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Fulltext Pulsatile operation of a continuous-flow right ventricular assist device (RVAD) to improve vascular pulsatility

Ng BC, Kleinheyer M, Smith PA, Timms D, Cohn WE, Lim E

PLoS One, 2018;13(4):e0195975.
PMID: 29677212 DOI: 10.1371/journal.pone.0195975

Despite the widespread acceptance of rotary blood pump (RBP) in clinical use over the past decades, the diminished flow pulsatility generated by a fixed speed RBP has been regarded as a potential factor that may lead to adverse events such as vasculature stiffening and hemorrhagic strokes. In this study, we investigate the feasibility of generating physiological pulse pressure in the pulmonary circulation by modulating the speed of a right ventricular assist device (RVAD) in a mock circulation loop. A rectangular pulse profile with predetermined pulse width has been implemented as the pump speed pattern with two different phase shifts (0% and 50%) with respect to the ventricular contraction. In addition, the performance of the speed modulation strategy has been assessed under different cardiovascular states, including variation in ventricular contractility and pulmonary arterial compliance. Our results indicated that the proposed pulse profile with optimised parameters (Apulse = 10000 rpm and ωmin = 3000 rpm) was able to generate pulmonary arterial pulse pressure within the physiological range (9-15 mmHg) while avoiding undesirable pump backflow under both co- and counter-pulsation modes. As compared to co-pulsation, stroke work was reduced by over 44% under counter-pulsation, suggesting that mechanical workload of the right ventricle can be efficiently mitigated through counter-pulsing the pump speed. Furthermore, our results showed that improved ventricular contractility could potentially lead to higher risk of ventricular suction and pump backflow, while stiffening of the pulmonary artery resulted in increased pulse pressure. In conclusion, the proposed speed modulation strategy produces pulsatile hemodynamics, which is more physiologic than continuous blood flow. The findings also provide valuable insight into the interaction between RVAD speed modulation and the pulmonary circulation under various cardiovascular states.
Assessing regional left ventricular thickening dysfunction and dyssynchrony via personalized modeling and 3D wall thickness measurements for acute myocardial infarction

Khalid A, Lim E, Chan BT, Abdul Aziz YF, Chee KH, Yap HJ, et al.

J Magn Reson Imaging, 2019 04;49(4):1006-1019.
PMID: 30211445 DOI: 10.1002/jmri.26302

BACKGROUND: Existing clinical diagnostic and assessment methods could be improved to facilitate early detection and treatment of cardiac dysfunction associated with acute myocardial infarction (AMI) to reduce morbidity and mortality.
PURPOSE: To develop 3D personalized left ventricular (LV) models and thickening assessment framework for assessing regional wall thickening dysfunction and dyssynchrony in AMI patients.
STUDY TYPE: Retrospective study, diagnostic accuracy.
SUBJECTS: Forty-four subjects consisting of 15 healthy subjects and 29 AMI patients.
FIELD STRENGTH/SEQUENCE: 1.5T/steady-state free precession cine MRI scans; LGE MRI scans.
ASSESSMENT: Quantitative thickening measurements across all cardiac phases were correlated and validated against clinical evaluation of infarct transmurality by an experienced cardiac radiologist based on the American Heart Association (AHA) 17-segment model.
STATISTICAL TEST: Nonparametric 2-k related sample-based Kruskal-Wallis test; Mann-Whitney U-test; Pearson's correlation coefficient.
RESULTS: Healthy LV wall segments undergo significant wall thickening (P 50% transmurality) underwent remarkable wall thinning during contraction (thickening index [TI] = 1.46 ± 0.26 mm) as opposed to healthy myocardium (TI = 4.01 ± 1.04 mm). For AMI patients, LV that showed signs of thinning were found to be associated with a significantly higher percentage of dyssynchrony as compared with healthy subjects (dyssynchrony index [DI] = 15.0 ± 5.0% vs. 7.5 ± 2.0%, P
The study of border zone formation in ischemic heart using electro-chemical coupled computational model

Wan Ab Naim WN, Mokhtarudin MJM, Lim E, Chan BT, Ahmad Bakir A, Nik Mohamed NA

Int J Numer Method Biomed Eng, 2020 11;36(11):e3398.
PMID: 32857480 DOI: 10.1002/cnm.3398

