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Importance: The effects of altered neural processing, defined as altering neural networks responsible for perceptions of pain and function, on chronic pain remains unclear. Objective:To estimate the effect of a graded sensorimotor retraining intervention (RESOLVE) on pain intensity in people with chronic low back pain. Design, setting and participants: This parallel, 2-group, randomized clinical trial recruited participants with chronic (>3 months) nonspecific low back pain from primary care and community settings. A total of 276 adults were randomized (in a 1:1 ratio) to the intervention or sham procedure and attention control groups delivered by clinicians at a medical research institute in Sydney, Australia. The first participant was randomized on December 10, 2015, and the last was randomized on July 25, 2019. Follow-up was completed on February 3, 2020. Interventions: Participants randomized to the intervention group (n = 138) were asked to participate in 12 weekly clinical sessions and home training designed to educate them about and assist them with movement and physical activity while experiencing lower back pain. Participants randomized to the control group (n = 138) were asked to participate in 12 weekly clinical sessions and home training that required similar time as the intervention but did not focus on education, movement, and physical activity. The control group included sham laser and shortwave diathermy applied to the back and sham noninvasive brain stimulation. Main outcomes and measures: The primary outcome was pain intensity at 18 weeks, measured on an 11-point numerical rating scale (range, 0 [no pain] to 10 [worst pain imaginable]) for which the between-group minimum clinically important difference is 1.0 point. Results: Among 276 randomized patients (mean [SD] age, 46 [14.3] years; 138 [50%] women), 261 (95%) completed follow-up at 18 weeks. The mean pain intensity was 5.6 at baseline and 3.1 at 18 weeks in the intervention group and 5.8 at ba

Purpose: There have been contradictory reports of the effects of epimuscular myofascial force transmission in humans. This study investigated the transmission of myofascial force to the human vastus lateralis muscle by determining whether vastus lateralis slack angle changed with hip angle. Since the distance between the origin and insertion of the vastus lateralis muscle does not change when hip angle changes, any change in vastus lateralis slack angle with hip position can be attributed to epimuscular myofascial force transmission. Methods: Nineteen young adults were tested in hip flexed (80 ∘) and neutral (0 ∘) positions. Ultrasound images of the vastus lateralis muscle were obtained as the knee was passively flexed at 5 ∘/s. The knee angle at which vastus lateralis muscle fascicles began to lengthen was used to identify muscle slack angle. Results: Overall, there was a negligible effect of hip position on vastus lateralis slack angle (0. 6 ∘ [- 0.7 to 1.9]; mean [95% confidence interval]). However, a small and variable effect was noted in 3/19 participants. Conclusion: This result indicates that, over the range of joint angles tested here, there is little or no epimuscular myofascial force transmission between the vastus lateralis muscle and neighbouring bi-articular structures under passive conditions. More broadly, this result provides additional evidence that epimuscular myofascial force transmission tends to be small and variable under passive conditions in healthy human muscle.

Introduction The accurate quantification of the proportion of fat in human muscles could help monitor disease status and test effectiveness of interventions in people with neurological conditions whose skeletal muscles are frequently infiltrated with fat. Methods We compared two commonly used magnetic resonance imaging methods to quantify fat in muscles. Measurements were obtained before and after 6 or 8 wk of strength training in a total of 116 muscles spanning the range of intramuscular fat proportions observed in able-bodied young adults and people with spinal cord injury. Results We successfully measured fat proportions in all muscles using the mDixon method but were unable to obtain plausible measurements with the T1-weighted method from muscles of able-bodied individuals or from the leaner 23% of muscles of people with spinal cord injury (muscles with less than approximately 8% fat). In muscles with more fat, measurements obtained with the two methods agreed well (intraclass correlation coefficient, 0.88; mean absolute difference, 5%). We also found that, compared with the T1-weighted method, the mDixon method provides a more detailed characterization of fat infiltration in muscle and a less variable measurement of the effect of training on the proportion of fat. The mDixon method showed that 6 or 8 wk of strength training did not appreciably change the proportion of intramuscular fat in either people with spinal cord injury or able-bodied people. Conclusion On the basis of these findings, we recommend the use of mDixon methods in preference to T1-weighted methods to determine the effectiveness of interventions aimed at reducing intramuscular fat.

