Jack Lee

King's College London | KCL · Department of Biomedical Engineering

Diffusion MRI classically uses gradient fields that vary linearly in space to encode the diffusion of water molecules in the signal magnitude by tempering its intensity. In spin ensembles, a presumably equal number of particles move in positive and negative direction, resulting in approximately zero change in net phase. Hence, in classical diffusio...

Subclinical leaflet thrombosis (LT) may occur following surgical and transcatheter aortic valve replacement. Computed tomography (CT) has become an established imaging modality to diagnose subclinical LT following bioprosthetic aortic valve replacement. Even so, there is a limited (but growing) experience in utilising CT imaging for this indication...

Understanding the cardiac-coronary interaction is fundamental to developing treatment strategies for ischemic heart disease. We sought to examine the impact of afterload reduction following isosorbide dinitrate (ISDN) administration on LV properties and coronary hemodynamics to further our understanding of the cardiac-coronary interaction. Novel me...

Background: Myocardial ischemia occurs in pediatrics, as a result of both congenital and acquired heart diseases, and can lead to further adverse cardiac events if untreated. The aim of this work is to assess the feasibility of fully automated, high resolution, quantitative stress myocardial perfusion cardiac magnetic resonance (CMR) in a cohort of...

Solid tumour growth is often associated with the accumulation of mechanical stresses acting on the surrounding host tissue. Due to tissue nonlinearity, the shear modulus of the peri-tumoural region inherits a signature from the tumour expansion which depends on multiple factors, including the soft tissue constitutive behaviour and its stress/strain...

Aims Durability of transcatheter aortic valve implantation (TAVI) is key to its expansion. We sought to identify incidence of valve thrombosis and predictors of valve thrombosis in our single centre with associated coagulation testing pre-TAVI and post-TAVI. Methods and results This single-centre observational study comprised patients undergoing t...

Coronary artery disease (CAD) can adversely affect left ventricular (LV) performance during exercise by impairment of contractile function in the presence of increasing afterload. By performing invasive measures of LV pressure-volume and coronary pressure and flow during exercise, we sought to accurately measure this with comparison to the control...

Background Patients who improve following cardiac resynchronization therapy (CRT) have left ventricular (LV) remodeling and improved cardiac output (CO). Effects on the systemic circulation are unknown. Objective To explore the effects of CRT on aortic and pulmonary blood flow and systemic afterload. Methods At CRT implant patients underwent a no...

Introduction It is increasingly evident that atrial function is an important marker of cardiovascular health. Impaired global left atrial strain has been associated with risk of thromboembolic events, atrial fibrillation and heart failure. When performed at high spatial resolution, CINE MRI allows the estimation of regional atrial strains, which ma...

Dynamic contrast-enhanced quantitative first-pass perfusion using magnetic resonance imaging enables non-invasive objective assessment of myocardial ischemia without ionizing radiation. However, quantification of perfusion is challenging due to the non-linearity between the magnetic resonance signal intensity and contrast agent concentration. Furth...

Myocardial blood flow can be quantified from dynamic contrast-enhanced magnetic resonance (MR) images through the fitting of tracer-kinetic models to the observed imaging data. The use of multi-compartment exchange models is desirable as they are physiologically motivated and resolve directly for both blood flow and microvascular function. However,...

Background: Quantitative myocardial perfusion cardiac MRI can provide a fast and robust assessment of myocardial perfusion status for the noninvasive diagnosis of myocardial ischemia while being more objective than visual assessment. However, it currently has limited use in clinical practice due to the challenging postprocessing required, particul...

Background Low gradient severe aortic stenosis (LGAS) is associated with unfavourable outcomes when compared to high gradient aortic stenosis (HGAS), yet the contributing pathophysiology is poorly understood. Methods Symptomatic LGAS and HGAS patients undergoing trans-catheter aortic valve implantation (TAVI) underwent 3T stress perfusion cardiac...

The effect of intra-aortic balloon counterpulsation (IABC) varies, and it is unknown whether this is due to a heterogeneous coronary physiological response. This study aimed to characterise the coronary and left ventricular (LV) effects of IABC and define responders in terms of their invasive physiology. Twenty-seven patients (LVEF 31 ± 9%) underwe...

The quantification of myocardial perfusion MRI has the potential to provide a fast, automated and user-independent assessment of myocardial ischaemia. However, due to the relatively high noise level and low temporal resolution of the acquired data and the complexity of the tracer-kinetic models, the model fitting can yield unreliable parameter esti...

Purpose: Tracer-kinetic models can be used for the quantitative assessment of contrast-enhanced MRI data. However, the model-fitting can produce unreliable results due to the limited data acquired and the high noise levels. Such problems are especially prevalent in myocardial perfusion MRI leading to the compromise of constrained numerical deconvol...

Kinetic parameter values, such as myocardial perfusion, can be quantified from dynamic contrast enhanced (DCE-) magnetic resonance imaging (MRI) data using tracer-kinetic modelling. However, respiratory motion affects the accuracy of this process. Motion compensation of the image series is difficult due to the rapid local signal enhancement caused...

