T V How

University of Liverpool, Liverpool, England, United Kingdom

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Publications (118)271.62 Total impact

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    Marco Hoedt · Thien How · Paul Poyck · Cees Wittens ·
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    ABSTRACT: Objective: Despite the theoretical favourable hemodynamic advantage of end-to-end anastomosis (ETE), femoropopliteal bypasses with distal ETE and end-to-side anastomosis (ETS) have comparable clinical patencies. We therefore studied the effects of different in vivo anastomotic configurations on hemodynamics in geometrically realistic ETE and ETS in vitro flow models to explain this phenomenon.Methods: Four ETE and two ETS models (30° and 60°) were constructed from in vivo Computed Tomography Angiography data. With flow visualization physiological flow conditions were studied.Results: In ETS, a flow separation and recirculation zone was apparent at anastomotic edges with a shifting stagnation point between them during systole. Secondary flow patterns developed with flow deceleration and reversal. Slight out of axis geometry of all ETE resulted in flow separation and recirculation areas comparable to ETS. Vortical flow patterns were more stable in wider and longer bevelled ETE.Conclusion: Primary flow disturbances in ETE are comparable to ETS and are related to the typical sites where myointimal hyperplasia develops. In ETS, reduction of anastomosis angle will diminish flow disturbances. To reduce flow disturbances in ETE, the creation of a bulbous spatulation with resulting axial displacement of graft in relation to recipient artery should be prevented.
    Annals of thoracic and cardiovascular surgery: official journal of the Association of Thoracic and Cardiovascular Surgeons of Asia 01/2015; 21(2). DOI:10.5761/atcs.oa.14-00121 · 0.72 Impact Factor
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    ABSTRACT: Secure fixation of endovascular stent grafts is essential for successful endovascular aneurysm repair. Hemodynamic distraction forces are generated by blood pressure and blood flow and act against fixation force to encourage migration that may eventually lead to late stent graft failure. The aim of this in silico study was to determine which morphologic features were associated with greater distraction force. Computer models of 54 in situ fenestrated stent grafts were constructed from postoperative computed tomography scans by use of image processing software. Computational fluid dynamic analysis was then performed by use of a commercial finite volume solver with boundary conditions representative of peak systole. Distraction force results were obtained for each component of the stent graft. Distraction force was correlated with lumen cross-sectional area (XSA) at the inlet and outlet of components and was compared between groups of components, depending on the magnitude of four predefined angles within the aortoiliac territory that we describe in detail. Median total resultant distraction force (RDF) acting on the fenestrated proximal bodies was 4.8N (1.3-15.7N); bifurcated distal bodies, 5.6N (1.0-8.0N); and limb extensions, 1.7N (0.6-8.4N). Inlet XSA exhibited strong, positive correlation with total RDF in proximal body and distal body components (Spearman correlation coefficient ρ, 0.883 and 0.802, respectively). Outlet XSA exhibited a similarly strong, positive correlation with total RDF in limb extension components (ρ, 0.822). Outlet angulation ≥45 degrees was associated with greater total RDF in the limb extension components only (P = .004). For a given blood pressure, XSA was the most important morphologic determinant of total RDF. Angulation within the aorta was not large enough to influence this, whereas iliac angulation affecting outlet angulation of limb extension components was associated with significantly greater total RDF. Copyright © 2014 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.