Myocardial infarction (MI) is the most common cause of a heart failure, which occurs due to myocardial ischemia leading to left ventricular (LV) remodeling. LV remodeling particularly occurs at the ischemic area and the region surrounds it, known as the border zone. The role of the border zone in initiating LV remodeling process urges the investigation on the correlation between early border zone changes and remodeling outcome. Thus, this study aims to simulate a preliminary conceptual work of the border zone formation and evolution during onset of MI and its effect towards early LV remodeling processes by incorporating the oxygen concentration effect on the electrophysiology of an idealized three-dimensional LV through electro-chemical coupled mathematical model. The simulation result shows that the region of border zone, represented by the distribution of electrical conductivities, keeps expanding over time. Based on this result, the border zone is also proposed to consist of three sub-regions, namely mildly, moderately, and seriously impaired conductivity regions, which each region categorized depending on its electrical conductivities. This division could be used as a biomarker for classification of reversible and irreversible myocardial injury and will help to identify the different risks for the survival of patient. Larger ischemic size and complete occlusion of the coronary artery can be associated with an increased risk of developing irreversible injury, in particular if the reperfusion treatment is delayed. Increased irreversible injury area can be related with cardiovascular events and will further deteriorate the LV function over time.
Fulltext An integrated fluid-structure interaction and thrombosis model for type B aortic dissection

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.
Effect of intimal flap motion on flow in acute type B aortic dissection by using fluid-structure interaction

Chong MY, Gu B, Chan BT, Ong ZC, Xu XY, Lim E

Int J Numer Method Biomed Eng, 2020 12;36(12):e3399.
PMID: 32862487 DOI: 10.1002/cnm.3399

A monolithic, fully coupled fluid-structure interaction (FSI) computational framework was developed to account for dissection flap motion in acute type B aortic dissection (TBAD). Analysis of results included wall deformation, pressure, flow, wall shear stress (WSS), von Mises stress and comparison of hemodynamics between rigid wall and FSI models. Our FSI model mimicked realistic wall deformation that resulted in maximum compression of the distal true lumen (TL) by 21.4%. The substantial movement of intimal flap mostly affected flow conditions in the false lumen (FL). Flap motion facilitated more flow entering the FL at peak systole, with the TL to FL flow split changing from 88:12 in the rigid model to 83:17 in the FSI model. There was more disturbed flow in the FL during systole (5.8% FSI vs 5.2% rigid) and diastole (13.5% FSI vs 9.8% rigid), via a λ2 -criterion. The flap-induced disturbed flow near the tears in the FSI model caused an increase of local WSS by up to 70.0% during diastole. This resulted in a significant reduction in the size of low time-averaged WSS (TAWSS) regions in the FL (113.11 cm2 FSI vs 177.44 cm2 rigid). Moreover, the FSI model predicted lower systolic pressure, higher diastolic pressure, and hence lower pulse pressure. Our results provided new insights into the possible impact of flap motion on flow in aortic dissections, which are particularly important when evaluating hemodynamics of acute TBAD. NOVELTY STATEMENT: Our monolithic fully coupled FSI computational framework is able to reproduce experimentally measured range of flap deformation in aortic dissection, thereby providing novel insights into the influence of physiological flap motion on the flow and pressure distributions. The drastic flap movement increases the flow resistance in the true lumen and causes more disturbed flow in the false lumen, as visualized through the λ2 criterion. The flap-induced luminal pressure is dampened, thereby affecting pressure measures, which may serve as potential prognostic indicators for late complications in acute uncomplicated TBAD patients.
Automatic localization of the left ventricular blood pool centroid in short axis cardiac cine MR images

Tan LK, Liew YM, Lim E, Abdul Aziz YF, Chee KH, McLaughlin RA

Med Biol Eng Comput, 2018 Jun;56(6):1053-1062.
PMID: 29147835 DOI: 10.1007/s11517-017-1750-7

