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  1. Guo T, Tsai D, Bai S, Morley JW, Suaning GJ, Lovell NH, et al.
    Crit Rev Biomed Eng, 2014;42(5):419-36.
    PMID: 25745804
    The vertebrate retina is a clearly organized signal-processing system. It contains more than 60 different types of neurons, arranged in three distinct neural layers. Each cell type is believed to serve unique role(s) in encoding visual information. While we now have a relatively good understanding of the constituent cell types in the retina and some general ideas of their connectivity, with few exceptions, how the retinal circuitry performs computation remains poorly understood. Computational modeling has been commonly used to study the retina from the single cell to the network level. In this article, we begin by reviewing retinal modeling strategies and existing models. We then discuss in detail the significance and limitations of these models, and finally, we provide suggestions for the future development of retinal neural modeling.
  2. Lim E, Dokos S, Salamonsen RF, Rosenfeldt FL, Ayre PJ, Lovell NH
    Artif Organs, 2012 May;36(5):E110-24.
    PMID: 22489799 DOI: 10.1111/j.1525-1594.2012.01449.x
    A heart-pump interaction model has been developed based on animal experimental measurements obtained with a rotary blood pump in situ. Five canine experiments were performed to investigate the interaction between the cardiovascular system and the implantable rotary blood pump over a wide range of operating conditions, including variations in cardiac contractility and heart rate, systemic vascular resistance (SVR), and total blood volume (V(total) ). It was observed in our experiments that SVR decreased with increasing mean pump speed under the healthy condition, but was relatively constant during the speed ramp study under reduced cardiac contractility conditions. Furthermore, we also found a significant increase in pulmonary vascular resistance with increasing mean pump speed and decreasing total blood volume, despite a relatively constant SVR. Least squares parameter estimation methods were utilized to fit a subset of model parameters in order to achieve better agreement with the experimental data and to evaluate the robustness and validity of the model under various operating conditions. The fitted model produced reasonable agreement with the experimental measurements, both in terms of mean values and steady-state waveforms. In addition, all the optimized parameters were within physiological limits.
  3. Lim E, Dokos S, Salamonsen RF, Rosenfeldt FL, Ayre PJ, Lovell NH
    Artif Organs, 2012 May;36(5):E125-37.
    PMID: 22489771 DOI: 10.1111/j.1525-1594.2012.01448.x
    Numerical models, able to simulate the response of the human cardiovascular system (CVS) in the presence of an implantable rotary blood pump (IRBP), have been widely used as a predictive tool to investigate the interaction between the CVS and the IRBP under various operating conditions. The present study investigates the effect of alterations in the model parameter values, that is, cardiac contractility, systemic vascular resistance, and total blood volume on the efficiency of rotary pump assistance, using an optimized dynamic heart-pump interaction model previously developed in our laboratory based on animal experimental measurements obtained from five canines. The effect of mean pump speed and the circulatory perturbations on left and right ventricular pressure volume loops, mean aortic pressure, mean cardiac output, pump assistance ratio, and pump flow pulsatility from both the greyhound experiments and model simulations are demonstrated. Furthermore, the applicability of some of the previously proposed control parameters, that is, pulsatility index (PI), gradient of PI with respect to pump speed, pump differential pressure, and aortic pressure are discussed based on our observations from experimental and simulation results. It was found that previously proposed control strategies were not able to perform well under highly varying circulatory conditions. Among these, control algorithms which rely on the left ventricular filling pressure appear to be the most robust as they emulate the Frank-Starling mechanism of the heart.
  4. Ong CW, Chan BT, Lim E, Abu Osman NA, Abed AA, Dokos S, et al.
    PMID: 23367368 DOI: 10.1109/EMBC.2012.6347433
    For patient's receiving mechanical circulatory support, malfunction of the left ventricular assist device (LVADs) as well as mal-positioning of the cannula imposes serious threats to their life. It is therefore important to characterize the flow pattern and pressure distribution within the ventricle in the presence of an LVAD. In this paper, we present a 2D axisymmetric fluid structure interaction model of the passive left ventricle (LV) incorporating an LVAD cannula to simulate the effect of the LVAD cannula placement on the vortex dynamics. Results showed that larger recirculation area was formed at the cannula tip with increasing cannula insertion depth, and this is believed to reduce the risk of thrombus formation. Furthermore, we also simulated suction events (collapse of the LV) by closing the inlet. Vortex patterns were significantly altered under this condition, and the greatest LV wall displacement was observed at the part of the myocardium closest to the cannula tip.
