3D Ultrasound Shear Wave Elastography for Musculoskeletal Tissue Assessment Under Compressive Load: A Feasibility Study.

Given its real-time capability to quantify mechanical tissue properties, ultrasound shear wave elastography holds significant promise in clinical musculoskeletal imaging. However, existing shear wave elastography methods fall short in enabling full-limb analysis of 3D anatomical structures under diverse loading conditions, and may introduce measurement bias due to sonographer-applied force on the transducer. These limitations pose numerous challenges, particularly for 3D computational biomechanical tissue modeling in areas like prosthetic socket design. In this feasibility study, a clinical linear ultrasound transducer system with integrated shear wave elastography capabilities was utilized to scan both a calibrated phantom and human limbs in a water tank imaging setup. By conducting 2D and 3D scans under varying compressive loads, this study demonstrates the feasibility of volumetric ultrasound shear wave elastography of human limbs. Our preliminary results showcase a potential method for evaluating 3D spatially varying tissue properties, offering future extensions to computational biomechanical modeling of tissue for various clinical scenarios.

Experimental and computational analysis of energy absorption characteristics of three biomimetic lattice structures under compression.

The objective of this study is to evaluate the mechanical properties and energy absorption characteristics of the gyroid, dual-lattice and spinodoid structures, as biomimetic lattices, through finite element analysis and experimental characterisation. As part of the study, gyroid and dual-lattice structures at 10% volume fraction were 3D-printed using an elastic resin, and mechanically tested under uniaxial compression. Computational models were calibrated to the observed experimental data and the response of higher volume fraction structures were simulated in an explicit finite element solver. Stress-strain data of groups of lattices at different volume fractions were studied and energy absorption parameters including total energy absorbed per unit volume, energy absorption efficiency and onset of densification strain were calculated. Also, the structures were characterized into bending-dominant and stretch-dominant structures, according to their nodal connectivity and Gibson-and-Ashby's law. The results of the study showed that the dual-lattice is capable of absorbing more energy at each volume fraction cohort. However, gyroid structures showed higher energy absorption efficiency and the onset of densification at higher strains. The spinodoid structure was found to be the poorest structure in terms of energy absorption, specifically at low volume fractions. Also, the results showed that the dual-lattice was a stretch dominated structure, while the gyroid structure was a bending dominated structure, which may be a reason that it is a better candidate for energy absorption applications.

Biomechanical Characterisation of Thoracic Ascending Aorta with Preserved Pre-Stresses.

Mechanical properties of an aneurysmatic thoracic aorta are potential markers of future growth and remodelling and can help to estimate the risk of rupture. Aortic geometries obtained from routine medical imaging do not display wall stress distribution and mechanical properties. Mechanical properties for a given vessel may be determined from medical images at different physiological pressures using inverse finite element analysis. However, without considering pre-stresses, the estimation of mechanical properties will lack accuracy. In the present paper, we propose and evaluate a mechanical parameter identification technique, which recovers pre-stresses by determining the zero-pressure configuration of the aortic geometry. We first validated the method on a cylindrical geometry and subsequently applied it to a realistic aortic geometry. The verification of the assessed parameters was performed using synthetically generated reference data for both geometries. The method was able to estimate the true mechanical properties with an accuracy ranging from 98% to 99%.

Additively manufactured polyethylene terephthalate scaffolds for scapholunate interosseous ligament reconstruction.

The regeneration of the ruptured scapholunate interosseous ligament (SLIL) represents a clinical challenge. Here, we propose the use of a Bone-Ligament-Bone (BLB) 3D-printed polyethylene terephthalate (PET) scaffold for achieving mechanical stabilisation of the scaphoid and lunate following SLIL rupture. The BLB scaffold featured two bone compartments bridged by aligned fibres (ligament compartment) mimicking the architecture of the native tissue. The scaffold presented tensile stiffness in the range of 260 ± 38 N/mm and ultimate load of 113 ± 13 N, which would support physiological loading. A finite element analysis (FEA), using inverse finite element analysis (iFEA) for material property identification, showed an adequate fit between simulation and experimental data. The scaffold was then biofunctionalized using two different methods: injected with a Gelatin Methacryloyl solution containing human mesenchymal stem cell spheroids (hMSC) or seeded with tendon-derived stem cells (TDSC) and placed in a bioreactor to undergo cyclic deformation. The first approach demonstrated high cell viability, as cells migrated out of the spheroid and colonised the interstitial space of the scaffold. These cells adopted an elongated morphology suggesting the internal architecture of the scaffold exerted topographical guidance. The second method demonstrated the high resilience of the scaffold to cyclic deformation and the secretion of a fibroblastic related protein was enhanced by the mechanical stimulation. This process promoted the expression of relevant proteins, such as Tenomodulin (TNMD), indicating mechanical stimulation may enhance cell differentiation and be useful prior to surgical implantation. In conclusion, the PET scaffold presented several promising characteristics for the immediate mechanical stabilisation of disassociated scaphoid and lunate and, in the longer-term, the regeneration of the ruptured SLIL.

