps tendon in healthy subjects using UHF MRI. METHODS: Eleven healthy subjects volunteered in an osteoarthritis imaging study. The inclusion criteria were: no knee trauma, Lequesne index = 0, less than 3 h of sport activities per week, and Kellgren and Lawrence grade = 0. 3D MR images were acquired at 7 T using GRE sequences and a T2* mapping. Regions of interest i.e., trabecular bone, subchondral bone, enthesis, and tendon body were identified, and T2* values were quantified and compared. RESULTS: Quadriceps tendon enthesis was visible as a hyper-intense signal. The largest and the lowest T2* values were quantified in the subchondral bone region and the tendon body respectively. T2* value within subchondral bone was significantly higher than T2* value within the enthesis. T2* in subchondral bone region was significantly higher than the whole tendon body T2*. CONCLUSION: A T2* gradient was observed along the axis from the enthesis toward the tendon body. It illustrates different water biophysical properties. These results provide normative values which could be used in the field of inflammatory rheumatologic diseases and mechanical disorders affecting the tendon.

CNN-based fully automatic wrist cartilage volume quantification in MR images: A comparative analysis between different CNN architectures.

PURPOSE: Automatic measurement of wrist cartilage volume in MR images. METHODS: We assessed the performance of four manually optimized variants of the U-Net architecture, nnU-Net and Mask R-CNN frameworks for the segmentation of wrist cartilage. The results were compared to those from a patch-based convolutional neural network (CNN) we previously designed. The segmentation quality was assessed on the basis of a comparative analysis with manual segmentation. The best networks were compared using a cross-validation approach on a dataset of 33 3D VIBE images of mostly healthy volunteers. Influence of some image parameters on the segmentation reproducibility was assessed. RESULTS: The U-Net-based networks outperformed the patch-based CNN in terms of segmentation homogeneity and quality, while Mask R-CNN did not show an acceptable performance. The median 3D DSC value computed with the U-Net_AL (0.817) was significantly larger than DSC values computed with the other networks. In addition, the U-Net_AL provided the lowest mean volume error (17%) and the highest Pearson correlation coefficient (0.765) with respect to the ground truth values. Of interest, the reproducibility computed using U-Net_AL was larger than the reproducibility of the manual segmentation. Moreover, the results indicate that the MRI-based wrist cartilage volume is strongly affected by the image resolution. CONCLUSIONS: U-Net CNN with attention layers provided the best wrist cartilage segmentation performance. In order to be used in clinical conditions, the trained network can be fine-tuned on a dataset representing a group of specific patients. The error of cartilage volume measurement should be assessed independently using a non-MRI method.

The Impact of Fatty Infiltration on MRI Segmentation of Lower Limb Muscles in Neuromuscular Diseases: A Comparative Study of Deep Learning Approaches.

BACKGROUND: Deep learning methods have been shown to be useful for segmentation of lower limb muscle MRIs of healthy subjects but, have not been sufficiently evaluated on neuromuscular disease (NDM) patients. PURPOSE: Evaluate the influence of fat infiltration on convolutional neural network (CNN) segmentation of MRIs from NMD patients. STUDY TYPE: Retrospective study. SUBJECTS: Data were collected from a hospital database of 67 patients with NMDs and 14 controls (age: 53 ± 17 years, sex: 48 M, 33 F). Ten individual muscles were segmented from the thigh and six from the calf (20 slices, 200 cm section). FIELD STRENGTH/SEQUENCE: A 1.5 T. Sequences: 2D T1 -weighted fast spin echo. Fat fraction (FF): three-point Dixon 3D GRE, magnetization transfer ratio (MTR): 3D MT-prepared GRE, T2: 2D multispin-echo sequence. ASSESSMENT: U-Net 2D, U-Net 3D, TransUNet, and HRNet were trained to segment thigh and leg muscles (101/11 and 95/11 training/validation images, 10-fold cross-validation). Automatic and manual segmentations were compared based on geometric criteria (Dice coefficient [DSC], outlier rate, absence rate) and reliability of measured MRI quantities (FF, MTR, T2, volume). STATISTICAL TESTS: Bland-Altman plots were chosen to describe agreement between manual vs. automatic estimated FF, MTR, T2 and volume. Comparisons were made between muscle populations with an FF greater than 20% (G20+) and lower than 20% (G20-). RESULTS: The CNNs achieved equivalent results, yet only HRNet recognized every muscle in the database, with a DSC of 0.91 ± 0.08, and measurement biases reaching -0.32% ± 0.92% for FF, 0.19 ± 0.77 for MTR, -0.55 ± 1.95 msec for T2, and - 0.38 ± 3.67 cm3 for volume. The performances of HRNet, between G20- and G20+ decreased significantly. DATA CONCLUSION: HRNet was the most appropriate network, as it did not omit any muscle. The accuracy obtained shows that CNNs could provide fully automated methods for studying NMDs. However, the accuracy of the methods may be degraded on the most infiltrated muscles (>20%). EVIDENCE LEVEL: 4. TECHNICAL EFFICACY: Stage 1.