    Journal of Vascular Surgery 12/2014; 60(6):1648-1656.e1. DOI:10.1016/j.jvs.2014.08.077 · 3.02 Impact Factor
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    ABSTRACT: Meta-analysis supports patch angioplasty after carotid endarterectomy (CEA); however, studies indicate considerable variation in practice. The hemodynamic effect of a patch is unclear and this study attempted to elucidate this and guide patch width selection. Four groups were selected: healthy volunteers and patients undergoing CEA with primary closure, trimmed patch (5 mm), or 8-mm patch angioplasty. Computer-generated three-dimensional models of carotid bifurcations were produced from transverse ultrasound images recorded at 1-mm intervals. Rapid prototyping generated models for flow visualization studies. Computational fluid dynamic studies were performed for each model and validated by flow visualization. Mean wall shear stress (WSS) and oscillatory shear index (OSI) maps were created for each model using pulsatile inflow at 300 mL/min. WSS of <0.4 Pa and OSI >0.3 were considered pathological, predisposing to accretion of intimal hyperplasia. The resultant WSS and OSI maps were compared. The four groups comprised 8 normal carotid arteries, 6 primary closures, 6 trimmed patches, and seven 8-mm patches. Flow visualization identified flow separation and recirculation at the bifurcation increased with a patch and was related to the patch width. Computational fluid dynamic identified that primary closure had the fewest areas of low WSS or elevated OSI but did have mild common carotid artery stenoses at the proximal arteriotomy that caused turbulence. Trimmed patches had more regions of abnormal WSS and OSI at the bifurcation, but 8-mm patches had the largest areas of deleteriously low WSS and high OSI. Qualitative comparison among the four groups confirmed that incorporation of a patch increased areas of low WSS and high OSI at the bifurcation and that this was related to patch width. Closure technique after CEA influences the hemodynamic profile. Patching does not appear to generate favorable flow dynamics. However, a trimmed 5-mm patch may offer hemodynamic benefits over an 8-mm patch and may be the preferred option.
    Journal of vascular surgery: official publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter 03/2014; 60(2). DOI:10.1016/j.jvs.2014.01.069 · 3.02 Impact Factor
  • A. Woywodt · T. How · M. Schulz ·

    Nieren- und Hochdruckkrankheiten 01/2014; 43(01):17-22. DOI:10.5414/NHX01569
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    ABSTRACT: The biodurability of the Nitinol wires used in stent-grafts retrieved from reoperations and autopsy was analyzed to assess the possible causes of fracture and/or corrosion of the stents. The Nitinol wires of six explanted devices presented a corrosion-free surface after in vivo service. The drawing lines in the control wires were still present, but neither burrs nor flakes were observed. Pits and crevices were rare, but some shallow ones were present. Some abrasions of the surfaces of the Nitinol wires were also observed. The chemical composition of the explanted devices showed the presence of organic contamination that covered the thick layer of titanium oxide before reaching the Nitinol itself. The durability of the Nitinol employed in the manufacture of the Talent stent-grafts was confirmed; the results of this study show the Nitinol to be resistant to corrosion. We have also concluded that the fractures of the Nitinol wires in two devices were unique adverse incidents caused by compression and bending related to the sharp angle of the Nitinol wires.
    Journal of Long-Term Effects of Medical Implants 11/2013; 23(1):45-59. DOI:10.1615/JLongTermEffMedImplants.2013007780
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    ABSTRACT: In this study, we aimed to investigate changes to the fabric of Talent stent-grafts following implantation of aortic endografts and to determine the possible causes of fatigue and/or failure of the grafts. Six devices were explanted at reoperation (N=5) and autopsy (N=1). Selected segments were assessed nondestructively by gross observation and destructively by analyzing textile characteristics and chemical properties. All of the devices showed a 4/4 twill woven fabric of monofilament polyester. These devices, explanted at reoperation and autopsy, presented different levels of fatigue and/or failure. Numerous holes were found in the fabric of two devices. The minor damage caused by the passage of the sutures through the weave to fasten the Nitinol wires did not progress significantly over time. The sutures remained relatively intact, except for some distortions. The main failure mode was the abrasion of the yarns at the apices of adjacent Nitinol stents. In two devices, this abrasion resulted in fraying of the yarns and holes in the fabric tubes. This short series of explanted devices provides evidence of damage to polyester fabric used in aortic endografts and raises questions regarding their resistance to abrasion and the risk of endoleak associated with monofilament fabric yarn.
    Journal of Long-Term Effects of Medical Implants 11/2013; 23(1):67-86. DOI:10.1615/JLongTermEffMedImplants.2013007769
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    ABSTRACT: In vascular interventional radiology, procedures generally start with the Seldinger technique to access the vasculature, using a needle through which a guidewire is inserted, followed by navigation of catheters within the vessels. Visual and tactile skills are learnt in a patient apprenticeship which is expensive and risky for patients. We propose a training alternative through a new virtual simulator supporting the Seldinger technique: ImaGiNe (imaging guided interventional needle) Seldinger. It is composed of two workstations: (1) a simulated pulse is palpated, in an immersive environment, to guide needle puncture and (2) two haptic devices provide a novel interface where a needle can direct a guidewire and catheter within the vessel lumen, using virtual fluoroscopy. Different complexities are provided by 28 real patient datasets. The feel of the simulation is enhanced by replicating, with the haptics, real force and flexibility measurements. A preliminary validation study has demonstrated training effectiveness for skills transfer.
