
Wahbi K. El-Bouri- DPhil (PhD)
- Senior Lecturer at University of Liverpool
Wahbi K. El-Bouri
- DPhil (PhD)
- Senior Lecturer at University of Liverpool
Building vascular digital twins and virtual populations for in silico clinical trials
About
80
Publications
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Introduction
I joined the University of Liverpool and the Liverpool Centre for Cardiovascular Sciences in November 2020 as a Tenure Track Fellow.
I work at the intersection of in-silico modelling, data science, and cardiovascular physiological understanding. The aim of my research is to develop in-silico models, informed by patient data, to develop personalised predictions for patient outcomes, as well as to develop population level in-silico clinical trials for cardiovascular disease and its treatment.
Current institution
Additional affiliations
November 2020 - present
Education
October 2013 - August 2017
October 2008 - July 2012
Publications
Publications (80)
The microvasculature plays a crucial role in the perfusion of blood through cerebral tissue. Current models of the cerebral microvasculature are discrete, and hence only able to model the perfusion over small voxel sizes before becoming computationally prohibitive. Larger models are required to provide comparisons and validation against imaging dat...
The effect of the microvasculature on observed clinical parameters, such as cerebral blood flow, is poorly understood. This is partly due to the gap between the vessels that can be individually imaged in humans and the microvasculature, meaning that mathematical models are required to understand the role of the microvasculature. As a result, a mult...
The cerebral microvasculature plays a key role in the transport of blood and the delivery of nutrients to the cells that perform brain function. Although recent advances in experimental imaging techniques mean that its structure and function can be interrogated to very small length scales, allowing individual vessels to be mapped to a fraction of 1...
Background
Microcirculation is a decisive factor in tissue reperfusion inadequacy following myocardial infarction (MI). Nonetheless, experimental assessment of blood flow in microcirculation remains a bottleneck. We sought to model blood flow properties in coronary microcirculation at different time points after MI and to compare them with healthy...
Many ischaemic stroke patients who have a mechanical removal of their clot (thrombectomy) do not get reperfusion of tissue despite the thrombus being removed. One hypothesis for this ‘no-reperfusion’ phenomenon is micro-emboli fragmenting off the large clot during thrombectomy and occluding smaller blood vessels downstream of the clot location. Thi...
Background
Cardiac complications may occur in patients following ischemic stroke (stroke‐heart syndrome [SHS]). We investigated the mortality risk in patients with SHS and across the SHS manifestations.
Methods and Results
Data were sought from the VISTA (Virtual International Stroke Trials Archive), an international repository of clinical trials...
Clinical risk scores that predict outcomes in patients with atrial fibrillation (AF) have modest predictive value. Machine learning (ML) may achieve greater results when predicting adverse outcomes in patients with recently diagnosed AF. Several ML models were tested and compared with current clinical risk scores on a cohort of 26,183 patients (mea...
Background
Adverse cardiac events following ischaemic stroke (stroke-heart syndrome, SHS) pose a clinical challenge. We investigated the association between initial blood pressure at stroke presentation and the risk of SHS.
Methods
We utilised data from the Virtual International Stroke Trials Archive (VISTA). We defined SHS as the incidence of car...
Background
Early cardiovascular (CV) complications in patients following intracerebral haemorrhage (ICH) is poorly understood. Such incident CV complications could be part of the so-called stroke-heart-syndrome occurring following ICH (SHS-ICH). We investigated the incidence and outcomes of patients with SHS-ICH.
Methods
Data were sought from the...
Background
Early cardiovascular complications may occur in patients following ischaemic stroke (stroke-heart-syndrome, SHS). We investigated the risk of death in patients with SHS, and across the SHS manifestations.
Methods
Data were sought from the Virtual International Stroke Trials Archive (VISTA), an international repository of clinical trials...
Background
The patient clinical phenotypes at particularly high risk for early cardiac complications after a recent acute ischaemic stroke (AIS), that is, stroke-heart syndrome (SHS), remain poorly defined. We utilised hierarchical cluster analysis to identify specific phenotypic profiles associated with this risk.
Methods
We gathered data on pati...
BACKGROUND
The incidence and outcomes of early cardiac complications in patients with intracerebral hemorrhage (ICH) are poorly understood. These cardiac complications may be part of the so-called stroke-heart syndrome in patients with ICH. We investigated this issue in an individual patient data pooled analysis from an international repository of...