A morphological, topological and mechanical investigation of gyroid, spinodoid and dual-lattice algorithms as structural models of trabecular bone.

In this study, we evaluate the performance of three algorithms as computational models of trabecular bone architecture, through systematic evaluation of morphometric, topological, and mechanical properties. Here, we consider the widely-used gyroid lattice structure, the recently-developed spinodoid structure and a structure similar to Voronoi lattices introduced here as the dual-lattice. While all computational models were calibrated to recreate the trabecular tissue volume (e.g. BV/TV), it was found that both the gyroid- and spinodoid-based structures showed substantial differences in many other morphometric and topological parameters and, in turn, showed lower effective mechanical properties compared to trabecular bone. The newly-developed dual-lattice structures better captured both morphometric parameters and mechanical properties, despite certain differences being evident their topological configuration compared to trabecular bone. Still, these computational algorithms provide useful platforms to investigate trabecular bone mechanics and for designing biomimetic structures, which could be produced through additive manufacturing for applications that include bone substitutes, scaffolds and porous implants. Furthermore, the software for the creation of the structures has been added to the open source toolbox GIBBON and is therefore freely available to the community.

Constitutive parameter identification of transtibial residual limb soft tissue using ultrasound indentation and shear wave elastography.

Finite element analysis (FEA) can be used to evaluate applied interface pressures and internal tissue strains for computational prosthetic socket design. This type of framework requires realistic patient-specific limb geometry and constitutive properties. In recent studies, indentations and inverse FEA with MRI-derived 3D patient geometries were used for constitutive parameter identification. However, long computational times and use of specialized equipment presents challenges for clinical, deployment. In this study, we present a novel approach for constitutive parameter identification using a combination of FEA, ultrasound indentation, and shear wave elastography. Local shear modulus measurement using elastography during an ultrasound indentation experiment has particular significance for biomechanical modeling of the residual limb since there are known regional dependencies of soft tissue properties such as varying levels of scarring and atrophy. Beyond prosthesis design, this work has broader implications to the fields of muscle health and monitoring of disease progression.

Development of a patient-specific cerebral vasculature fluid-structure-interaction model.

Development of in-silico models of patient-specific cerebral artery networks presents several significant technical challenges: (i) The resolution and smoothness of medical CT images are much lower than the required element/cell length for FEA/CFD/FSI models; (ii) contact between vessels, and indeed self contact of high tortuosity vessel segments are not clearly identifiable from medical CT images. Commercial model construction software does not provide customised solutions for such technical challenges, with the result that accurate, efficient and automated development of patient-specific models of the cerebral vessels is not facilitated. This paper presents the development of a customised and highly automated platform for the generation of high resolution patient-specific FEA/CFD/FSI models from clinical images. This platform is used to perform the first fluid-structure-interaction patient-specific analysis of blood flow and artery deformation of an occluded cerebral vessel. Results demonstrate that in addition to flow disruption, clot occlusion significantly alters the geometry and strain distribution in the vessel network, with the blocked M2 segment undergoing axial elongation. The new computational approach presented in this study can be further developed as a clinical diagnostic tool and as a platform for thrombectomy device design.

Finite element analysis of the performance of additively manufactured scaffolds for scapholunate ligament reconstruction.

