Myobolica: A Stochastic Approach to Estimate Physiological Muscle Control Variability.

The inherent redundancy of the musculoskeletal systems is traditionally solved by optimizing a cost function. This approach may not be correct to model non-adult or pathological populations likely to adopt a "non-optimal" motor control strategy. Over the years, various methods have been developed to address this limitation, such as the stochastic approach. A well-known implementation of this approach, Metabolica, samples a wide number of plausible solutions instead of searching for a single one, leveraging Bayesian statistics and Markov Chain Monte Carlo algorithm, yet allowing muscles to abruptly change their activation levels. To overcome this and other limitations, we developed a new implementation of the stochastic approach (Myobolica), adding constraints and parameters to ensure the identification of physiological solutions. The aim of this study was to evaluate Myobolica, and quantify the differences in terms of width of the solution band (muscle control variability) compared to Metabolica. To this end, both muscle forces and knee joint force solutions bands estimated by the two approaches were compared to one another, and against (i) the solution identified by static optimization and (ii) experimentally measured knee joint forces. The use of Myobolica led to a marked narrowing of the solution band compared to Metabolica. Furthermore, the Myobolica solutions well correlated with the experimental data (R 2 = 0.92 , RMSE = 0.3 BW), but not as much with the optimal solution (R 2 = 0.82 , RMSE = 0.63 BW). Additional analyses are required to confirm the findings and further improve this implementation.

Identification of a lumped-parameter model of the intervertebral joint from experimental data.

Through predictive simulations, multibody models can aid the treatment of spinal pathologies by identifying optimal surgical procedures. Critical to achieving accurate predictions is the definition of the intervertebral joint. The joint pose is often defined by virtual palpation. Intervertebral joint stiffnesses are either derived from literature, or specimen-specific stiffnesses are calculated with optimisation methods. This study tested the feasibility of an optimisation method for determining the specimen-specific stiffnesses and investigated the influence of the assigned joint pose on the subject-specific estimated stiffness. Furthermore, the influence of the joint pose and the stiffness on the accuracy of the predicted motion was investigated. A computed tomography based model of a lumbar spine segment was created. Joints were defined from virtually palpated landmarks sampled with a Latin Hypercube technique from a possible Cartesian space. An optimisation method was used to determine specimen-specific stiffnesses for 500 models. A two-factor analysis was performed by running forward dynamic simulations for ten different stiffnesses for each successfully optimised model. The optimisations calculated a large range of stiffnesses, indicating the optimised specimen-specific stiffnesses were highly sensitive to the assigned joint pose and related uncertainties. A limited number of combinations of optimised joint stiffnesses and joint poses could accurately predict the kinematics. The two-factor analysis indicated that, for the ranges explored, the joint pose definition was more important than the stiffness. To obtain kinematic prediction errors below 1 mm and 1° and suitable specimen-specific stiffnesses the precision of virtually palpated landmarks for joint definition should be better than 2.9 mm.

Towards a comprehensive biomechanical assessment of the elderly combining in vivo data and in silico methods.

The aging process is commonly accompanied by a general or specific loss of muscle mass, force and/or function that inevitably impact on a person's quality of life. To date, various clinical tests and assessments are routinely performed to evaluate the biomechanical status of an individual, to support and inform the clinical management and decision-making process (e.g., to design a tailored rehabilitation program). However, these assessments (e.g., gait analysis or strength measures on a dynamometer) are typically conducted independently from one another or at different time points, providing clinicians with valuable yet fragmented information. We hereby describe a comprehensive protocol that combines both in vivo measurements (maximal voluntary isometric contraction test, superimposed neuromuscular electrical stimulation, electromyography, gait analysis, magnetic resonance imaging, and clinical measures) and in silico methods (musculoskeletal modeling and simulations) to enable the full characterization of an individual from the biomechanical standpoint. The protocol, which requires approximately 4 h and 30 min to be completed in all its parts, was tested on twenty healthy young participants and five elderlies, as a proof of concept. The implemented data processing and elaboration procedures allowing for the extraction of several biomechanical parameters (including muscle volumes and cross-sectional areas, muscle activation and co-contraction levels) are thoroughly described to enable replication. The main parameters extracted are reported as mean and standard deviation across the two populations, to highlight the potential of the proposed approach and show some preliminary findings (which were in agreement with previous literature).

