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  • Journal article
    Malkawi A, Pirianov G, Torsney E, Chetter I, Sakalihasan N, Loftus IM, Nordon I, Huggins C, Charolidi N, Thompson M, Xu XY, Cockerill GWet al., 2015,

    Increased Expression of Lamin A/C Correlate with Regions of High Wall Stress in Abdominal Aortic Aneurysms.

    , Aorta (Stamford), Vol: 3, Pages: 152-166, ISSN: 2325-4637

    BACKGROUND: Since aortic diameter is the most -significant risk factor for rupture, we sought to identify stress-dependent changes in gene expression to illuminate novel molecular processes in aneurysm rupture. MATERIALS AND METHODS: We constructed finite element maps of abdominal computerized tomography scans (CTs) of seven abdominal aortic aneurysm (AAA) patients to map wall stress. Paired biopsies from high- and low-stress areas were collected at surgery using vascular landmarks as coordinates. Differential gene expression was evaluated by Illumina Array analysis, using the whole genome DNA-mediated, annealing, selection, extension, and ligation (DASL) gene chip (n = 3 paired samples). RESULTS: The sole significant candidate from this analysis, Lamin A/C, was validated at the protein level, using western blotting. Lamin A/C expression in the inferior mesenteric vein (IMV) of AAA patients was compared to a control group and in aortic smooth muscle cells in culture in response to physiological pulsatile stretch. -Areas of high wall stress (n = 7) correlate to those -regions which have the thinnest walls [778 µm (585-1120 µm)] in comparison to areas of lowest wall stress [1620 µm (962-2919 µm)]. Induced expression of Lamin A/C -correlated with areas of high wall stress from AAAs but was not significantly induced in the IMV from AAA patients compared to controls (n = 16). Stress-induced expression of Lamin A/C was mimicked by exposing aortic smooth muscle cells to prolonged pulsatile stretch. CONCLUSION: Lamin A/C protein is specifically increased in areas of high wall stress in AAA from patients, but is not increased on other vascular beds of aneurysm patients, suggesting that its elevation may be a compensatory response to the pathobiology leading to aneurysms.

  • Journal article
    Su J, Gu Z, Chen C, Xu XYet al., 2015,

    A two-layer mesh method for discrete element simulation of gas-particle systems with arbitrarily polyhedral mesh

  • Conference paper
    Zhan W, Gedroyc W, Xu X, 2015,

    Drug Delivery to Solid Tumour with High Intensity Focused Ultrasound Heating

    , The 21st CLSS-UK Annual Conference
  • Journal article
    Li Z-Y, Tan FPP, Soloperto G, Wood NB, Xu XY, Gillard JHet al., 2015,

    Flow pattern analysis in a highly stenotic patient-specific carotid bifurcation model using a turbulence model

  • Journal article
    Liu C, Krishnan J, Xu X-Y, 2015,

    Intrinsic and induced drug resistance mechanisms at the cellular and tissue scales

    , Integrative Biology, ISSN: 1757-9694
  • Journal article
    Singh SD, Xu XY, Pepper JR, Treasure T, Mohiaddin RHet al., 2015,

    Biomechanical properties of the Marfan's aortic root and ascending aorta before and after personalised external aortic root support surgery.

    , Medical Engineering & Physics, Vol: 37, Pages: 759-766, ISSN: 1873-4030

    Marfan syndrome is an inherited systemic connective tissue disease which may lead to aortic root disease causing dilatation, dissection and rupture of the aorta. The standard treatment is a major operation involving either an artificial valve and aorta or a complex valve repair. More recently, a personalised external aortic root support (PEARS) has been used to strengthen the aorta at an earlier stage of the disease avoiding risk of both rupture and major surgery. The aim of this study was to compare the stress and strain fields of the Marfan aortic root and ascending aorta before and after insertion of PEARS in order to understand its biomechanical implications. Finite element (FE) models were developed using patient-specific aortic geometries reconstructed from pre and post-PEARS magnetic resonance images in three Marfan patients. For the post-PEARS model, two scenarios were investigated-a bilayer model where PEARS and the aortic wall were treated as separate layers, and a single-layer model where PEARS was incorporated into the aortic wall. The wall and PEARS materials were assumed to be isotropic, incompressible and linearly elastic. A static load on the inner wall corresponding to the patients' pulse pressure was applied. Results from our FE models with patient-specific geometries show that peak aortic stresses and displacements before PEARS were located at the sinuses of Valsalva but following PEARS surgery, these peak values were shifted to the aortic arch, particularly at the interface between the supported and unsupported aorta. Further studies are required to assess the statistical significance of these findings and how PEARS compares with the standard treatment.

