2 Meeting of the EPSRC Patient-Specific Modelling Network

nd

28 - 29 September 2011 Prestonfield Room, John McIntyre Conference Centre, The University of Edinburgh

TRANSLATION FROM BASIC RESEARCH TO CLINICAL PRACTICE

www.patientspecific.net
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The EPSRC Patient-Specific Modelling Network would like to thank the following sponsors for their contribution to both this meeting and the network as a whole.

EPSRC PATIENT-SPECIFIC MODELLING NETWORK PATIENT-SPECIFIC MODELLING: TRANSLATION FROM BASIC RESEARCH TO CLINICAL PRACTICE

Network Coordinator: Organisers:

Prof. Perumal Nithiarasu (University of Swansea) Dr. Pete Hoskins (The University of Edinburgh) Dr. Barry Doyle (The University of Edinburgh) Dr. Pankaj Pankaj (The University of Edinburgh)

Location:

Contact (general info):

Prestonfield Room, John McIntyre Conference Centre, Holyrood Park Road, Edinburgh. Louise Dryburgh at Edinburgh First Tel: +44 131 651 2008 www.edinburghfirst.co.uk

Directions from Prince's Street (Waverly Train Station) to Masson House (accommodation)

Directions from conference centre to Royal Infirmary (MRE demonstration in CRIC) 4

PROGRAMME
Wednesday 28th September Session 1. Cardiovascular I Chair: Peter Hoskins 8.58 Welcome - Peter Hoskins 9.00-9.40 Patient-specific modelling: Background for abdominal aortic aneurysm. Janet Powell, Imperial College 9.40-10.20 USPIO imaging of AAA. Jennifer Richards, The University of Edinburgh 10.20-10.50 Tea, coffee and posters

Session 2. Cardiovascular II Chair: Janet Powell 10.50-11.30 Plaque rupture from FEA and USPIO imaging. Jonathan Gillard, University of Cambridge 11.30-12.00 Aneurysms and FEA. Barry Doyle, University of Limerick & The University of Edinburgh 12.00 Discussion led by Janet Powell 13.00-14.00 Lunch and posters

Session 3. The path to translation into routine use I Chair: Barry Doyle 14.00-14.30 Optimisation of patient specific modelling for cardiovascular surgeries' Ajit Yoganathan, Georgia Institute of Technology, USA 14.30-15.00 Getting a medical device into clinical practice - the AAA stent graft Tim McGloughlin, University of Limerick 15.00-15.30 Tea, coffee and posters

Session 4. Musculoskeletal I: Bone quality and trauma Chair: Pankaj Pankaj 3.30-4.00 Questions that clinicians want modellers to help answer in trauma Hamish Simpson, The University of Edinburgh 4.00-4.30 Patient specific modelling for osteoporosis fracture prediction Ralph Mller, ETH Zurich 4.30-5.30 Discussion led by Hamish Simpson

Thursday 29th September Session 5. Musculoskeletal II: Joint replacement Chair: Ralph Mller 9.00-9.30 Moving towards population based modelling of total joint replacement Mark Taylor, University of Southampton 9.30-10.00 Patient specific modelling in joint replacement and trauma care Pankaj Pankaj, The University of Edinburgh 10.00-10.30 Discussion led by Ralph Mller 10.30-11.00 Tea, coffee and posters

Session 6. The path to translation into routine use II Chair: Tim McGloughlin 11.00-11.30 Drug development; from lab to clinical use. Simon Maxwell, The University of Edinburgh 11.30-12.00 Manufacturer perspective. Patient-specific modelling Nikhil Sindhwani, Mimics, Materialise, Belgium 12.00-12.30 Manufacturers perspective. Image-based modelling for patient-specific solutions Philippe Young, Simpleware & University of Exeter 12.30-13.00 Discussion led by Tim McGloughlin - What needs to be done to translate patient-specific modelling into clinical practice? 13.00-14.00 Lunch

Session 7. Elastography Chair: Peter Hoskins 14.00-14.45 Magnetic resonance elastography (MRE). Jrgen Braun, Charit - Universittsmedizin, Berlin, Germany 14.45-15.30 Ultrasound elastography Jeff Bamber, Institute of Cancer Research, Sutton, Surrey Session 8. MRE demonstration Chair: Neil Roberts 16.00-17.00 Practical demonstration of MRE, at the Clinical Research Imaging Centre in the Queens Medical Research Institute, Little France. This is located about 2 miles from the conference venue. Numbers attending may be restricted due to the size of the room. More information including travel arrangements will be available at the meeting. 17.00 Close of meeting

LIST OF POSTERS
P-01: Simulation of haemodynamic flow in head and neck cancer chemotherapy: A patient specific modelling Stephan Rhode, Manosh Paul, Eckhard Martens, Duncan Campbell GlasgowHeart: a personalized computational platform for human left ventricle Hao Gao, Colin Berry, John Soraghan, Xiaoyu Luo Age-related changes in geometry and blood flow in the rabbit aorta Vronique Peiffer, Min Rowland, Peter D. Weinberg, Spencer J. Sherwin Accurate shear stress characterization in porcine arteries for future transcriptome analysis A. De Luca, C.M. Warboys, N. Amini, R. Krams, D.O. Haskard, D. Firmin, S. Sherwin, P.C. Evans Multicompartmental poroelasticity for the multiscalar modelling of CSF production and circulation in the brain John Vardakis, Brett Tully, Yiannis Ventikos A computational model of thrombus development Malebogo Ngoepe, Timothy Bowker, Yiannis Ventikos Establishment of magnetic resonance elastography at the clinical research imaging centre (CRIC) Paul Kennedy, David Gow, David Donaldson, Angus Hunter, Fredericke van Wijck, Edwin van Beek, Neil Roberts The importance of modelling bone-implant interface in locking plate finite element models Alisdair MacLeod, Pankaj Pankaj, Hamish Simpson Modelling to capture the mechanical environment in the femur Noel Conlisk, Pankaj Pankaj, Colin Howie A biomechanical study on the effect of fracture intrusion distances in three-part trochanteric fractures treated with Gamma nail and sliding hip screw Jerome Goffin, Pankaj Pankaj, Hamish Simpson Photogrammetry as a cost effective geometric reconstruction technique: Investigation of reliability and suitability for bioengineering use Stephen Broderick, Barry Doyle, Michael Walsh

