Role of multi-layer tissue composition of musculoskeletal extremities for prediction of in vivo surface indentation response and layer deformations.

Emergent mechanics of musculoskeletal extremities (surface indentation stiffness and tissue deformation characteristics) depend on the underlying composition and mechanics of each soft tissue layer (i.e. skin, fat, and muscle). Limited experimental studies have been performed to explore the layer specific relationships that contribute to the surface indentation response. The goal of this study was to examine through statistical modeling how the soft tissue architecture contributed to the aggregate mechanical surface response across 8 different sites of the upper and lower extremities. A publicly available dataset was used to examine the relationship of soft tissue thickness (fat and muscle) to bulk tissue surface compliance. Models required only initial tissue layer thicknesses, making them usable in the future with only a static ultrasound image. Two physics inspired models (series of linear springs), which allowed reduced statistical representations (combined locations and location specific), were explored to determine the best predictability of surface compliance and later individual layer deformations. When considering the predictability of the experimental surface compliance, the physics inspired combined locations model showed an improvement over the location specific model (percent difference of 25.4 +/- 27.9% and 29.7 +/- 31.8% for the combined locations and location specific models, respectively). While the statistical models presented in this study show that tissue compliance relies on the individual layer thicknesses, it is clear that there are other variables that need to be accounted for to improve the model. In addition, the individual layer deformations of fat and muscle tissues can be predicted reasonably well with the physics inspired models, however additional parameters may improve the robustness of the model outcomes, specifically in regard to capturing subject specificity.

Specimen specific imaging and joint mechanical testing data for next generation virtual knees.

Virtual knees, with specimen-specific anatomy and mechanics, require heterogeneous data collected on the same knee. Specimen-specific data such as the specimen geometry, physiological joint kinematics-kinetics and contact mechanics are necessary in the development of virtual knee specimens for clinical and scientific simulations. These data are also required to capture or evaluate the predictive capacity of the model to represent joint and tissue mechanical response. This document details the collection of magnetic resonance imaging data and, tibiofemoral joint and patellofemoral joint mechanical testing data. These data were acquired for a cohort of eight knee specimens representing different populations with varying gender, age and perceived health of the joint. These data were collected as part of the Open Knee(s) initiative. Imaging data when combined with joint mechanics data, may enable development and assessment of authentic specimen-specific finite element models of the knee. The data may also guide prospective studies for association of anatomical and biomechanical markers in a specimen-specific manner.

Reference tool kinematics-kinetics and tissue surface strain data during fundamental surgical acts.

Haptic based surgical simulations are popular training aids in medicine. Previously, surgical tool loads and motion were measured during cutting and needle insertion on non-human tissue and several haptic based simulations were developed to enhance surgical training. However, there was a lack of realistic foundational data regarding the mechanical responses of human tissue and tools during fundamental acts of surgery, i.e., cutting, suturing, retracting, pinching and indenting. This study used four recently developed surgical tools in a variety of procedures on a diverse set of cadaver leg specimens from human donors. The kinematics and kinetics of surgical tools were recorded along with topical three-dimensional strain during commonly performed surgical procedures. Full motion and load signatures of foundational surgical acts can also be used beyond the development of authentic visual and haptic simulations of surgery, i.e., they provide mechanical specifications for the development of autonomous surgical systems.

Reference data on in vitro anatomy and indentation response of tissue layers of musculoskeletal extremities.

The skin, fat, and muscle of the musculoskeletal system provide essential support and protection to the human body. The interaction between individual layers and their composite structure dictate the body's response during mechanical loading of extremity surfaces. Quantifying such interactions may improve surgical outcomes by enhancing surgical simulations with lifelike tissue characteristics. Recently, a comprehensive tissue thickness and anthropometric database of in vivo extremities was acquired using a load sensing instrumented ultrasound to enhance the fidelity of advancing surgical simulations. However detailed anatomy of tissue layers of musculoskeletal extremities was not captured. This study aims to supplement that database with an enhanced dataset of in vitro specimens that includes ultrasound imaging supported by motion tracking of the ultrasound probe and two additional full field imaging modalities (magnetic resonance and computed tomography). The additional imaging datasets can be used in conjunction with the ultrasound/force data for more comprehensive modeling of soft tissue mechanics. Researchers can also use the image modalities in isolation if anatomy of legs and arms is needed.