  5. Chan BT, Ong CW, Lim E, Abu Osman NA, Al Abed A, Lovell NH, et al.
    PMID: 23367367 DOI: 10.1109/EMBC.2012.6347432
    Dilated cardiomyopathy (DCM) is a common cardiac disease which leads to the deterioration in cardiac performance. A computational fluid dynamics (CFD) approach can be used to enhance our understanding of the disease, by providing us with a detailed map of the intraventricular flow and pressure distributions. In the present work, effect of ventricular size on the intraventricular flow dynamics and intraventricular pressure gradients (IVPGs) was studied using two different implementation methods, i.e. the geometry-prescribed and the fluid structure interaction (FSI) methods. Results showed that vortex strength and IVPGs are significantly reduced in a dilated heart, leading to an increased risk of thrombus formation and impaired ventricular filling. We suggest FSI method as the ultimate method in studying ventricular dysfunction as it provides additional cardiac disease prognostic factors and more realistic model implementation.
  6. Leong CN, Lim E, Andriyana A, Al Abed A, Lovell NH, Hayward C, et al.
    PMID: 27043925 DOI: 10.1002/cnm.2794
    Infarct extension, a process involving progressive extension of the infarct zone (IZ) into the normally perfused border zone (BZ), leads to continuous degradation of the myocardial function and adverse remodelling. Despite carrying a high risk of mortality, detailed understanding of the mechanisms leading to BZ hypoxia and infarct extension remains unexplored. In the present study, we developed a 3D truncated ellipsoidal left ventricular model incorporating realistic electromechanical properties and fibre orientation to examine the mechanical interaction among the remote, infarct and BZs in the presence of varying infarct transmural extent (TME). Localized highly abnormal systolic fibre stress was observed at the BZ, owing to the simultaneous presence of moderately increased stiffness and fibre strain at this region, caused by the mechanical tethering effect imposed by the overstretched IZ. Our simulations also demonstrated the greatest tethering effect and stress in BZ regions with fibre direction tangential to the BZ-remote zone boundary. This can be explained by the lower stiffness in the cross-fibre direction, which gave rise to a greater stretching of the IZ in this direction. The average fibre strain of the IZ, as well as the maximum stress in the sub-endocardial layer, increased steeply from 10% to 50% infarct TME, and slower thereafter. Based on our stress-strain loop analysis, we found impairment in the myocardial energy efficiency and elevated energy expenditure with increasing infarct TME, which we believe to place the BZ at further risk of hypoxia. Copyright © 2016 John Wiley & Sons, Ltd.
  7. Chong MY, Gu B, Armour CH, Dokos S, Ong ZC, Xu XY, et al.
    Biomech Model Mechanobiol, 2022 Feb;21(1):261-275.
    PMID: 35079931 DOI: 10.1007/s10237-021-01534-5
    False lumen thrombosis (FLT) in type B aortic dissection has been associated with the progression of dissection and treatment outcome. Existing computational models mostly assume rigid wall behavior which ignores the effect of flap motion on flow and thrombus formation within the FL. In this study, we have combined a fully coupled fluid-structure interaction (FSI) approach with a shear-driven thrombosis model described by a series of convection-diffusion reaction equations. The integrated FSI-thrombosis model has been applied to an idealized dissection geometry to investigate the interaction between vessel wall motion and growing thrombus. Our simulation results show that wall compliance and flap motion can influence the progression of FLT. The main difference between the rigid and FSI models is the continuous development of vortices near the tears caused by drastic flap motion up to 4.45 mm. Flap-induced high shear stress and shear rates around tears help to transport activated platelets further to the neighboring region, thus speeding up thrombus formation during the accelerated phase in the FSI models. Reducing flap mobility by increasing the Young's modulus of the flap slows down the thrombus growth. Compared to the rigid model, the predicted thrombus volume is 25% larger using the FSI-thrombosis model with a relatively mobile flap. Furthermore, our FSI-thrombosis model can capture the gradual effect of thrombus growth on the flow field, leading to flow obstruction in the FL, increased blood viscosity and reduced flap motion. This model is a step closer toward simulating realistic thrombus growth in aortic dissection, by taking into account the effect of intimal flap and vessel wall motion.
