Biology subjects

Johnston, R. D.

Publications and source records attributed to Johnston, R. D..

10 recordsLinked to original sources

bioRxiv2026

Assessing the Clinical Utility of Finite Element Analysis Using Post-operative CT-Derived Models: A Material Comparison of Multi-level Spinal Fusion Constructs

Successful instrumented fusion of the lumbar spine is a complex surgical challenge, with positive patient outcomes dependent on careful surgical planning. Material selection is of critical importance to a mechanical construct supporting successful spinal fusion. Therefore, the aims of this study were to (a) evaluate the potential clinical use of finite element analysis (FEA) and (b) conduct a retrospective mechanical analysis of different implant materials in patients having undergone spinal fusion using FEA. Our methodology involved segmenting the spine from post-operative computed tomography (CT) image data from patients with previous spinal fusion. FEA models representing post-surgery cases were developed and different biomechanical loading conditions such as compression, flexion, bending and extension whilst testing pedicle screws of different materials were simulated. Patient specific finite element models were created, and biomechanical analysis were completed for all three patients. Polyetheretherketone (PEEK) constructs typically demonstrated lower peak implant stress when compared to titanium constructs for all spinal fusion levels. Furthermore, increasing the spinal fusion level resulted in significant differences in the maximum von Mises stress within both the bone and the instrumentation, whereas the 2-level fusion exhibited comparable stress levels in the bone irrespective of the instrumentation material. This pilot explores the potential of FEA as a clinical tool for assessing device and bone stresses. In our cohort, different materials can influence the stresses in both the instrumentation and the instrumented vertebrae, suggesting FEA can be useful pre- operative tool with regards to instrument selection and post-operatively to assess instrumentation and bone stresses. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=74 SRC="FIGDIR/small/742715v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@1399da7org.highwire.dtl.DTLVardef@19d73e2org.highwire.dtl.DTLVardef@2337c8org.highwire.dtl.DTLVardef@232c90_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2025

FE-DOE: Finite element informed design of experiments to optimise bioinspired melt electrowritten (MEW) polymeric heart valves

Aortic stenosis is predominantly treated through transcatheter bioprosthetic heart valve implantation. The materials used in these devices, however, suffer from premature failure. Polymer heart valves have the potential to improve current commercial devices, offering materials with extended durability and customisation through fibre-reinforcement. Due to the wide range of available materials and structures, there is a need for a methodical approach to the design and optimisation of novel, bioinspired polymeric leaflets. This work presents a framework using FE and DOE tools to enable the creation of optimised bioinspired, 3D-printed, fibre-reinforced polymer leaflets using MEW. Here, FE models are created to represent MEW fibre-reinforced polymer leaflets for application in a transcatheter aortic heart valve. The behaviour of this valve under physiological loading conditions is modelled to predict valve performance and leaflet material response. These models were first used to investigate the impact of fibre orientation on valve performance and leaflet response, showing the benefit of using a bioinspired fibre reinforcement structure. Using DOE, the structural combination of MEW fibre-reinforcement and elastomeric matrix was optimised based on valve performance and leaflet stress and strain. Overall, the framework offers an efficient and versatile methodology for optimising fibre-reinforced polymer leaflets by utilising an in-silico approach to remove the need for manufacturing and testing of these devices.

bioengineering↗

bioRxiv2024

Inverse Finite Element Framework Combining Ultrasound Imaging and Inflation Testing of PVA Artery Phantoms