A pragmatic approach to understand peripheral artery lumen surface stiffness due to plaque heterogeneity.

The goal of this study was to develop a pragmatic approach to build patient-specific models of the peripheral artery that are aware of plaque inhomogeneity. Patient-specific models using element-specific material definition (to understand the role of plaque composition) and homogeneous material definition (to understand the role of artery diameter and thickness) were automatically built from intravascular ultrasound images of three artery segments classified with low, average, and high calcification. The element-specific material models had average surface stiffness values of 0.0735, 0.0826, and 0.0973 MPa/mm, whereas the homogeneous material models had average surface stiffness values of 0.1392, 0.1276, and 0.1922 MPa/mm for low, average, and high calcification, respectively. Localization of peak lumen stiffness and differences in patient-specific average surface stiffness for homogeneous and element-specific models suggest the role of plaque composition on surface stiffness in addition to local arterial diameter and thickness.

Regional variations of in vivo surface stiffness of soft tissue layers of musculoskeletal extremities.

Surface stiffness of bulk soft tissue in musculoskeletal extremities is important to consider in the design of prosthetics, exoskeletons, and protective gear. This knowledge is also foundational for surgical simulation and clinical interventions leveraging manipulation of the musculoskeletal surfaces. Injuries to musculoskeletal extremities are common and surgical and preventive interventions require interactions between various objects such as surgical tools and support surfaces with tissue boundaries. While a handful of investigations examined the variations in indentation mechanics due to pathology or injury specific sites, a comprehensive analysis across the surfaces of musculoskeletal extremities has not been completed. In this study we examine variations of surface stiffness across 8 sites of the upper and lower arms and legs for 95 subjects using an instrumented ultrasound device. Differences in surface stiffness were observed between gender, activity level, and indentation location groups. The lower arm posterior location had the highest average stiffness (3.89 × 10-3 MPa/mm), while the lowest stiffness was observed at the upper leg posterior location (0.98 × 10-3 MPa/mm). The differences between indentation sites were larger in magnitude when compared to differences due to demographics (gender and activity level). However the large ranges of the 95% confidence intervals suggest that an aggregated metric based on population or sub-group may not capture individual variations. This study implicates the motivation to explore tissue composition variations within the indentation sites as well as the potential importance to include variations in surface stiffness during surgical simulations.

Instrumentation of off-the-shelf ultrasound system for measurement of probe forces during freehand imaging.

Ultrasound is a popular and affordable imaging modality, but the nature of freehand ultrasound operation leads to unknown applied loads at non-quantifiable angles. The purpose of this paper was to demonstrate an instrumentation strategy for an ultrasound system to measure probe forces and orientation during freehand imaging to characterize the interaction between the probe and soft-tissue as well as enhance repeatability. The instrumentation included a 6-axis load cell, an inertial measurement unit, and an optional sensor for camera-based motion capture. A known method for compensation of the ultrasound probe weight was implemented, and a novel method for temporal synchronization was developed. While load and optical sensing was previously achieved, this paper presents a strategy for potential instrumentation on a variety of ultrasound machines. A key feature was the temporal synchronization, utilizing the electrocardiogram (EKG) feature built-in to the ultrasound. The system was used to perform anatomical imaging of tissue layers of musculoskeletal extremities and imaging during indentation on an in vivo subject and an in vitro specimen. The outcomes of the instrumentation strategy were demonstrated during minimal force and indentation imaging. In short, the system presented robust instrumentation of an existing ultrasound system to fully characterize the probe force, orientation, and optionally its movement during imaging while efficiently synchronizing all data. Researchers may use the instrumentation strategy on any EKG capable ultrasound systems if mechanical characterization of soft tissue or minimization of forces and deformations of tissue during anatomical imaging are desired.