Figure S1. Validation of in vitro model of coronary circulation. Figure S2. Theoretical model derivation. Figure S3. Example clinical case demonstrating utility of mathematical correction model.

Goal: Non-invasive cardiac electrophysiology (EP) model personalisation has raised interest for instance in the scope of predicting EP cardiac resynchronization therapy (CRT) response. However, the restricted clinical applicability of current methods is due in particular to the limitation to simple situations and the important computational cost....

Introduction Myocardial scar and ischaemia frequently coexist in patients with ischaemic heart failure (IHF). In clinical practice, stress-perfusion (SP) is assessed visually together with late gadolinium enhancement (LGE) images, however the feasibility of simultaneous LGE and SP quantification has only been recently demonstrated (Villa, JCMR 2016...

Background Exertional angina and the response to nitrates have been recognised for over two centuries. This ischaemic cascade and the mechanistic relief by nitrates has not been extensively studied. The aim was to identify these precise haemodynamic changes. Methods In 31 patients with exertional angina and coronary artery disease, real-time simul...

Background Diffusion tensor imaging (DTI) is widely used to assess tissue microstructure non-invasively. Cardiac DTI enables inference of cell and sheetlet orientations, which are altered under pathological conditions. However, DTI is affected by many factors, therefore robust validation is critical. Existing histological validation is intrinsicall...

Myocardial stiffness is a valuable clinical biomarker for the monitoring and stratification of heart failure (HF). Cardiac finite element models provide a biomechanical framework for the assessment of stiffness through the determination of the myocardial constitutive model parameters. The reported parameter intercorrelations in popular constitutive...

In the scope of modelling cardiac electrophysiology (EP) for understanding pathologies and predicting the response to therapies, patient-specific model parameters need to be estimated. Although personalisation from non-invasive data (body surface potential mapping, BSPM) has been investigated on simple cases mostly with a single pacing site, there...

Modelling the cardiac electrophysiology (EP) can help understand pathologies and predict the response to therapies such as cardiac resynchronization. To this end, estimating patient-specific model parameters is crucial. In the case of patients with bundle branch blocks (BBB), part of the Purkinje system is often affected. The aim of this work is to...

Coronary wave intensity analysis (cWIA) is a diagnostic technique based on invasive measurement of coronary pressure and velocity waveforms. The theory of WIA allows the forward- and backward-propagating coronary waves to be separated and attributed to their origin and timing, thus serving as a sensitive and specific cardiac functional indicator. I...

Modelling cardiac electrophysiology (EP) can help understand pathologies and predict the response to therapies. Moreover, estimating patient-specific parameters of the EP model is crucial to obtain personalised information. The novelty of this paper is to use non-invasive data (body surface potential mapping, BSPM) in order to personalise the main...

Advances in medical imaging and image processing are paving the way for personalised cardiac biomechanical modelling. However, for clinical utility to be achieved, model-based analyses mandate robust model selection and parameterisation. In this paper we introduce a patient-specific biomechanical model for the left ventricle aiming to balance model...

Biomedical research, combining multi-modal image and geometry data, presents unique challenges for data visualization, processing, and quantitative analysis. Medical imaging provides rich information, from anatomical to deformation, but extracting this to a coherent picture across image modalities with preserved quality is not trivial. Addressing t...

Patient-specific modelling has emerged as a tool for studying heart function, demonstrating the potential to provide non-invasive estimates of tissue passive stiffness. However, reliable use of model-derived stiffness requires sufficient model accuracy and unique estimation of model parameters. In this paper we present personalised models of cardia...

Micro-computed tomography systems are widely used for high-resolution, non-destructive analysis of internal microvascular networks. When the scale of the targeted vessel approaches the imaging resolution limit, the level of noise becomes a limiting factor for accurate reconstruction. Denoising algorithms provided by vendors are often suboptimal for...

Objective: coronary wave intensity analysis (cWIA) has increasingly been applied in the clinical research setting to distinguish between the proximal and distal mechanical influences on coronary blood flow. Recently, a cWIA-derived clinical index demonstrated prognostic value in predicting functional recovery post-myocardial infarction. Nevertheles...

Supported by the wide range of medical data available, cardiac biomechanical modeling has exhibited sig- nificant potential in improving our understanding of the complex heart function and assisting in patient diagnosis and treatment. A critical step towards the development of accurate patient-specific models is the deployment of boundary condition...

The branching pattern of the coronary vasculature is a key determinant of its function and plays a crucial role in shaping the pressure and velocity waveforms measured for clinical diagnosis. However, although multiple scaling laws have been proposed to characterize the branching pattern, the implications they have on wave propagation remains unass...

Background A first-in-human study of simultaneous invasive real-time left ventricular (LV) and coronary haemodynamics in the cardiac catheter lab enabling accurate delineation of the complex cardiac-coronary interaction and influence of antianginal therapy in coronary artery disease (CAD). Method 15 patients completed the protocol (Figure;A&B). Cor...