P-02

P-03

P-04

P-05

P-06

P-07

P-08

P-09

P-10

P-11

P-12

A computational simulation of MRE through patient specific diseased arterial geometry Lauren Thomas-Seale, Dieter Klatt, Ingolf Sack, Pankaj Pankaj, Neil Roberts, Peter Hoskins The importance of biomechanical modelling in abdominal aortic aneurysm rupturerisk prediction Barry Doyle, Peter Hoskins, Tim McGloughlin

P-13

ABSTRACTS FOR ORAL PRESENTATION

Patient Specific Modelling: Background For Abdominal Aortic Aneurysm Janet Powell*
Imperial College London

Abstract
An abdominal aortic aneurysm (AAA) is a balloon like swelling of the infrarenal abdominal aorta. These AAA are quite common in older men and often remain without symptoms until they rupture catastrophically. For this reason there is an active programme to detect and repair the larger aneurysms before they rupture. There are many pathological changes in the aortic wall that precede rupture. These include thinning of the aortic media, atherosclerosis and inflammation throughout the wall but particularly in the outer layer, the adventitia. Unsurprisingly different patients with AAA have a very different clinical course. In most patients (about 90%), the aneurysm expands steadily, with growth rate increasing as the aneurysm enlarges. The most important risk factor associated with fast expansion is smoking and in contrast AAA expand less rapidly in the presence of diabetes and large atherosclerotic burden. Haemodynamic factors such as blood pressure do not appear to influence AAA expansion. The risk and rate of AAA rupture increases with aneurysm diameter, the risk is very low for aneurysms <5.5 cm in diameter. The rate of aneurysm rupture is increased in women, current smokers and increases with increasing mean arterial pressure. The anatomy or shape of the aneurysm also is influential, with long aneurysm necks stabilizing the aneurysm and acting to decrease the rate of aneurysm rupture. Therefore there are different risk factors for aneurysm growth and rupture, with physical influences being more important for rupture. There are 2 methods of repairing AAA, by open surgery or minimally invasive endovascular surgery. In the latter the graft to repair the aneurysm is not sewn into place and there is a risk of continuing blood perfusion of the aneurysm sac, which is known as endoleak. These endoleaks, if not corrected, can cause secondary rupture. One of the important risk factors for both endoleak and secondary rupture is age. We know that the aorta gets stiffer with age and it possible that the fixation of endovascular devices is less satisfactory in the stiffer aortas. The varying natural history of abdominal aortic aneurysms in different patients is an important reason to consider patient-specific modelling.

*Corresponding author. Email address: j.powell@imperial.ac.uk (Prof. Janet T. Powell)

Abdominal Aortic Aneurysm Growth is Predicted by Uptake of Ultrasmall Superparamagnetic Particles of Iron Oxide Jennifer M. Richardsa,b*, Scott I. Semplea, Thomas J. MacGillivraya, Calum Graya, Jeremy P. Langrisha,b, Michelle Williamsa,b, Marc Dwecka,b, William A. Wallacea,b, Graham McKillopa,b, Roderick T. Chalmersa,b, O. James Gardena,b, David E Newbya,b
a

The University of Edinburgh, Edinburgh, United Kingdom b NHS Lothian, Edinburgh, United Kingdom

Abstract
Background: Abdominal aortic aneurysms are a major cause of death. Prediction of aneurysm expansion and rupture is challenging and currently relies on the simple measure of aneurysm diameter. Using magnetic resonance imaging, we aimed to assess whether areas of cellular inflammation correlated with the rate of abdominal aortic aneurysm expansion. Methods: Stable patients (n=29; 27 male; aged 705 years) with asymptomatic abdominal aortic aneurysms (4 6.6 cm) were recruited from a surveillance programme and were imaged in a 3T magnetic resonance imaging scanner before and 2436 h after administration of ultrasmall superparamagnetic particles of iron oxide (USPIO). The change in T2* value on T2*-weighted imaging was used to detect accumulation of USPIO within the abdominal aortic aneurysm. The aneurysm growth rate was calculated from serial ultrasound measurements. In patients undergoing surgery, a sample of aortic wall was fixed and stained for CD68 (macrophages) and Prussian blue (iron). Results: Histological examination of aneurysm tissue confirmed co-localisation and uptake of USPIOs in areas with macrophage infiltration. Patients with distinct hotspots of USPIO uptake (n=13) had a three-fold higher growth rate (0.66 cm/yr; P=0.020) than those with no (n=7; 0.22 cm/yr) or with non-specific USPIO uptake (n=9; 0.24 cm/yr) despite having similar aneurysm diameters (P=ns). In one patient with an inflammatory aneurysm, there was a strong and widespread uptake of USPIO extending beyond the aortic wall. Conclusions: Uptake of USPIOs in abdominal aortic aneurysms identifies cellular inflammation and appears to distinguish those patients with more rapidly progressive abdominal aortic aneurysm expansion. This technique holds major promise as a new method of risk-stratifying patients with abdominal aortic aneurysms that extends beyond the simple anatomical measure of aneurysm diameter.