  8. Chan BT, Abu Osman NA, Lim E, Chee KH, Abdul Aziz YF, Abed AA, et al.
    PLoS One, 2013;8(6):e67097.
    PMID: 23825628 DOI: 10.1371/journal.pone.0067097
    Dilated cardiomyopathy (DCM) is the most common myocardial disease. It not only leads to systolic dysfunction but also diastolic deficiency. We sought to investigate the effect of idiopathic and ischemic DCM on the intraventricular fluid dynamics and myocardial wall mechanics using a 2D axisymmetrical fluid structure interaction model. In addition, we also studied the individual effect of parameters related to DCM, i.e. peak E-wave velocity, end systolic volume, wall compliance and sphericity index on several important fluid dynamics and myocardial wall mechanics variables during ventricular filling. Intraventricular fluid dynamics and myocardial wall deformation are significantly impaired under DCM conditions, being demonstrated by low vortex intensity, low flow propagation velocity, low intraventricular pressure difference (IVPD) and strain rates, and high-end diastolic pressure and wall stress. Our sensitivity analysis results showed that flow propagation velocity substantially decreases with an increase in wall stiffness, and is relatively independent of preload at low-peak E-wave velocity. Early IVPD is mainly affected by the rate of change of the early filling velocity and end systolic volume which changes the ventriculo:annular ratio. Regional strain rate, on the other hand, is significantly correlated with regional stiffness, and therefore forms a useful indicator for myocardial regional ischemia. The sensitivity analysis results enhance our understanding of the mechanisms leading to clinically observable changes in patients with DCM.
  9. Lim E, Chan GS, Dokos S, Ng SC, Latif LA, Vandenberghe S, et al.
    PLoS One, 2013;8(10):e77357.
    PMID: 24204817 DOI: 10.1371/journal.pone.0077357
    A lumped parameter model of the cardiovascular system has been developed and optimized using experimental data obtained from 13 healthy subjects during graded head-up tilt (HUT) from the supine position to [Formula: see text]. The model includes descriptions of the left and right heart, direct ventricular interaction through the septum and pericardium, the systemic and pulmonary circulations, nonlinear pressure volume relationship of the lower body compartment, arterial and cardiopulmonary baroreceptors, as well as autoregulatory mechanisms. A number of important features, including the separate effects of arterial and cardiopulmonary baroreflexes, and autoregulation in the lower body, as well as diastolic ventricular interaction through the pericardium have been included and tested for their significance. Furthermore, the individual effect of parameter associated with heart failure, including LV and RV contractility, baseline systemic vascular resistance, pulmonary vascular resistance, total blood volume, LV diastolic stiffness and reflex gain on HUT response have also been investigated. Our fitted model compares favorably with our experimental measurements and published literature at a range of tilt angles, in terms of both global and regional hemodynamic variables. Compared to the normal condition, a simulated congestive heart failure condition produced a blunted response to HUT with regards to the percentage changes in cardiac output, stroke volume, end diastolic volume and effector response (i.e., heart contractility, venous unstressed volume, systemic vascular resistance and heart rate) with progressive tilting.