Estimation of subvoxel fat infiltration in neurodegenerative muscle disorders using quantitative multi-T2 analysis.

MRI's T2 relaxation time is a valuable biomarker for neuromuscular disorders and muscle dystrophies. One of the hallmarks of these pathologies is the infiltration of adipose tissue and a loss of muscle volume. This leads to a mixture of two signal components, from fat and from water, to appear in each imaged voxel, each having a specific T2 relaxation time. In this proof-of-concept work, we present a technique that can separate the signals from water and from fat within each voxel, measure their separate T2 values, and calculate their relative fractions. The echo modulation curve (EMC) algorithm is a dictionary-based technique that offers accurate and reproducible mapping of T2 relaxation times. We present an extension of the EMC algorithm for estimating subvoxel fat and water fractions, alongside the T2 and proton-density values of each component. To facilitate data processing, calf and thigh anatomy were automatically segmented using a fully convolutional neural network and FSLeyes software. The preprocessing included creating two signal dictionaries, for water and for fat, using Bloch simulations of the prospective protocol. Postprocessing included voxelwise fitting for two components, by matching the experimental decay curve to a linear combination of the two simulated dictionaries. Subvoxel fat and water fractions and relaxation times were generated and used to calculate a new quantitative biomarker, termed viable muscle index, and reflecting disease severity. This biomarker indicates the fraction of remaining muscle out of the entire muscle region. The results were compared with those using the conventional Dixon technique, showing high agreement (R = 0.98, p < 0.001). It was concluded that the new extension of the EMC algorithm can be used to quantify abnormal fat infiltration as well as identify early inflammatory processes corresponding to elevation in the T2 value of the water (muscle) component. This new ability may improve the diagnostic accuracy of neuromuscular diseases, help stratification of patients according to disease severity, and offer an efficient tool for tracking disease progression.

Effects of hydroxyurea on skeletal muscle energetics and force production in a sickle cell disease murine model.

Hydroxyurea (HU) is commonly used as a treatment for patients with sickle cell disease (SCD) to enhance fetal hemoglobin production. This increased production is expected to reduce anemia (which depresses oxygen transport) and abnormal Hb content alleviating clinical symptoms such as vaso-occlusive crisis and acute chest syndrome. The effects of HU on skeletal muscle bioenergetics in vivo are still unknown. Due to the beneficial effects of HU upon oxygen delivery, improved skeletal muscle energetics and function in response to a HU treatment have been hypothesized. Muscle energetics and function were analyzed during a standardized rest-exercise-recovery protocol, using 31P-magnetic resonance spectroscopy in Townes SCD mice. Measurements were performed in three groups of mice: one group of 2-mo-old mice (SCD2m, n = 8), another one of 4-mo-old mice (SCD4m, n = 8), and a last group of 4-mo-old mice that have been treated from 2 mo of age with HU at 50 mg/kg/day (SCD4m-HU, n = 8). As compared with SCD2m mice, SCD4m mice were heavier and displayed a lower acidosis. As lower specific forces were developed by SCD4m compared with SCD2m, greater force-normalized phosphocreatine consumption and oxidative and nonoxidative costs of contraction were also reported. HU-treated mice (SCD4m-HU) displayed a significantly higher specific force production as compared with untreated mice (SCD4m), whereas muscle energetics was unchanged. Overall, our results support a beneficial effect of HU on muscle function.NEW & NOTEWORTHY Our results highlighted that force production decreases between 2 and 4 mo of age in SCD mice thereby indicating a decrease of muscle function during this period. Of interest, HU treatment seemed to blunt the observed age effect given that SCD4m-HU mice displayed a higher specific force production as compared with SCD4m mice. In that respect, HU treatment would help to maintain a higher capacity of force production during aging in SCD.

