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  1. Oshkour AA, Abu Osman NA, Davoodi MM, Yau YH, Tarlochan F, Wan Abas WA, et al.
    Int J Numer Method Biomed Eng, 2013 Dec;29(12):1412-27.
    PMID: 23922316 DOI: 10.1002/cnm.2583
    This study focused on developing a 3D finite element model of functionally graded femoral prostheses to decrease stress shielding and to improve total hip replacement performance. The mechanical properties of the modeled functionally graded femoral prostheses were adjusted in the sagittal and transverse planes by changing the volume fraction gradient exponent. Prostheses with material changes in the sagittal and transverse planes were considered longitudinal and radial prostheses, respectively. The effects of cemented and noncemented implantation methods were also considered in this study. Strain energy and von Mises stresses were determined at the femoral proximal metaphysis and interfaces of the implanted femur components, respectively. Results demonstrated that the strain energy increased proportionally with increasing volume fraction gradient exponent, whereas the interface stresses decreased on the prostheses surfaces. A limited increase was also observed at the surfaces of the bone and cement. The periprosthetic femur with a noncemented prosthesis exhibited higher strain energy than with a cemented prosthesis. Radial prostheses implantation displayed more strain energy than longitudinal prostheses implantation in the femoral proximal part. Functionally graded materials also increased strain energy and exhibited promising potentials as substitutes of conventional materials to decrease stress shielding and to enhance total hip replacement lifespan.
  2. 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.
  3. Mokhtarudin MJ, Payne SJ
    PMID: 26991256 DOI: 10.1002/cnm.2784
    Brain oedema is thought to form and to clear through the use of water-protein channels, aquaporin-4 (AQP4), which are found in the astrocyte endfeet. The model developed here is used to study the function of AQP4 in the formation and elimination of oedema fluid in ischaemia-reperfusion injury. The cerebral space is assumed to be made of four fluid compartments: astrocyte, neuron, ECS and blood microvessels, and a solid matrix for the tissue, and this is modelled using multiple-network poroelastic theory. AQP4 allows the movement of water between astrocyte and the ECS and the microvessels. It is found that the presence of AQP4 may help in reducing vasogenic oedema shown by a decrease in brain tissue extracellular pressure. However, the astrocyte pressure will increase to compensate for this decrease, which may lead to cytotoxic oedema. In addition, the swelling will also depend on the ionic concentrations in the astrocyte and extracellular space, which may change after ischaemic stroke. Understanding the role of AQP4 in oedema may thus help the development of a treatment plan in reducing brain swelling after ischaemia-reperfusion.
  4. Alias MA, Buenzli PR
    Int J Numer Method Biomed Eng, 2020 01;36(1):e3279.
    PMID: 31724309 DOI: 10.1002/cnm.3279
    Most biological tissues grow by the synthesis of new material close to the tissue's interface, where spatial interactions can exert strong geometric influences on the local rate of growth. These geometric influences may be mechanistic or cell behavioural in nature. The control of geometry on tissue growth has been evidenced in many in vivo and in vitro experiments, including bone remodelling, wound healing, and tissue engineering scaffolds. In this paper, we propose a generalisation of a mathematical model that captures the mechanistic influence of curvature on the joint evolution of cell density and tissue shape during tissue growth. This generalisation allows us to simulate abrupt topological changes such as tissue fragmentation and tissue fusion, as well as three dimensional cases, through a level-set-based method. The level-set method developed introduces another Eulerian field than the level-set function. This additional field represents the surface density of tissue-synthesising cells, anticipated at future locations of the interface. Numerical tests performed with this level-set-based method show that numerical conservation of cells is a good indicator of simulation accuracy, particularly when cusps develop in the tissue's interface. We apply this new model to several situations of curvature-controlled tissue evolutions that include fragmentation and fusion.
  5. 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.
  6. 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.
  7. 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.
  8. Kwan Z, Khairu Najhan NN, Yau YH, Luximon Y, M Nor F
    Int J Numer Method Biomed Eng, 2020 11;36(11):e3390.