  10. Ong C, Dokos S, Chan B, Lim E, Al Abed A, Bin Abu Osman NA, et al.
    PMID: 23680359 DOI: 10.1186/1742-4682-10-35
    Despite the rapid advancement of left ventricular assist devices (LVADs), adverse events leading to deaths have been frequently reported in patients implanted with LVADs, including bleeding, infection, thromboembolism, neurological dysfunction and hemolysis. Cannulation forms an important component with regards to thrombus formation in assisted patients by varying the intraventricular flow distribution in the left ventricle (LV). To investigate the correlation between LVAD cannula placement and potential for thrombus formation, detailed analysis of the intraventricular flow field was carried out in the present study using a two way fluid structure interaction (FSI), axisymmetric model of a passive LV incorporating an inflow cannula. Three different cannula placements were simulated, with device insertion near the LV apex, penetrating one-fourth and mid-way into the LV long axis. The risk of thrombus formation is assessed by analyzing the intraventricular vorticity distribution and its associated vortex intensity, amount of stagnation flow in the ventricle as well as the level of wall shear stress. Our results show that the one-fourth placement of the cannula into the LV achieves the best performance in reducing the risk of thrombus formation. Compared to cannula placement near the apex, higher vortex intensity is achieved at the one-fourth placement, thus increasing wash out of platelets at the ventricular wall. One-fourth LV penetration produced negligible stagnation flow region near the apical wall region, helping to reduce platelet deposition on the surface of the cannula and the ventricular wall.
  11. Lim E, Alomari AH, Savkin AV, Dokos S, Fraser JF, Timms DL, et al.
    Artif Organs, 2011 Aug;35(8):E174-80.
    PMID: 21843286 DOI: 10.1111/j.1525-1594.2011.01268.x
    We propose a deadbeat controller for the control of pulsatile pump flow (Q(p) ) in an implantable rotary blood pump (IRBP). Noninvasive measurements of pump speed and current are used as inputs to a dynamical model of Q(p) estimation, previously developed and verified in our laboratory. The controller was tested using a lumped parameter model of the cardiovascular system (CVS), in combination with the stable dynamical models of Q(p) and differential pressure (head) estimation for the IRBP. The control algorithm was tested with both constant and sinusoidal reference Q(p) as input to the CVS model. Results showed that the controller was able to track the reference input with minimal error in the presence of model uncertainty. Furthermore, Q(p) was shown to settle to the desired reference value within a finite number of sampling periods. Our results also indicated that counterpulsation yields the minimum left ventricular stroke work, left ventricular end diastolic volume, and aortic pulse pressure, without significantly affecting mean cardiac output and aortic pressure.
  12. Leong CN, Dokos S, Andriyana A, Liew YM, Chan BT, Abdul Aziz YF, et al.
    Int J Numer Method Biomed Eng, 2020 01;36(1):e3291.
    PMID: 31799767 DOI: 10.1002/cnm.3291
    Myocardial infarct extension, a process involving the enlargement of infarct and border zone, leads to progressive degeneration of left ventricular (LV) function and eventually gives rise to heart failure. Despite carrying a high risk, the causation of infarct extension is still a subject of much speculation. In this study, patient-specific LV models were developed to investigate the correlation between infarct extension and impaired regional mechanics. Subsequently, sensitivity analysis was performed to examine the causal factors responsible for the impaired regional mechanics observed in regions surrounding the infarct and border zone. From our simulations, fibre strain, fibre stress and fibre stress-strain loop (FSSL) were the key biomechanical variables affected in these regions. Among these variables, only FSSL was correlated with infarct extension, as reflected in its work density dissipation (WDD) index value, with high WDD indices recorded at regions with infarct extension. Impaired FSSL is caused by inadequate contraction force generation during the isovolumic contraction and ejection phases. Our further analysis revealed that the inadequacy in contraction force generation is not necessarily due to impaired myocardial intrinsic contractility, but at least in part, due to inadequate muscle fibre stretch at end-diastole, which depresses the ability of myocardium to generate adequate contraction force in the subsequent systole (according to the Frank-Starling law). Moreover, an excessively stiff infarct may cause its neighbouring myocardium to be understretched at end-diastole, subsequently depressing the systolic contractile force of the neighbouring myocardium, which was found to be correlated with infarct extension.
