Biology subjects

Stone, A. J.

Publications and source records attributed to Stone, A. J..

7 recordsLinked to original sources

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

Exploring DTI-derived metrics to non-invasively track recellularisation in vascular tissue engineering

Despite significant growth in the field of tissue engineering over the past decades, non-invasive, non-destructive methods to characterise recellularisation of grafts are lacking. Here, we investigate a non-invasive magnetic resonance imaging technique, diffusion tensor imaging (DTI), within acellular and recellularised vascular grafts. Using two decellularised porcine carotid grafts, smooth muscle cells were cultured dynamically for two weeks with terminal time points at day 3, 7, and 14. Grafts were fixed at each time point and investigated by DTI in an ex vivo set up. Semi-quantitative histology was carried out to investigate collagen, elastin, and cell density changes over time. DTI-derived metrics, namely the fractional anisotropy, mean diffusivity and tractography, not only were significantly different between day 3 and day 7 grafts, but also distinguished between acellular and recellularised grafts. Specifically, within the wet decellularised grafts, increasing fractional anisotropy was strongly correlated to increasing cell density. The results from this study show, for the first time, DTIs place in the field of tissue engineering, offering non-invasive, non-destructive insight into graft recellularisation.

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

Improving qBOLD based measures of oxygen extraction fraction using hyperoxia-BOLD derived measures of blood volume

PurposeStreamlined-qBOLD (sqBOLD) is a refinement of the quantitative BOLD (qBOLD) technique capable of producing non-invasive and quantitative maps of oxygen extraction fraction (OEF) in a clinically feasible scan time. However, sqBOLD measurements of OEF have been reported as being systematically lower than expected in healthy brain. Since the qBOLD framework infers OEF from the ratio of the reversible transverse relaxation rate (R2') and deoxygenated blood volume (DBV), this underestimation has been attributed the overestimation of DBV. Therefore, this study proposes the use of an independent measure of DBV using hyperoxia-BOLD and investigates whether this results in improved estimates of OEF. MethodsMonte Carlo simulations were used to simulate the qBOLD and hyperoxia-BOLD signals and to compare the systematic and noise related errors of sqBOLD and the new hyperoxia-qBOLD (hqBOLD) technique. Experimentally, sqBOLD and hqBOLD measurements were performed and compared with TRUST (T2 relaxation under spin tagging) based oximetry in the sagittal sinus. ResultsSimulations showed a large improvement in the uncertainty of DBV measurements leading to a much improved dynamic range for OEF measurements with hqBOLD. In a group of ten healthy volunteers, hqBOLD produced measurements of OEF in cortical grey matter (OEFhqBOLD = 38.1 {+/-} 10.1 %) that were not significantly different to TRUST oximetry measures (OEFTRUST = 40.4 {+/-} 7.7 %), whilst sqBOLD derived measures (OEFsqBOLD = 16.1 {+/-} 3.1 %) were found to be significantly different. ConclusionThe simulations and experiments in this study demonstrate that an independent measure of DBV provides improved estimates of OEF.

physiology↗

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↗

bioRxiv2019

The effect of diffusion on asymmetric spin echo based quantitative BOLD: An investigation of the origin of deoxygenated blood volume overestimation

Quantitative BOLD (qBOLD) is a technique for mapping oxygen extraction fraction (OEF) and deoxygenated blood volume (DBV) in the human brain. Recent measurements using an asymmetric spin echo (ASE) based qBOLD approach produced estimates of DBV which were systematically higher than measurements from other techniques. In this study, we investigate two hypotheses for the origin of this DBV overestimation using simulations and consider the implications for experimental measurements. Investigations were performed by combining Monte Carlo simulations of extravascular signal with an analytical model of the intravascular signal.\n\nHypothesis 1DBV overestimation is due to the presence of intravascular signal which is not accounted for in the analysis model. Intravascular signal was found to have a weak effect on qBOLD parameter estimates.\n\nHypothesis 2DBV overestimation is due to the effects of diffusion which are not accounted for in the analysis model. The effect of diffusion on the extravascular signal was found to result in a vessel radius dependent variation in qBOLD parameter estimates. In particular, DBV overestimation peaks for vessels with radii from 20 to 30 m and is OEF dependent. This results in the systematic underestimation of OEF.\n\nImplicationsThe impact on experimental qBOLD measurements was investigated by simulating a more physiologically realistic distribution of vessel sizes with a small number of discrete radii. Overestimation of DBV consistent with previous experiments was observed, which was also found to be OEF dependent. This results in the progressive underestimation of the measured OEF. Furthermore, the relationship between the measured OEF and the true OEF was found to be dependent on echo time and spin echo displacement time.\n\nThe results of this study demonstrate the limitations of current ASE based qBOLD measurements and provide a foundation for the optimisation of future acquisition approaches.

neuroscience↗

bioRxiv2017

Serial quantification of brain oxygenation in acute stroke using streamlined-qBOLD

It has been proposed that metabolic markers of baseline brain oxygenation have a role to play in the early identification of the ischemic penumbra. Streamlined-qBOLD is a magnetic resonance imaging technique that does not require exogenous contrast. It is a refinement of the quantitative BOLD methodology that provides a simplified approach to mapping and quantifying baseline brain oxygenation related parameters (reversible transverse relaxation rate (R2'), deoxygenated blood volume (DBV) and deoxyhaemoglobin concentration ([dHb])) in a clinically relevant manner. Streamlined-qBOLD was applied to an exploratory cohort of acute stroke patients in a serial imaging study. Detailed voxel-level analysis was used to quantify the metabolic profile of ischaemic tissue on presentation and investigate these metrics in relation to tissue outcome. Individual patient examples illustrate the appropriate interpretation of R2', DBV and [dHb] in acute stroke and demonstrate the ability of this method to deliver regional information related to oxygen metabolism in the ischaemic tissue. Regional analysis confirms that R2', DBV and [dHb] vary between regions of ischaemia with different tissue outcomes.

neuroscience↗