Cerebral palsy is a neurological condition that is known to affect muscle growth. Detailed investigations of muscle growth require segmentation of muscles from MRI scans, which is typically done manually. In this study, we evaluated the performance of 2D, 3D, and hybrid deep learning models for automatic segmentation of 11 lower leg muscles and two bones from MRI scans of children with and without cerebral palsy. All six models were trained and evaluated on manually segmented T1-weighted MRI scans of the lower legs of 20 children, six of whom had cerebral palsy. The segmentation results were assessed using the median Dice similarity coefficient (DSC), average symmetric surface distance (ASSD), and volume error (VError) of all 13 labels of every scan. The best performance was achieved by H-DenseUNet, a hybrid model (DSC 0.90, ASSD 0.5 mm, and VError 2.6 cm3). The performance was equivalent to the inter-rater performance of manual segmentation (DSC 0.89, ASSD 0.6 mm, and VError 3.3 cm3). Models trained with the Dice loss function outperformed models trained with the cross-entropy loss function. Near-optimal performance could be attained using only 11 scans for training. Segmentation performance was similar for scans of typically developing children (DSC 0.90, ASSD 0.5 mm, and VError 2.8 cm3) and children with cerebral palsy (DSC 0.85, ASSD 0.6 mm, and VError 2.4 cm3). These findings demonstrate the feasibility of fully automatic segmentation of individual muscles and bones from MRI scans of children with and without cerebral palsy.

Study design: Randomised controlled trial. Objectives: To determine the effectiveness of a sustainable community-based intervention designed to prevent serious complications and death 2 years after discharge in people with spinal cord injury in Bangladesh. Setting: Bangladesh. Methods: A pragmatic randomised controlled trial was undertaken. People who had sustained a spinal cord injury in the preceding 2 years, were wheelchair-dependent, and were about to be discharged from hospital in Bangladesh were recruited and randomised to an Intervention or Control group using a concealed allocation procedure stratified by level of lesion (tetraplegia/paraplegia). Participants in the Intervention group received 36 phone calls and three home visits over the first 2 years following discharge. All participants received usual post-discharge care. Survival status and date of death were determined by blinded assessors 2 years after randomisation. Results: Between July 2015 and March 2018, 410 participants were randomised (204 to Intervention, 206 to Control). There was no loss to follow up. At 2 years, 15 (7.4%) participants in the Intervention group and 16 (7.8%) participants in the Control group had died (hazard ratio from unadjusted Cox model = 0.93 [95% CI, 0.46 to 1.89]; p from log rank test 0.85). There were no clinically important or statistically significant average causal effects of intervention on the incidence or severity of complications. Conclusion: A program of community-based care for people with recent spinal cord injury in Bangladesh involving frequent phone contact and occasional in-person contact with a health professional after discharge from hospital is no better at preventing death at 2 years than usual care.

People who have had a stroke often develop ankle contractures which may be caused by changes in architecture of calf muscles. Anatomically constrained diffusion tensor imaging has recently been used to make three-dimensional, whole-muscle measurements of muscle architecture. Here, we compared the architecture of the medial gastrocnemius muscle in the paretic and non-paretic sides of people who have had a hemiparetic stroke and control participants using novel imaging techniques. Methods: MRI techniques (diffusion tensor imaging and mDixon imaging) were used to obtain muscle volume, fascicle length, pennation angle, physiological cross-sectional area and curvature in 14 stroke patients (mean age 60 SD 13 years) and 18 control participants (mean age 66 SD 12 years). Findings: On average, the ankle on the paretic side had 11° (95% confidence interval 8 to 13°) less dorsiflexion range than on the non-paretic side, and 6° (1 to 13°) less dorsiflexion range than ankles of control participants. The medial gastrocnemius muscles on the paretic side were, on average, 15% (35.2 cm3, 95% confidence interval 5.2 to 65.2 cm3) smaller in volume than the muscles on the non-paretic side, and 16% (36.9 cm3, 95% confidence interval 3.1 to 70.6 cm3) smaller than in control participants. No statistically significant differences between paretic, non-paretic and control muscles were detected for fascicle length, pennation angle, physiological cross-sectional area or curvature. Conclusions: People with hemiparetic stroke and reduced range of motion have, on average, a smaller medial gastrocnemius muscle on the paretic side than on the non-paretic side. Other muscle architectural parameters appear unchanged.