Malignant stroke can lead to a death rate as high as 80%. Although early interventions can improve patient outcomes, they also lead to side effects. Therefore, the early prediction of stroke outcomes is crucial for clinical strategies. Imaging markers such as brain swelling volume and midline shift have been critical predictors in various stroke sc...
Background
Enhanced detection of large vessel occlusion (LVO) through machine learning (ML) for acute ischemic stroke appears promising. This systematic review explored the capabilities of ML models compared with prehospital stroke scales for LVO prediction.
Methods and Results
Six bibliographic databases were searched from inception until October...
Background
Atrial fibrillation (AF) patients are characterized by a great clinical heterogeneity and complexity across the world. Usual classifications may not adequately characterize this population. Data-driven cluster analysis reveals different possible classifications of patients.
Purpose
To identify different clusters of AF patients who share...
PURPOSE. This study explored the relationship among microvascular parameters as delineated by optical coherence tomography angiography (OCTA) and retinal perfusion. Here, we introduce a versatile framework to examine the interplay between the retinal vascular structure and function by generating virtual vasculatures from central retinal vessels to...
This protocol describes the A-EYE Study and provides information about procedures for entering participants. Every care was taken in its drafting, but corrections or amendments may be necessary. These will be circulated to investigators in the Study. Problems relating to this Study should be referred, in the first instance, to the Chief Investigato...
Purpose
This study explores the relationship between microvascular parameters as delineated by optical coherence tomography angiography (OCTA) and retinal perfusion. We introduce a versatile framework to examine the interplay between the retinal vasculature structure and function, generating virtual vasculatures from central retinal vessels to macu...
Background
Atrial fibrillation is associated with important mortality included in patients with low or intermediate thromboembolic risk. Usual clinical risk scores are challenged in this specific population and predict only modestly mortality. Machine learning approach helps to identify new risk factors and outperform existing tools for the predict...
Aims:
Atrial fibrillation is associated with important mortality but the usual clinical risk factor based scores only modestly predict mortality. This study aimed to develop machine learning models for the prediction of death occurrence within the year following atrial fibrillation diagnosis and compare predictive ability against usual clinical ri...
Background:
Pulmonary embolism (PE) is a severe condition that causes significant mortality and morbidity. Due to its acute nature, scores have been developed to stratify patients at high risk of 30-day mortality. Here we develop a machine-learning based score to predict 30-day, 90-day, and 365-day mortality in PE patients.
Methods:
The Birmingh...
Background:
Patients with atrial fibrillation are characterized by great clinical heterogeneity and complexity. The usual classifications may not adequately characterize this population. Data-driven cluster analysis reveals different possible patient classifications.
Aims:
To identify different clusters of patients with atrial fibrillation who s...
Funding Acknowledgements
Type of funding sources: None.
Background
Atrial fibrillation (AF) is associated with important mortality. Dedicated clinical scores to predict mortality have been developed but perform modestly and are not specific for this population. Machine learning models are developing in the field of AF and may be able to outperform...
In this review, we provide a summary of the state-of-the-art in the in silico modelling of cerebral blood flow (CBF) and its application in in silico clinical trials. CBF plays a key role in the transport of nutrients, including oxygen and glucose, to brain cells, and the cerebral vasculature is a highly complex, multi-scale, dynamic system that ac...
Objective: Haemorrhagic transformation (HT) is one of the most common complications after ischaemic stroke. HT can be the result of stroke progression or a complication of reperfusion treatment for stroke. The aim of this study is to apply a previously proposed HT mathematical model within a computational whole brain model to determine the factors...
Treating retinal diseases to prevent sight loss is an increasingly important challenge. Thanks to the configuration of the eye, the retina can be examined relatively easily in situ. Owing to recent technological development in scanning devices, much progress has been made in understanding the structure of the retina and characterising retinal bioma...
Catheter ablation (CA) is a well-established treatment of atrial fibrillation (AF). Data-driven cluster analysis is able to better distinguish prognostically-relevant phenotype clusters among patients with AF. We performed a hierarchical cluster analysis in a cohort of AF patients undergoing a first CA and evaluate associations between identified c...
Background
Atrial fibrillation (AF) negatively impacts health systems worldwide. We aimed to capture perceptions of and barriers and facilitators for AF care in Brazilian primary care units (PCUs) from the perspective of healthcare professionals (HCPs).