    PMID: 32735083 DOI: 10.1002/cnm.3390
    A realistic three-dimensional (3D) computational model of skin flap closures using Asian-like head templates from two different genders, male and female, has been developed. The current study aimed to understand the biomechanics of the local flap designs along with the effect of wound closures on the respective genders. Two Asian head templates from opposite genders were obtained to use as base models. A third-order Yeoh hyperelastic model was adapted to characterize as skin material properties. A single layer composed of combined epidermis and dermis was considered, and the models were thickened according to respective anatomical positions. Each model gender was excised with a fixed defect size which was consequently covered by three different local flap designs, namely advancement, rotation, and rhomboid flaps. Post-operative simulation presented various scenarios of skin flap closures. Rotation and rhomboid flaps demonstrated maximal tension at the apex of the flap for both genders as well as advancement flap in the female face model. However, advancement flap closure in the male face model was presented otherwise. Yet, the deformation patterns and the peak tension of the discussed flaps were consistent with conventional local flap surgery. Moreover, male face models generated higher stresses compared to the female face models with a 70.34% mean difference. Overall, the skin flap operations were executed manually, and the designed surgery model met the objectives successfully while acknowledging the study limitations. NOVELTY FILE: 3D head templates were considered to address the gap as 3D face models were uncommonly employed in understanding the biomechanics of the local flaps realistically. Most of the existing studies focus on the 2D and 3D planar geometry in their models. As gender comparison has yet to be addressed, we intended to fill this gap by exploring the stress contours of the local flap designs in different genders. Create a 3D face model from two opposite genders which is capable of simulating closure of wounds using local flaps with a focus on advancement, rotation, and rhomboid flaps.
  9. Cheong JKK, Ooi EH, Ooi ET
    Int J Numer Method Biomed Eng, 2020 09;36(9):e3374.
    PMID: 32519516 DOI: 10.1002/cnm.3374
    Recent studies have demonstrated the effectiveness of switching bipolar radiofrequency ablation (bRFA) in treating liver cancer. Nevertheless, the clinical use of the treatment remains less common than conventional monopolar RFA - likely due to the lack of understanding of how the tissues respond thermally to the switching effect. The problem is exacerbated by the numerous possible switching combinations when bRFA is performed using bipolar needles, thus making theoretical deduction and experimental studies difficult. This article addresses this issue via computational modelling by examining if significant variation in the treatment outcome exists amongst six different electrode configurations defined by the X-, C-, U-, N-, Z- and O-models. Results indicated that the tissue thermal and thermal damage responses varied depending on the electrode configuration and the operating conditions (input voltage and ablation duration). For a spherical tumour, 30 mm in diameter, complete ablation could not be attained in all configurations with 70 V input voltage and 5 minutes ablation duration. Increasing the input voltage to 90 V enlarged the coagulation zone in the X-model only. With the other configurations, extending the ablation duration to 10 minutes was found to be the better at enlarging the coagulation zone.
  10. 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.
  11. 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.
  12. Mustapha KB, Hawwa MA, Abakr YA
    Int J Numer Method Biomed Eng, 2022 Jan;38(1):e3531.
    PMID: 34536263 DOI: 10.1002/cnm.3531
    Research evidence abounds on the effectiveness of micropillar-based microelectromechanical systems for the detection of a wide variety of ultrasmall biological objects for clinical and non-clinical applications. However, the standard micropillar-based sensing platforms rely on a single-column micropillar with a spot at the tip for binding of objects. Although this long-standing form has shown immense potential, performance improvement is hindered by the fundamental limits enforced by physical laws. Moreover, the single-column micropillar has a lower sensing area and is ill-suited for a simultaneous differential sensing of chemical/biological objects of different mass. Here, we report a new set of nature-inspired, branched micropillar-based sensing resonators to address the highlighted issues. The characteristics of the newly proposed branched micropillars are comprehensively examined with three payloads (Bartonella Bacilliformis, Escherichia coli, and Micro magnetic beads). Anchored on the capability of continuum theoretical framework, the mathematical model of the micropillar is formulated through the synthesis of the modified couple stress, the Rayleigh-Love, and the Timoshenko theories. The finite element method is employed to shed light on the variability of the structures' resonant response under performance reduction factors (payload's rotary inertia, damaged substrate, and density of a surrounding fluid). The results obtained indicate superior performance indicators for the triply-branched micropillar: enhanced response sensitivity for multiple payloads and less susceptibility to deterioration in resonant frequencies due to fluid immersion.
