American Society of Biomechanics Journal of Biomechanics Award 2022: Computer models do not accurately predict human muscle passive muscle force and fiber length: Evaluating subject-specific modeling impact on musculoskeletal model predictions.

Musculoskeletal models are valuable for studying and understanding the human body in a variety of clinical applications that include surgical planning, injury prevention, and prosthetic design. Subject-specific models have proven to be more accurate and useful compared to generic models. Nevertheless, it is important to validate all models when possible. To this end, gracilis muscle-tendon parameters were directly measured intraoperatively and used to test model predictions. The aim of this study was to evaluate the benefits and limitations of systematically incorporating subject-specific variables into muscle models used to predict passive force and fiber length. The results showed that incorporating subject-specific values generally reduced errors, although significant errors still existed. Optimization of the modeling parameter "tendon slack length" was explored in two cases: minimizing fiber length error and minimizing passive force error. The results showed that using all subject-specific values yielded the most favorable outcome in both models and optimization cases. However, the trade-off between fiber length error and passive force error will depend on the specific circumstances and research objectives due to significant individual errors. Notably, individual fiber length and passive force errors were as high as 20% and 37% respectively. Finally, the modeling parameter "tendon slack length" did not correlate with any real-world anatomical length.

Direct intraoperative measurement of isometric contractile properties in living human muscle.

Skeletal muscle's isometric contractile properties are one of the classic structure-function relationships in all of biology allowing for extrapolation of single fibre mechanical properties to whole muscle properties based on the muscle's optimal fibre length and physiological cross-sectional area (PCSA). However, this relationship has only been validated in small animals and then extrapolated to human muscles, which are much larger in terms of length and PCSA. The present study aimed to measure directly the in situ properties and function of the human gracilis muscle to validate this relationship. We leveraged a unique surgical technique in which a human gracilis muscle is transferred from the thigh to the arm, restoring elbow flexion after brachial plexus injury. During this surgery, we directly measured subject specific gracilis muscle force-length relationship in situ and properties ex vivo. Each subject's optimal fibre length was calculated from their muscle's length-tension properties. Each subject's PCSA was calculated from their muscle volume and optimal fibre length. From these experimental data, we established a human muscle fibre-specific tension of 171 kPa. We also determined that average gracilis optimal fibre length is 12.9 cm. Using this subject-specific fibre length, we observed an excellent fit between experimental and theorical active length-tension curves. However, these fibre lengths were about half of the previously reported optimal fascicle lengths of 23 cm. Thus, the long gracilis muscle appears to be composed of relatively short fibres acting in parallel that may not have been appreciated based on traditional anatomical methods. KEY POINTS: Skeletal muscle's isometric contractile properties represent one of the classic structure-function relationships in all of biology and allow scaling single fibre mechanical properties to whole muscle properties based on the muscle's architecture. This physiological relationship has only been validated in small animals but is often extrapolated to human muscles, which are orders of magnitude larger. We leverage a unique surgical technique in which a human gracilis muscle is transplanted from the thigh to the arm to restore elbow flexion after brachial plexus injury, aiming to directly measure muscles properties in situ and test directly the architectural scaling predictions. Using these direct measurements, we establish human muscle fibre-specific tension of ∼170 kPa. Furthermore, we show that the gracilis muscle actually functions as a muscle with relatively short fibres acting in parallel vs. long fibres as previously assumed based on traditional anatomical models.

A Musculoskeletal Model of the Hand and Wrist Capable of Simulating Functional Tasks.

OBJECTIVE: The purpose of this work was to develop an open-source musculoskeletal model of the hand and wrist and to evaluate its performance during simulations of functional tasks. METHODS: The current model was developed by adapting and expanding upon existing models. An optimal control theory framework that combines forward-dynamics simulations with a simulated-annealing optimization was used to simulate maximum grip and pinch force. Active and passive hand opening were simulated to evaluate coordinated kinematic hand movements. RESULTS: The model's maximum grip force production matched experimental measures of grip force, force distribution amongst the digits, and displayed sensitivity to wrist flexion. Simulated lateral pinch strength replicated in vivo palmar pinch strength data. Additionally, predicted activations for 7 of 8 muscles fell within variability of EMG data during palmar pinch. The active and passive hand opening simulations predicted reasonable activations and demonstrated passive motion mimicking tenodesis, respectively. CONCLUSION: This work advances simulation capabilities of hand and wrist models and provides a foundation for future work to build upon. SIGNIFICANCE: This is the first open-source musculoskeletal model of the hand and wrist to be implemented during both functional kinetic and kinematic tasks. We provide a novel simulation framework to predict maximal grip and pinch force which can be used to evaluate how potential surgical and rehabilitation interventions influence these functional outcomes while requiring minimal experimental data.