Rupture of the scapholunate interosseous ligament can cause the dissociation of scaphoid and lunate bones, resulting in impaired wrist function. Current treatments (e.g., tendon-based surgical reconstruction, screw-based fixation, fusion, or carpectomy) may restore wrist stability, but do not address regeneration of the ruptured ligament, and may result in wrist functional limitations and osteoarthritis. Recently a novel multiphasic bone-ligament-bone scaffold was proposed, which aims to reconstruct the ruptured ligament, and which can be 3D-printed using medical-grade polycaprolactone. This scaffold is composed of a central ligament-scaffold section and features a bone attachment terminal at either end. Since the ligament-scaffold is the primary load bearing structure during physiological wrist motion, its geometry, mechanical properties, and the surgical placement of the scaffold are critical for performance optimisation. This study presents a patient-specific computational biomechanical evaluation of the effect of scaffold length, and positioning of the bone attachment sites. Through segmentation and image processing of medical image data for natural wrist motion, detailed 3D geometries as well as patient-specific physiological wrist motion could be derived. This data formed the input for detailed finite element analysis, enabling computational of scaffold stress and strain distributions, which are key predictors of scaffold structural integrity. The computational analysis demonstrated that longer scaffolds present reduced peak scaffold stresses and a more homogeneous stress state compared to shorter scaffolds. Furthermore, it was found that scaffolds attached at proximal sites experience lower stresses than those attached at distal sites. However, scaffold length, rather than bone terminal location, most strongly influences peak stress. For each scaffold terminal placement configuration, a basic metric was computed indicative of bone fracture risk. This metric was the minimum distance from the bone surface to the internal scaffold bone terminal. Analysis of this minimum bone thickness data confirmed further optimisation of terminal locations is warranted.

The first virtual patient-specific thrombectomy procedure.

Treatment of acute ischemic stroke has been recently improved with the introduction of endovascular mechanical thrombectomy, a minimally invasive procedure able to remove a clot using aspiration devices and/or stent-retrievers. Despite the promising and encouraging results, improvements to the procedure and to the stent design are the focus of the recent efforts. Computational studies can pave the road to these improvements, providing their ability to describe and accurately reproduce a real procedure. A patient with ischemic stroke due to intracranial large vessel occlusion was selected and after the creation of the cerebral vasculature from computed tomography images and a histologic analysis to determine the clot composition, the entire thrombectomy procedure was virtually replicated. As in the real situation, the computational replica showed that two attempts were necessary to remove the clot, as a result of the position of the stent retriever with respect to the clot. Furthermore, the results indicated that clot fragmentation did not occur as the deformations were mainly in a compressive state without the possibility for clot cracks to propagate. The accurate representation of the procedure can be used as an important step for operative optimization planning and future improvements of stent designs.

Additive Manufacturing of Multi-Scale Porous Soft Tissue Implants That Encourage Vascularization and Tissue Ingrowth.

Medical devices, such as silicone-based prostheses designed for soft tissue implantation, often induce a suboptimal foreign-body response which results in a hardened avascular fibrotic capsule around the device, often leading to patient discomfort or implant failure. Here, it is proposed that additive manufacturing techniques can be used to deposit durable coatings with multiscale porosity on soft tissue implant surfaces to promote optimal tissue integration. Specifically, the "liquid rope coil effect", is exploited via direct ink writing, to create a controlled macro open-pore architecture, including over highly curved surfaces, while adapting atomizing spray deposition of a silicone ink to create a microporous texture. The potential to tailor the degree of tissue integration and vascularization using these fabrication techniques is demonstrated through subdermal and submuscular implantation studies in rodent and porcine models respectively, illustrating the implant coating's potential applications in both traditional soft tissue prosthetics and active drug-eluting devices.

A new compressible hyperelastic model for the multi-axial deformation of blood clot occlusions in vessels.

Mechanical thrombectomy can be significantly affected by the mechanical properties of the occluding thrombus. In this study, we provide the first characterisation of the volumetric behaviour of blood clots. We propose a new hyperelastic model for the volumetric and isochoric deformation of clot. We demonstrate that the proposed model provides significant improvements over established models in terms of accurate prediction of nonlinear stress-strain and volumetric behaviours of clots with low and high red blood cell compositions. We perform a rigorous investigation of the factors that govern clot occlusion of a tapered vessel. The motivation for such an analysis is twofold: (i) the role of clot composition on the in vivo occlusion location is an open clinical question that has significant implications for thrombectomy procedures; (ii) in vitro measurement of occlusion location in an engineered tapered tube can be used as a quick and simple methodology to assess the mechanical properties/compositions of clots. Simulations demonstrate that both isochoric and volumetric behaviours of clots are key determinants of clot lodgement location, in addition to clot-vessel friction. The proposed formulation is shown to provide accurate predictions of in vitro measurement of clot occlusion location in a silicone tapered vessel, in addition to accurately predicting the deformed shape of the clot.