Methods
This mixed-methods, cross-sectional study utilised an exploratory sequential design, be...
Background
Targeting ischemic strokes patients at risk of incident atrial fibrillation (AF) for prolonged cardiac monitoring and oral anticoagulation remains a challenge. Clinical risk scores have been developed to predict post-stroke AF with suboptimal performances. Machine learning (ML) models are developing in the field of AF prediction and may...
Background
Most epidemiological studies into venous thromboembolism (VTE) are based on the white Caucasian population and unrepresentative of VTE outcomes in non-white ethnicities.
Purpose
Our VTE registry aims to get an insight into the outcomes of VTE patients as applicable to a developed world population with a multi-ethnic background. This wil...
Background:
The association between ideal cardiovascular health (ICVH) status and atrial fibrillation or flutter (AFF) diagnosis has been less studied compared to other cardiovascular diseases.
Objective:
To analyze the association between AFF diagnosis and ICVH metrics and scores in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)...
Background
Atrial fibrillation (AF) is the most common cardiac arrhythmia that affects 60 million people worldwide. Limited evidence on AF management exists from low- and middle-income countries and none from Sri Lanka. We aimed to investigate the existing AF care pathway and patients’ perception on AF management to identify barriers and enablers f...
Defects in the oxygen supply to the retina are a common cause of several retinal diseases. The inner retinal vasculature can be imaged noninvasively and numerous quantitative vascular biomarkers have been suggested for certain diseases. However, the links between vascular alterations and the development of pathologies are not yet clear. We propose...
The cerebral microcirculation plays a key role in the transport of oxygen to cerebral tissue; its impairment is also known to be implicated in several cerebral diseases. However, modelling it in humans is highly challenging due to the difficulties encountered in imaging at these length scales. We present here our work on modelling the cerebral micr...
Background:
Cerebral blood flow is known to decline with increasing age and is a potential biomarker to distinguish between healthy and unhealthy ageing, where healthy ageing is defined as an absence of comorbidities in senescence. This review aims to synthesize evidence of cerebral blood flow changes over multiple brain regions, for use as a clin...
Objective Haemorrhagic transformation (HT) is one of the most common complications after ischaemic stroke caused by damage to the blood–brain barrier (BBB) that could be the result of stroke progression or a complication of stroke treatment with reperfusion therapy. The aim of this study is to develop further a previous simple HT mathematical model...
To test the hypothesis that pulsing of intracranial pressure has an association with cognition, we measured cognitive score and pulsing of the tympanic membrane in 290 healthy subjects. This hypothesis was formed on the assumptions that large intracranial pressure pulses impair cognitive performance and tympanic membrane pulses reflect intracranial...
The Birmingham Black Country Venous Thromboembolism registry (BBC-VTE) is a multi-ethnic cohort of patients who suffered a first episode of venous thromboembolism (VTE) and were admitted to various hospital sites across the West Midlands and Black Country regions in the United Kingdom. The BBC-VTE registry is a retrospective, observational cohort s...
Background
Venous thromboembolism (VTE) is a condition which causes significant morbidity and mortality in hospitalised patients as well as in the community. These are related to adverse outcomes associated with the first incidence of VTE, such as recurrence, major haemorrhage and mortality. These outcomes are difficult to measure and compare among...
Introduction
Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is one of the main causes of preventable death in hospitals in the UK. Current clinical risk scores to predict mortality of patients with VTE are the pulmonary embolism severity index (PESI) and the simplified PESI (sPESI) which have similar...
Ageing causes extensive structural changes to the human cerebral microvasculature, which have a significant effect on capillary bed perfusion and oxygen transport. Current models of brain capillary networks in the literature focus on healthy adult brains and do not capture the effects of ageing, which is critical when studying neurodegenerative dis...
Thrombectomy, the mechanical removal of a clot, is the most common way to treat ischaemic stroke with large vessel occlusions. However, perfusion cannot always be restored after such an intervention. It has been hypothesised that the absence of reperfusion is at least partially due to the clot fragments that block the downstream vessels. In this pa...
An in silico trial simulates a disease and its corresponding therapies on a cohort of virtual patients to support the development and evaluation of medical devices, drugs and treatment. in silico trials have the potential to refine, reduce cost, and partially replace current in vivo studies, namely clinical trials and animal testing. We present the...
