Advances in computational modelling for personalised medicine after myocardial infarction

Myocardial infarction (MI) is a leading cause of premature morbidity and mortality worldwide. Determining which patients will experience heart failure and sudden cardiac death after an acute MI is notoriously difficult for clinicians. The extent of heart damage after an acute MI is informed by cardiac imaging, typically using echocardiography or sometimes, cardiac magnetic resonance (CMR). These scans provide complex data sets that are only partially exploited by clinicians in daily practice, implying potential for improved risk assessment. Computational modelling of left ventricular (LV) function can bridge the gap towards personalised medicine using cardiac imaging in patients with post-MI. Several novel biomechanical parameters have theoretical prognostic value and may be useful to reflect the biomechanical effects of novel preventive therapy for adverse remodelling post-MI. These parameters include myocardial contractility (regional and global), stiffness and stress. Further, the parameters can be delineated spatially to correspond with infarct pathology and the remote zone. While these parameters hold promise, there are challenges for translating MI modelling into clinical practice, including model uncertainty, validation and verification, as well as time-efficient processing. More research is needed to (1) simplify imaging with CMR in patients with post-MI, while preserving diagnostic accuracy and patient tolerance (2) to assess and validate novel biomechanical parameters against established prognostic biomarkers, such as LV ejection fraction and infarct size. Accessible software packages with minimal user interaction are also needed. Translating benefits to patients will be achieved through a multidisciplinary approach including clinicians, mathematicians, statisticians and industry partners

Outflow boundary conditions for 3D simulations of non-periodic blood flow and pressure fields in deformable arteries

The simulation of blood flow and pressure in arteries requires outflow boundary conditions that incorporate models of downstream domains. We previously described a coupled multidomain method to couple analytical models of the downstream domains with 3D numerical models of the upstream vasculature. This prior work either included pure resistance boundary conditions or impedance boundary conditions based on assumed periodicity of the solution. However, flow and pressure in arteries are not necessarily periodic in time due to heart rate variability, respiration, complex transitional flow or acute physiological changes. We present herein an approach for prescribing lumped parameter outflow boundary conditions that accommodate transient phenomena. We have applied this method to compute haemodynamic quantities in different physiologically relevant cardiovascular models, including patient-specific examples, to study non-periodic flow phenomena often observed in normal subjects and in patients with acquired or congenital cardiovascular disease. The relevance of using boundary conditions that accommodate transient phenomena compared with boundary conditions that assume periodicity of the solution is discussed

Analyzing the human liver vascular architecture by combining vascular corrosion casting and micro-CT scanning: a feasibility study

Although a full understanding of the hepatic circulation is one of the keys to successfully perform liver surgery and to elucidate liver pathology, relatively little is known about the functional organization of the liver vasculature. Therefore, we materialized and visualized the human hepatic vasculature at different scales, and performed a morphological analysis by combining vascular corrosion casting with novel micro-computer tomography (CT) and image analysis techniques. A human liver vascular corrosion cast was obtained by simultaneous resin injection in the hepatic artery (HA) and portal vein (PV). A high resolution (110 mu m) micro-CT scan of the total cast allowed gathering detailed macrovascular data. Subsequently, a mesocirculation sample (starting at generation 5; 88 x 68 x 80 mm(3)) and a microcirculation sample (terminal vessels including sinusoids; 2.0 x 1.5 x 1.7 mm(3)) were dissected and imaged at a 71-mu m and 2.6-mu m resolution, respectively. Segmentations and 3D reconstructions allowed quantifying the macro- and mesoscale branching topology, and geometrical features of HA, PV and hepatic venous trees up to 13 generations (radii ranging from 13.2 mm to 80 mu m; lengths from 74.4 mm to 0.74 mm), as well as microvascular characteristics (mean sinusoidal radius of 6.63 mu m). Combining corrosion casting and micro-CT imaging allows quantifying the branching topology and geometrical features of hepatic trees using a multiscale approach from the macro- down to the microcirculation. This may lead to novel insights into liver circulation, such as internal blood flow distributions and anatomical consequences of pathologies (e.g. cirrhosis)

From homogeneous to fractal normal and tumorous microvascular networks in the brain

We studied normal and tumorous three-dimensional (3D) microvascular networks in primate and rat brain. Tissues were prepared following a new preparation technique intended for high-resolution synchrotron tomography of microvascular networks. The resulting 3D images with a spatial resolution of less than the minimum capillary diameter permit a complete description of the entire vascular network for volumes as large as tens of cubic millimeters. The structural properties of the vascular networks were investigated by several multiscale methods such as fractal and power- spectrum analysis. These investigations gave a new coherent picture of normal and pathological complex vascular structures. They showed that normal cortical vascular networks have scale- invariant fractal properties on a small scale from 1.4 lm up to 40 to 65 lm. Above this threshold, vascular networks can be considered as homogeneous. Tumor vascular networks show similar characteristics, but the validity range of the fractal regime extend to much larger spatial dimensions. These 3D results shed new light on previous two dimensional analyses giving for the first time a direct measurement of vascular modules associated with vessel-tissue surface exchange

Modelling mitral valvular dynamics–current trend and future directions

Dysfunction of mitral valve causes morbidity and premature mortality and remains a leading medical problem worldwide. Computational modelling aims to understand the biomechanics of human mitral valve and could lead to the development of new treatment, prevention and diagnosis of mitral valve diseases. Compared with the aortic valve, the mitral valve has been much less studied owing to its highly complex structure and strong interaction with the blood flow and the ventricles. However, the interest in mitral valve modelling is growing, and the sophistication level is increasing with the advanced development of computational technology and imaging tools. This review summarises the state-of-the-art modelling of the mitral valve, including static and dynamics models, models with fluid-structure interaction, and models with the left ventricle interaction. Challenges and future directions are also discussed

A Review of Mathematical Models for the Formation of\ud Vascular Networks

Mainly two mechanisms are involved in the formation of blood vasculature: vasculogenesis and angiogenesis. The former consists of the formation of a capillary-like network from either a dispersed or a monolayered population of endothelial cells, reproducible also in vitro by specific experimental assays. The latter consists of the sprouting of new vessels from an existing capillary or post-capillary venule. Similar phenomena are also involved in the formation of the lymphatic system through a process generally called lymphangiogenesis.\ud \ud A number of mathematical approaches have analysed these phenomena. This paper reviews the different modelling procedures, with a special emphasis on their ability to reproduce the biological system and to predict measured quantities which describe the overall processes. A comparison between the different methods is also made, highlighting their specific features