The clinical decision to establish if a patient with carotid disease should undergo surgical intervention is primarily based on the percent stenosis. Whilst this applies for high-grade stenosed vessels (>70%), it falls short for other cases. Due to the heterogeneity of plaque tissue, probing the mechanics of the tissue would likely provide further insights into why some plaques are more prone to rupture. Mechanical characterisation of such tissue is nontrivial, however, due to the difficulties in collecting fresh, intact plaque tissue and using physiologically relevant mechanical testing of such material. The use of polyvinyl alcohol (PVA) is thus highly convenient because of its acoustic properties and tuneable mechanical properties. MethodsThe aim of this study is to demonstrate the potential of polyvinyl alcohol phantoms to simulate atherosclerotic features. In addition, a testing and simulation framework is developed for full PVA vessel material characterization using ring tensile testing and inflation testing combined with non-invasive ultrasound imaging and computational modelling. ResultsStrain stiffening behaviour was observed in PVA through ring tensile tests, particularly at high freeze-thaw cycles. Inflation testing of bi-layered phantoms featuring lipid pool inclusions demonstrated high strains at shoulder regions. The application of an inverse finite element framework successfully recovered boundaries and determined the shear moduli for the PVA wall to lie within the range 27 kPa to 53 kPa. ConclusionThe imaging-modelling framework presented facilitates the use and characterisation of arterial mimicking phantoms to further explore plaque rupture. It also shows translational potential for non-invasive mechanical characterisation of atherosclerotic plaques to improve the identification of clinically relevant metrics of plaque vulnerability.

bioengineering↗

bioRxiv2024

An arch worth revisiting: A study on the feline humeral supracondylar foramen and its evolutionary significance

The supracondylar foramen with a seemingly osseous peripheral arch noticed on the medio-distal feline humeri had remained disputed among anatomists. Some scholars have argued in favor of homology between this foramen and the supracondyloid foramen formed in the presence of the ligament of Struthers in humans. Other theories include its presence as a retinaculum holding the median nerve and brachial artery to their anatomical position in a flexed elbow. Unfortunately, these theories lack investigative rigor. The emergence of non-invasive imaging modalities, such as micro-computed tomography, has enabled researchers to inspect the internal anatomy of bones without dismantling. Thus, a micro-computed tomographic investigation was conducted on three feline humeri specimens while the internal anatomy of the supracondylar foramina was examined. Unlike the humerus, the thin peripheral arch of the feline supracondylar foramen failed to elicit any osseous trabeculae or foci of calcification. While adhering to the humeral periosteum at its origin, the non-osseous arch, typical of a muscular tendon or a ligament, inserts into a bony spur attached to the medial humeral epicondyle suggestive of a ligament or aponeurotic extension of a (vestigial) brachial muscle, with the coracobrachialis longus emerging to be the most likely candidate.

evolutionary biology↗

bioRxiv2022

Microstructural and mechanical insight into atherosclerotic plaques - an ex vivo DTI study to better assess plaque vulnerability

Non-invasive microstructural characterisation has the potential to determine the stability, or lack thereof, of atherosclerotic plaques and ultimately aid in better assessing plaques risk to rupture. If linked with mechanical characterisation using a clinically relevant imaging technique, mechanically sensitive rupture risk indicators could be possible. This study aims to provide this link - between a clinically relevant imaging technique and mechanical characterisation within human atherosclerotic plaques. Ex vivo diffusion tensor imaging, mechanical testing, and histological analysis were carried out on human carotid atherosclerotic plaques. DTI-derived tractography was found to yield significant mechanical insight into the mechanical properties of more stable and more vulnerable microstructures. Coupled with insights from digital image correlation and histology, specific failure characteristics of different microstructural arrangements furthered this finding. More circumferentially uniform microstructures failed at higher stresses and strains when compared to samples which had multiple microstructures, like those seen in a plaque cap. The novel findings in this study motivate diagnostic measures which use non-invasive characterisation of the underlying microstructure of plaques to determine their vulnerability to rupture. Statements and DeclarationsThe authors have no competing interests or declarations to declare. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=133 SRC="FIGDIR/small/508689v1_ufig1.gif" ALT="Figure 1"> View larger version (61K): org.highwire.dtl.DTLVardef@15174d8org.highwire.dtl.DTLVardef@ce3db1org.highwire.dtl.DTLVardef@344257org.highwire.dtl.DTLVardef@ef8f19_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2022

Phosphotungstic acid (PTA) preferentially binds to collagen-rich regions of porcine carotid arteries and human atherosclerotic plaques using 3D micro-computed tomography (CE-μCT)