    Computer methods and programs in biomedicine 06/2013; 111(2). DOI:10.1016/j.cmpb.2013.05.014 · 1.90 Impact Factor
  • Alexander Woywodt · Thien How · Michael Schulz ·
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    ABSTRACT: Aims: To construct a simple and affordable simulator for ultrasoundguided percutaneous renal biopsy. Material and methods: The kidney biopsy phantom was constructed by embedding a porcine kidney in gelatine. Silicon carbide and aluminium oxide were used as scattering particles in order to mimic the ultrasound appearance of human tissues. Two porcine ribs were also embedded. A latex sheet was placed over the top of the gel layer to resemble skin. The simulator was used and feedback from participants obtained during a renal ultrasound course with an international audience of middle-grade trainees from adult and pediatric nephrology, many of whom had never done a renal biopsy. Biopsy was carried out a single-use biopsy gun. Results: All participants were able to perform a biopsy and obtain a satisfactory sample. All trainees felt that our simulator was very realistic. 94% of participants agreed that the simulator would help to allay their fears in relation to renal biopsy The total cost of the simulator was around £ 50,- for consumables per simulator. Conclusions: We describe a purpose-built and affordable simulator for percutaneous ultrasound-guided renal biopsy. We suggest that others evaluate our simulator used as part of a structured approach to teach this important procedure.
    Clinical nephrology 03/2013; 79(3):241-5. DOI:10.5414/CN107236 · 1.13 Impact Factor
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    ABSTRACT: Purpose: The purpose of the study is to quantify the variation in the metric equivalent of French size in a range of medical devices, from various manufacturers, used in interventional radiology. Methods: The labelling of a range of catheters, introducers, drains, balloons, stents, and endografts was examined. Products were chosen to achieve a broad range of French sizes from several manufacturers. To assess manufacturing accuracy, eight devices were selected for measurement using a laser micrometer. The external diameters of three specimens of each device were measured at centimeter intervals along the length of the device to ensure uniformity. Results: A total of 200 labels of interventional radiology equipment were scrutinized. The results demonstrate a wide variation in the metric equivalent of French sizing. Labelled products can vary in diameter across the product range by up to 0.79 mm. The devices selected for measurement with the non-contact laser micrometer demonstrate acceptable manufacturing consistency. The external diameter differed by 0.05 mm on average. Conclusions: Our results demonstrate wide variation in the interpretation of the French scale by different manufacturers of medical devices. This has the potential to lead to problems using coaxial systems especially when the products are from different manufacturers. It is recommended that standard labelling should be employed by all manufacturers conveying specific details of the equipment. Given the wide variation in the interpretation of the French scale, our opinion is that this scale either needs to be abandoned or be strictly defined and followed.
    CardioVascular and Interventional Radiology 01/2013; 36(4). DOI:10.1007/s00270-013-0557-7 · 2.07 Impact Factor
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    ABSTRACT: Using the retrieved devices from one autopsy and five reoperations, the biocompatibility of explanted Talent stent-grafts was investigated to highlight the capacity of the fabric to act as an effective scaffold to regenerate a blood conduit. The autopsy device was encapsulated both internally and externally, but the capsules did not penetrate through the fabric structure. The reoperation devices showed discrete patches of compact fibrin and irregularly scattered mural thrombi. Positive staining of α-actin, tissue plasminogen activator (tPA), urokinase (uPA), urokinase receptor (uPAR), and urokinase inhibitors (PAI 1, PAI 2, PAI 3, and protease nexin), and D-dimer was more frequently identified in the autopsy sample than in the reoperation samples. This preliminary assessment shows that the stent-graft retrieved during autopsy was better healed than those explanted at reoperation.