  • Journal article
    Kandail H, Hamady M, Xu XY, 2015,

    Comparison of blood flow in branched and fenestrated stent-grafts for endovascular repair of abdominal aortic aneurysms.

    , Journal of Endovascular Therapy, Vol: 22, Pages: 578-590, ISSN: 1545-1550

    PURPOSE: To report a computational study assessing the hemodynamic outcomes of branched stent-grafts (BSGs) for different anatomic variations. METHODS: Idealized models of BSGs and fenestrated stent-grafts (FSGs) were constructed with different visceral takeoff angles (ToA) and lateral aortic neck angles. ToA was defined as the angle between the centerlines of the main stent-graft and side branch, with 90° representing normal alignment, and 30° and 120° representing angulated side branches. Computational simulations were performed by solving the conservation equations governing the blood flow under physiologically realistic conditions. RESULTS: The largest renal flow recirculation zones (FRZs) were observed in FSGs at a ToA of 30°, and the smallest FRZ was also found in FSGs (at a ToA of 120°). For straight-neck stent-grafts with a ToA of 90°, mean flow in each renal artery was 0.54, 0.46, and 0.62 L/min in antegrade BSGs, retrograde BSGs, and FSGs, respectively. For angulated stent-grafts, the corresponding values were 0.53, 0.48, and 0.63 L/min. All straight-neck stent-grafts experienced equal cycle-averaged displacement forces of 1.25, 1.69, and 1.95 N at ToAs of 30°, 90°, and 120°, respectively. Angulated main stent-grafts experienced an equal cycle-averaged displacement force of 3.6 N. CONCLUSION: The blood flow rate in renal arteries depends on the configuration of the stent-graft, with an FSG giving maximum renal flow and a retrograde BSG resulting in minimum renal flow. Nevertheless, the difference was small, up to 0.09 L/min. Displacement forces exerted on stent-grafts are very sensitive to lateral neck angle but not on the configuration of the stent-graft.

  • Journal article
    Wang Z, Wood NB, Xu XY, 2015,

    A viscoelastic fluid-structure interaction model for carotid arteries under pulsatile flow

  • Journal article
    Liu C, Xu XY, 2015,

    A systematic study of temperature sensitive liposomal delivery of doxorubicin using a mathematical model

    , Computers in Biology and Medicine, Vol: 60, Pages: 107-116, ISSN: 0010-4825
  • Journal article
    Cheng Z, Wood NB, Gibbs RGJ, Xu XYet al., 2015,

    Geometric and Flow Features of Type B Aortic Dissection: Initial Findings and Comparison of Medically Treated and Stented Cases

    , ANNALS OF BIOMEDICAL ENGINEERING, Vol: 43, Pages: 177-189, ISSN: 0090-6964
  • Journal article
    Liu C, Krishnan J, Xu XY, 2015,

    Intrinsic and induced drug resistance mechanisms: <i>in silico</i> investigations at the cellular and tissue scales

    , INTEGRATIVE BIOLOGY, Vol: 7, Pages: 1044-1060, ISSN: 1757-9694
  • Journal article
    Kidher E, Cheng Z, Jarral OA, O'Regan DP, Xu XY, Athanasiou Tet al., 2014,

    In-vivo assessment of the morphology and hemodynamic functions of the BioValsalva (TM) composite valve-conduit graft using cardiac magnetic resonance imaging and computational modelling technology

    , Journal of Cardiothoracic Surgery, Vol: 9, ISSN: 1749-8090

    Background: The evaluation of any new cardiac valvular prosthesis should go beyond the classical morbidityand mortality rates and involve hemodynamic assessment. As a proof of concept, the objective of this study wasto characterise for the first time the hemodynamics and the blood flow profiles at the aortic root in patientsimplanted with BioValsalva™ composite valve-conduit using comprehensive MRI and computer technologies.Methods: Four male patients implanted with BioValsalva™ and 2 age-matched normal controls (NC) underwent cardiacmagnetic resonance imaging (MRI). Phase-contrast imaging with velocity-mapping in 3 orthogonal directions wasperformed at the level of the aortic root and descending thoracic aorta. Computational fluid dynamic (CFD) simulationswere performed for all the subjects with patient-specific flow information derived from phase-contrast MR data.Results: The maximum and mean flow rates throughout the cardiac cycle at the aortic root level were very comparablebetween NC and BioValsalva™ patients (541 ± 199 vs. 567 ± 75 ml/s) and (95 ± 46 vs. 96 ± 10 ml/s), respectively.The maximum velocity (cm/s) was higher in patients (314 ± 49 vs. 223 ± 20; P = 0.06) due to relatively smaller effectiveorifice area (EOA), 2.99 ± 0.47 vs. 4.40 ± 0.24 cm2 (P = 0.06), however, the BioValsalva™ EOA was comparable to otherreported prosthesis. The cross-sectional area and maximum diameter at the root were comparable between the twogroups. BioValsalva™ conduit was stiffer than the native aortic wall, compliance (mm2 • mmHg−1 • 10−3) values were(12.6 ± 4.2 vs 25.3 ± 0.4.; P = 0.06). The maximum time-averaged wall shear stress (Pa), at the ascending aorta wasequivalent between the two groups, 17.17 ± 2.7 (NC) vs. 17.33 ± 4.7 (BioValsalva™ ). Flow streamlines at the root andascending aorta were also similar between the two groups apa