Key Words: Abdominal aortic aneurysm, Inflammation, Magnetic resonance imaging

*Corresponding author. Email address: jenny.richards@ed.ac.uk

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Plaque Rupture From FEA And USPIO Imaging Jonathan Gillard*

University of Cambridge

Abstract
Despite tremendous advances in the recognition and management of risk factors for atheromatous disease as well as the treatment of acute events, it remains responsible for substantial morbidity and mortality in the Western world. Until recently the risk of carotid disease in symptomatic patients was determined by simple luminal measurements based conventional angiography, all on more subjective changes in Doppler ultrasound measurements which would establish whether a patient should undergo carotid endarterectomy or optimal medical therapy. Developments in MR and CT over the past decade have given us alternative tools to measure luminal stenosis which have reduced risks when compared with conventional X ray angiography. The relentless progression of faster, more robust sequences and contrast agents have only recently allowed us to assess plaque itself, rather than its effect on the degree of stenosis. We are now able to image individual plaque components including the fibrous cap, lipid core and haemorrhage. The current goal is to be better able to characterise plaque risk, whether it is in the carotid, coronary or peripheral vasculature. MR imaging of the carotid is feasible due to its size and superficial position, equivalent reproducible imaging of the coronary arteries being considerably more challenging. Although the carotid artery may be viewed as a surrogate for disease in the coronaries, this is probably an oversimplification. Nevertheless it remains an important and practical target. Our understanding of the natural history of atheroma development continues to grow. Whilst the assessment of risk is aided by the quantification of individual morphological components in plaque viewed with MR, it has been difficult to image true plaque function. We can use MR to assess the contribution of local flow dynamics and the individual components of plaque to produce maps of stress in a specific patient. In addition, enticing studies of plaque activity demonstrated by FDG PET have shown that it is possible to image inflammatory activity in man. We now have MR contrast media that are taken up by macrophages and are visible with highresolution MR. We are also able to image not only individual plaque structure, but also function allowing an improved understanding of why two patients will identical degrees of luminal stenosis may have completely different degrees of vulnerability; why one patient should be symptomatic and the other asymptomatic. The presence of intraplaque haemorrhage in the acute setting has been shown to be a significant risk factor for subsequent events. Indeed the interactions between biomechanical stresses and inflammation are probably extremely complex as it is not yet possible to define the initiating process and their interactions. The mechanical properties of plaque and the interaction of plaque with overlying blood flow are extremely complex. Plaque stresses, strain and geometry may play a role. The spatial localisation of individual plaque components such as calcium also appears important. This might have implications for assessing cardiac risk using CT calcium scores. The realisation that there may be many micro-ruptures occurring which are subclinical is obviously of great importance. There have been tremendous advances in our ability to access plaque vulnerability using MR over the last few years. The challenge is to validate these techniques in the carotid and to take them into the coronary as the relentless progress of technology continues.

*Corresponding author. Email address: jhg21@cam.ac.uk (Prof. Jonathan Gillard)

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Aneurysms and Finite Element Analysis: Applications of Patient-Specific Modelling Barry Doylea,b*
Centre for Applied Biomedical Engineering Research (CABER), Department of Mechanical, Aeronautical and Biomedical Engineering, and the Materials and Surface Science Institute, University of Limerick, Limerick, Ireland. b Medical Physics, The University of Edinburgh, Edinburgh, United Kingdom
a

Abstract
An aneurysm is an abnormal dilation of a blood vessel and can potentially form in any vessel of the body. They are usually defined as having a diameter greater than 50% of the original diameter. The most common sites for aneurysm development are the arteries of the brain, typically around the Circle of Willis, and in the upper and lower regions of the aorta. The majority of aortic aneurysms occur in the section distal to the renal arteries and are called abdominal aortic aneurysms (AAAs). Aneurysms that develop in the ascending and descending aorta are called thoracic aortic aneurysms (TAAs) and less common than AAAs. The maximum diameter is often used as the clinical guideline to indicate rupture-risk, with growth rate also usually considered. Therefore, large aneurysms or those expanding rapidly will usually be repaired if the patient is fit for surgery. However, over recent years, several studies have reported that alternative risk factors, in particular those based on the biomechanics of the disease, may be important. Numerical modelling of aneurysms can reveal important estimations of the in vivo stress/strain condition of the aneurysm, data which cannot be determined from two dimensional (2D) medical images. This presentation will firstly discuss some of the recent advances in the area of patient-specific modelling (PSM) of aneurysms and report some potentially useful alternatives to the current clinical guidelines. Secondly, a pre and post-operative aneurysmal aorta with both TAA and AAA will be presented. PSM using finite element analysis (FEA) reveals the estimated in vivo stress distributions both before and after surgery with an implanted stent-graft. Thirdly, a case of PSM of a ruptured AAA (rAAA) will be presented where the tissue (both AAA wall and intraluminal thrombus) of the patient was excised during an open surgical repair of the aneurysm. Mechanical testing and resultant data can then be incorporated into the numerical models. Finally, some preliminary results will be presented showing how the stress distribution of AAAs correlates to the inflammation in AAAs, as assessed by the uptake of ultrasmall superparamagnetic particles of iron oxide (USPIO) measured with magnetic resonance imaging (MRI).

Figure: (A) Pre-op TAA, (B) Post-op TAA with implanted stent-graft, (C) 3D model of rAAA case superimposed on CT, (D) 3D models of rAAA and (E) Patient-specific wall data (top) and thrombus data (bottom) compared to commonly employed data from the literature. Keywords: aneurysms, patient-specific modelling (PSM), rupture-risk *Corresponding author. Tel.: +353 61 2026309, +44 131 2426307 Email address: Barry.Doyle@ul.ie (Dr. Barry Doyle)

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Patient-Specific Surgical Planning of the Fontan Procedure: Developing Robust Solutions to Counter Failure Christopher M. Haggertya, Diane A. de Zlicourta, Maria Restrepoa, Lucia Mirabellaa, Jarek R. Rossignacb, Kirk R. Kanterc, J. William Gaynord, Thomas L. Sprayd, Mark A. Fogele, Ajit P. Yoganathana*
Wallace H. Coulter School of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, United States b College of Computing, Georgia Institute of Technology, Atlanta, GA, United States c Division of Cardiothoracic Surgery, Emory University School of Medicine, Atlanta, GA, United States d Division of Cardiothoracic Surgery, Childrens Hospital of Philadelphia, Philadelphia, PA, United States e Division of Cardiology, Childrens Hospital of Philadelphia, Philadelphia, PA, United States
a