Muscle synergy-informed neuromusculoskeletal modelling to estimate knee contact forces in children with cerebral palsy.

Cerebral palsy (CP) includes a group of neurological conditions caused by damage to the developing brain, resulting in maladaptive alterations of muscle coordination and movement. Estimates of joint moments and contact forces during locomotion are important to establish the trajectory of disease progression and plan appropriate surgical interventions in children with CP. Joint moments and contact forces can be estimated using electromyogram (EMG)-informed neuromusculoskeletal models, but a reduced number of EMG sensors would facilitate translation of these computational methods to clinics. This study developed and evaluated a muscle synergy-informed neuromusculoskeletal modelling approach using EMG recordings from three to four muscles to estimate joint moments and knee contact forces of children with CP and typically developing (TD) children during walking. Using only three to four experimental EMG sensors attached to a single leg and leveraging an EMG database of walking data of TD children, the synergy-informed approach estimated total knee contact forces comparable to those estimated by EMG-assisted approaches that used 13 EMG sensors (children with CP, n = 3, R2 = 0.95 ± 0.01, RMSE = 0.40 ± 0.14 BW; TD controls, n = 3, R2 = 0.93 ± 0.07, RMSE = 0.19 ± 0.05 BW). The proposed synergy-informed neuromusculoskeletal modelling approach could enable rapid evaluation of joint biomechanics in children with unimpaired and impaired motor control within a clinical environment.

Hip-spine relationship: clinical evidence and biomechanical issues.

The hip-spine relationship is a critical consideration in total hip arthroplasty (THA) procedures. While THA is generally successful in patient, complications such as instability and dislocation can arise. These issues are significantly influenced by the alignment of implant components and the overall balance of the spine and pelvis, known as spinopelvic balance. Patients with alteration of those parameters, in particular rigid spines, often due to fusion surgery, face a higher risk of THA complications, with an emphasis on complications in instability, impingement and dislocation. For these reasons, over the years, computer modelling and simulation techniques have been developed to support clinicians in the different steps of surgery. The aim of the current review is to present current knowledge on hip-spine relationship to serve as a common platform of discussion among clinicians and engineers. The offered overview aims to update the reader on the main critical aspects of the issue, from both a theoretical and practical perspective, and to be a valuable introductory tool for those approaching this problem for the first time.

Variability of intervertebral joint stiffness between specimens and spine levels.

Introduction: Musculoskeletal multibody models of the spine can be used to investigate the biomechanical behaviour of the spine. In this context, a correct characterisation of the passive mechanical properties of the intervertebral joint is crucial. The intervertebral joint stiffness, in particular, is typically derived from the literature, and the differences between individuals and spine levels are often disregarded. Methods: This study tested if an optimisation method of personalising the intervertebral joint stiffnesses was able to capture expected stiffness variation between specimens and between spine levels and if the variation between spine levels could be accurately captured using a generic scaling ratio. Multibody models of six T12 to sacrum spine specimens were created from computed tomography data. For each specimen, two models were created: one with uniform stiffnesses across spine levels, and one accounting for level dependency. Three loading conditions were simulated. The initial stiffness values were optimised to minimize the kinematic error. Results: There was a range of optimised stiffnesses across the specimens and the models with level dependent stiffnesses were less accurate than the models without. Using an optimised stiffness substantially reduced prediction errors. Discussion: The optimisation captured the expected variation between specimens, and the prediction errors demonstrated the importance of accounting for level dependency. The inaccuracy of the predicted kinematics for the level-dependent models indicated that a generic scaling ratio is not a suitable method to account for the level dependency. The variation in the optimised stiffnesses for the different loading conditions indicates personalised stiffnesses should also be considered load-specific.