    Journal of Long-Term Effects of Medical Implants 01/2013; 23(4):339-57. DOI:10.1615/JLongTermEffMedImplants.2013006657
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    ABSTRACT: Fig 1. a, Lateral abdominal radiograph showing fractured superior mesenteric artery (SMA) stent with the aortic portion at the level of the fenestration (arrow). b, Fluoroscopic image showing a guidewire and balloon catheter in the SMA. The aortic fragment of the SMA stent is no longer visible and has embolized. c, Aortic portion of the Palmaz Genesis stent shown in the right limb of the bifurcated graft (circle). d, Aortic portion well aligned with the stent graft. e, Aortic portion of the Palmaz Genesis stent apposing the iliac segment securely after ballooning. SMA, Superior mesenteric artery.
    Journal of vascular surgery: official publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter 10/2012; 57(2). DOI:10.1016/j.jvs.2012.08.043 · 3.02 Impact Factor
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    ABSTRACT: Balloon expandable stents may on occasion be deployed in close proximity to the anchoring barbs of endovascular grafts. The aim of this study was to determine the risk and effect of balloon perforation by anchoring barbs and to assess whether these risks are different if the balloon is protected by a covered stent mounted upon it. A bench-top model was developed to mimic the penetration of anchoring barbs into the lumen of medium sized blood vessels. The model allowed variation of angle and depth of vessel penetration. Both bare balloons and those with covered stents mounted upon them were tested in the model to determine whether there was a risk of perforation and which factors increased or decreased this risk. All combinations of barb angle and depth caused balloon perforation but this was most marked when the barb was placed perpendicular to the long axis of the balloon. When the deployment of covered stents was attempted balloon perforation occurred in some cases but full stent deployment was achieved in all cases where the perforation was in the portion of the balloon covered by the stent. The only situation in which stent deployment failed was where the barb was intentionally placed in the uncovered portion of the balloon. This resulted in only partial deployment of the stent. Balloon rupture is a distinct possibility when deploying balloon-expandable stents in close proximity to anchoring barbs. Care should be taken in this circumstance to ensure that the barb is well away from the uncovered portion of the balloon.
    European journal of vascular and endovascular surgery: the official journal of the European Society for Vascular Surgery 07/2012; 44(3):327-31. DOI:10.1016/j.ejvs.2012.06.003 · 2.49 Impact Factor
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    J R H Scurr · R G McWilliams · T V How ·
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    ABSTRACT: To examine the longitudinal migratory force required to cause disconnection of the bifurcated distal body component from the tubular proximal body of a fenestrated stent-graft. Using a previously reported mathematical model distal distraction forces were calculated prior to performing in vitro pullout testing. The top end of the proximal body and the iliac limbs of the distal body were attached to the grips of a tensile tester via plastic sealing plugs and pneumatic clamps. Channels within the plugs allowed pressurisation of the inside of the stent-graft. Pullout tests were conducted in the vertical plane. Force and displacement data were recorded and tests repeated 8 times at room temperature with the stent-grafts either dry or wet and unpressurized, at 100 mmHg or at 120 mmHg. The median maximum pullout force was 2.9 N (2.6-4.1) when dry, 3.9 N (3.5-5.4) when wet and unpressurized, 6.3 N (4.8-8.3) when wet and pressurized at 100 mmHg and 6.5 N (4.8-7.2) when wet and pressurized at 120 mmHg. There was a significant difference between pressurized and unpressurized conditions (P < 0.01). The force required to distract the distal bifurcated component of a fenestrated stent graft is much lower than the reported proximal fixation strength of both a standard and fenestrated Zenith stent graft. Although this helps protect the fenestrated proximal body from the effects of longitudinal migration forces in vivo the current strength of the body overlap zone may actually be unnecessarily weak and requires careful surveillance in follow up.
    European journal of vascular and endovascular surgery: the official journal of the European Society for Vascular Surgery 07/2012; 44(3):281-6. DOI:10.1016/j.ejvs.2012.05.026 · 2.49 Impact Factor
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    ABSTRACT: Computer-based simulation for interventional radiology training has attracted increasing attention in recent years because of its potential to train remotely from patients and to provide objective assessment of proficiency. Yet developing a high fidelity simulator with realistic tactile feedback requires accurate knowledge of forces exerted on medical devices during interventional radiology procedures. This paper presents the development and validation of a force sensor for the measurement of axial forces generated during needle, and combined cannula/trocar, puncture procedures in patients. In order to assess the performance of this sensor, in vitro measurements were obtained using needle penetration of porcine liver, kidney and muscle. The results were compared with forces measured by means of a tensile tester. Calibration results showed that the force sensor has high sensitivity and linearity. Comparison of the force profiles obtained from the sensor and the tensile tester shows that good agreement was achieved in the in vitro studies for all the tissues tested. Preliminary clinical force measurements during arterial puncture and liver biopsy procedures have been performed in patients. An example of force recording for each procedure type is presented.