Vertebral trabecular bone texture analysis in opportunistic MRI and CT scan can distinguish patients with and without osteoporotic vertebral fracture: A preliminary study.

PURPOSE: To investigate the potential of texture parameters from opportunistic MRI and CT for the detection of patients with vertebral fragility fracture, to design a decision tree and to compute a Random Forest analysis for the prediction of fracture risk. METHODS: One hundred and eighty vertebrae of sixty patients with at least one (30) or without (30) a fragility fracture were retrospectively assessed. Patients had a DXA, an MRI and a CT scan from the three first lumbar vertebrae. Vertebrae texture analysis was performed in routine abdominal or lumbar CT and lumbar MRI using 1st and 2nd order texture parameters. Hounsfield Unit Bone density (HU BD) was also measured on CT-scan images. RESULTS: Twelve texture parameters, Z-score and HU BD were significantly different between the two groups whereas T score and BMD were not. The inter observer reproducibility was good to excellent. Decision tree showed that age and HU BD were the most relevant factors to predict the fracture risk with a 93 % sensitivity and 56 % specificity. AUC was 0.91 in MRI and 0.92 in CT-scan using the Random Forest analysis. The corresponding sensitivity and specificity were 72 % and 93 % in MRI and 83 and 89 % in CT. CONCLUSIONS: This study is the first to compare texture indices computed from opportunistic CT and MR images. Age and HU-BD together with selected texture parameters could be used to assess risk fracture. Machine learning algorithm can detect fracture risk in opportunistic CT and MR imaging and might be of high interest for the diagnosis of osteoporosis.

Texture Parameters Measured by UHF-MRI and CT Scan Provide Information on Bone Quality in Addition to BMD: A Biomechanical Ex Vivo Study.

The current definition of osteoporosis includes alteration of bone quality. The assessment of bone quality is improved by the development of new texture analysis softwares. Our objectives were to assess if proximal femoral trabecular bone texture measured in Ultra high field (UHF) 7 Tesla MRI and CT scan were related to biomechanical parameters, and if the combination of texture parameters and areal bone mineral density (aBMD) measured by dual-energy X-ray absorptiometry provided a better prediction of femoral failure than aBMD alone. The aBMD of 16 proximal femur ends from eight cadavers were investigated. Nineteen textural parameters were computed in three regions or volumes of interest for each specimen on UHF MRI and CT scan. Then, the corresponding failure load and failure stress were calculated thanks to mechanical compression test. aBMD was not correlated to failure load (R2 = 0.206) and stress (R2 = 0.153). The failure load was significantly correlated with ten parameters in the greater trochanter using UHF MRI, and with one parameter in the neck and the greater trochanter using CT scan. Eight parameters in the greater trochanter using UHF MRI combined with aBMD improved the failure load prediction, and seven parameters improved the failure stress prediction. Our results suggest that textural parameters provide additional information on the fracture risk of the proximal femur when aBMD is not contributive.

Multiscale Femoral Neck Imaging and Multimodal Trabeculae Quality Characterization in an Osteoporotic Bone Sample.

Although multiple structural, mechanical, and molecular factors are definitely involved in osteoporosis, the assessment of subregional bone mineral density remains the most commonly used diagnostic index. In this study, we characterized bone quality in the femoral neck of one osteoporotic patients as compared to an age-matched control subject, and so used a multiscale and multimodal approach including X-ray computed microtomography at different spatial resolutions (pixel size: 51.0, 4.95 and 0.9 µm), microindentation and Fourier transform infrared spectroscopy. Our results showed abnormalities in the osteocytes lacunae volume (358.08 ± 165.00 for the osteoporotic sample vs. 287.10 ± 160.00 for the control), whereas a statistical difference was found neither for shape nor for density. The osteoporotic femoral head and great trochanter reported reduced elastic modulus (Es) and hardness (H) compared to the control reference (−48% (p < 0.0001) and −34% (p < 0.0001), respectively for Es and H in the femoral head and −29% (p < 0.01) and −22% (p < 0.05), respectively for Es and H in the great trochanter), whereas the corresponding values in the femoral neck were in the same range. The spectral analysis could distinguish neither subregional differences in the osteoporotic sample nor between the osteoporotic and healthy samples. Although, infrared spectroscopic measurements were comparable among subregions, and so regardless of the bone osteoporotic status, the trabecular mechanical properties were comparable only in the femoral neck. These results illustrate that bone remodeling in osteoporosis is a non-uniform process with different rates in different bone anatomical regions, hence showing the interest of a clear analysis of the bone microarchitecture in the case of patients' osteoporotic evaluation.