In this paper, we develop and validate an open source, fully automatic algorithm to localize the left ventricular (LV) blood pool centroid in short axis cardiac cine MR images, enabling follow-on automated LV segmentation algorithms. The algorithm comprises four steps: (i) quantify motion to determine an initial region of interest surrounding the heart, (ii) identify potential 2D objects of interest using an intensity-based segmentation, (iii) assess contraction/expansion, circularity, and proximity to lung tissue to score all objects of interest in terms of their likelihood of constituting part of the LV, and (iv) aggregate the objects into connected groups and construct the final LV blood pool volume and centroid. This algorithm was tested against 1140 datasets from the Kaggle Second Annual Data Science Bowl, as well as 45 datasets from the STACOM 2009 Cardiac MR Left Ventricle Segmentation Challenge. Correct LV localization was confirmed in 97.3% of the datasets. The mean absolute error between the gold standard and localization centroids was 2.8 to 4.7 mm, or 12 to 22% of the average endocardial radius. Graphical abstract Fully automated localization of the left ventricular blood pool in short axis cardiac cine MR images.
Fully automated segmentation of the left ventricle in cine cardiac MRI using neural network regression

Tan LK, McLaughlin RA, Lim E, Abdul Aziz YF, Liew YM

J Magn Reson Imaging, 2018 07;48(1):140-152.
PMID: 29316024 DOI: 10.1002/jmri.25932

BACKGROUND: Left ventricle (LV) structure and functions are the primary assessment performed in most clinical cardiac MRI protocols. Fully automated LV segmentation might improve the efficiency and reproducibility of clinical assessment.
PURPOSE: To develop and validate a fully automated neural network regression-based algorithm for segmentation of the LV in cardiac MRI, with full coverage from apex to base across all cardiac phases, utilizing both short axis (SA) and long axis (LA) scans.
STUDY TYPE: Cross-sectional survey; diagnostic accuracy.
SUBJECTS: In all, 200 subjects with coronary artery diseases and regional wall motion abnormalities from the public 2011 Left Ventricle Segmentation Challenge (LVSC) database; 1140 subjects with a mix of normal and abnormal cardiac functions from the public Kaggle Second Annual Data Science Bowl database.
FIELD STRENGTH/SEQUENCE: 1.5T, steady-state free precession.
ASSESSMENT: Reference standard data generated by experienced cardiac radiologists. Quantitative measurement and comparison via Jaccard and Dice index, modified Hausdorff distance (MHD), and blood volume.
STATISTICAL TESTS: Paired t-tests compared to previous work.
RESULTS: Tested against the LVSC database, we obtained 0.77 ± 0.11 (Jaccard index) and 1.33 ± 0.71 mm (MHD), both metrics demonstrating statistically significant improvement (P < 0.001) compared to previous work. Tested against the Kaggle database, the signed difference in evaluated blood volume was +7.2 ± 13.0 mL and -19.8 ± 18.8 mL for the end-systolic (ES) and end-diastolic (ED) phases, respectively, with a statistically significant improvement (P < 0.001) for the ED phase.
DATA CONCLUSION: A fully automated LV segmentation algorithm was developed and validated against a diverse set of cardiac cine MRI data sourced from multiple imaging centers and scanner types. The strong performance overall is suggestive of practical clinical utility.
LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.
Continuous positive airway pressure (CPAP) for apnoea of prematurity

Ho JJ, Zakarija-Grkovic I, Lok JW, Lim E, Subramaniam P, Leong JJ

Cochrane Database Syst Rev, 2023 Jul 18;7(7):CD013660.
PMID: 37481707 DOI: 10.1002/14651858.CD013660.pub2