Background: Many children with cerebral palsy develop muscle contractures. The mechanisms of contracture are not well understood. We investigated the possibility that, because fat is stiffer than passive muscle, elevated intramuscular fat contributes to contracture. In this cross-sectional study, we compared the quantity and distribution of intramuscular fat in muscles from typically developing children and children with cerebral palsy who have contractures. Methods: mDixon magnetic resonance images were obtained from the legs of 20 ambulant children with unilateral spastic cerebral palsy who had ankle contractures (mean age 11 SD 3 years, 13 male, mean moderate level contracture) and 20 typically developing children (mean age 11 SD 4 years, 13 male). The images were analyzed to quantify the intramuscular fat fraction of the medial gastrocnemius muscles. The amount and distribution of intramuscular fat were compared between muscles of children with cerebral palsy and typically developing children. Findings: In typically developing children, the medial gastrocnemius muscles had a mean intramuscular fat fraction of 4.7% (SD 1.6%). In children with cerebral palsy, the mean intramuscular fat fractions in the more- and less-affected medial gastrocnemius muscle were 11.4% (8.1%) and 6.9% (3.4%) respectively. There were small but statistically significant regional differences in the distribution of intramuscular fat. There was no evidence of a relationship between intramuscular fat fraction and severity of contracture. Interpretation: Children with cerebral palsy have higher proportions of intramuscular fat than typically developing children. There is no clear relationship between intramuscular fat fraction and dorsiflexion range of motion in children with cerebral palsy.

Objective: To compare intramuscular fat fraction in people who have ankle contractures following stroke with the intramuscular fat fraction in control participants. Design: mDixon MRI images were used to quantify intramuscular fat fractions in the medial gastrocnemius muscles of people who had experienced a hemiparetic stroke (n = 14, mean age 60 ± 13 years) and control participants (n = 18, mean age 66 ± 12 years). Results: Intramuscular fat fractions were similar in the paretic and non-paretic sides of stroke patients (mean on paretic side 14.5%, non-paretic side 12.8%, difference 1.6%, 95% confidence interval −0.7 to 4.1%). The intramuscular fat fraction on the paretic side was higher than in the control group (mean intramuscular fat fraction in control muscles 7.6%; difference 7.8%, 95% confidence interval 4.6–10.9%). The difference between intramuscular fat fractions in non-paretic and control legs increased with age. Body mass index was similar in stroke patients and controls. There was no association between medial gastrocnemius intramuscular fat fraction and dorsiflexion range. Conclusion: Muscles of stroke patients had elevated intramuscular fat fractions compared to muscles from control participants which were not explained by differences in body mass index. There is no clear relationship between intramuscular fat in the medial gastrocnemius muscle and dorsiflexion range of motion.