Abstract
The total cavopulmonary connection (TCPC) is the surgical procedure that is currently employed in single ventricle congenital heart diseases. Despite improvements in the outcome obtained with this procedure, these patients are still subject to numerous long-term complications, motivating additional studies to improve the success of the surgical operation. The hypothesis for the current study is that by haemodynamically optimizing the design of the surgical connection, the patient outcome would improve. The steps to test this hypothesis are: 1) reconstruct the patient specific geometry from magnetic resonance (MR) images; 2) derive velocity data from phase contrast MRI, to be used as patient-specific boundary conditions; 3) generate different alternatives for the TCPC design, using a software tool that has been developed within this project to mimic surgical manipulation of baffles in a virtual environment; 4) simulate the fluid dynamics inside the generated models; 5) analyze the energetic efficiency and flow distribution through the connection for the different options. The results of these patient-specific studies can then be exploited by the surgeon, to implement a robust, haemodynamically efficient connection for each patient. This pipeline has been applied so far to the treatment of a number of failing Fontan patients, primarily to reduce pulmonary arteriovenous malformations (PAVM), which occur as a result of a lack of hepatic nutrients produced by the liver. These studies have shown a high dependence on patient-specific characteristics, which motivate the use of patient-specific models. However, some common features have been highlighted, to serve as a guide for the treatment of similar patients in the future.

Figure: Simulated hepatic venous streamlines for five patient case studies demonstrating a desirable distribution of hepatic flow to both left and right pulmonary arteries. Keywords: haemodynamics; congenital heart defects; computational fluid dynamics; surgery planning

*Corresponding author. Tel.: +1 404 8942849; Fax: +1 404 8944243. Email address: ajit.yoganathan@bme.gatech.edu (Prof. Ajit P. Yoganathan)

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Getting A Medical Device Into Clinical Practice - The AAA Stent Graft Timothy M. McGloughlina* and Liam G. Morrisb
a

Centre for Applied Biomedical Engineering Research, Department of Mechanical, Aeronautical and Biomedical Engineering, and the Materials and Surface Science Institute, University of Limerick, Limerick, Ireland b Department of Mechanical and Industrial Engineering, Galway Mayo Institute of Technology, Galway, Ireland

Abstract
Current treatments of AAA include surgical and endovascular methods. The surgical approach is highly invasive and requires long hospital stays. The endovascular method has shown reduced hospital stays however some clinical challenges remain with stent graft migration, endoleaks and stent graft thrombosis all being reported. An additional major problem with the AAA graft is that pressure augmentation may occur due to graft implantation. Previous studies have found that implanting a stiff synthetic graft into the aorta can serve to increase the systolic blood pressures acting within the graft. This may be a result of increased vascular resistance to flow, pressure wave reflections at the junction, or both. Isolator Graft: The Isolator graft was developed to address some of the problems associated with the traditional AAA graft and stent graft by introducing streamlined characteristics into the graft. Central to this design is the characteristic of a tapering cross-section from the aortic inlet to the iliac outlets. It has been found that in many commercially available grafts and stent-grafts this area ratio is closer to 2 (healthy subjects typically 1.3). The figure illustrates the tapering characteristic of the Isolator graft compared to a conventional graft. It is expected that the Isolator graft can serve to reduce the drag on the graft and reduce the flow disturbance. The process to develop this concept into a product will be described. Numerical models of the Isolator were developed based on CT scans of implanted stent-grafts. Computational Fluid Dynamics (CFD) was used to determine the drag force and flow behaviour of the Isolator. The CFD studies demonstrated that in straight models the Isolator improved blood flow haemodynamics. Blood flow and fluid forces were investigated using CFD and it was found that the Isolator (tapered graft) does not have a negative effect on stent-graft drag force in patient specific models. Velocity Profiles and Shear stresses: The Isolator (tapered graft) maintained a more uniform flow in straight planar grafts Cross section velocity plots were created prior to the iliac bifurcation and after the iliac bifurcation to investigate the realistic scenario. The velocity magnitude in the iliac legs in the Isolator is less than that in the conventional graft. Disease formation is more likely in this region. The wall shear stress (WSS) magnitude in the Isolator was less than that in the conventional graft. This was most evident in patient C. These results were as expected due to the smaller velocity magnitude in the Isolator. It has been suggested that areas of high WSS may overstimulate platelet thrombosis causing occlusion in vascular grafts. Findings from animal studies on prototype devices will also be presented.

Figure: A stent-graft implantation (left) and geometrical configurations of current (centre) and new (Isolator) stent graft (right). *Corresponding author. Email address: tim.mcgloughlin@ul.ie (Prof. Tim McGloughlin)

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Patient Specific Modelling for Osteoporosis Fracture Prediction Ralph Mllera*

a

Institute for Biomechanics, ETH Zurich, Zurich, Switzerland

Abstract
The principal function of the skeleton is to withstand the loads that are acting on it. When these loads exceed the bone tissues ability to support them, fractures inevitably occur. Hence, osteoporosis and other bone diseases would be best diagnosed by in vivo measurements of bone strength. Nevertheless, the current gold standard for determining bone strength is an experimental, mechanical test, which is a straight-forward procedure, but is limited by its destructiveness. Therefore, this method is not applicable in vivo, and although it can be used in vitro, a sample can only be tested once limiting the assessment of direction-dependent failure characteristics. Alternatively, computational analysis tools can be used to non-destructively evaluate bone strength in individual patients for better osteoporosis fracture risk prediction. Finite element (FE) analysis it is the most widely used computational method in engineering for structural analysis. The strength of FE is that it can deal with the highly irregular geometry and architecture of bones. Furthermore, it can handle complicated loading and material behavior. A great advantage of FE is that models can be analyzed multiple times under different conditions to simulate various types of loading. In addition, FE models of bone have provided better insight into the relationship of structure and strength by allowing researchers to look inside the bone to see where stresses are concentrating, and therefore where they may cause fracture. Moderate to good estimates of bone strength have been obtained from continuum-level FE models. Improved predictive capacity for individual patients is expected from microstructural FE models that represent the trabecular architecture in detail. With the advent of recently developed high-resolution in vivo bone imaging systems and the steady increase in computational power, such microstructural FE analyses are now becoming available to non-destructively estimate bone strength in humans in a clinical setting (Figure 1). Image-based FE analysis of mechanical bone competence is becoming a new gold standard for in vivo evaluation of bone strength and in the future might be able to help improve predictions of fracture risk, clarify the pathophysiology of skeletal diseases, and monitor the response to therapy using patient specific modelling.