Modeling the effect of collagen fibril alignment on ligament mechanical behavior.

Ligament mechanical behavior is primarily regulated by fibrous networks of type I collagen. Although these fibrous networks are typically highly aligned, healthy and injured ligament can also exhibit disorganized collagen architecture. The objective of this study was to determine whether variations in the collagen fibril network between neighboring ligaments can predict observed differences in mechanical behavior. Ligament specimens from two regions of bovine fetlock joints, which either exhibited highly aligned or disorganized collagen fibril networks, were mechanically tested in uniaxial tension. Confocal microscopy and FiberFit software were used to quantify the collagen fibril dispersion and mean fibril orientation in the mechanically tested specimens. These two structural parameters served as inputs into an established hyperelastic constitutive model that accounts for a continuous distribution of planar fibril orientations. The ability of the model to predict differences in the mechanical behavior between neighboring ligaments was tested by (1) curve fitting the model parameters to the stress response of the ligament with highly aligned fibrils and then (2) using this model to predict the stress response of the ligament with disorganized fibrils by only changing the parameter values for fibril dispersion and mean fibril orientation. This study found that when using parameter values for fibril dispersion and mean fibril orientation based on confocal imaging data, the model strongly predicted the average stress response of ligaments with disorganized fibrils ([Formula: see text]); however, the model only successfully predicted the individual stress response of ligaments with disorganized fibrils in half the specimens tested. Model predictions became worse when parameters for fibril dispersion and mean fibril orientation were not based on confocal imaging data. These findings emphasize the importance of collagen fibril alignment in ligament mechanics and help advance a mechanistic understanding of fibrillar networks in healthy and injured ligament.

Reference data on thickness and mechanics of tissue layers and anthropometry of musculoskeletal extremities.

Musculoskeletal extremities exhibit a multi-layer tissue structure that is composed of skin, fat, and muscle. Body composition and anthropometric measurements have been used to assess health status and build anatomically accurate biomechanical models of the limbs. However, comprehensive datasets inclusive of regional tissue anatomy and response under mechanical manipulation are missing. The goal of this study was to acquire and disseminate anatomical and mechanical data collected on extremities of the general population. An ultrasound system, instrumented with a load transducer, was used for in vivo characterization of skin, fat, and muscle thicknesses in the extremities of 100 subjects at unloaded (minimal force) and loaded (through indentation) states. For each subject, the unloaded and loaded state provided anatomic tissue layer measures and tissue indentation response for 48 and 8 regions, respectively. A publicly available web-based system has been used for data management and dissemination. This comprehensive database will provide the foundation for comparative studies in regional musculoskeletal composition and improve visual and haptic realism for computational models of the limbs.

Extracellular Matrix Expression and Production in Fibroblast-Collagen Gels: Towards an In Vitro Model for Ligament Wound Healing.

Ligament wound healing involves the proliferation of a dense and disorganized fibrous matrix that slowly remodels into scar tissue at the injury site. This remodeling process does not fully restore the highly aligned collagen network that exists in native tissue, and consequently repaired ligament has decreased strength and durability. In order to identify treatments that stimulate collagen alignment and strengthen ligament repair, there is a need to develop in vitro models to study fibroblast activation during ligament wound healing. The objective of this study was to measure gene expression and matrix protein accumulation in fibroblast-collagen gels that were subjected to different static stress conditions (stress-free, biaxial stress, and uniaxial stress) for three time points (1, 2 or 3 weeks). By comparing our in vitro results to prior in vivo studies, we found that stress-free gels had time-dependent changes in gene expression (col3a1, TnC) corresponding to early scar formation, and biaxial stress gels had protein levels (collagen type III, decorin) corresponding to early scar formation. This is the first study to conduct a targeted evaluation of ligament healing biomarkers in fibroblast-collagen gels, and the results suggest that biomimetic in-vitro models of early scar formation should be initially cultured under biaxial stress conditions.