Design: Mixed methods study Setting: Community, Bangladesh Objectives: To understand how a community-based intervention for people with spinal cord injury (SCI) in Bangladesh was delivered as part of a randomised controlled trial and to gauge the perceptions of participants and healthcare professionals to the intervention. Methods: A community-based intervention was administered to 204 participants as part of a large randomised controlled trial (called the CIVIC trial). Case-managers followed-up participants with regular telephone calls and home visits over the first 2 years after discharge. The following data were collected alongside the trial: (i) chart audit of telephone calls and home visits (ii) recordings of 20 telephone calls (iii) interviews with 14 Intervention participants and four healthcare professionals including three case-managers. Results: Participants received the target number of telephone calls and home visits. Pressure injuries were identified as a problem during at least one telephone call by 43% of participants. Participants and case-managers valued regular telephone calls and home visits, and believed that calls and visits prevented complications and alleviated social isolation. Participants trusted case-managers and were confident in the care and advice provided. Case-managers expressed concerns that people with SCI in Bangladesh face many problems impacting on well-being and motivation stemming from poverty, limited employment opportunities, societal attitudes and inaccessible environments. Conclusion: A community-based intervention involving regular telephone calls and home visits was administered as intended and was well received by the recipients of the care. Nonetheless, people with SCI in Bangladesh face economic and social problems which cannot be fully addressed by this type of intervention alone.

The slack length of a relaxed skeletal muscle can be reduced by isometric contraction at short lengths ("contract-short conditioning"). This study explored how the effect of contract-short conditioning on muscle slack length is modified by 1) the intensity of the contraction, 2) the delay between the contraction and measurement of slack length, and 3) the amplitude of a stretch delivered to the relaxed muscle after the contraction. Muscle fascicles in the human vastus lateralis muscle were observed with ultrasound imaging while the relaxed muscle was lengthened by flexing the knee. The knee angle at which muscle fascicle slack was taken up was used as a proxy for muscle slack length. Conditioning the muscle with voluntary isometric (fixed-end) contractions at short muscle lengths reduced vastus lateralis muscle slack length, measured 60 s later, by a mean of 10. This effect was independent of contraction intensity from 5% to 100% maximal voluntary contraction. The effect was largest when first observed 5 s after the contraction, decayed about one-third by 60 s, and then remained nearly constant until the last observation 5 min after the contraction. A slow stretch given to the relaxed muscle after contract-short conditioning increased slack length (i.e., reduced the effect of contract-short conditioning). Slack length increased nonlinearly with stretch amplitude. Very large stretches (>30, possibly as large as 90) were required to abolish the effect of contract-short conditioning. The phenomena described here share some characteristics with, and may involve similar mechanisms to, passive force enhancement and muscle thixotropy.NEW & NOTEWORTHY The slack length of a relaxed human skeletal muscle is not fixed; it can be modified by contraction and stretch. Contraction of the human vastus lateralis muscle at short lengths reduces the muscles slack length. Even very weak contractions are sufficient to induce this effect. The effect persists for at least 5 min, Funding agencies: Australian National Health and MedicalResearch Council (NHMRC; Program Grant APP1055084). RDH is supportedby an NHMRC research fellowship.

Background: People who sustain spinal cord injuries in low- and middle-income countries are vulnerable to life-threatening complications after discharge. The aim of this trial is to determine the effect on all-cause mortality of a sustainable model of community-based care provided over the first 2 years after discharge. Methods and analysis: The CIVIC trial is a single centre, parallel group trial with concealed and stratified randomisation. The protocol has been previously published (BMJ Open 2016;6:e010350). This paper provides the accompanying detailed statistical plan. In total, 410 people with recent spinal cord injury who are wheelchair dependent and about to be discharged from the Centre for the Rehabilitation of the Paralysed in Bangladesh are randomised to intervention or control groups. Participants assigned to the intervention group receive a model of community-based care in which a case manager provides ongoing telephone-based support and visits participants in their homes over a 2-year period. Participants assigned to the control group receive usual care which may involve a follow-up phone call or a home visit. The primary outcome is all-cause mortality at 2 years as determined by a blinded assessor (Bangladesh does not have a death registry). The primary effectiveness analysis will compare Kaplan-Meier survival curves (time from allocation to death) in the intervention and control groups using the log-rank test (two-tailed α = 0.05). Participants will be censored at the time they were last known to be alive or at the time of the follow-up assessment. Recruitment finished in March 2018 and the last assessment will be conducted in March 2020. Discussion: The CIVIC trial will provide unbiased and precise estimates of the effectiveness of a model of community-based care for people with spinal cord injuries in Bangladesh. The results will have implications for provision of health services for people with spinal cord injuries and other conditions that cau