Impact of the Internal Carotid Artery Morphology on in silico Stent-Retriever Thrombectomy Outcome.

The aim of this work is to propose a methodology for identifying relationships between morphological features of the cerebral vasculature and the outcome of in silico simulations of thrombectomy, the mechanical treatment for acute ischemic stroke. Fourteen patient-specific cerebral vasculature segmentations were collected and used for geometric characterization of the intracranial arteries mostly affected by large vessel occlusions, i.e., internal carotid artery (ICA), middle cerebral artery (MCA) and anterior cerebral artery (ACA). First, a set of global parameters was created, including the geometrical information commonly provided in the clinical context, namely the total length, the average diameter and the tortuosity (length over head-tail distance) of the intracranial ICA. Then, a more exhaustive geometrical analysis was performed to collect a set of local parameters. A total of 27 parameters was measured from each patient-specific vascular configuration. Fourteen virtual thrombectomy simulations were performed with a blood clot with the same length and composition placed in the middle of the MCA. The model of TREVO ProVue stent-retriever was used for all the simulations. Results from simulations produced five unsuccessful outcomes, i.e., the clot was not removed from the vessels. The geometric parameters of the successful and unsuccessful simulations were compared to find relations between the vascular geometry and the outcome. None of the global parameters alone or combined proved able to discriminate between positive and negative outcome, while a combination of local parameters allowed to correctly identify the successful from the unsuccessful simulations. Although these results are limited by the number of patients considered, this study indicates a promising methodology to relate patient-specific geometry to virtual thrombectomy outcome, which might eventually guide decision making in the treatment of acute ischemic stroke.

A Framework for Measuring the Time-Varying Shape and Full-Field Deformation of Residual Limbs Using 3-D Digital Image Correlation.

Effective prosthetic socket design following lower limb amputation depends upon the accurate characterization of the shape of the residual limb as well as its volume and shape fluctuations. OBJECTIVE: This study proposes a novel framework for the measurement and analysis of residual limb shape and deformation, using a high-resolution and low-cost system. METHODS: A multi-camera system was designed to capture sets of simultaneous images of the entire residuum surface. The images were analyzed using a specially developed open-source three-dimensional digital image correlation (3D-DIC) toolbox, to obtain the accurate time-varying shapes as well as the full-field deformation and strain maps on the residuum skin surface. Measurements on a transtibial amputee residuum were obtained during knee flexions, muscle contractions, and swelling upon socket removal. RESULTS: It was demonstrated that 3D-DIC can be employed to quantify with high resolution time-varying residuum shapes, deformations, and strains. Additionally, the enclosed volumes and cross-sectional areas were computed and analyzed. CONCLUSION: This novel low-cost framework provides a promising solution for the in vivo evaluation of residuum shapes and strains, as well as has the potential for characterizing the mechanical properties of the underlying soft tissues. SIGNIFICANCE: These data may be used to inform data-driven computational algorithms for the design of prosthetic sockets, as well as of other wearable technologies mechanically interfacing with the skin.

3D Ultrasound Imaging of Residual Limbs With Camera-Based Motion Compensation.

Ultrasound is a cost-effective, readily available, and non-ionizing modality for musculoskeletal imaging. Though some research groups have pursued methods that involve submerging the transducer and imaged body segment into a water bath, many limitations remain in regards to acquiring an unloaded volumetric image of an entire human limb in a fast, safe, and adequately accurate manner. A 3D dataset of a limb is useful in several rehabilitative applications including biomechanical modeling of soft tissue, prosthetic socket design, monitoring muscle condition and disease progression, bone health, and orthopedic surgery. This paper builds on previous work from our group and presents the design, prototyping, and preliminary testing of a novel multi-modal imaging system for rapidly acquiring volumetric ultrasound imagery of human limbs, with a particular focus on residual limbs for improved prosthesis design. Our system employs a mechanized water tank setup to scan a limb with a clinical ultrasound transducer and 3D optical imagery to track motion during a scan. The iterative closest point algorithm is utilized to compensate for motion and stitch the images into a final dataset. The results show preliminary 2D and 3D imaging of both a tissue-mimicking phantom and residual limbs. A volumetric error compares the ultrasound image data obtained to a previous MRI method. The results indicate potential for future clinical implementation. Concepts presented in this paper could reasonably transfer to other imaging applications such as acoustic tomography, where motion artifact may distort image reconstruction.