Background and aimsAtherosclerotic plaque rupture in the carotid artery can cause small emboli to travel to cerebral arteries, causing blockages and preventing blood flow leading to stroke. Contrast enhanced micro computed tomography (CECT) using a novel stain, phosphotungstic acid (PTA) can provide insights into the microstructure of the vessel wall and atherosclerotic plaque, and hence their likelihood to rupture. Furthermore, it has been suggested that collagen content and orientation can be related to mechanical integrity. This study aims to build on existing literature and establish a robust and reproducible staining and imaging technique to non-destructively quantify the collagen content within arteries and plaques as an alternative to routine histology. MethodsPorcine carotid arteries and human atherosclerotic plaques were stained with a concentration of 1% PTA staining solution and imaged using MicroCT to establish the in-situ architecture of the tissue and measure collagen content. A histological assessment of the collagen content was also performed from picrosirius red (PSR) staining. ResultsPTA stained arterial samples highlight the reproducibility of the PTA staining and MicroCT imaging technique used with a quantitative analysis showing a positive correlation between the collagen content measured from CECT and histology. Furthermore, collagen-rich areas can be clearly visualised in both the vessel wall and atherosclerotic plaque. 3D reconstruction was also performed showing that different layers of the vessel wall and various atherosclerotic plaque components can be differentiated using Hounsfield Unit (HU) values. ConclusionsThe work presented here is unique as it offers a quantitative method of segmenting the vessel wall into its individual components and non-destructively quantifying the collagen content withing these tissues, whilst also delivering a visual representation of the fibrous structure using a single contrast agent. Graphical Abstract O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY

bioengineering↗

bioRxiv2022

Inverse Material Parameter Estimation of Patient Specific Finite Element Models at the Carotid Bifurcation: The Impact of Excluding the Zero Pressure Configuration and Residual Stress

Abstract SummaryThe carotid bifurcation experiences a complex loading environment due to its anatomical structure. Previous in-vivo material parameter estimation methods often use simplified model geometries, isotropic hyperelastic constitutive equations or neglect key aspects of the vessel, such as the zero-pressure configuration or residual stress. These factors have independently been shown to alter the stress environment of the vessel wall. Characterising the location of high stress in the vessel wall has often been proposed as a potential indicator of structural weakness. However, excluding the afore-mentioned zero-pressure configuration, residual stress and patient specific material parameters can lead to an incorrect estimation of the true stress values observed, meaning stress alone as a risk indicator of rupture is insufficient. In this study, we investigate how the estimated material parameters and overall stress distributions in geometries of carotid bifurcations, extracted from in-vivo MR images, alter with the inclusion of the zero-pressure configuration and residual stress. This approach consists of the following steps: (1) geometry segmentation and hexahedral meshing from in-vivo MRI images at two known phases; (2) computation of the zero-pressure configuration and the associated residual stresses; (3) minimisation of an objective function built on the difference between the stress states of an " almost true" stress field at two known phases and a "deformed" stress field by altering the input material parameters to determine patient specific material properties; and (4) comparison of the stress distributions throughout these carotid bifurcations for all cases with estimated material parameters. This numerical approach provides insights into the need for estimation of both the zero-pressure configuration and residual stress for accurate material property estimation and stress analysis for the carotid bifurcation, establishing the reliability of stress as a rupture risk metric. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=56 SRC="FIGDIR/small/487823v1_ufig1.gif" ALT="Figure 1"> View larger version (20K): org.highwire.dtl.DTLVardef@a63f0forg.highwire.dtl.DTLVardef@7612f1org.highwire.dtl.DTLVardef@1d5beb7org.highwire.dtl.DTLVardef@1dbfbfd_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2021

Quantitative susceptibility mapping of carotid arterial tissue ex vivo: assessing sensitivity to vessel microstructural composition