Comparative validation of two patient-specific modelling pipelines for predicting knee joint forces during level walking.

Over the past few years, the use of computer models and simulations tailored to the patient's physiology to assist clinical decision-making has increased enormously.While several pipelines to develop personalized models exist, their adoption on a large scale is still limited due to the required niche computational skillset and the lengthy operations required. Novel toolboxes, such as STAPLE, promise to streamline and expedite the development of image-based skeletal lower limb models. STAPLE-generated models can be rapidly generated, with minimal user input, and present similar joint kinematics and kinetics compared to models developed employing the established INSIGNEO pipeline. Yet, it is unclear how much the observed discrepancies scale up and affect joint contact force predictions. In this study, we compared image-based musculoskeletal models developed (i) with the INSIGNEO pipeline and (ii) with a semi-automated pipeline that combines STAPLE and nmsBuilder, and assessed their accuracy against experimental implant data.Our results showed that both pipelines predicted similar total knee joint contact forces between one another in terms of profiles and average values, characterized by a moderately high level of agreement with the experimental data. Nonetheless, the Student t-test revealed statistically significant differences between both pipelines. Of note, the STAPLE-based pipeline required considerably less time than the INSIGNEO pipeline to generate a musculoskeletal model (i.e., 60 vs 160 min). This is likely to open up opportunities for the use of personalized musculoskeletal models in clinical practice, where time is of the essence.

Modeling Human Suboptimal Control: A Review.

This review paper provides an overview of the approaches to model neuromuscular control, focusing on methods to identify nonoptimal control strategies typical of populations with neuromuscular disorders or children. Where possible, the authors tightened the description of the methods to the mechanisms behind the underlying biomechanical and physiological rationale. They start by describing the first and most simplified approach, the reductionist approach, which splits the role of the nervous and musculoskeletal systems. Static optimization and dynamic optimization methods and electromyography-based approaches are summarized to highlight their limitations and understand (the need for) their developments over time. Then, the authors look at the more recent stochastic approach, introduced to explore the space of plausible neural solutions, thus implementing the uncontrolled manifold theory, according to which the central nervous system only controls specific motions and tasks to limit energy consumption while allowing for some degree of adaptability to perturbations. Finally, they explore the literature covering the explicit modeling of the coupling between the nervous system (acting as controller) and the musculoskeletal system (the actuator), which may be employed to overcome the split characterizing the reductionist approach.

Magnetic resonance-based hip muscles retrospective analysis shows deconditioning and recovery after total hip arthroplasty surgery.

PURPOSE: The purpose of this study is to estimate the effect of unilateral hip osteoarthritis (OA) on hip muscle volume and fatty infiltration and to evaluate changes of muscles after total hip arthroplasty (THA) surgery. METHODS: A retrospective analysis was conducted on patients with unilateral hip OA subjected to THA with perioperative pelvic girdle 1.5 T magnetic resonance imaging (MRI). Thirty-five patients were included. Ten of these have also postoperative MRIs. Medius gluteus (MG) and iliopsoas (IP) muscles were manually segmented on the MRI scans, the corresponding 3D muscle geometries were reconstructed, and the volumes extracted. Muscle quality was assessed using the Goutallier classification on coronal MRI images. Volume and muscle quality differences were calculated between healthy and affected side. RESULTS: Pre-operatively, MG and IP on the affected side presented a mean muscle volume 17.5 ± 18% (p < 0.001) and 14.4 ± 15.8% (p < 0.001) smaller than the healthy counterpart, respectively. Muscles on the affected side showed a significant higher grade of fatty infiltration compared to the healthy side (p < 0.05 for MG; p < 0.001 for IP). At an average follow-up of 13 ± 5.3 months after THA, MG, and IP muscles of the affected hip showed an average 22.8% (p < 0.001) and 28.2% (p < 0.001) volume increase after THA. Also, the healthy side showed a significant increase of muscle volume for IP (17.1% p < 0.001). No significant change for MG muscle was observed. CONCLUSIONS: The study demonstrated preoperative reduced muscle volume and higher fatty infiltration at the muscles of the OA hip compared to the contralateral healthy one. A significant positive effect of THA on hip muscle volume was observed. These findings give an interesting insight on muscle deconditioning and recovery in patients undergoing THA.