For detailed analyses of muscle adaptation mechanisms during growth, ageing or disease, reliable measurements of muscle architecture are required. Diffusion tensor imaging (DTI) and DTI tractography have been used to reconstruct the architecture of human muscles in vivo. However, muscle architecture measurements reconstructed with conventional DTI techniques are often anatomically implausible because the reconstructed fascicles do not terminate on aponeuroses, as real muscle fascicles are known to do. In this study, we tested the reliability of an anatomically constrained DTI-based method for measuring three-dimensional muscle architecture. Anatomical magnetic resonance images and diffusion tensor images were obtained from the left legs of eight healthy participants on two occasions one week apart. Muscle volumes, fascicle lengths, pennation angles and fascicle curvatures were measured in the medial and lateral gastrocnemius, soleus and the tibialis anterior muscles. Averaged across muscles, the intraclass correlation coefficient was 0.99 for muscle volume, 0.81 for fascicle length, 0.73 for pennation angle and 0.76 for fascicle curvature. Measurements of muscle architecture obtained using conventional DTI tractography were highly sensitive to variations in the stopping criteria for DTI tractography. The application of anatomical constraints reduced this sensitivity significantly. This study demonstrates that anatomically constrained DTI tractography can provide reliable and robust three-dimensional measurements of whole-muscle architecture. The algorithms used to constrain tractography have been made publicly available.

Background: Children with cerebral palsy frequently have ankle contractures which may be caused by changes in architecture of calf muscles. Here, we compared the architecture of medial gastrocnemius muscles in children with unilateral cerebral palsy and typically developing children using novel imaging techniques. Methods and procedures: Muscle volumes, fascicle lengths, pennation angles and physiological cross-sectional areas were measured from diffusion tensor images and mDixon scans obtained from 20 ambulant children with unilateral spastic cerebral palsy who had ankle contractures (age 11 ± 3 years; mean ± standard deviation) and 20 typically developing children (11 ± 4 years). Findings: In children with cerebral palsy, the more-affected side had, on average, 13° less dorsiflexion range and the medial gastrocnemius muscle had 4.9 mm shorter fascicles, 50 cm3 smaller volume and 9.5 cm2 smaller physiological cross-sectional area than the less-affected side. Compared to typically developing children, the more-affected side had 10° less dorsiflexion range and the medial gastrocnemius muscle had 4.2 mm shorter fascicles, 51 cm3 smaller volume and 10 cm2 smaller physiological cross-sectional area. We did not detect differences between the less-affected and typically developing legs. Interpretation: Three-dimensional measurement of whole medial gastrocnemius muscles confirmed that the architecture of muscles on the more-affected side of children with cerebral palsy differs from the less-affected side and from muscles of typically developing children. Reductions in fascicle length, muscle volume and physiological cross-sectional area may contribute to muscle contracture.

Muscle performance is closely related to the structure and function of tendons and aponeuroses, the sheet-like, intramuscular parts of tendons. The architecture of aponeuroses has been difficult to study with magnetic resonance imaging (MRI) because these thin, collagen-rich connective tissues have very short transverse relaxation (T2) times and therefore provide a weak signal with conventional MRI sequences. Here, we validated measurements of aponeurosis dimensions from two MRI sequences commonly used in muscle-tendon research (mDixon and T1-weighted images), and an ultrashort echo time (UTE) sequence designed for imaging tissues with short T2 times. MRI-based measurements of aponeurosis width, length, and area of 20 sheep leg muscles were compared to direct measurements made with three-dimensional (3D) quantitative microdissection. The errors in measurement of aponeurosis width relative to the mean width were 1.8% for UTE, 3.7% for T1, and 18.8% for mDixon. For aponeurosis length, the errors were 7.6% for UTE, 1.9% for T1, and 21.0% for mDixon. Measurements from T1 and UTE scans were unbiased, but mDixon scans systematically underestimated widths, lengths, and areas of the aponeuroses. Using the same methods, we then found high inter-rater reliability (intraclass correlation coefficients >0.92 for all measures) of measurements of the dimensions of the central aponeurosis of the human tibialis anterior muscle from T1-weighted scans. We conclude that valid and reliable measurements of aponeurosis dimensions can be obtained from UTE and from T1-weighted scans. When the goal is to study the macroscopic architecture of aponeuroses, UTE does not hold an advantage over T1-weighted imaging.