MRI based 3D finite element modelling to investigate deep tissue injury.

Pressure ulcers occur due to sustained mechanical loading. Deep tissue injury is a severe type of pressure ulcer, which is believed to originate in subcutaneous tissues adjacent to bony prominences. In previous experimental-numerical studies the relationship between internal tissue state and damage development was investigated using a 2D analysis. However, recent studies suggest that a local analysis is not sufficient. In the present study we developed a method to create animal-specific 3D finite element models of an indentation test on the tibialis anterior muscle of rats based on MRI data. A detailed description on how the animal specific models are created is given. Furthermore, two indenter geometries are compared and the influence of errors in determining the indenter orientation on the resulting internal strain distribution in a defined volume of tissue was investigated. We conclude that with a spherically-shaped indenter errors in estimating the indenter orientation do not unduly influence the results of the simulation.

Journal of Open Source Software (JOSS): design and first-year review.

This article describes the motivation, design, and progress of the Journal of Open Source Software (JOSS). JOSS is a free and open-access journal that publishes articles describing research software. It has the dual goals of improving the quality of the software submitted and providing a mechanism for research software developers to receive credit. While designed to work within the current merit system of science, JOSS addresses the dearth of rewards for key contributions to science made in the form of software. JOSS publishes articles that encapsulate scholarship contained in the software itself, and its rigorous peer review targets the software components: functionality, documentation, tests, continuous integration, and the license. A JOSS article contains an abstract describing the purpose and functionality of the software, references, and a link to the software archive. The article is the entry point of a JOSS submission, which encompasses the full set of software artifacts. Submission and review proceed in the open, on GitHub. Editors, reviewers, and authors work collaboratively and openly. Unlike other journals, JOSS does not reject articles requiring major revision; while not yet accepted, articles remain visible and under review until the authors make adequate changes (or withdraw, if unable to meet requirements). Once an article is accepted, JOSS gives it a digital object identifier (DOI), deposits its metadata in Crossref, and the article can begin collecting citations on indexers like Google Scholar and other services. Authors retain copyright of their JOSS article, releasing it under a Creative Commons Attribution 4.0 International License. In its first year, starting in May 2016, JOSS published 111 articles, with more than 40 additional articles under review. JOSS is a sponsored project of the nonprofit organization NumFOCUS and is an affiliate of the Open Source Initiative (OSI).

A MRI-Compatible Combined Mechanical Loading and MR Elastography Setup to Study Deformation-Induced Skeletal Muscle Damage in Rats.

Deformation of skeletal muscle in the proximity of bony structures may lead to deep tissue injury category of pressure ulcers. Changes in mechanical properties have been proposed as a risk factor in the development of deep tissue injury and may be useful as a diagnostic tool for early detection. MRE allows for the estimation of mechanical properties of soft tissue through analysis of shear wave data. The shear waves originate from vibrations induced by an external actuator placed on the tissue surface. In this study a combined Magnetic Resonance (MR) compatible indentation and MR Elastography (MRE) setup is presented to study mechanical properties associated with deep tissue injury in rats. The proposed setup allows for MRE investigations combined with damage-inducing large strain indentation of the Tibialis Anterior muscle in the rat hind leg inside a small animal MR scanner. An alginate cast allowed proper fixation of the animal leg with anatomical perfect fit, provided boundary condition information for FEA and provided good susceptibility matching. MR Elastography data could be recorded for the Tibialis Anterior muscle prior to, during, and after indentation. A decaying shear wave with an average amplitude of approximately 2 µm propagated in the whole muscle. MRE elastograms representing local tissue shear storage modulus Gd showed significant increased mean values due to damage-inducing indentation (from 4.2 ± 0.1 kPa before to 5.1 ± 0.6 kPa after, p<0.05). The proposed setup enables controlled deformation under MRI-guidance, monitoring of the wound development by MRI, and quantification of tissue mechanical properties by MRE. We expect that improved knowledge of changes in soft tissue mechanical properties due to deep tissue injury, will provide new insights in the etiology of deep tissue injuries, skeletal muscle damage and other related muscle pathologies.