Intra-operator Repeatability of Manual Segmentations of the Hip Muscles on Clinical Magnetic Resonance Images.

The manual segmentation of muscles on magnetic resonance images is the gold standard procedure to reconstruct muscle volumes from medical imaging data and extract critical information for clinical and research purposes. (Semi)automatic methods have been proposed to expedite the otherwise lengthy process. These, however, rely on manual segmentations. Nonetheless, the repeatability of manual muscle volume segmentations performed on clinical MRI data has not been thoroughly assessed. When conducted, volumetric assessments often disregard the hip muscles. Therefore, one trained operator performed repeated manual segmentations (n = 3) of the iliopsoas (n = 34) and gluteus medius (n = 40) muscles on coronal T1-weighted MRI scans, acquired on 1.5 T scanners on a clinical population of patients elected for hip replacement surgery. Reconstructed muscle volumes were divided in sub-volumes and compared in terms of volume variance (normalized variance of volumes - nVV), shape (Jaccard Index-JI) and surface similarity (maximal Hausdorff distance-HD), to quantify intra-operator repeatability. One-way repeated measures ANOVA (or equivalent) tests with Bonferroni corrections for multiple comparisons were conducted to assess statistical significance. For both muscles, repeated manual segmentations were highly similar to one another (nVV: 2-6%, JI > 0.78, HD < 15 mm). However, shape and surface similarity were significantly lower when muscle extremities were included in the segmentations (e.g., iliopsoas: HD -12.06 to 14.42 mm, P < 0.05). Our findings show that the manual segmentation of hip muscle volumes on clinical MRI scans provides repeatable results over time. Nonetheless, extreme care should be taken in the segmentation of muscle extremities.

On the use of wearable sensors as mobility biomarkers in the marketing authorization of new drugs: A regulatory perspective.

The loss of mobility is a common trait in multiple health conditions (e.g., Parkinson's disease) and is associated with reduced quality of life. In this context, being able to monitor mobility in the real world, is important. Until recently, the technology was not mature enough for this; but today, miniaturized sensors and novel algorithms promise to monitor mobility accurately and continuously in the real world, also in pathological populations. However, before any such methodology can be employed to support the development and testing of new drugs in clinical trials, they need to be qualified by the competent regulatory agencies (e.g., European Medicines Agency). Nonetheless, to date, only very narrow scoped requests for regulatory qualification were successful. In this work, the Mobilise-D Consortium shares its positive experience with the European regulator, summarizing the two requests for Qualification Advice for the Mobilise-D methodologies submitted in October 2019 and June 2020, as well as the feedback received, which resulted in two Letters of Support publicly available for consultation on the website of the European Medicines Agency. Leveraging on this experience, we hereby propose a refined qualification strategy for the use of digital mobility outcome (DMO) measures as monitoring biomarkers for mobility in drug trials.

Multi-level personalization of neuromusculoskeletal models to estimate physiologically plausible knee joint contact forces in children.