4000

controls
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Bone strength [N]

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Figure 1: Association of ultradistal radius bone volume with overall ultradistal radius strength by FE among 18 Rochester, MN women with a forearm fracture () and their 18 age-matched controls (). Keywords: bone, osteoporosis, fracture risk, finite element analysis

*Corresponding author. Tel.: +41 44 632 4592; Fax: +41 44 632 1214. Email address: ram@ethz.ch (Prof. Ralph Mller)

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Moving Towards Population Based Modelling of Total Joint Replacement Mark Taylora*
a

Bioengineeing Sciences Research Group, Engineering Sciences, University of Southampton, Highfield, Southampton, United Kindom

Abstract
It is becoming increasingly difficult to differentiate the performance of new hip and knee replacement designs using current pre-clinical test methods. The vast majority of published finite element studies are performed on a representative subjects anatomy, with optimal implant placement, subjected to idealised loading conditions. Extrapolating these results to the larger patient population is unlikely to predict the potential risk of failure. It is well accepted that there can be significant variation between patients (mass, activity levels and bone quality) and also in surgery (implant size and orientation) and it is only by integrating these parameters into our models that we may better assess the risk of failure. Historically, parametric analyses have been performed to try and assess the impact of one or two variables, for example implant alignment. However, this simplistic approach ignores interaction with other parameters which could be significant and does not account for the likelihood that a particular combination may occur. Increases in computational power are leading to the application of probabilistic and stochastic techniques to examine the influence of multiple variables simultaneously, such as the Monte Carlo method or more computationally efficient reliability methods. The challenge in developing these techniques is automating the simulation process, particularly when aiming to generate hundreds or thousands of models. Various groups are using these techniques to examine the influence of surgical variability. Early studies used isolated TKR components to explore the influence of mal-positioning on joint kinematics and wear, as this only required the repositioning of the components without the need for re-meshing. Recently, such studies have been extended to examine the influence of prosthesis orientation in the implanted proximal femur. The challenge here is the generation of the mesh for each unique instance of implant position. Approaches using deformed meshes or automated mesh generation are being explored. In order to efficiently account for patient variability, the use of statistical shape and intensity models to describe anatomical variation within a patient population is being explored. Such models have the potential to generate thousands of representative models from a much smaller training set. A logical progression of this methodology is to convert these intact femurs into implanted models, thus providing a way for interpatient variability to be included in orthopaedic implant testing. Coupled with the probabilistic techniques, this offers a potentially powerful tool for assessing the next generation of implant designs. Finally, if patient and surgical variability are simulated, there will be a need to integrate musculoskeletal models to ensure that the variation in loads is also accounted for.

Keywords: FEA, statistical shape and intensity models, joint replacement *Corresponding author. Tel.: +44 (0)2380597660; Email address: mtaylor@soton.ac.uk (Prof. Mark Taylor)

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Patient Specific Modelling in Joint Replacement and Trauma Care Pankaj Pankaja*
a

School of Engineering, The University of Edinburgh, Edinburgh, UK

Abstract
Simulating the mechanical behaviour using a numerical representation created on a computer is the definition of modelling employed in this presentation. For modelling of musculoskeletal systems the most commonly used technique is finite element (FE) analysis. The presentation considers briefly the input information required by an FE analysis from the patient specific modelling perspective: geometry; material properties; boundary conditions and interactions; and loadings. It is proposed that the requirements of input quality and patient specificity are determined by the output sought from the FE analysis i.e. many of the questions can be answered well with approximate input data. The examples considered to illustrate this include revision hip replacement with impaction grafting; knee replacement; and fracture fixation using external fixators. The major focus of the presentation is on the assignment of patient specific material properties to bone. We have found that cortical bone becomes more anisotropic with age/increased porosity (see figure below) and as a result it becomes more vulnerable to yielding (or failure) in the less frequently loaded directions. As a result it is important to incorporate both decreased stiffness and increased anisotropy while modelling older patients. Our recent research shows that, for at least some anatomic sites, it is possible to assign these properties using patient specific bone quality parameters measured clinically. The presentation also considers modelling the post-elastic behaviour of bone. For this a simple isotropic, strain-based criterion is proposed. Strain-based criteria require relatively few material properties to be evaluated and no a-priori identification of material orientation. Contrastingly, an anisotropic stress-based criterion requires numerous material parameters to be determined and must be oriented with the physical structure of the bone. This suggests that for bone a strain based criterion is not only biofidelic but also numerically more convenient to employ. The presentation concludes with examples of our ongoing attempts to develop tools that will permit surgeons to use modelling research in the area of fracture fixation.