Background Complex cardiac-coronary interaction has been debated. We developed novel technology (A) and software (B) to analyse real-time simultaneous LV and coronary haemodynamics with delineation of the interdependence during rest, exercise, ischaemia and ISDN in coronary artery disease (CAD). Methods 25 patients. Coronary measurements (pressure-...

From basic science to translation, modern biomedical research demands computational models which integrate several interacting physical systems. This paper describes the infrastructural framework for a generic multi- physics integration implemented in the software CHeart, a finite-element code for biomedical research. To generalize the coupling of...

With heart and cardiovascular diseases continually challenging healthcare systems worldwide, translating basic research on cardiac (patho)physiology into clinical care is essential. Exacerbating this already extensive challenge is the complexity of the heart, relying on its hierarchical structure and function to maintain car- diovascular flow. Comp...

From basic science to translation, modern biomedical research demands computational models which integrate several interacting physical systems. This paper describes the infrastructural framework for generic multiphysics integration implemented in the software CHeart, a finite-element code for biomedical research. To generalize the coupling of phys...

Microvascular ischemia is one of the hallmarks of hypertrophic cardiomyopathy (HCM) and has been associated with poor outcome. However, myocardial fibrosis, seen on cardiovascular magnetic resonance (CMR) as late gadolinium enhancement (LGE), can be responsible for rest perfusion defects in up to 30 % of patients with HCM, potentially leading to an...

Ischemic heart disease that comprises both coronary artery disease and microvascular disease is the single greatest cause of death globally. In this context, enhancing our understanding of the interaction of coronary structure and function is not only fundamental for advancing basic physiology but also crucial for identifying new targets for treati...

The importance of compression on coronary vessels is well known, but the isolated effect of isochoric tissue deformation has largely been ignored. In this study, we present results on the computational modelling of myocardial perfusion with a focus on the parameterisation of multiscale fluid domains, and the effect of strain on arterial resistance....

Particle skimming is a phenomenon where particles suspended in fluid flowing through vessels distribute disproportionately to bulk fluid volume at junctions. Microspheres are considered a gold standard of intra-organ perfusion measurements and are used widely in studies of flow distribution and quantification. It has previously been hypothesised th...

A scientific understanding of individual variation is key to personalized medicine, integrating genotypic and phenotypic information via computational physiology. Genetic effects are often context-dependent, differing between genetic backgrounds or physiological states such as disease. Here, we analyse in silico genotype-phenotype maps (GP map) for...

In this paper we outline our approach for creating subject-specific whole-cycle canine left-ventricular models, as part of the 2014 STACOM Challenge. Each canine heart was modeled using the principle of stationary potential energy, with the myocardium treated as a nearly incompressible hyperelastic material. Given incomplete data on the motion and...

To elucidate the mechanisms governing coronary blood flow in health and disease requires an understanding of the structure-function relationship of the coronary system, which exhibits distinct characteristics over multiple scales. Given the complexities arising from the multiscale and distributed nature of the coronary system and myocardial mechani...

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Background Coronary Wave Intensity Analysis (cWIA) is a technique capable of separating the effects of proximal arterial haemodynamics from cardiac mechanics. Studies have identified WIA-derived indices that are closely correlated with several disease processes and predictive of functional recovery following myocardial infarction. The cWIA clinical...

Coronary Wave Intensity Analysis (cWIA) is a technique capable of separating the effects of proximal arterial haemodynamics from cardiac mechanics. The cWIA ability to establish a mechanistic link between coronary haemodynamics measurements and the underlying pathophysiology has been widely demonstrated. Moreover, the prognostic value of a cWIA-der...

The Lagrange Multiplier (LM) and penalty methods are commonly used to enforce incompressibility and compressibility in models of cardiac mechanics. In this paper we show how both formulations may be equivalently thought of as a weakly penalized system derived from the statically condensed Perturbed Lagrangian formulation, which may be directly disc...

Transmural variations in the relationship between structural and fluid transport properties of myocardial capillary networks are determined via continuum modeling approaches using recent three-dimensional (3D) data on the microvascular structure. Specifically, the permeability tensor, which quantifies the inverse of the blood flow resistivity of th...

In this paper, we look at the acceleration of weakly coupled electromechanics using the graphics processing unit (GPU). Specifically, we port to the GPU a number of components of CHeart-a CPU-based finite element code developed for simulating multi-physics problems. On the basis of a criterion of computational cost, we implemented on the GPU the OD...

A method to extract myocardial coronary permeabilities appropriate to parameterise a continuum porous perfusion model using the underlying anatomical vascular network is developed. Canine and porcine whole-heart discrete arterial models were extracted from high-resolution cryomicrotome vessel image stacks. Five parameterisation methods were conside...

Coronary artery disease, CAD, is associated with both narrowing of the epicardial coronary arteries and microvascular disease, thereby limiting coronary flow and myocardial perfusion. CAD accounts for almost 2 million deaths within the European Union on an annual basis. In this paper, we review the physiological and pathophysiological processes und...