Low-Cost Methodology for Skin Strain Measurement of a Flexed Biological Limb.

OBJECTIVE: The purpose of this manuscript is to compute skin strain data from a flexed biological limb, using portable, inexpensive, and easily available resources. METHODS: We apply and evaluate this approach on a person with bilateral transtibial amputations, imaging left and right residual limbs in extended and flexed knee postures. We map 3-D deformations to a flexed biological limb using freeware and a simple point-and-shoot camera. Mean principal strain, maximum shear strain, as well as lines of maximum, minimum, and nonextension are computed from 3-D digital models to inform directional mappings of the strain field for an unloaded residual limb. RESULTS: Peak tensile strains are ∼0.3 on the anterior surface of the knee in the proximal region of the patella, whereas peak compressive strains are ∼ -0.5 on the posterior surface of the knee. Peak maximum shear strains are ∼0.3 on the posterior surface of the knee. The accuracy and precision of this methodology are assessed for a ground-truth model. The mean point location distance is found to be 0.08 cm, and the overall standard deviation for point location difference vectors is 0.05 cm. CONCLUSION: This low-cost and mobile methodology may prove critical for applications such as the prosthetic socket interface where whole-limb skin strain data are required from patients in the field outside of traditional, large-scale clinical centers. SIGNIFICANCE: Such data may inform the design of wearable technologies that directly interface with human skin.

On the importance of 3D, geometrically accurate, and subject-specific finite element analysis for evaluation of in-vivo soft tissue loads.

Pressure ulcers are a type of local soft tissue injury due to sustained mechanical loading and remain a common issue in patient care. People with spinal cord injury (SCI) are especially at risk of pressure ulcers due to impaired mobility and sensory perception. The development of load improving support structures relies on realistic tissue load evaluation e.g. using finite element analysis (FEA). FEA requires realistic subject-specific mechanical properties and geometries. This study focuses on the effect of geometry. MRI is used for the creation of geometrically accurate models of the human buttock for three able-bodied volunteers and three volunteers with SCI. The effect of geometry on observed internal tissue deformations for each subject is studied by comparing FEA findings for equivalent loading conditions. The large variations found between subjects confirms the importance of subject-specific FEA.

Multi-material 3-D viscoelastic model of a transtibial residuum from in-vivo indentation and MRI data.

Although the socket is critical in a prosthetic system for a person with limb amputation, the methods of its design are largely artisanal. A roadblock for a repeatable and quantitative socket design process is the lack of predictive and patient specific biomechanical models of the residuum. This study presents the evaluation of such a model using a combined experimental-numerical approach. The model geometry and tissue boundaries are derived from magnetic resonance imaging (MRI). The soft tissue non-linear elastic and viscoelastic mechanical behavior was evaluated using inverse finite element analysis (FEA) of in-vivo indentation experiments. A custom designed robotic in-vivo indentation system was used to provide a rich experimental data set of force versus time at 18 sites across a limb. During FEA, the tissues were represented by two layers, namely the skin-adipose layer and an underlying muscle-soft tissue complex. The non-linear elastic behavior was modeled using 2nd order Ogden hyperelastic formulations, and viscoelasticity was modeled using the quasi-linear theory of viscoelasticity. To determine the material parameters for each tissue, an inverse FEA based optimization routine was used that minimizes the combined mean of the squared force differences between the numerical and experimental force-time curves for indentations at 4 distinct anatomical regions on the residuum. The optimization provided the following material parameters for the skin-adipose layer: [c=5.22kPam=4.79γ=3.57MPaτ=0.32s] and for the muscle-soft tissue complex [c=5.20kPam=4.78γ=3.47MPaτ=0.34s]. These parameters were evaluated to predict the force-time curves for the remaining 14 anatomical locations. The mean percentage error (mean absolute error/ maximum experimental force) for these predictions was 7±3%. The mean percentage error at the 4 sites used for the optimization was 4%.