Accurately predicting brain tissue perfusion and infarct volume after an acute ischaemic stroke requires the two-way coupling of perfusion models on multiple scales. We present a method for such two-way coupling of a one-dimensional arterial blood flow model and a three-dimensional tissue perfusion model. The two-way coupling occurs through the pia...
Computational physiological models are promising tools to enhance the design of clinical trials and to assist in decision making. Organ-scale haemodynamic models are gaining popularity to evaluate perfusion in a virtual environment both in healthy and diseased patients. Recently, the principles of verification, validation, and uncertainty quantific...
Computational physiological models are promising tools to enhance the design of clinical trials and to assist in decision making. Organ-scale haemodynamic models are gaining popularity to evaluate perfusion in a virtual environment both in healthy and diseased patients. Recently, the principles of verification, validation, and uncertainty quantific...
Thrombectomy, the mechanical removal of a clot, is the most common way to treat ischaemic stroke with large vessel occlusions. However, perfusion cannot always be restored after such an intervention. It has been hypothesised that the absence of reperfusion is due to the clot fragments that block the downstream vessels. In this paper, we present a n...
The advancement of ischaemic stroke treatment relies on resource-intensive experiments and clinical trials. In order to improve ischaemic stroke treatments, such as thrombolysis and thrombectomy, we target the development of computational tools for in silico trials which can partially replace these animal and human experiments with fast simulations...
An acute ischaemic stroke is due to the sudden blockage of an intracranial blood vessel by an embolized thrombus. In the context of setting up in silico trials for the treatment of acute ischaemic stroke, the effect of a stroke on perfusion and metabolism of brain tissue should be modelled to predict final infarcted brain tissue. This requires coup...
Many ischaemic stroke patients who have a mechanical removal of their clot (thrombectomy) do not get reperfusion of tissue despite the thrombus being removed. One hypothesis for this ‘no-reperfusion’ phenomenon is micro-emboli fragmenting off the large clot during thrombectomy and occluding smaller blood vessels downstream of the clot location. Thi...
Many ischaemic stroke patients who have a mechanical removal of their clot (thrombectomy) do not get reperfusion of tissue despite the thrombus being removed. One hypothesis for this ‘no-reperfusion’ phenomenon is micro-emboli fragmenting off the large clot during thrombectomy and occluding smaller blood vessels downstream of the clot location. Thi...
This work focuses on developing a statistically accurate multiscale, multi-compartment oxygen model of the entire human brain. Coupled with a blood flow model, this oxygen model will be used to predict hypoxia and tissue death post stroke.
The in-silico clinical trials for the treatment of acute ischemic stroke (INSIST) consortium is a multidisciplinary , multi-sectorial undertaking aiming to advance the understanding and treatment of ischemic stroke through computational simulations and clinical trials. The work presented here is a part of this project which aims to model oxygen tra...
Demonstrating the framework to develop full brain multi-scale models of blood flow and oxygen transport
Data S1. Supplemental Methods.
Table S1. Characteristics of the Participants in the Study. Table reproduced from Gkontra et al9 (Creative Commons license10)
Figure S1. Mirroring of the original image colour‐coded with light green (7 color scale). 2D slices along x,y and z directions of the 3D resulting mirrored image that con‐tains 8 copies of th...
Although previous studies have shown associations between patient symptoms/outcomes and the spontaneous tympanic membrane displacement (spTMD) pulse amplitude, the contribution of the underlying intracranial pressure (ICP) signal to the spTMD pulse remains largely unknown. We have assessed the relative contributions of ICP and arterial blood pressu...
Linking macro-scale voxel behaviour to the microvasculature using a multi-scale model
Objective:
Models of the cerebral microvasculature are required at many different scales in order to understand the effects of microvascular topology on CBF. There are, however, no data-driven models at the arteriolar/venular scale. In this paper, we develop a data-driven algorithm based on available data to generate statistically accurate penetra...
Homogenization theory is used to derive macro-scale models of the mass transport equation. Seven cases are considered depending on what combinations of advection, diffusion, and metabolism dominate on the large scale. The order of the Péclet and Damköhler numbers determines the form of the averaged mass transport equation. It is found that for oxyg...
This retrospective study analysed the diagnostic yield of single-site, two-site, and three-site anatomical surveillance cultures in a population of 4,769 patients at high risk for methicillin-resistant Staphylococcus aureus (MRSA) colonisation. Cultures of seven anatomical sites were used as the gold standard against which to measure the sensitivit...