BACKGROUND: Apnoea of prematurity (AoP) is defined as a pause in breathing for 20 seconds or longer, or for less than 20 seconds when accompanied by bradycardia and hypoxaemia, in a preterm infant. An association between the severity of apnoea and neurodevelopmental delay has been reported. Continuous positive airway pressure (CPAP) is a form of non-invasive ventilatory assistance that has been shown to be relatively safe and effective in preventing and treating respiratory distress among preterm infants. It is less clear whether CPAP treatment is safe and effective in the prevention and treatment of AoP.
OBJECTIVES: 1. To assess the effects of CPAP on AoP in preterm infants (this may be compared to supportive care or mechanical ventilation). 2. To assess the effects of different CPAP delivery systems on AoP in preterm infants.
SEARCH METHODS: Searches were conducted in September 2022 in the following databases: Cochrane Library, MEDLINE, Embase, and CINAHL. We also searched clinical trial registries and the reference lists of studies selected for inclusion.
SELECTION CRITERIA: We included all randomised and quasi-randomised controlled trials (RCTs) in which researchers determined that CPAP was necessary for AoP in preterm infants (born before 37 weeks). Cross-over studies were also included, provided sufficient data were available for analysis.
DATA COLLECTION AND ANALYSIS: We used the standard methods of Cochrane and Cochrane Neonatal, including independent assessment of risk of bias and extraction of data by at least two review authors. Discrepancies were resolved by involvement of a third author. We used the GRADE approach to assess the certainty of evidence for the following outcomes: 1) failed CPAP; 2) apnoea; 3) adverse effects of CPAP.
MAIN RESULTS: We included four single-centre trials conducted in Malaysia, Spain, Germany, and North America, involving 138 infants with a mean/median gestation of 26 to 28 weeks. Two studies were parallel-group RCTs and two were cross-over trials. None of the studies compared CPAP with supportive care. All trials compared one form of CPAP with another. Two compared a variable flow device with ventilator CPAP, one compared two different variable flow devices, and one compared a variable flow device with bubble CPAP. Interventions were administered for periods ranging between six and 48 hours, with pressures between 4 and 6 cm H2O. We assessed all trials as having a high risk of bias for blinding of participants and personnel, and two studies for blinding of outcome assessors. We found a high risk of a carry-over effect in two studies where the washout period was not adequately described, and a high risk of bias in a study that appeared to use an analysis method not generally accepted for cross-over studies. Comparison 1. CPAP and supportive care compared to supportive care alone We did not identify any study for inclusion in this comparison. Comparison 2. CPAP delivered by different types of devices 2a. Variable flow compared to ventilator CPAP Two studies were included in this comparison. We are very uncertain whether there is any difference in the incidence of failed CPAP, defined as the need for mechanical ventilation (risk ratio (RR) 0.16, 95% confidence interval (CI) 0.01 to 2.90; 1 study, 26 participants; very low-certainty). We are very uncertain whether there is any difference in the frequency of apnoea events (mean difference (MD) per four-hour interval -0.10, 95% CI -1.30 to 1.10; 1 study, 26 participants; very low-certainty). We are uncertain whether there is any difference in adverse events. Neurodevelopmental outcomes were not reported. 2b. Variable flow compared to bubble CPAP We included one study in this comparison, but it did not report our pre-specified outcomes. 2c. Infant Flow variable flow CPAP compared to Medijet variable flow CPAP We are very uncertain whether there is any difference in the incidence of failed CPAP (RR 2.62, 95% CI 0.91 to 7.53; 1 study, 80 participants; very low-certainty). The frequency of apnoea was not reported, and we do not know whether there is any difference in adverse events. Neurodevelopmental outcomes were not reported. Comparison 3. CPAP compared to mechanical ventilation We did not identify any studies for inclusion in this comparison.
AUTHORS' CONCLUSIONS: Due to the limited available evidence, we are very uncertain whether any CPAP device is more effective than other forms of supportive care, other CPAP devices, or mechanical ventilation for the prevention and treatment of AoP. The devices used in these studies included two types of variable flow CPAP device: bubble CPAP and ventilator CPAP. For each comparison, data were only available from a single study. There are theoretical reasons why these devices might have different effects on AoP, therefore further trials are indicated.
Mindfulness-based therapy for smoking cessation and mental health: a randomised controlled trial

Hemanath S, Robinson F, Pang NTP, Lim EK, Ong SJ, Alyssa S, et al.

Med J Malaysia, 2023 May;78(3):336-343.
PMID: 37271843

INTRODUCTION: Effective smoking cessation programmes are essential for assisting smokers in quitting, indirectly lowering mortality and morbidity associated with smoking. Numerous studies have indicated positive outcomes when using mindfulness treatment (MT) to treat psychological or behavioural health issues. Although to date, no study has looked at the effectiveness of online MT for quitting smoking while addressing mental health, particularly among the Asian population. Therefore, this study compares the efficiency of online MT to traditional counselling therapy (CT) in aiding smoking cessation programmes while also addressing mental health.
MATERIALS AND METHODS: A randomised control study with a two-group, single-blind design and baseline evaluation was selected. Social media sites were used to advertise for participants, who were then admitted after meeting the requirements. Participants who met the eligibility requirements were randomly split into two groups. Each group received a total of three sessions of online therapy (MT or CT), once every two weeks, as well as one phone call per week as reinforcement. At the beginning and end of the intervention, participants completed questionnaires (1st week and 5th week). Generalized Estimating Equation (GEE) statistical analysis was used to analyse all the variables.
RESULTS: The MT group experienced a statistically significant decrease in cigarette consumption (β: -3.50, 95% Wald CI: - 4.62, -2.39) compared to the CT group over time. Furthermore, the MT group demonstrated significant improvements in their scores for the AAQ-2, anxiety, stress, depression and mindfulness compared to the CT group.
CONCLUSION: Online MT is more successful at assisting smokers in lowering their daily cigarette intake and supporting their mental health during the smoking cessation process. Further longitudinal comparisons of the effectiveness of online MT should be undertaken using online platforms in future studies.
Hemodynamic response to exercise and head-up tilt of patients implanted with a rotary blood pump: a computational modeling study