Neuromusculoskeletal models are a powerful tool to investigate the internal biomechanics of an individual. However, commonly used neuromusculoskeletal models are generated via linear scaling of generic templates derived from elderly adult anatomies and poorly represent a child, let alone children with a neuromuscular disorder whose musculoskeletal structures and muscle activation patterns are profoundly altered. Model personalization can capture abnormalities and appropriately describe the underlying (altered) biomechanics of an individual. In this work, we explored the effect of six different levels of neuromusculoskeletal model personalization on estimates of muscle forces and knee joint contact forces to tease out the importance of model personalization for normal and abnormal musculoskeletal structures and muscle activation patterns. For six children, with and without cerebral palsy, generic scaled models were developed and progressively personalized by (1) tuning and calibrating musculotendon units' parameters, (2) implementing an electromyogram-assisted approach to synthesize muscle activations, and (3) replacing generic anatomies with image-based bony geometries, and physiologically and physically plausible muscle kinematics. Biomechanical simulations of gait were performed in the OpenSim and CEINMS software on ten overground walking trials per participant. A mixed-ANOVA test, with Bonferroni corrections, was conducted to compare all models' estimates. The model with the highest level of personalization produced the most physiologically plausible estimates. Model personalization is crucial to produce physiologically plausible estimates of internal biomechanical quantities. In particular, personalization of musculoskeletal anatomy and muscle activation patterns had the largest effect overall. Increased research efforts are needed to ease the creation of personalized neuromusculoskeletal models.

Development of predictive statistical shape models for paediatric lower limb bones.

BACKGROUND AND OBJECTIVE: Accurate representation of bone shape is important for subject-specific musculoskeletal models as it may influence modelling of joint kinematics, kinetics, and muscle dynamics. Statistical shape modelling is a method to estimate bone shape from minimal information, such as anatomical landmarks, and to avoid the time and cost associated with reconstructing bone shapes from comprehensive medical imaging. Statistical shape models (SSM) of lower limb bones have been developed and validated for adult populations but are not applicable to paediatric populations. This study aimed to develop SSM for paediatric lower limb bones and evaluate their reconstruction accuracy using sparse anatomical landmarks. METHODS: We created three-dimensional models of 56 femurs, 29 pelves, 56 tibias, 56 fibulas, and 56 patellae through segmentation of magnetic resonance images taken from 29 typically developing children (15 females; 13 ± 3.5 years). The SSM for femur, pelvis, tibia, fibula, patella, haunch (i.e., combined femur and pelvis), and shank (i.e., combined tibia and fibula) were generated from manual segmentation of comprehensive magnetic resonance images to describe the shape variance of the cohort. We implemented a leave-one-out cross-validation method wherein SSM were used to reconstruct novel bones (i.e., those not included in SSM generation) using full- (i.e., full segmentation) and sparse- (i.e., anatomical landmarks) input, and then compared these reconstructions against bones segmented from magnetic resonance imaging. Reconstruction performance was evaluated using root mean squared errors (RMSE, mm), Jaccard index (0-1), Dice similarity coefficient (DSC) (0-1), and Hausdorff distance (mm). All results reported in this abstract are mean ± standard deviation. RESULTS: Femurs, pelves, tibias, fibulas, and patellae reconstructed via SSM using full-input had RMSE between 0.89 ± 0.10 mm (patella) and 1.98 ± 0.38 mm (pelvis), Jaccard indices between 0.77 ± 0.03 (pelvis) and 0.90 ± 0.02 (tibia), DSC between 0.87 ± 0.02 (pelvis) and 0.95 ± 0.01 (tibia), and Hausdorff distances between 2.45 ± 0.57 mm (patella) and 9.01 ± 2.36 mm (pelvis). Reconstruction using sparse-input had RMSE ranging from 1.33 ± 0.61 mm (patella) to 3.60 ± 1.05 mm (pelvis), Jaccard indices ranging from 0.59 ± 0.10 (pelvis) to 0.83 ± 0.03 (tibia), DSC ranging from 0.74 ± 0.08 (pelvis) to 0.90 ± 0.02 (tibia), and Hausdorff distances ranging from 3.21 ± 1.19 mm (patella) to 12.85 ± 3.24 mm (pelvis). CONCLUSIONS: The SSM of paediatric lower limb bones showed reconstruction accuracy consistent with previously developed SSM and outperformed adult-based SSM when used to reconstruct paediatric bones.