PurposeTo characterise microstructural contributions to the magnetic susceptibility of carotid arteries. MethodArterial vessels were scanned using high resolution quantitative susceptibility mapping (QSM) at 7T. Models of vessel degradation were generated using ex vivo porcine carotid arteries that were subjected to several different enzymatic digestion treatments that selectively removed microstructural components (smooth muscle cells, collagen and elastin). Magnetic susceptibilities measured in these tissue models were compared to those in untreated (native) porcine arteries. Magnetic susceptibility measured in native porcine carotid arteries was further compared to the susceptibility of cadaveric human carotid arteries to investigate their similarity. ResultsThe magnetic susceptibility of native porcine vessels was diamagnetic ([X]native = -0.1820ppm), with higher susceptibilities in all models of vessel degradation ([X]elastin degraded = -0.0163ppm; [X]collagen degraded = -0.1158ppm; [X]decellularised = -0.1379ppm; [X]fixed native = -0.2199ppm). Magnetic susceptibility was significantly higher in collagen degraded compared to native porcine vessels (Tukey-Kramer, p<0.01) and between elastin degraded and all other models (including native, Tukey-Kramer, p<0.001). The susceptibility of fixed healthy human arterial tissue was diamagnetic and no significant difference was found between fixed human and fixed porcine arterial tissue susceptibilities (ANOVA, p>0.05). ConclusionsMagnetic susceptibility measured using QSM is sensitive to the microstructural composition of arterial vessels - most notably to collagen. The similarity of human and porcine arterial tissue susceptibility values provides a solid basis for translational studies. As vessel microstructure becomes disrupted during the onset and progression of carotid atherosclerosis, QSM has the potential to provide a sensitive and specific marker of vessel disease.

bioengineering↗

bioRxiv2020

An investigation into the critical role of fibre orientation in the ultimate tensile strength and stiffness of human carotid plaque caps

The development and subsequent rupture of atherosclerotic plaques in human carotid arteries is a major cause of ischemic stroke. Mechanical characterization of atherosclerotic plaques can aid our understanding of this rupture risk. Despite this however, experimental studies on human atherosclerotic carotid plaques, and fibrous plaque caps in particular, are very limited. This study aims to provide further insights into atherosclerotic plaque rupture by mechanically testing human fibrous plaque caps, the region of the atherosclerotic lesion most often attributed the highest risk of rupture. The results obtained highlight the variability in the ultimate tensile stress, strain and stiffness experienced in atherosclerotic plaque caps. By pre-screening all samples using small angle light scattering (SALS) to determine the dominant fibre direction in the tissue, along with supporting histological analysis, this work suggests that the collagen fibre alignment in the circumferential direction plays the most dominant role for determining plaque structural stability. The work presented in this study could provide the basis for new diagnostic approaches to be developed, which non-invasively identify carotid plaques at greatest risk of rupture. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=95 SRC="FIGDIR/small/264457v1_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@185109forg.highwire.dtl.DTLVardef@1067820org.highwire.dtl.DTLVardef@1b8baf3org.highwire.dtl.DTLVardef@f9b3af_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2020

Diffusion tensor imaging and arterial tissue: establishing the influence of arterial tissue microstructure on fractional anisotropy, mean diffusivity and tractography

In this study we investigated the potential of diffusion tensor imaging (DTI) for providing insight into microstructural changes in arterial tissue by exploring the influence that cell, collagen and elastin content have on fractional anisotropy (FA), mean diffusivity (MD) and tractography. Five ex vivo porcine carotid artery models (n = 6 vessels each) - native, fixed native, collagen degraded, elastin degraded and decellularised - were developed to selectively remove components of arterial microstructure. Intact vessels were imaged at 7 T using a DTI protocol with b = 0 and 800 s/mm2 and 10 isotopically distributed directions. FA and MD values were evaluated in the medial layer of vessels and compared across tissue models. FA values measured in native and fixed native vessels were significantly higher (p<0.0001) than those in the elastin degraded and decellularised arteries. Collagen degraded vessels had a significantly higher (p<0.01) FA than elastin degraded and decellularised vessels. Native and fixed vessels had significantly lower (p<0.0001) MD values than elastin degraded, while the MD in decellularised arteries was significantly higher than that in both native (p<0.01) and fixed (p<0.005) tissue. Significantly lower (p<0.005) MD was measured in collagen degraded compared with the elastin degraded model. Tractography results yielded similar helically arranged tracts for native and collagen degraded vessels, whilst elastin degraded and decellularised vessels showed no consistent tracts. FA, MD and tractography were found to be highly sensitive to changes in the microstructural composition of arterial tissue, with cell content being a dominant source of the measured anisotropy in the vessel wall.

bioengineering↗