Lim E, Salamonsen RF, Mansouri M, Gaddum N, Mason DG, Timms DL, et al.

Artif Organs, 2015 Feb;39(2):E24-35.
PMID: 25345482 DOI: 10.1111/aor.12370

The present study investigates the response of implantable rotary blood pump (IRBP)-assisted patients to exercise and head-up tilt (HUT), as well as the effect of alterations in the model parameter values on this response, using validated numerical models. Furthermore, we comparatively evaluate the performance of a number of previously proposed physiologically responsive controllers, including constant speed, constant flow pulsatility index (PI), constant average pressure difference between the aorta and the left atrium, constant average differential pump pressure, constant ratio between mean pump flow and pump flow pulsatility (ratioP I or linear Starling-like control), as well as constant left atrial pressure ( P l a ¯ ) control, with regard to their ability to increase cardiac output during exercise while maintaining circulatory stability upon HUT. Although native cardiac output increases automatically during exercise, increasing pump speed was able to further improve total cardiac output and reduce elevated filling pressures. At the same time, reduced venous return associated with upright posture was not shown to induce left ventricular (LV) suction. Although P l a ¯ control outperformed other control modes in its ability to increase cardiac output during exercise, it caused a fall in the mean arterial pressure upon HUT, which may cause postural hypotension or patient discomfort. To the contrary, maintaining constant average pressure difference between the aorta and the left atrium demonstrated superior performance in both exercise and HUT scenarios. Due to their strong dependence on the pump operating point, PI and ratioPI control performed poorly during exercise and HUT. Our simulation results also highlighted the importance of the baroreflex mechanism in determining the response of the IRBP-assisted patients to exercise and postural changes, where desensitized reflex response attenuated the percentage increase in cardiac output during exercise and substantially reduced the arterial pressure upon HUT.
Fulltext Sensitivity analysis of left ventricle with dilated cardiomyopathy in fluid structure simulation

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.
Fulltext A cardiovascular mathematical model of graded head-up tilt

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.
Fulltext Numerical investigation of the effect of cannula placement on thrombosis

Ong C, Dokos S, Chan B, Lim E, Al Abed A, Bin Abu Osman NA, et al.

Theor Biol Med Model, 2013;10:35.
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.
A method for control of an implantable rotary blood pump for heart failure patients using noninvasive measurements

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.
Motion corrected LV quantification based on 3D modelling for improved functional assessment in cardiac MRI

Liew YM, McLaughlin RA, Chan BT, Abdul Aziz YF, Chee KH, Ung NM, et al.

Phys Med Biol, 2015 Apr 7;60(7):2715-33.
PMID: 25768708 DOI: 10.1088/0031-9155/60/7/2715

Cine MRI is a clinical reference standard for the quantitative assessment of cardiac function, but reproducibility is confounded by motion artefacts. We explore the feasibility of a motion corrected 3D left ventricle (LV) quantification method, incorporating multislice image registration into the 3D model reconstruction, to improve reproducibility of 3D LV functional quantification. Multi-breath-hold short-axis and radial long-axis images were acquired from 10 patients and 10 healthy subjects. The proposed framework reduced misalignment between slices to subpixel accuracy (2.88 to 1.21 mm), and improved interstudy reproducibility for 5 important clinical functional measures, i.e. end-diastolic volume, end-systolic volume, ejection fraction, myocardial mass and 3D-sphericity index, as reflected in a reduction in the sample size required to detect statistically significant cardiac changes: a reduction of 21-66%. Our investigation on the optimum registration parameters, including both cardiac time frames and number of long-axis (LA) slices, suggested that a single time frame is adequate for motion correction whereas integrating more LA slices can improve registration and model reconstruction accuracy for improved functional quantification especially on datasets with severe motion artefacts.
The study of myocardial ischemia-reperfusion treatment through computational modelling