A muscle synergy-based method to estimate muscle activation patterns of children with cerebral palsy using data collected from typically developing children.

Preparing children with cerebral palsy prior to gait analysis may be a challenging and time-intensive task, especially when large number of sensors are involved. Collecting minimum number of electromyograms (EMG) and yet providing adequate information for clinical assessment might improve clinical workflow. The main goal of this study was to develop a method to estimate activation patterns of lower limb muscles from EMG measured from a small set of muscles in children with cerebral palsy. We developed and implemented a muscle synergy extrapolation method able to estimate the full set of lower limbs muscle activation patterns from only three experimentally measured EMG. Specifically, we extracted a set of hybrid muscle synergies from muscle activation patterns of children with cerebral palsy and their healthy counterparts. Next, those muscle synergies were used to estimate activation patterns of muscles, which were not initially measured in children with cerebral palsy. Two best combinations with three (medial gastrocnemius, semi membranous, and vastus lateralis) and four (lateral gastrocnemius, semi membranous, sartorius, and vastus medialis) experimental EMG were able to estimate the full set of 10 muscle activation patterns with mean (± standard deviation) variance accounted for of 79.93 (± 9.64)% and 79.15 (± 6.40)%, respectively, using only three muscle synergies. In conclusion, muscle activation patterns of unmeasured muscles in children with cerebral palsy can be estimated from EMG measured from three to four muscles using our muscle synergy extrapolation method. In the future, the proposed muscle synergy-based method could be employed in gait clinics to minimise the required preparation time.

Using Musculoskeletal Models to Estimate in vivo Total Knee Replacement Kinematics and Loads: Effect of Differences Between Models.

Total knee replacement (TKR) is one of the most performed orthopedic surgeries to treat knee joint diseases in the elderly population. Although the survivorship of knee implants may extend beyond two decades, the poor outcome rate remains considerable. A recent computational approach used to better understand failure modes and improve TKR outcomes is based on the combination of musculoskeletal (MSK) and finite element models. This combined multiscale modeling approach is a promising strategy in the field of computational biomechanics; however, some critical aspects need to be investigated. In particular, the identification and quantification of the uncertainties related to the boundary conditions used as inputs to the finite element model due to a different definition of the MSK model are crucial. Therefore, the aim of this study is to investigate this problem, which is relevant for the model credibility assessment process. Three different generic MSK models available in the OpenSim platform were used to simulate gait, based on the experimental data from the fifth edition of the "Grand Challenge Competitions to Predict in vivo Knee Loads." The outputs of the MSK analyses were compared in terms of relative kinematics of the knee implant components and joint reaction (JR) forces and moments acting on the tibial insert. Additionally, the estimated knee JRs were compared with those measured by the instrumented knee implant so that the "global goodness of fit" was quantified for each model. Our results indicated that the different kinematic definitions of the knee joint and the muscle model implemented in the different MSK models influenced both the motion and the load history of the artificial joint. This study demonstrates the importance of examining the influence of the model assumptions on the output results and represents the first step for future studies that will investigate how the uncertainties in the MSK models propagate on disease-specific finite element model results.

Effect of Suboptimal Neuromuscular Control on the Risk of Massive Wear in Total Knee Replacement.