    Medical Engineering & Physics 06/2012; 35(3). DOI:10.1016/j.medengphy.2012.05.012 · 1.83 Impact Factor
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    ABSTRACT: Interventional Radiology procedures (e.g., angioplasty, embolization, stent graft placement) provide minimally invasive therapy to treat a wide range of conditions. These procedures involve the use of flexible tipped guidewires to advance diagnostic or therapeutic catheters into a patient's vascular or visceral anatomy. This paper presents a real-time physically based hybrid modeling approach to simulating guidewire insertions. The long, slender body of the guidewire shaft is simulated using nonlinear elastic Cosserat rods, and the shorter flexible tip composed of a straight, curved, or angled design is modeled using a more efficient generalized bending model. Therefore, the proposed approach efficiently computes intrinsic dynamic behaviors of guidewire interactions within vascular structures. The efficacy of the proposed method is demonstrated using detailed numerical simulations inside 3-D blood vessel structures derived from preprocedural volumetric data. A validation study compares positions of four physical guidewires deployed within a vascular phantom, with the co-ordinates of the corresponding simulated guidewires within a virtual model of the phantom. An optimization algorithm is also implemented to further improve the accuracy of the simulation. The presented simulation model is suitable for interactive virtual reality-based training and for treatment planning.
    IEEE transactions on bio-medical engineering 05/2012; 59(8):2211-8. DOI:10.1109/TBME.2012.2199319 · 2.35 Impact Factor
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    ABSTRACT: This study evaluated the accuracy of central luminal line (CLL) measurements in quantifying stent graft migration. The bias of the CLL technique together with observer variability were assessed. Stent grafts were deployed in plastic aortic phantoms at fixed locations from two side branches. Each phantom was filled with iodinated contrast, and a 2-mm multislice computed tomography (CT) scan was performed. The stent graft was then displaced caudally, its new location determined, and again, a CT scan performed. This created a series of 15 cases with known stent graft migration. CLLs were used to measure stent graft position on the CT scans and calculate migration (3 observers). In vivo stent graft migration was then evaluated in a similar manner using a series of follow-up CT scans from nine patients (2 observers). All CLL measurements were performed independently and were repeated on a separate occasion. The mean difference in CLL migration between the actual and observed measurements (bias) in the aortic phantoms was <1 mm. The 95% confidence intervals for the bias were within the interval (-1 and 1 mm), and the 95% limits of agreement were within -3 mm and +3 mm. The 95% limits of agreement for measurements within and between observers were -4 to 2 mm and -2 to 2 mm, respectively. The phantom study generated a coefficient of repeatability (RC) of 1 mm for within-observer measurements. Clinically, CLLs generated 95% limits of agreement within and between observers of -3 to 4 mm (RC, 2 mm) and -3 to +3 mm, respectively. Bias from CLL-determined migration is small and insignificant from a practical point of view. A small amount of measurement variability within and between observers does exist; it should be feasible to detect changes in stent graft position that are ≥4 mm.
    Journal of vascular surgery: official publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter 01/2012; 55(4):895-905. DOI:10.1016/j.jvs.2011.10.083 · 3.02 Impact Factor
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    ABSTRACT: To measure the stiffness of commonly used "stiff" guidewires in terms of their flexural modulus, an engineering parameter related to bending stiffness. Eleven different intact stiff guidewires were selected to undergo a 3-point bending test performed using a tensile testing machine. Testing was performed on 3 new and intact specimens of each guidewire at 10 locations along the wire's length, excluding the floppy tip. The flexural modulus (in gigapascals, GPa) was calculated from the results of the bending test. The flexural modulus of the plain Amplatz wire was 9.5 GPa compared to 11.4 to 14.5 GPa for the "heavy duty" wires. Within the Amplatz family of guidewires, the flexural modulus was 17 GPa for the "stiff," 29.2 GPa for the "extra stiff," 60.3 GPa for the "super stiff," and 65.4 GPa for the "ultra stiff." The Backup Meier measured 139.6 GPa and the Lunderquist Extra Stiff 158.4 GPa. The Instructions for Use of some endovascular devices specify a wire type selected from a range of undefined "stiffness" descriptors. These descriptors have little correlation with the measured flexural modulus. Two guidewires with the description "extra stiff" can have a 5-fold difference in flexural modulus. We recommend that guidewire catalogues and packaging include the flexural modulus and that device manufacturers amend their Instructions for Use accordingly.