Whole-muscle fat analysis identifies distal muscle end as disease initiation site in facioscapulohumeral muscular dystrophy.

BACKGROUND: Facioscapulohumeral dystrophy (FSHD) is a major muscular dystrophy characterized by asymmetric fatty replacement of muscles. We aimed to determine the initiation site and progression profile of the disease in lower extremity muscles of FSHD patients by assessing fat infiltration along their full proximo-distal axis using quantitative MRI. METHODS: Nine patients underwent MRI of lower extremities to assess end-to-end muscle fat fractions (FFs) and inflammatory lesions. Seven patients underwent the same MRI ~3.5 years later. Individual muscles (n = 396) were semi-automatically segmented to calculate average FFs over all slices covering whole muscles. To assess disease progression we determined FF changes in 5 adjacent muscle segments. RESULTS: We provide evidence that fat replacement commonly starts at the distal end of affected muscles where the highest FFs occur (p < 0.001). It progresses in a wave-like manner in the proximal direction at an increasing rate with the highest value (4.9 ± 2.7%/year) for muscles with baseline FFs of 30-40%. Thereafter it proceeds at a slower pace towards the proximal muscle end. In early phases of disease, inflammatory lesions preferentially occur at the distal muscle end. Compared with whole-muscle analysis, the common FF assessments using only few MR slices centrally placed in muscles are significantly biased (~50% in progression rate). CONCLUSIONS: These findings identify the distal end of leg muscles as a prime location for disease initiation in FSHD and demonstrate a wave-like progression towards the proximal end, consistent with proposed disease mechanisms. End-to-end whole-muscle fat assessment is essential to properly diagnose FSHD and its progression.

Infiltration of fat in muscle is a feature of muscular diseases. One example is facioscapulohumeral muscular dystrophy. Here, we investigated where fat infiltration starts and how it progresses in leg muscles of patients with this disorder. We used magnetic resonance imaging to visualise the fat content of all the leg muscles. This showed that in nearly all affected muscles, fat infiltration begins in the muscles' extreme lower end, which means that disease starts at this end. Subsequently, fat infiltration progresses as a wave towards the muscle's upper end. Our observations also suggest that assessing fat content in whole muscle, rather than the common approach of only assessing the middle part of muscles, measures fat infiltration more accurately. These findings are relevant to identify factors involved in disease onset, to develop and evaluate therapies, and in disease diagnosis.

Intra Articular Injection of Autologous Microfat and Platelets-Rich Plasma in the Treatment of Wrist Osteoarthritis: A Pilot Study.

No injection treatment has been proven to be effective in wrist osteoarthritis. When conservative measures fail, its management involves invasive surgery. Emergence of biotherapies based on adipose derived stem cells (ADSC) offers promising treatments for chondral degenerative diseases. Microfat (MF) and platelets-rich plasma (PRP) mixture, rich in growth factors and ADSC could be a minimally invasive injectable option in the treatment of wrist osteoarthritis. The aim of this uncontrolled prospective study was to evaluate the safety of a 4 mL autologous MF-PRP intra-articular injection, performed under local anesthesia. The secondary purpose was to describe the clinical and MRI results at 12 months of follow-up. Patients' data collected were: occurrence of adverse effects, Visual analog scale (VAS), Disabilities of the Arm, Shoulder and Hand score (DASH) and Patient-Rated Wrist Evaluation (PRWE) scores, wrist strength, wrist range of motion and 5-level satisfaction scale. No serious adverse event was recorded. A statistically significant decrease in pain, DASH, PRWE and force was observed at each follow-up. Our preliminary results suggest that intra-articular autologous MF and PRP injection may be a new therapeutic strategy for wrist osteoarthritis resistant to medical symptomatic treatment prior to surgical interventions.