Wan Ab Naim WN, Mohamed Mokhtarudin MJ, Chan BT, Lim E, Ahmad Bakir A, Nik Mohamed NA

J Theor Biol, 2021 01 21;509:110527.
PMID: 33096094 DOI: 10.1016/j.jtbi.2020.110527

Reperfusion of the blood flow to ischemic myocardium is the standard treatment for patients suffering myocardial infarction. However, the reperfusion itself can also induce myocardial injury, in which the actual mechanism and its risk factors remain unclear. This work aims to study the mechanism of ischemia-reperfusion treatment using a three-dimensional (3D) oxygen diffusion model. An electrical model is then coupled to an oxygen model to identify the possible region of myocardial damage. Our findings show that the value of oxygen exceeds its optimum (>1.0) at the ischemic area during early reperfusion period. This complication was exacerbated in a longer ischemic period. While a longer reperfusion time causes a continuous excessive oxygen supply to the ischemic area throughout the reperfusion time. This work also suggests the use of less than 0.8 of initial oxygen concentration in the reperfusion treatment to prevent undesired upsurge at the early reperfusion period and further myocardial injury. We also found the region at risk for myocardial injury is confined in the ischemic vicinity revealed by its electrical conductivity impairment. Although there is a risk that reperfusion leads to myocardial injury for excessive oxygen accumulation, the reperfusion treatment is helpful in reducing the infarct size.
Left ventricular flow propagation velocity measurement: Is it cast in stone?

Chan BT, Yeoh HK, Liew YM, Aziz YFA, Sridhar GS, Hamilton-Craig C, et al.

Med Biol Eng Comput, 2017 Oct;55(10):1883-1893.
PMID: 28321684 DOI: 10.1007/s11517-017-1639-5

This study aims to investigate the measurement of left ventricular flow propagation velocity, V p, using phase contrast magnetic resonance imaging and to assess the discrepancies resulting from inflow jet direction and individual left ventricular size. Three V p measuring techniques, namely non-adaptive (NA), adaptive positions (AP) and adaptive vectors (AV) method, were suggested and compared. We performed the comparison on nine healthy volunteers and nine post-infarct patients at four measurement positions, respectively, at one-third, one-half, two-thirds and the conventional 4 cm distances from the mitral valve leaflet into the left ventricle. We found that the V p measurement was affected by both the inflow jet direction and measurement positions. Both NA and AP methods overestimated V p, especially in dilated left ventricles, while the AV method showed the strongest correlation with the isovolumic relaxation myocardial strain rate (r = 0.53, p
Fulltext Preload-based Starling-like control of rotary blood pumps: An in-vitro evaluation

Mansouri M, Gregory SD, Salamonsen RF, Lovell NH, Stevens MC, Pauls JP, et al.

PLoS One, 2017;12(2):e0172393.
PMID: 28212401 DOI: 10.1371/journal.pone.0172393

Due to a shortage of donor hearts, rotary left ventricular assist devices (LVADs) are used to provide mechanical circulatory support. To address the preload insensitivity of the constant speed controller (CSC) used in conventional LVADs, we developed a preload-based Starling-like controller (SLC). The SLC emulates the Starling law of the heart to maintain mean pump flow ([Formula: see text]) with respect to mean left ventricular end diastolic pressure (PLVEDm) as the feedback signal. The SLC and CSC were compared using a mock circulation loop to assess their capacity to increase cardiac output during mild exercise while avoiding ventricular suction (marked by a negative PLVEDm) and maintaining circulatory stability during blood loss and severe reductions in left ventricular contractility (LVC). The root mean squared hemodynamic deviation (RMSHD) metric was used to assess the clinical acceptability of each controller based on pre-defined hemodynamic limits. We also compared the in-silico results from our previously published paper with our in-vitro outcomes. In the exercise simulation, the SLC increased [Formula: see text] by 37%, compared to only 17% with the CSC. During blood loss, the SLC maintained a better safety margin against left ventricular suction with PLVEDm of 2.7 mmHg compared to -0.1 mmHg for CSC. A transition to reduced LVC resulted in decreased mean arterial pressure (MAP) and [Formula: see text] with CSC, whilst the SLC maintained MAP and [Formula: see text]. The results were associated with a much lower RMSHD value with SLC (70.3%) compared to CSC (225.5%), demonstrating improved capacity of the SLC to compensate for the varying cardiac demand during profound circulatory changes. In-vitro and in-silico results demonstrated similar trends to the simulated changes in patient state however the magnitude of hemodynamic changes were different, thus justifying the progression to in-vitro evaluation.
Segmentation of left ventricle in late gadolinium enhanced MRI through 2D-4D registration for infarct localization in 3D patient-specific left ventricular model

Leong CO, Lim E, Tan LK, Abdul Aziz YF, Sridhar GS, Socrates D, et al.