Figure: Cortical bone images from the anterior femoral mid-shaft of: (a) a 20-year-old female; (b) a 61-yearold female; and (c) an 84-year-old female. Keywords: bone properties, anisotropy, yield criterion

*Corresponding author. Tel.: +44 131 6505800; Fax: +44 131 6506781. Email address:pankaj@ed.ac.uk

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Manufacturers Perspective: Patient Specific Modelling Nikhil Sindhwania*, Erik Boelenb

a

Application Engineer, Mimics Innovation Suite, Materialise NV, Leuven, Belgium b Marketing Manager - Mimics Innovation Suite

Abstract
There is a growing trend towards the personalization of ever more in a variety of surgical disciplines, including orthopaedics, CMF and cardiovascular. The use of 3D medical image information, combined with computer aided engineering tools and processes is vital for the rapid product development of custom and standard implantable devices. Patient-specific implants and guides significantly reduce surgery time. Herein we describe the use of novel techniques to achieve a virtual process flow from patient image data to implant design and analysis, shortening the product development cycle. Figure 1 shows the application of patient specific modeling for simulating wall stresses on a stented and unstented aneurysm. Figure 2 below is an example of a workflow for testing a hip implant. patient care. Personalized treatment planning is adopted

Materialise aims to earn and hold your respect and loyalty by providing products and services of the highest quality and the greatest possible value. On a company level, we maintain ISO 9001 standards. Materialise understands the challenges faced by researchers, manufacturers, or clinicians in the medical (device) industry. Our software, services and production techniques are all certified with CE marks and 510K pre-market clearance, which enables faster translation of our customers products from R&D to clinical applications.

Fig. 1: Comparison of wall stress and flow velocity in a stented and unstented aneurysm; (A) and (B) show wall stress reduction due to stenting, (C) and (D) show that the stent prohibits turbulent flow into the aneurysm, guiding the blood through the artery

Fig. 2: Workflow from image data to FEA model; (A) the original image data, (B) segmentation, (C) 3D model, (D) optimized mesh, (E) material assignment, based on the gray values in (A).

Keywords: Biomedical R&D, Surgical simulation, medical device design, Mimics, 3-matic, quality. *Corresponding author: Nikhil Sindhwani Application Engineer, Mimics Innovation Suite Tel.: +32 16 396 038 Email address: Nikhil.sindhwani@materialise.be

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Image-Based Modelling For Patient-Specific Solutions Philippe Younga,b*, David Raymonta, Ross Cottonb, Rebecca Bryanb
a

School of Engineering, Mathematics and Physical Sciences, University of Exeter, Exeter, UK b Simpleware Ltd., Exeter, UK

Abstract
Although a wide range of mesh generation techniques are currently available, these on the whole have not been developed for meshing from segmented 3D imaging data. The paper will focus on techniques specific to imagebased mesh generation and will also discuss the interface with commercial FEA and CFD packages. A number of examples that cover different applications within patient-specific modelling will be presented. Automated mesh generation techniques can easily generate millions of nodes, leading to larger models to solve. Reducing the model size can therefore have a dramatic impact on computation time, memory and processing power requirements. A proprietary technique allowing the setting of different density zones throughout the model will be highlighted. This allows the overall number of elements required to capture a given geometry to be reduced, while allowing an increase in the mesh density around areas of greater interest will be highlighted. Figure a and b show an example of different density zones on a glenohumeral joint model. Micro-architectures can be generated to conform to an existing domain. Control of the domains mechanical properties is achieved using a re-iso-surfacing technique allowing density variations throughout the architecture and micro-architectures with specific porosities to be generated (c.f. Figure c). The concept of a relative density map to represent the desired relative densities in the micro-architecture where the minimum and maximum porosity values can be specified is introduced. Examples are given of functionally and arbitrary graded structures in both 2 and 3 dimensions. Finally, a new homogenisation algorithm has been implemented. Orthotropic mechanical properties from higher resolution scans can be computed through the innovative use of the meshing techniques discussed here and parallel processing strategies, enhancing the value of the information obtained at micro level, enabling it to be used for macro models on desktop computers. The ability to automatically convert any 3D image dataset into high quality meshes is becoming the new modus operandi for anatomical analysis. New tools for image-based modelling have been demonstrated, improving the ease of generating meshes for computational mechanics and opening up areas of research that would not be possible otherwise.

Figure: Selection of a high density zone (a) and final mesh with different densities on the scapula and the humeral head (b); Variation of the Young's modulus visualised over a functionally graded structure (c) using 2 visualisation techniques - direct (d) and interpolated (e)

Keywords: image-based meshing, micro-architecture, homogenisation

*Corresponding author. Tel.: +44 1392 428750; Fax: +44 1392 428769. Email address: Philippe.G.Young@exeter.ac.uk (Prof. Philippe G. Young)

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Magnetic Resonance Elastography Principles and Applications Jrgen Braun*

Department of Medical Informatics, Charit Universittsmedizin Berlin, Berlin, Germany

Abstract
Magnetic Resonance Elastography (MRE) is an emerging non invasive technology for quantitatively assessing mechanical properties of tissue. The technology can be considered to be an imaging-based counterpart to palpation which is since centuries successfully applied as diagnostic method. Today palpation is still commonly used by physicians to diagnose various diseases located close to the surface of the body. The success of palpation is based on the fact that mechanical properties of tissues are often considerably affected by diseases such as fibrosis, neurodegenerative processes, cardiac insufficiency and cancer. MRE obtains information about elastic and viscous properties of tissue by assessing the propagation of mechanical waves through the tissue with synchronized motion sensitive magnetic resonance imaging (MRI) techniques. MRE involves three essential steps: (i) generation of low frequency shear waves in tissue, (ii) encoding of the resulting harmonic tissue motion into MR phase images, and (iii) processing the acquired image data to generate quantitative maps of elastic tissue properties. To achieve sustained diagnostic success and a better understanding of the progression of diseases it would be preferable to link measured macroscopic properties to underlying changes in cellular structure. For this purpose rheological models can be used and fitted to experimental data. MRE is already being used clinically for the staging of hepatic fibrosis and was recently successfully applied to various types of neurodegenerative diseases like multiple sclerosis and normal pressure hydrocephalus. MRE is also being used for the measurement of pressure related properties, e.g. for the assessment of myocardial function and diagnoses of cardiac insufficiency. Furthermore, the technique is investigated for the application to pathologies of other organs including the lung, skeletal muscle, breast, kidneys and prostate. The purpose of the presentation is to introduce the basic principles of MRE, to present results of some of the current applications in human and animal studies and to show how changes of viscolelastic tissue properties may be linked to structural alterations on the cellular level.