The optimal neuromuscular control (muscle activation strategy that minimises the consumption of metabolic energy) during level walking is very close to that which minimises the force transmitted through the joints of the lower limbs. Thus, any suboptimal control involves an overloading of the joints. Some total knee replacement patients adopt suboptimal control strategies during level walking; this is particularly true for patients with co-morbidities that cause neuromotor control degeneration, such as Parkinson's Disease (PD). The increase of joint loading increases the risk of implant failure, as reported in one study in PD patients (5.44% of failures at 9 years follow-up). One failure mode that is directly affected by joint loading is massive wear of the prosthetic articular surface. In this study we used a validated patient-specific biomechanical model to estimate how a severely suboptimal control could increase the wear rate of total knee replacements. Whereas autopsy-retrieved implants from non-PD patients typically show average polyethylene wear of 17 mm3 per year, our simulations suggested that a severely suboptimal control could cause a wear rate as high as of 69 mm3 per year. Assuming the risk of implant failure due to massive wear increase linearly with the wear rate, a severely suboptimal control could increase the risk associated to that failure mode from 0.1% to 0.5%. Based on these results, such increase would not be not sufficient to justify alone the higher incidence rate of revision in patients affected by Parkinson's Disease, suggesting that other failure modes may be involved.

Computational modelling of the scoliotic spine: A literature review.

Scoliosis is a deformity of the spine that in severe cases requires surgical treatment. There is still disagreement among clinicians as to what the aim of such treatment is as well as the optimal surgical technique. Numerical models can aid clinical decision-making by estimating the outcome of a given surgical intervention. This paper provided some background information on the modelling of the healthy spine and a review of the literature on scoliotic spine models, their validation, and their application. An overview of the methods and techniques used to construct scoliotic finite element and multibody models was given as well as the boundary conditions used in the simulations. The current limitations of the models were discussed as well as how such limitations are addressed in non-scoliotic spine models. Finally, future directions for the numerical modelling of scoliosis were addressed.

Toward a Regulatory Qualification of Real-World Mobility Performance Biomarkers in Parkinson's Patients Using Digital Mobility Outcomes.

Wearable inertial sensors can be used to monitor mobility in real-world settings over extended periods. Although these technologies are widely used in human movement research, they have not yet been qualified by drug regulatory agencies for their use in regulatory drug trials. This is because the first generation of these sensors was unreliable when used on slow-walking subjects. However, intense research in this area is now offering a new generation of algorithms to quantify Digital Mobility Outcomes so accurate they may be considered as biomarkers in regulatory drug trials. This perspective paper summarises the work in the Mobilise-D consortium around the regulatory qualification of the use of wearable sensors to quantify real-world mobility performance in patients affected by Parkinson's Disease. The paper describes the qualification strategy and both the technical and clinical validation plans, which have recently received highly supportive qualification advice from the European Medicines Agency. The scope is to provide detailed guidance for the preparation of similar qualification submissions to broaden the use of real-world mobility assessment in regulatory drug trials.

The Free Achilles Tendon Is Shorter, Stiffer, Has Larger Cross-Sectional Area and Longer T2* Relaxation Time in Trained Middle-Distance Runners Compared to Healthy Controls.

Tendon geometry and tissue properties are important determinants of tendon function and injury risk and are altered in response to ageing, disease, and physical activity levels. The purpose of this study was to compare free Achilles tendon geometry and mechanical properties between trained elite/sub-elite middle-distance runners and a healthy control group. Magnetic resonance imaging (MRI) was used to measure free Achilles tendon volume, length, average cross-sectional area (CSA), regional CSA, moment arm, and T2* relaxation time at rest, while freehand three-dimensional ultrasound (3DUS) was used to quantify free Achilles tendon mechanical stiffness, Young's modulus, and length normalised mechanical stiffness. The free Achilles tendon in trained runners was significantly shorter and the average and regional CSA (distal end) were significantly larger compared to the control group. Mechanical stiffness of the free Achilles tendon was also significantly higher in trained runners compared to controls, which was explained by the group differences in tendon CSA and length. T2* relaxation time was significantly longer in trained middle-distance runners when compared to healthy controls. There was no relationship between T2* relaxation time and Young's modulus. The longer T2* relaxation time in trained runners may be indicative of accumulated damage, disorganised collagen, and increased water content in the free Achilles tendon. A short free Achilles tendon with large CSA and higher mechanical stiffness may enable trained runners to rapidly transfer high muscle forces and possibly reduce the risk of tendon damage from mechanical fatigue.