Background. Most data on the architecture of the human soleus muscle have been obtained from cadaveric dissection or two-dimensional ultrasound imaging. We present the first comprehensive, quantitative study on the three-dimensional anatomy of the human soleus muscle in vivo using diffusion tensor imaging (DTI) techniques. Methods. We report three-dimensional fascicle lengths, pennation angles, fascicle curvatures, physiological cross-sectional areas and volumes in four compartments of the soleus at ankle joint angles of 69±12° (plantarflexion, short muscle length; average ± SD across subjects) and 108 ± 7° (dorsiflexion, long muscle length) of six healthy young adults. Microdissection and three-dimensional digitisation on two cadaveric muscles corroborated the compartmentalised structure of the soleus, and confirmed the validity of DTI-based muscle fascicle reconstructions. Results. The posterior compartments of the soleus comprised 80 ± 5% of the total muscle volume (356 ± 58 cm3). At the short muscle length, the average fascicle length, pennation angle and curvature was 37 ± 8 mm, 31 ± 3° and 17 ± 4/m, respectively. We did not find differences in fascicle lengths between compartments. However, pennation angles were on average 12° larger (p < 0:01) in the posterior compartments than in the anterior compartments. For every centimetre that the muscle-tendon unit lengthened, fascicle lengths increased by 3.7 ± 0.8 mm, pennation angles decreased by -3.2 ± 0.9° and curvatures decreased by -2.7 ± 0.8/m. Fascicles in the posterior compartments rotated almost twice as much as in the anterior compartments during passive lengthening. Discussion. The homogeneity in fascicle lengths and inhomogeneity in pennation angles of the soleus may indicate a functionally different role for the anterior and posterior compartments. The data and techniques presented here demonstrate how DTI can be used to obtain detailed, quantitative measurements of the anatomy of complex s

Key points: In reduced muscle preparations, the slack length and passive stiffness of muscle fibres have been shown to be influenced by previous muscle contraction or stretch. In human muscles, such behaviours have been inferred from measures of muscle force, joint stiffness and reflex magnitudes and latencies. Using ultrasound imaging, we directly observed that isometric contraction of the vastus lateralis muscle at short lengths reduces the slack lengths of the muscle–tendon unit and muscle fascicles. The effect is apparent 60 s after the contraction. These observations imply that muscle contraction at short lengths causes the formation of bonds which reduce the effective length of structures that generate passive tension in muscles. Abstract: In reduced muscle preparations, stretch and muscle contraction change the properties of relaxed muscle fibres. In humans, effects of stretch and contraction on properties of relaxed muscles have been inferred from measurements of time taken to develop force, joint stiffness and reflex latencies. The current study used ultrasound imaging to directly observe the effects of stretch and contraction on muscle–tendon slack length and fascicle slack length of the human vastus lateralis muscle in vivo. The muscle was conditioned by (a) strong isometric contractions at long muscle–tendon lengths, (b) strong isometric contractions at short muscle–tendon lengths, (c) weak isometric contractions at long muscle–tendon lengths and (d) slow stretches. One minute after conditioning, ultrasound images were acquired from the relaxed muscle as it was slowly lengthened through its physiological range. The ultrasound image sequences were used to identify muscle–tendon slack angles and fascicle slack lengths. Contraction at short muscle–tendon lengths caused a mean 13.5 degree (95% CI 11.8–15.0 degree) shift in the muscle–tendon slack angle towards shorter muscle–tendon lengths, and a mean 5 mm (95% CI 2–8 mm) reduction in fascicle slack lengt