Keywords: elasticity imaging, mechanical properties, rheological models

*Corresponding author. Tel.: +49 30 450544511; Fax: +49 30 450544901. Email address: juergen.braun@charite.de (Dr. Jrgen Braun)

20

Ultrasound Elastography Jeffrey C. Bamber*

Joint Department of Physics, The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey, SM2 5PT, UK

Abstract
Ultrasound elastography aims to display images that are related to a broad range of tissue biomechanical characteristics, and does so by processing time-varying echo data to extract the spatial and/or temporal variation of a stress-induced tissue displacement or strain. Once extracted, the displacement or strain may be viewed directly as a qualitative image which has useful biomechanical property contrast, or may undergo further processing to generate quantitative images, such as those of Youngs modulus. Many sources and types of stress have been employed, including hand-induced motion at the surface of the body, impulsive acoustic radiation force deep within it, harmonic vibrations, and natural (cardiovascular) sources of motion. The method, in relatively early form, has emerged as a real-time imaging modality, and is available as an option on most highend commercial ultrasound systems. It was also the primary motivation for the development of novel commercial ultrasound system architecture, necessary for the creation of an ultrasound scanner that images Youngs modulus by measuring the speed of shear waves generated using acoustic radiation force. All of these systems have started to prove clinically valuable in many areas, including breast cancer diagnosis, thyroid conditions, cardiovascular disease, characterisation of liver disease and intra-operative surgical guidance. Nevertheless, there is considerable potential for improvement, in image quality, speed of measurement and presentation, correction for sources of unwanted variation, separation of variables and image property quantification. Current research is focusing on these areas, and particularly on making the images more robust, taking advantage of three dimensional ultrasound echo acquisition methods, gaining a better understanding of the relative importance of the many different mechanical characteristics of tissue (such as shear storage modulus, loss modulus, frequency dispersion, non-linearity, anisotropy, porosity, permeability, and mechanical continuity) in disease specific situations, and solving inverse mechanical problems while taking account of organ and disease specific boundary conditions. This presentation reviews some of this work and describes a selection of recent studies. It is concluded that ultrasound elastography encompasses a broad range of imaging techniques which may produce data that have considerable potential for use as input to patient-specific biomechanical models, and that there may be potential to improve the quality of elastograms, and further broaden the use and value of elastography, through the application of situation-specific modelling techniques.

Keywords: ultrasound, imaging, elasticity, biomechanical

*Tel.: +44 20 661 3343; Fax: +44 20 8643 3812. Email address: jeff@icr.ac.uk (Dr. Jeffrey C. Bamber)

21

ABSTRACTS FOR POSTER PRESENTATION

22

Simulation Of Haemodynamic Flow In Head And Neck Cancer Chemotherapy: A Patient Specific Modelling Stephan Rhodea, Manosh C. Paula*, Eckhard Martensb, Duncan F. Campbellc
School of Engineering, University of Glasgow, Glasgow G12 8QQ, UK Department of Mechanical Engineering, University of Applied Sciences, 76133 Karlsruhe, Germany c Department of Oral & Maxillofacial Surgery, Queen Margaret's Hospital, Fife, UK
b a

Abstract
Intra arterial chemotherapy has become an important component in head and neck cancer treatment. However, therapy success varies significantly and consistent treatment guidelines are missing. The purpose of this study was to create a computer simulation of the chemical agent injection in the head and neck arteries to investigate the distribution and concentration of the chemical. Realistic three-dimensional patient specific geometry was created from image scan data. Pulsatile blood flow, turbulence, the chemical agent injection via a catheter, and the mixture between blood and the chemical were then simulated through the arterial network. The results show that the modelled catheter position produces an ineffective chemical distribution consistent throughout all the arteries. In addition, due to high wall shear stress and turbulence at the inner bifurcation wall, serious complications during the treatment could occur, for instance haemolysis or thrombosis.

Keywords: patient specific model, blood flow dynamics, non-Newtonian, chemotherapy, multiphase model

*Corresponding author. Tel.: +44 0141 330 8466; fax: +44 0141 330 4343. Email address: Manosh.Paul@glasgow.ac.uk (Manosh C. Paul)

23

GlasgowHeart: A Personalized Computational Platform For Human Left Ventricle Hao Gao a,b, Colin Berrya,c, John Soraghanb, Xiaoyu Luod*
BHF GCRC, University of Glasgow, CeSIP, Dept. of EEE, University of Strathclyde, c Golden Jubilee National Hospital, Scotland, d School of Mathematics and Statistics, University of Glasgow
b a

Abstract
Heart failure resulted from myocardial infarction (MI) has been considered to be one of the leading causes of death in the world. Currently more and more people are living with injured heart, while the quality of life varies from patients to patients. Therefore there is a need to apply personalized treatments to different patients. Computational models have evolved to be an important tool for understanding heart diseases, and have the potential for guiding and optimizing the treatments. In this project, a platform named the GlasgowHeart is being developed which aims to bring magnetic resonance imaging (MRI) of human left ventricle, medical imaging processing, and mathematical modelling together. MRI imaging: has been widely used in clinical diagnosis of heart disease, including (1) anatomical MRI, which can provide the geometry information and motion; (2) pathological MRI, such as late-enhanced MRI for MI scar, T2-weighted MRI for edema which has been used to guide the therapy[1]; (3) other MRI sequences, such as in-vivo strain measurement by DENSE, and myocardial fibre reconstruction by DT-MRI. Medical Imaging Processing: is the first step for computational modelling of human hearts. Since the images from a MRI scan consist of many slices, manual processing is tedious and time-consuming. Therefore computerized processing methods are required. We have developed the level set methods for left ventricle (LV) boundary segmentation with possible manual adjustment if needed. This can provide an accurate LV boundary for 3D geometry reconstruction. In addition, a fully automatic method has been proposed for edema quantification[2]. The reliable and accurate imaging processing will be essential for successful modelling of individual human heart. Computational modelling: After imaging processing, personalized geometry and pathological information can be integrated together for comprehensive patient specific modelling, such as geometry/motion analysis, strain/stress computation using the finite element method. Fluid structure interaction inside the LV can also be simulated using the immersed boundary methods[3]. The results from computational modelling will be translated into clinical benefits for the patient in the future. In conclusion, a platform (GlasgowHeart) for the computational modelling of individual patients heart has been outlined. This represents the first step towards a personalized modelling of human heart. References [1] Payne AR, et al., Circ Cardiovasc Imaging 2011. [2] Kadir K, et al., EMBS 2011, Boston [3] Luo XY, et al., Effect of bending rigidity in a dynamic model of a polyurethane prosthetic mitral vlave, (under revision) Biomechanics and modelling in mechanobiology