Ankle stiffness modulation during different gait speeds in individuals post-stroke.

BACKGROUND: Neurotypical individuals alter their ankle joint quasi-stiffness in response to changing walking speed; however, for individuals post-stroke, the ability to alter their ankle quasi-stiffness is unknown. Individuals post-stroke commonly have weak plantarflexor muscles, which may limit their ability to alter ankle quasi-stiffness. The objective was to investigate the relationship between ankle quasi-stiffness and propulsion, at two walking speeds. We hypothesized that in individuals post-stroke, there would be no difference in their paretic ankle quasi-stiffness between walking at a self-selected versus a fast speed. However, we hypothesized that ankle quasi-stiffness would correlate with gait speed and propulsion across individuals. METHODS: Twenty-eight participants with chronic stroke walked on an instrumented treadmill at their self-selected and fast-walking speeds. Multilevel models were used to determine the relationships between ankle quasi-stiffness, speed, and propulsion. FINDINGS: Overall, ankle quasi-stiffness did not increase within individuals from a self-selected to a fast gait speed (p = 0.69). A 1 m/s increase in speed across participants predicted an increase in overall ankle quasi-stiffness of 0.02 Nm/deg./kg (p = 0.03) and a 1 N/BW change in overall propulsion across participants predicted a 0.265 Nm/deg./kg increase in overall ankle quasi-stiffness (p < 0.0001). INTERPRETATION: Individuals post-stroke did not modulate their ankle quasi-stiffness with increased speed, but across individuals there was a positive relationship between ankle quasi-stiffness and both speed and peak propulsion. Walking speed and propulsion are limited in individuals post-stroke, therefore, improving either could lead to a higher functional status. Understanding post-stroke ankle stiffness may be important in the design of therapeutic interventions and exoskeletons, where these devices augment the biological ankle quasi-stiffness to improve walking performance.

Systematic review of skeletal muscle passive mechanics experimental methodology.

Understanding passive skeletal muscle mechanics is critical in defining structure-function relationships in skeletal muscle and ultimately understanding pathologically impaired muscle. In this systematic review, we performed an exhaustive literature search using PRISMA guidelines to quantify passive muscle mechanical properties, summarized the methods used to create these data, and make recommendations to standardize future studies. We screened over 7500 papers and found 80 papers that met the inclusion criteria. These papers reported passive muscle mechanics from single muscle fiber to whole muscle across 16 species and 54 distinct muscles. We found a wide range of methodological differences in sample selection, preparation, testing, and analysis. The systematic review revealed that passive muscle mechanics is species and scale dependent-specifically within mammals, the passive mechanics increases non-linearly with scale. However, a detailed understanding of passive mechanics is still unclear because the varied methodologies impede comparisons across studies, scales, species, and muscles. Therefore, we recommend the following: smaller scales may be maintained within storage solution prior to testing, when samples are tested statically use 2-3 min of relaxation time, stress normalization at the whole muscle level be to physiologic cross-sectional area, strain normalization be to sarcomere length when possible, and an exponential equation be used to fit the data. Additional studies using these recommendations will allow exploration of the multiscale relationship of passive force within and across species to provide the fundamental knowledge needed to improve our understanding of passive muscle mechanics.

In vivo human gracilis whole-muscle passive stress-sarcomere strain relationship.

We measured the passive mechanical properties of intact, living human gracilis muscles (n=11 individuals, 10 male and 1 female, age: 33±12 years, mass: 89±23 kg, height: 177±8 cm). Measurements were performed in patients undergoing surgery for free-functioning myocutaneous tissue transfer of the gracilis muscle to restore elbow flexion after brachial plexus injury. Whole-muscle force of the gracilis tendon was measured in four joint configurations (JC1-JC4) with a buckle force transducer placed at the distal tendon. Sarcomere length was also measured by biopsy from the proximal gracilis muscle. After the muscle was removed, a three-dimensional volumetric reconstruction of the muscle was created via photogrammetry. Muscle length from JC1 to JC4 increased by 3.3±1.0, 7.7±1.2, 10.5±1.3 and 13.4±1.2 cm, respectively, corresponding to 15%, 34%, 46% and 59% muscle fiber strain, respectively. Muscle volume and an average optimal fiber length of 23.1±0.7 cm yielded an average muscle physiological cross-sectional area of 6.8±0.7 cm2 which is approximately 3 times that measured previously from cadaveric specimens. Absolute passive tension increased from 0.90±0.21 N in JC1 to 16.50±2.64 N in JC4. As expected, sarcomere length also increased from 3.24±0.08 µm at JC1 to 3.63±0.07 µm at JC4, which are on the descending limb of the human sarcomere length-tension curve. Peak passive muscle stress was 27.8±5.5 kPa in JC4 and muscle modulus ranged from 44.8 MPa in JC1 to 125.7 MPa in JC4. Comparison with other mammalian species indicates that human muscle passive mechanical properties are more similar to rodent muscle than to rabbit muscle. These data provide direct measurements of whole-human muscle passive mechanical properties that can be used in modeling studies and for understanding comparative passive mechanical properties among mammalian muscles.