  13. Wan Ab Naim WN, Ganesan PB, Sun Z, Lei J, Jansen S, Hashim SA, et al.
    Int J Numer Method Biomed Eng, 2018 05;34(5):e2961.
    PMID: 29331052 DOI: 10.1002/cnm.2961
    Endovascular stent graft repair has become a common treatment for complicated Stanford type B aortic dissection to restore true lumen flow and induce false lumen thrombosis. Using computational fluid dynamics, this study reports the differences in flow patterns and wall shear stress distribution in complicated Stanford type B aortic dissection patients after endovascular stent graft repair. Five patients were included in this study: 2 have more than 80% false lumen thrombosis (group 1), while 3 others had less than 80% false lumen thrombosis (group 2) within 1 year following endovascular repair. Group 1 patients had concentrated re-entry tears around the abdominal branches only, while group 2 patients had re-entry tears that spread along the dissection line. Blood flow inside the false lumen which affected thrombus formation increased with the number of re-entry tears and when only small amounts of blood that entered the false lumen exited through the branches. In those cases where dissection extended below the abdominal branches (group 2), patients with fewer re-entry tears and longer distance between the tears had low wall shear stress contributing to thrombosis. This work provides an insight into predicting the development of complete or incomplete false lumen thrombosis and has implications for patient selection for treatment.
  14. Johari NH, Menichini C, Hamady M, Xu XY
    PMID: 37730441 DOI: 10.1002/cnm.3772
    Restenosis typically occurs in regions of low and oscillating wall shear stress, which also favor the accumulation of atherogenic macromolecules such as low-density lipoprotein (LDL). This study aims to evaluate LDL transport and accumulation at the carotid artery bifurcation following carotid artery stenting (CAS) by means of computational simulation. The computational model consists of coupled blood flow and LDL transport, with the latter being modeled as a dilute substance dissolved in the blood and transported by the flow through a convection-diffusion transport equation. The endothelial layer was assumed to be permeable to LDL, and the hydraulic conductivity of LDL was shear-dependent. Anatomically realistic geometric models of the carotid bifurcation were built based on pre- and post-stent computed tomography (CT) scans. The influence of stent design was investigated by virtually deploying two different types of stents (open- and closed-cell stents) into the same carotid bifurcation model. Predicted LDL concentrations were compared between the post-stent carotid models and the relatively normal contralateral model reconstructed from patient-specific CT images. Our results show elevated LDL concentration in the distal section of the stent in all post-stent models, where LDL concentration is 20 times higher than that in the contralateral carotid. Compared with the open-cell stents, the closed-cell stents have larger areas exposed to high LDL concentration, suggesting an increased risk of stent restenosis. This computational approach is readily applicable to multiple patient studies and, once fully validated against follow-up data, it can help elucidate the role of stent strut design in the development of in-stent restenosis after CAS.
  15. Lim WTH, Ooi EH, Foo JJ, Ng KH, Wong JHD, Leong SS
    PMID: 39075679 DOI: 10.1002/cnm.3857
    Renal anisotropy is a complex property of the kidney and often poses a challenge in obtaining consistent measurements when using shear wave elastography to detect chronic kidney disease. To circumvent the challenge posed by renal anisotropy in clinical settings, a dimensionless biomarker termed the 'anisotropic ratio' was introduced to establish a correlation between changes in degree of renal anisotropy and progression of chronic kidney disease through an in silico perspective. To achieve this, an efficient model reduction approach was developed to model the anisotropic property of kidneys. Good agreement between the numerical and experimental data were obtained, as percentage errors of less than 5.5% were reported when compared against experimental phantom measurement from the literature. To demonstrate the applicability of the model to clinical measurements, the anisotropic ratio of sheep kidneys was quantified, with both numerical and derived experimental results reporting a value of .667. Analysis of the anisotropic ratio with progression of chronic kidney disease demonstrated that patients with normal kidneys would have a lower anisotropic ratio of .872 as opposed to patients suffering from renal impairment, in which the anisotropic ratio may increase to .904, as determined from this study. The findings demonstrate the potential of the anisotropic ratio in improving the detection of chronic kidney disease using shear wave elastography.
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