Effect of citrulline malate supplementation on muscle function and bioenergetics during short-term repeated bouts of fatiguing exercise.

Citrulline malate (CM) has been shown to improve muscle performance in healthy participants during a single exercise session. Yet, within the framework of exercises repeated at close time interval, the consequences of CM ingestion on mechanical performance are controversial and the bioenergetics side remains undocumented. The aim of this double-blind placebo-controlled study was to evaluate in vivo the effect of short-term (7 doses in 48 h) oral administration of CM upon gastrocnemius muscle function and bioenergetics using non-invasive multimodal NMR techniques in healthy rats. The experimental protocol consisted of two 6-min bouts of fatiguing exercise spaced by an 8-min recovery period. CM treatment did not affect the basal bioenergetics status and increased the half-fatigue time during the first exercise bout. With exercise repetition, it prevented PCr cost alteration and decreased both the glycolytic ATP production and the contractile ATP cost in working muscle, but these changes were not associated to any improvement in mechanical performance. In addition, CM did not influence the replenishment of high-energy phosphorylated compounds during the post-exercise recovery periods. Therefore, short-term CM administration enhances muscle bioenergetics throughout fatiguing bouts of exercise repeated at close time interval but this enhancement does not benefit to mechanical performance.

Effects of Hydroxyurea on Skeletal Muscle Energetics and Function in a Mildly Anemic Mouse Model.

Hydroxyurea (HU) is a ribonucleotide reductase inhibitor most commonly used as a therapeutic agent in sickle cell disease (SCD) with the aim of reducing the risk of vaso-occlusion and improving oxygen transport to tissues. Previous studies suggest that HU may be even beneficial in mild anemia. However, the corresponding effects on skeletal muscle energetics and function have never been reported in such a mild anemia model. Seventeen mildly anemic HbAA Townes mice were subjected to a standardized rest-stimulation (transcutaneous stimulation)-protocol while muscle energetics using 31Phosphorus magnetic resonance spectroscopy and muscle force production were assessed and recorded. Eight mice were supplemented with hydroxyurea (HU) for 6 weeks while 9 were not (CON). HU mice displayed a higher specific total force production compared to the CON, with 501.35 ± 54.12 N/mm3 and 437.43 ± 57.10 N/mm3 respectively (+14.6%, p < 0.05). Neither the total rate of energy consumption nor the oxidative metabolic rate were significantly different between groups. The present results illustrated a positive effect of a HU chronic supplementation on skeletal muscle function in mice with mild anemia.

Concentric or eccentric physical activity for patients with symptomatic osteoarthritis of the knee: a randomized prospective study.

Background: Knee osteoarthritis-related pain limits physical function and leads to functional disability. Physical activity is one of the central recommendations for the management of knee osteoarthritis. Although concentric muscle activities are often preferred to eccentric ones, the corresponding rationale remains controversial. Objective: To explore the effect of a 6-week exercise program on function, pain, and performance in patients with symptomatic knee osteoarthritis. Methods: Patients with symptomatic knee osteoarthritis were included in the prospective EX-ART project (Walking performance in osteoARThritic subjects: effect of an ECCentric muscle strengthening program) and randomized in a 6-week rehabilitation program including either eccentric or concentric activities. Metrics of interest chosen as end points measured before and after the rehabilitation were WOMAC score, pain, and muscular performance (quadriceps power PMAX and contraction strength MMAX). MRI was also used to assess muscle volume and fat infiltration changes. Results: 30 patients were included in each group; mean age was 74 (±7.6); 69% were women. At week 6, both groups showed a significant improvement in the WOMAC without difference between the two groups (p = 0.7). No difference between the two groups was identified for the pain reduction (p = 0.7). A significant improvement in the change in PMAX and MMAX at high velocity (p = 0.001 and p = 0.002) was observed in the eccentric group only. A vastus medialis hypertrophy was quantified in the eccentric group only (p = 0.002), whereas fat infiltration in the quadriceps muscles was unchanged. Conclusion: Physical activity, whether eccentric or concentric, has a benefit on function and pain in patients with symptomatic knee osteoarthritis. A few differences have been identified between the two types of rehabilitation. More particularly, a gain in muscle performance and vastus medialis volume was found with eccentric rehabilitation only. Registration: www.ClinicalTrials.gov, registration number NCT03167502.