Modelling the evolution of cerebral aneurysms: biomechanics, mechanobiology and multiscale modelling

Intracranial aneurysms (IAs) are abnormal dilatations of the cerebral vasculature. Computational modelling may shed light on the aetiology of the disease and lead to improved criteria to assist diagnostic decisions. We briefly review models of aneurysm evolution to date and present a novel fluid-solid-growth (FSG) framework for patient-specific modelling of IA evolution. We illustrate its application to 4 clinical cases depicting an IA. The section of arterial geometry containing the IA is removed and replaced with a cylindrical section: this represents an idealised section of healthy artery upon which IA evolution is simulated. The utilisation of patient-specific geometries enables G&R to be explicitly linked to physiologically realistic spatial distributions and magnitudes of haemodynamic stimuli. In this study, we investigate the hypothesis that elastin degradation is driven by locally low wall shear stress (WSS). In 3 out of 4 cases, the evolved model IA geometry is qualitatively similar to the corresponding in vivo IA geometry. This suggests some tentative support for the hypothesis that low WSS plays a role in the mechanobiology of IA evolution

A novel chemo–mechano–biological model of arterial tissue growth and remodelling

Arterial growth and remodelling (GandR) is mediated by vascular cells in response to their chemical and mechanical environment. To date, mechanical and biochemical stimuli tend to be modelled separately, however this ignores their complex interplay. Here, we present a novel mathematical model of arterial chemo–mechano–biology. We illustrate its application to the development of an inflammatory aneurysm in the descending human aorta. The arterial wall is modelled as a bilayer cylindrical non–linear elastic membrane, which is internally pressurized and axially stretched. The medial degradation that accompanies aneurysm development is driven by an inflammatory response. Collagen remodelling is simulated by adaption of the natural reference configuration of constituents; growth is simulated by changes in normalised mass–densities. We account for the distribution of attachment stretches that collagen fibres are configured to the matrix and, innovatively, allow this distribution to remodel. This enables the changing functional role of the adventitia to be simulated. Fibroblast-mediated collagen growth is represented using a biochemical pathway model: a system of coupled non-linear ODEs governs the evolution of fibroblast properties and levels of key biomolecules under the regulation of Transforming Growth Factor (TGF)-β, a key promoter of matrix deposition. Given physiologically realistic targets, different modes of aneurysm development can be captured, while the predicted evolution of biochemical variables is qualitatively consistent with trends observed experimentally. Interestingly, we observe that increasing the levels of collagen–promoting TGF-β results in arrest of aneurysm growth, what seems to be consistent with experimental evidence. We conclude that this novel Chemo–Mechano–Biological (CMB) mathematical model has the potential to provide new mechanobiological insight into vascular disease progression and therapy.</p

A mechanobiological model of the urinary bladder : integrative modelling of outlet obstruction

We present the first model to simulate the adaptive growth and remodeling (G&R) response of the bladder wall to bladder outlet obstruction (BOO). The model is calibrated and validated with an experimental rodent model of BOO. The bladder is modeled as a multi-layered, nonlinear elastic spherical membrane using a constrained mixture model that includes both passive and active components. The mechanical model is integrated with a shorter time scale micturition model that accounts for the active mechanics of voiding and dependence of flowrate on urethral resistance. Over a second time scale, constituents are configured and subsequently remodel to achieve a homeostatic state at the onset of voiding. Simulations of remodeling in response to the tenfold increase in outlet resistance arising from BOO, predict an initial loss of voiding capacity. Subsequent smooth muscle cell (SMC) hypertrophy enables the bladder wall to generate sufficient active tension to restore voiding functionality. Consistent with the experimental observations, the model predicts: hypertrophy of SMC and enlargement of the bladder over realistic timescales; collagen remodeling to maintain its role as a protective sheath; and increased voiding duration with lower average flow rate. This integrative G&R modeling approach provides fundamental insight into the adaptation of the bladder’s structural-functional relationship in response to outlet obstruction

PANC Study (Pancreatitis: A National Cohort Study): national cohort study examining the first 30 days from presentation of acute pancreatitis in the UK