Passive Properties of the Wrist and Fingers Following Chronic Hemiparetic Stroke: Interlimb Comparisons in Persons With and Without a Clinical Treatment History That Includes Botulinum Neurotoxin.

Background: Neural impairments that follow hemiparetic stroke may negatively affect passive muscle properties, further limiting recovery. However, factors such as hypertonia, spasticity, and botulinum neurotoxin (BoNT), a common clinical intervention, confound our understanding of muscle properties in chronic stroke. Objective: To determine if muscle passive biomechanical properties are different following prolonged, stroke-induced, altered muscle activation and disuse. Methods: Torques about the metacarpophalangeal and wrist joints were measured in different joint postures in both limbs of participants with hemiparetic stroke. First, we evaluated 27 participants with no history of BoNT; hand impairments ranged from mild to severe. Subsequently, seven participants with a history of BoNT injections were evaluated. To mitigate muscle hypertonia, torques were quantified after an extensive stretching protocol and under conditions that encouraged participants to sleep. EMGs were monitored throughout data collection. Results: Among participants who never received BoNT, no significant differences in passive torques between limbs were observed. Among participants who previously received BoNT injections, passive flexion torques about their paretic wrist and finger joints were larger than their non-paretic limb (average interlimb differences = +42.0 ± 7.6SEM Ncm, +26.9 ± 3.9SEM Ncm, respectively), and the range of motion for passive finger extension was significantly smaller (average interlimb difference = -36.3° ± 4.5°SEM; degrees). Conclusion: Our results suggest that neural impairments that follow chronic, hemiparetic stroke do not lead to passive mechanical changes within the wrist and finger muscles. Rather, consistent with animal studies, the data points to potential adverse effects of BoNT on passive muscle properties post-stroke, which warrant further consideration.

Biochemical and structural basis of the passive mechanical properties of whole skeletal muscle.

Passive mechanical properties of whole skeletal muscle are not as well understood as active mechanical properties. Both the structural basis for passive mechanical properties and the properties themselves are challenging to determine because it is not clear which structures within skeletal muscle actually bear passive loads and there are not established standards by which to make mechanical measurements. Evidence suggests that titin bears the majority of the passive load within the single muscle cell. However, at larger scales, such as fascicles and muscles, there is emerging evidence that the extracellular matrix bears the major part of the load. Complicating the ability to quantify and compare across size scales, muscles and species, definitions of muscle passive properties such as stress, strain, modulus and stiffness can be made relative to many reference parameters. These uncertainties make a full understanding of whole muscle passive mechanical properties and modelling these properties very difficult. Future studies defining the specific load bearing structures and their composition and organization are required to fully understand passive mechanics of the whole muscle and develop therapies to treat disorders in which passive muscle properties are altered such as muscular dystrophy, traumatic laceration, and contracture due to upper motor neuron lesion as seen in spinal cord injury, stroke and cerebral palsy.

Intramuscular Anatomy Drives Collagen Content Variation Within and Between Muscles.