Magn Reson Med, 2019 02;81(2):1385-1398.
PMID: 30230606 DOI: 10.1002/mrm.27486

PURPOSE: To evaluate a 2D-4D registration-cum-segmentation framework for the delineation of left ventricle (LV) in late gadolinium enhanced (LGE) MRI and for the localization of infarcts in patient-specific 3D LV models.
METHODS: A 3-step framework was proposed, consisting of: (1) 3D LV model reconstruction from motion-corrected 4D cine-MRI; (2) Registration of 2D LGE-MRI with 4D cine-MRI; (3) LV contour extraction from the intersection of LGE slices with the LV model. The framework was evaluated against cardiac MRI data from 27 patients scanned within 6 months after acute myocardial infarction. We compared the use of local Pearson's correlation (LPC) and normalized mutual information (NMI) as similarity measures for the registration. The use of 2 and 6 long-axis (LA) cine-MRI scans was also compared. The accuracy of the framework was evaluated using manual segmentation, and the interobserver variability of the scar volume derived from the segmented LV was determined using Bland-Altman analysis.
RESULTS: LPC outperformed NMI as a similarity measure for the proposed framework using 6 LA scans, with Hausdorrf distance (HD) of 1.19 ± 0.53 mm versus 1.51 ± 2.01 mm (endocardial) and 1.21 ± 0.48 mm versus 1.46 ± 1.78 mm (epicardial), respectively. Segmentation using 2 LA scans was comparable to 6 LA scans with a HD of 1.23 ± 0.70 mm (endocardial) and 1.25 ± 0.74 mm (epicardial). The framework yielded a lower interobserver variability in scar volumes compared with manual segmentation.
CONCLUSION: The framework showed high accuracy and robustness in delineating LV in LGE-MRI and allowed for bidirectional mapping of information between LGE- and cine-MRI scans, crucial in personalized model studies for treatment planning.
Adaptive template matching of photoplethysmogram pulses to detect motion artefact

Lim PK, Ng SC, Lovell NH, Yu YP, Tan MP, McCombie D, et al.

Physiol Meas, 2018 10 11;39(10):105005.
PMID: 30183675 DOI: 10.1088/1361-6579/aadf1e

OBJECTIVE: The photoplethysmography (PPG) signal, commonly used in the healthcare settings, is easily affected by movement artefact leading to errors in the extracted heart rate and SpO2 estimates. This study aims to develop an online artefact detection system based on adaptive (dynamic) template matching, suitable for continuous PPG monitoring during daily living activities or in the intensive care units (ICUs).
APPROACH: Several master templates are initially generated by applying principal component analysis to data obtained from the PhysioNet MIMIC II database. The master template is then updated with each incoming clean PPG pulse. The correlation coefficient is used to classify the PPG pulse into either good or bad quality categories. The performance of our algorithm was evaluated using data obtained from two different sources: (i) our own data collected from 19 healthy subjects using the wearable Sotera Visi Mobile system (Sotera Wireless Inc.) as they performed various movement types; and (ii) ICU data provided by the PhysioNet MIMIC II database. The developed algorithm was evaluated against a manually annotated 'gold standard' (GS).
MAIN RESULTS: Our algorithm achieved an overall accuracy of 91.5% ± 2.9%, with a sensitivity of 94.1% ± 2.7% and a specificity of 89.7% ± 5.1%, when tested on our own data. When applying the algorithm to data from the PhysioNet MIMIC II database, it achieved an accuracy of 98.0%, with a sensitivity and specificity of 99.0% and 96.1%, respectively.
SIGNIFICANCE: The proposed method is simple and robust against individual variations in the PPG characteristics, thus making it suitable for a diverse range of datasets. Integration of the proposed artefact detection technique into remote monitoring devices could enhance reliability of the PPG-derived physiological parameters.

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