    Journal of Endovascular Therapy 12/2011; 18(6):797-801. DOI:10.1583/11-3592.1 · 3.35 Impact Factor
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    V Wong · R Ward · J Taylor · S Selvakumar · T V How · A Bakran ·
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    ABSTRACT: The radiocephalic arteriovenous fistula remains the method of choice for haemodialysis access. In order to assess their suitability for fistula formation, the radial arteries and cephalic veins were examined preoperatively by ultrasound colour flow scanner in conjunction with a pulse-generated run-off system. Intraoperative blood flow was measured after construction of the fistulae. Post-operative follow-up was performed at various intervals to monitor the development of the fistulae. Radial artery and cephalic vein diameter less than 1.6 mm was associated with early fistula failure. The intraoperative fistula blood flow did not correlate with the outcome of the operation probably due to vessel spasm from manipulation. However, blood flow velocities measured non-invasively 1 day after the operation were significantly lower in fistulae that failed early compared with those that were adequate for haemodialysis. Most of the increase in fistula diameter and blood flow occur within the first 2 weeks of surgery.
    European journal of vascular and endovascular surgery: the official journal of the European Society for Vascular Surgery 09/2011; 42 Suppl 1:S48-54. DOI:10.1016/j.ejvs.2011.06.023 · 2.49 Impact Factor
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    ABSTRACT: To quantify the compression force acting on target vessel stents as a consequence of the misalignment between the native aortic anatomy and the fenestrated stent-graft owing to measuring errors during the design of the device. The material properties of a fenestrated Zenith stent-graft were determined using a standardized tensile testing protocol. Aortic anatomy was modeled using fresh porcine aortas that were subjected to tensile testing. The net force acting on a target vessel stent due to incremental discrepancy between the target vessel ostia and the stent-graft fenestrations was calculated as the difference in wall tension between the aorta and the stent-graft in diastole and systole. The change in diameter between diastole and systole was set to 8%. Using the diastole model, underestimation of circumferential target vessel position by 15°, 22.5°, and 30° resulted in net forces on the target vessel stent of 0.6, 0.8, and 1.1 N, respectively. Overestimation of target vessel position by the same increments resulted in net forces of 0.3, 0.6, and 0.9 N, respectively. With the systolic model, underestimating target vessel position by 30° resulted in a 2.1-N maximum force on the stent, which potentially threatened the seal. In the longitudinal direction, underestimating target vessel separation by up to 10 mm resulted in a maximal force on the stent of 6.1 N, while overestimating target vessel separation did not result in any additional force on the stent due to fabric infolding. The magnitude of the forces generated solely due to mismatch between stent-graft design and native anatomy is modest and is unlikely to cause significant deformation of target vessel stents. Mismatch, however, may cause loss of seal.
    Journal of Endovascular Therapy 08/2011; 18(4):569-75. DOI:10.1583/11-3471.1 · 3.35 Impact Factor
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    Journal of Vascular Surgery 06/2011; 53(6). DOI:10.1016/j.jvs.2011.03.172 · 3.02 Impact Factor

Publication Stats

2k Citations
271.62 Total Impact Points


  • 1984-2015
    • University of Liverpool
      • • Department of Electrical Engineering and Electronics
      • • Department of Clinical Sciences
      • • School of Engineering
      Liverpool, England, United Kingdom
  • 1987-2010
    • Royal Liverpool and Broadgreen University Hospitals NHS Trust
      • • Department of Radiology
      • • Department of Clinical Engineering
      Liverpool, England, United Kingdom
  • 1996
    • University of Wales
      Cardiff, Wales, United Kingdom
  • 1995
    • Laval University
      • Department of Surgery
      Quebec City, Quebec, Canada