  13. Chan BT, Ahmad Bakir A, Al Abed A, Dokos S, Leong CN, Ooi EH, et al.
    Int J Numer Method Biomed Eng, 2019 06;35(6):e3204.
    PMID: 30912313 DOI: 10.1002/cnm.3204
    Flow energetics have been proposed as early indicators of progressive left ventricular (LV) functional impairment in patients with myocardial infarction (MI), but its correlation with individual MI parameters has not been fully explored. Using electro-fluid-structure interaction LV models, this study investigated the correlation between four MI parameters: infarct size, infarct multiplicity, regional enhancement of contractility at the viable myocardium area (RECVM), and LV mechanical dyssynchrony (LVMD) with intraventricular vortex and flow energetics. In LV with small infarcts, our results showed that infarct appearance amplified the energy dissipation index (DI), where substantial viscous energy loss was observed in areas with high flow velocity and near the infarct-vortex interface. The LV with small multiple infarcts and RECVM showed remarkable DI increment during systole and diastole. In correlation analysis, the systolic kinetic energy fluctuation index (E') was positively related to ejection fraction (EF) (R2  = 0.982) but negatively correlated with diastolic E' (R2  = 0.970). Diastolic E' was inversely correlated with vortex kinetic energy (R2  = 0.960) and vortex depth (R2  = 0.876). We showed an excessive systolic DI could differentiate infarcted LV with normal EF from healthy LV. Strong flow acceleration, LVMD, and vortex-infarct interactions were predominant factors that induced excessive DI in infarcted LVs. Instead of causing undesired flow turbulence, high systolic E' suggested the existence of energetic flow acceleration, while high diastolic E' implied an inefficient diastolic filling. Thus, systolic E' is not a suitable early indicator for progressive LV dysfunction in MI patients, while diastolic E' may be a useful index to indicate diastolic impairment in these patients.
  14. Leong CO, Leong CN, Liew YM, Al Abed A, Aziz YFA, Chee KH, et al.
    Int J Numer Method Biomed Eng, 2021 08;37(8):e3501.
    PMID: 34057819 DOI: 10.1002/cnm.3501
    Infarct extension involves necrosis of healthy myocardium in the border zone (BZ), progressively enlarging the infarct zone (IZ) and recruiting the remote zone (RZ) into the BZ, eventually leading to heart failure. The mechanisms underlying infarct extension remain unclear, but myocyte stretching has been suggested as the most likely cause. Using human patient-specific left-ventricular (LV) numerical simulations established from cardiac magnetic resonance imaging (MRI) of myocardial infarction (MI) patients, the correlation between infarct extension and regional mechanics abnormality was investigated by analysing the fibre stress-strain loops (FSSLs). FSSL abnormality was characterised using the directional regional external work (DREW) index, which measures FSSL area and loop direction. Sensitivity studies were also performed to investigate the effect of infarct stiffness on regional myocardial mechanics and potential for infarct extension. We found that infarct extension was correlated to severely abnormal FSSL in the form of counter-clockwise loop at the RZ close to the infarct, as indicated by negative DREW values. In regions demonstrating negative DREW values, we observed substantial fibre stretching in the isovolumic relaxation (IVR) phase accompanied by a reduced rate of systolic shortening. Such stretching in IVR phase in part of the RZ was due to its inability to withstand the high LV pressure that was still present and possibly caused by regional myocardial stiffness inhomogeneity. Further analysis revealed that the occurrence of severely abnormal FSSL due to IVR fibre stretching near the RZ-BZ boundary was due to a large amount of surrounding infarcted tissue, or an excessively stiff IZ.
  15. Martin DM, Bakir AA, Lin F, Francis-Taylor R, Alduraywish A, Bai S, et al.
    Brain Stimul, 2021 10 06;14(6):1489-1497.
    PMID: 34626843 DOI: 10.1016/j.brs.2021.09.014
    BACKGROUND: The electrode placement and pulse width for electroconvulsive therapy (ECT) are important treatment parameters associated with ECT related retrograde memory side-effects. Modification of these parameters with right unilateral (RUL) ECT may have utility for further reducing these side-effects.