  • Journal article
    Zhan W, Gedroyc W, Xu XY, 2014,

    Effect of heterogeneous microvasculature distribution on drug delivery to solid tumour

  • Journal article
    Kandail H, Hamady M, Xu XY, 2014,

    Patient-specific analysis of displacement forces acting on fenestrated stent grafts for endovascular aneurysm repair

    , JOURNAL OF BIOMECHANICS, Vol: 47, Pages: 3546-3554, ISSN: 0021-9290
  • Journal article
    Botto L, Preuss K, Robertson LX, Xu XYet al., 2014,

    Physical characterisation and yield stress of a concentrated <i>Miscanthus</i> suspension

    , RHEOLOGICA ACTA, Vol: 53, Pages: 805-815, ISSN: 0035-4511
  • Journal article
    Takizawa K, Torii R, Takagi H, Tezduyar TE, Xu XYet al., 2014,

    Coronary arterial dynamics computation with medical-image-based time-dependent anatomical models and element-based zero-stress state estimates

    , COMPUTATIONAL MECHANICS, Vol: 54, Pages: 1047-1053, ISSN: 0178-7675
  • Journal article
    Cheng Z, Juli C, Wood NB, Gibbs RGJ, Xu XYet al., 2014,

    Predicting flow in aortic dissection: Comparison of computational model with PC-MRI velocity measurements

    , MEDICAL ENGINEERING & PHYSICS, Vol: 36, Pages: 1176-1184, ISSN: 1350-4533
  • Journal article
    Zhan W, Gedroyc W, Xu XY, 2014,

    Mathematical Modelling of Drug Transport and Uptake in a Realistic Model of Solid Tumour.

    , Protein and Peptide Letters, Vol: 21, Pages: 1146-1156, ISSN: 1875-5305

    Effective delivery of therapeutic agents to tumour cells is essential to the success of most cancer treatment therapies except for surgery. The transport of drug in solid tumours involves multiple biophysical and biochemical processes which are strongly dependent on the physicochemical properties of the drug and biological properties of the tumour. Owing to the complexities involved, mathematical models are playing an increasingly important role in identifying the factors leading to inadequate drug delivery to tumours. In this study, a computational model is developed which incorporates real tumour geometry reconstructed from magnetic resonance images, drug transport through the tumour vasculature and interstitium, as well as drug uptake by tumour cells. The effectiveness of anticancer therapy is evaluated based on the percentage of survival tumour cells by directly solving the pharmacodynamics equation using predicted intracellular drug concentrations. Computational simulations are performed for the delivery of doxorubicin through different administration modes and doses. Our predictions show that continuous infusion is far more effective than bolus injection in maintaining high levels of intracellular drug concentration, thereby increasing drug uptake by tumour cells. On the other hand, bolus injection leads to higher extracellular concentration in both tumour and normal tissues compared to continuous infusion, which is undesirable as high drug concentration in normal tissues may increase the risk of associated side effects.

  • Journal article
    Massai D, Pisani G, Rodriguez A, Logrand F, Isu G, Labate GFD, Xu XY, Bignardi C, Tarone G, Morbiducci Uet al., 2014,

    A bioreactor-based model system for cardiac tissue investigation and culture

  • Journal article
    Kousera CA, Nijjer S, Torii R, Petraco R, Sen S, Foin N, Hughes AD, Francis DPP, Xu XY, Davies JEet al., 2014,

    Patient-Specific Coronary Stenoses Can Be Modeled Using a Combination of OCT and Flow Velocities to Accurately Predict Hyperemic Pressure Gradients

    , IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING, Vol: 61, Pages: 1902-1913, ISSN: 0018-9294

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