Abstract Background Acute pancreatitis is a common, yet complex, emergency surgical presentation. Multiple guidelines exist and management can vary significantly. The aim of this first UK, multicentre, prospective cohort study was to assess the variation in management of acute pancreatitis to guide resource planning and optimize treatment. Methods All patients aged greater than or equal to 18 years presenting with acute pancreatitis, as per the Atlanta criteria, from March to April 2021 were eligible for inclusion and followed up for 30 days. Anonymized data were uploaded to a secure electronic database in line with local governance approvals. Results A total of 113 hospitals contributed data on 2580 patients, with an equal sex distribution and a mean age of 57 years. The aetiology was gallstones in 50.6 per cent, with idiopathic the next most common (22.4 per cent). In addition to the 7.6 per cent with a diagnosis of chronic pancreatitis, 20.1 per cent of patients had a previous episode of acute pancreatitis. One in 20 patients were classed as having severe pancreatitis, as per the Atlanta criteria. The overall mortality rate was 2.3 per cent at 30 days, but rose to one in three in the severe group. Predictors of death included male sex, increased age, and frailty; previous acute pancreatitis and gallstones as aetiologies were protective. Smoking status and body mass index did not affect death. Conclusion Most patients presenting with acute pancreatitis have a mild, self-limiting disease. Rates of patients with idiopathic pancreatitis are high. Recurrent attacks of pancreatitis are common, but are likely to have reduced risk of death on subsequent admissions. </jats:sec

Mechanobiology of the arterial wall

No abstract available

An integrative approach to cerebrovascular disease healthcare: IT for cerebral aneurysms

No abstract available

A thick-walled fluid–solid-growth model of abdominal aortic aneurysm evolution: application to a patient-specific geometry

We propose a novel thick-walled fluid–solid-growth (FSG) computational framework for modeling vascular disease evolution. The arterial wall is modeled as a thick-walled nonlinearly elastic cylindrical tube consisting of two layers corresponding to the media-intima and adventitia, where each layer is treated as a fiber-reinforced material with the fibers corresponding to the collagenous component. Blood is modeled as a Newtonian fluid with constant density and viscosity; no slip and no-flux conditions are applied at the arterial wall. Disease progression is simulated by growth and remodeling (G&amp;R) of the load bearing constituents of the wall. Adaptions of the natural reference configurations and mass densities of constituents are driven by deviations of mechanical stimuli from homeostatic levels. We apply the novel framework to model abdominal aortic aneurysm (AAA) evolution. Elastin degradation is initially prescribed to create a perturbation to the geometry which results in a local decrease in wall shear stress (WSS). Subsequent degradation of elastin is driven by low WSS and an aneurysm evolves as the elastin degrades and the collagen adapts. The influence of transmural G&amp;R of constituents on the aneurysm development is analyzed. We observe that elastin and collagen strains evolve to be transmurally heterogeneous and this may facilitate the development of tortuosity. This multiphysics framework provides the basis for exploring the influence of transmural metabolic activity on the progression of vascular disease

Transitional flow in aneurysms and the computation of haemodynamic parameters

Haemodynamic forces appear to play an influential role in the evolution of aneurysms. This has led to numerous studies, usually based on computational fluid dynamics. Their focus is predominantly on the wall shear stress (WSS) and associated derived parameters, attempting to find correlations between particular patterns of haemodynamic indices and regions subjected to disease formation and progression. The indices are generally determined by integration of flow properties over a single cardiac cycle. In this study, we illustrate that in some cases the transitional flow in aneurysms can lead to significantly different WSS distributions in consecutive cardiac cycles. Accurate determination of time-averaged haemodynamic indices may thus require simulation of a large number of cycles, which contrasts with the common approach to determine parameters using data from a single cycle. To demonstrate the role of transitional flow, two exemplary cases are considered: flow in an abdominal aortic aneurysm and in an intracranial aneurysm. The key differences that are observed between these cases are explained in terms of the integral timescale of the transitional flows in comparison with the cardiac cycle duration: for relatively small geometries, transients will decay before the next cardiac cycle. In larger geometries, transients are still present when the systolic phase produces new instabilities. These residual fluctuations serve as random initial conditions and thus seed different flow patterns in each cycle. To judge whether statistics are converged, the derived indices from at least two successive cardiac cycles should be compared

Coupling the Haemodynamic Environment to the Evolution of Cerebral Aneurysms

Cerebral aneurysms are thought to be present in 2–5% of the general population. Most aneurysms remain asymptomatic and of those that are detected, the risk of rupture is relatively low, i.e. 0.1–1% per year. However, very high morbidity and mortality rates are associated with an aneurysm that does rupture (30–50%). Consequently, elective repair of an aneurysm at high risk of rupture may be deemed appropriate. Unfortunately, interventional procedures are themselves not without risk and have morbidity rates of up to 6%. Moreover, it is difficult to quantify the risk of rupture on a patient specific basis: more sophisticated diagnostic criteria are required. Computational models of aneurysm evolution aim to improve the understanding of the aetiology of the disease. The ultimate aim is to predict future evolution and rupture