The passive load bearing properties of muscle are poorly understood partly due to challenges in identifying the connective tissue structures that bear loads. Prior attempts to correlate passive mechanical properties with collagen content (often expressed as a mass ratio and used as a surrogate for connective tissue quantity within muscle) have not been successful. This is likely a result of not accounting for variability in intramuscular connective tissue throughout a muscle such that a single collagen content value likely does not adequately represent the connective tissue load bearing capacity of a muscle. Therefore, the purpose of this study was to determine how intramuscular connective tissue distribution throughout a muscle impacts measured collagen content. For this analysis, four mouse hindlimb muscles were chosen because of their varying actions and anatomy; rectus femoris, semimembranosus, tibialis anterior, and lateral gastrocnemius. Collagen content throughout each muscle was determined biochemically using an optimized hydroxyproline assay. Dense connective tissue distribution throughout each muscle's length was quantified histologically. We found that collagen content varied widely within and between muscles, from 3.6 ± 0.40 SEM µg/mg wet weight to 15.6 ± 1.58 SEM µg/mg, which is dependent on both the specific location within a muscle and particular muscle studied. Both collagen content and connective tissue structures demonstrated stereotypically patterns with the highest quantity at the proximal and distal ends of the muscles. Additionally, using three independent approaches: (1) linear regression, (2) predictive modeling, and (3) non-linear optimization, we found complementary and corroborating evidence suggesting a causal relationship between a muscle's connective tissue distribution and collagen content. Specifically, we found that muscle collagen content is driven primarily by its dense connective tissue structures due to the extremely high collagen content of connective tissue (227.52-334.69 µg/mg) compared to muscle tissue (1.93-4.03 µg/mg). A consequence of these findings is that a single collagen content measurement does not accurately represent a muscle's complex distribution of connective tissue. Future studies should account for collagen content variations and connective tissue anatomy to establish more accurate relationships between collagen content measurements and whole muscle passive mechanics.

The Biomechanical Basis of the Claw Finger Deformity: A Computational Simulation Study.

PURPOSE: Claw finger deformity occurs during attempted finger extension in patients whose intrinsic finger muscles are weakened or paralyzed by neural impairments. The deformity is generally not acutely present after intrinsic muscle palsy. The delayed onset, with severity progressing over time, suggests soft tissue changes that affect the passive biomechanics of the hand exacerbate and advance the deformity. Clinical interventions may be more effective if such secondary biomechanical changes are effectively addressed. Using a computational model, we simulated these altered soft tissue biomechanical properties to quantify their effects on coordinated finger extension. METHODS: To evaluate the effects of maladaptive changes in soft tissue biomechanical properties on the development and progression of the claw finger deformity after intrinsic muscle palsy, we completed 45 biomechanical simulations of cyclic index finger flexion and extension, varying the muscle excitation level, clinically relevant biomechanical factors, and wrist position. We evaluated to what extent (1) increased joint laxity, (2) decreased mechanical advantage of the extensors about the proximal interphalangeal joint, and (3) shortening of the flexor muscles contributed to the development of claw finger deformity in an intrinsic-minus hand model. RESULTS: Of the mechanisms studied, shortening (or contracture) of the extrinsic finger flexors was the factor most associated with the development of claw finger deformity in simulation. CONCLUSIONS: These simulations suggest that adaptive shortening of the extrinsic finger flexors is required for the development of claw finger deformity. Increased joint laxity and decreased extensor mechanical advantage only contributed to the severity of the deformity in simulations when shortening of the flexor muscles was present. CLINICAL RELEVANCE: In both the acute and chronic stages of intrinsic finger paralysis, maintaining extrinsic finger flexor length should be an area of focus in rehabilitation to prevent formation of the claw finger deformity and achieve optimal outcomes after surgical interventions.

Incorporating the length-dependent passive-force generating muscle properties of the extrinsic finger muscles into a wrist and finger biomechanical musculoskeletal model.

Dynamic movement trajectories of low mass systems have been shown to be predominantly influenced by passive viscoelastic joint forces and torques compared to momentum and inertia. The hand is comprised of 27smallmass segments. Because of the influence of the extrinsic finger muscles, the passive torques about each finger joint become a complex function dependent on the posture of multiple joints of the distal upper limb. However, biomechanical models implemented for the dynamic simulation of hand movements generally don't extend proximally to include the wrist and distal upper limb. Thus, they cannot accurately represent these complex passive torques. The purpose of this short communication is to both describe a method to incorporate the length-dependent passive properties of the extrinsic index finger muscles into a biomechanical model of the upper limb and to demonstrate their influence on combined movement of the wrist and fingers. Leveraging a unique set of experimental data, that describes the net passive torque contributed by the extrinsic finger muscles about the metacarpophalangeal joint of the index finger as a function of both metacarpophalangeal and wrist postures, we simulated the length-dependent passive properties of the extrinsic finger muscles. Dynamic forward simulations demonstrate that a model including these properties passively exhibits coordinated movement between the wrist and finger joints, mimicking tenodesis, a behavior that is absent when the length-dependent properties are removed. This work emphasizes the importance of incorporating the length-dependent properties of the extrinsic finger muscles into biomechanical models to study healthy and impaired hand movements.