    OBJECTIVE: This study explored use of the frontoparietal (FP) placement for reducing retrograde memory side effects with ECT. We hypothesised that superior retrograde memory outcomes would occur with FP compared to temporoparietal (TP) placement and with ultrabrief (UB: 0.3 ms) compared to brief pulse (BP: 1.0 ms) width ECT.

    METHODS: In this randomised cross-over, double-blinded study, participants received a single treatment of BP TP, BP FP, UB TP and UB FP ECT. Neuropsychological testing was conducted prior to and immediately following each treatment. Computational modelling was conducted to explore associations between E-fields in regions-of-interest associated with memory.

    RESULTS: Nine participants completed the study. The FP placement was not superior to TP for retrograde memory outcomes. For both electrode placements UB pulse width was associated with significantly better visual retrograde memory compared to BP (p 

  16. Ding CCA, Dokos S, Bakir AA, Zamberi NJ, Liew YM, Chan BT, et al.
    Biomed Eng Online, 2024 Feb 22;23(1):24.
    PMID: 38388416 DOI: 10.1186/s12938-024-01206-2
    Aortic stenosis, hypertension, and left ventricular hypertrophy often coexist in the elderly, causing a detrimental mismatch in coupling between the heart and vasculature known as ventricular-vascular (VA) coupling. Impaired left VA coupling, a critical aspect of cardiovascular dysfunction in aging and disease, poses significant challenges for optimal cardiovascular performance. This systematic review aims to assess the impact of simulating and studying this coupling through computational models. By conducting a comprehensive analysis of 34 relevant articles obtained from esteemed databases such as Web of Science, Scopus, and PubMed until July 14, 2022, we explore various modeling techniques and simulation approaches employed to unravel the complex mechanisms underlying this impairment. Our review highlights the essential role of computational models in providing detailed insights beyond clinical observations, enabling a deeper understanding of the cardiovascular system. By elucidating the existing models of the heart (3D, 2D, and 0D), cardiac valves, and blood vessels (3D, 1D, and 0D), as well as discussing mechanical boundary conditions, model parameterization and validation, coupling approaches, computer resources and diverse applications, we establish a comprehensive overview of the field. The descriptions as well as the pros and cons on the choices of different dimensionality in heart, valve, and circulation are provided. Crucially, we emphasize the significance of evaluating heart-vessel interaction in pathological conditions and propose future research directions, such as the development of fully coupled personalized multidimensional models, integration of deep learning techniques, and comprehensive assessment of confounding effects on biomarkers.
  17. Chan BT, Yeoh HK, Liew YM, Dokos S, Al Abed A, Chee KH, et al.
    Coron Artery Dis, 2018 06;29(4):316-324.
    PMID: 29261521 DOI: 10.1097/MCA.0000000000000596
    OBJECTIVE: This study investigated the intraventricular flow dynamics in ischaemic heart disease patients.

    PATIENTS AND METHODS: Fourteen patients with normal ejection fraction and 16 patients with reduced ejection fraction were compared with 20 healthy individuals. Phase-contrast MRI was used to assess intraventricular flow variables and speckle-tracking echocardiography to assess myocardial strain and left ventricular (LV) dyssynchrony. Infarct size was acquired using delayed-enhancement MRI.

    RESULTS: The results obtained showed no significant differences in intraventricular flow variables between the healthy group and the patients with normal ejection fraction group, whereas considerable reductions in kinetic energy (KE) fluctuation index, E' (P<0.001) and vortex KE (P=0.003) were found in the patients with reduced ejection fraction group. In multivariate analysis, only vortex KE and infarct size were significantly related to LV ejection fraction (P<0.001); furthermore, vortex KE was correlated negatively with energy dissipation, energy dissipation index (r=-0.44, P=0.021).

    CONCLUSION: This study highlights that flow energetic indices have limited applicability as early predictors of LV progressive dysfunction, whereas vortex KE could be an alternative to LV performance.

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