Keywords: Left Ventricle, MRI, Medical Imaging Processing, Computational modelling

*Corresponding Author. Tel.: +44 (0)141-330 5176 Email: xiaoyu.luo@glasgow.ac.uk

24

Age-Related Changes In Geometry And Blood Flow In The Rabbit Aorta Vronique Peifferab*, Min Rowland a,b, Peter D. Weinbergb, Spencer J. Sherwina
b

Department of Aeronautics, Imperial College London, London, United Kingdom Department of Bioengineering, Imperial College London, London, United Kingdom

Abstract
A better understanding of atherosclerosis, the disease underlying most heart attacks and strokes, is an essential step in the efforts to decrease the global burden of cardiovascular disease. The distribution of atherosclerotic lesions has been observed to change with age in the aorta of humans and rabbits: atherosclerosis moves from downstream to the lateral sides and upstream of aortic branch ostia, and longitudinal streaks of disease in the descending aorta become more pronounced. We investigated if this reflects a change in geometry or blood flow characteristics such as wall shear stress (WSS). Luminal geometries of thoracic aortas from immature and mature rabbits were obtained by vascular corrosion casting. Micro-CT scanning of these casts resulted in high quality in silico reconstructions (voxel sizes of ~50 m). The aortic anatomy clearly varied between rabbits; most striking were the differences in the branching configuration of the aortic arch (see Figure). A geometric analysis showed that there was no clear age-related difference in the evolution of curvature and torsion along the aortic centreline, but the aortic arch was more tapered in mature than in immature animals. Steady blood flow was simulated in the aortic geometries using a spectral/hp element solver (Nr, www.nektar.info). At the aortic root a blunt velocity profile (Re=300) was applied; flow splits to the branches were based on in vivo measurements and Murrays law. Dean-type vortical structures developed in all geometries. Whilst these were confined to the aortic arch in the immature geometries, they extended into the descending aorta in the mature geometries. This difference could be explained by the change in the degree of aortic taper. The non-dimensional WSS was higher on the dorsal side of the descending thoracic aorta than on the ventral side. This stripe of high WSS was more pronounced in mature rabbits, and coincided with a highly diseased zone in this age group. WSS was increased downstream and to a lesser extent upstream of the origins of intercostal arteries. These results do not obviously correlate with the hypothesis that low shear promotes atherosclerosis disease. Relaxation of modelling assumptions (e.g. steady instead of pulsatile flow) could not alter this conclusion.

Figure: In silico reconstructions of immature (left) and mature (right) rabbit aortas.

Keywords: Atherosclerosis, Shear stress, Computational Fluid Dynamics, Age

*Corresponding author. Tel.: +44 20 7594 5126. Email address: v.peiffer09@imperial.ac.uk (Vronique Peiffer)

25

Accurate Shear Stress Characterization In Porcine Arteries For Future Transcriptome Analysis A. De Lucaa,b*, C.M. Warboysa, N. Aminia, R. Kramsc, D.O. Haskarda, D. Firmind, S. Sherwinb, P.C. Evansa
a b

British Heart Foundation Cardiovascular Sciences Unit, National Heart and Lung Institute, Department of Aeronautics, c Department of Bioengineering, and d Biomedical Imaging Unit, National Heart and Lung Institute, Imperial College London, UK.

Abstract
Atherosclerosis is a focal disease that occurs predominantly at regions of the arterial tree that are exposed to disturbed blood flow. Wall shear stress (WSS), a mechanical force that is exerted by flowing blood on the lumen of arteries, influences the focal nature of atherosclerosis by altering endothelial cell (EC) physiology. Although the molecular mechanisms underlying the effects of shear stress on EC physiology are poorly understood, they are known to involve transcriptional changes. Previous studies1,2 have compared EC physiology at atheroprotected and atherosusceptible regions of the porcine aorta, these observations have not been correlated to spatial differences in WSS. Here we employed magnetic resonance imaging (MRI) and computational fluid dynamics to characterize the flow patterns in the porcine aortic arch. Geometries of the aorta were acquired by ECG-gated Black Blood Turbo Spin Echo vessel-wall imaging MR using a 3T whole body MR scanner (Siemens). Flow was measured in the volume of interest using 3D Phase Contrast MRI. The three velocity components were acquired over the cardiac cycle at a site just above the aortic valve, at the descending aorta and at the branches of the aortic arch. The wall shear stress analysis was carried out using Fluent 6.2, a commercial CFD solver, and the fluid behaviour was modelled in steady conditions. We observed that the inner curvature of the aortic arch was exposed to lower average WSS compared to the outer curvature. Interestingly, the inner aspect of the descending thoracic aorta (a region considered to be protected from atherosclerosis) was relatively low. The outer curvature exhibited more heterogeneous patterns with high shear stress downstream the subclavian arteries. The WSS maps were used as an indication for EC isolation for subsequent transcriptome analysis. Our results revealed significant spatial heterogeneity in WSS in porcine arteries and challenged common assumptions about the mechanical environment at atherosusceptible and atheroprotected regions. Shear stress maps of porcine arteries will inform future studies of the influence of mechanical forces on endothelial physiology.

References 1. Passerini, A, et al. "Coexisting pro-inflammatory and anti-oxidative endothelial transcription profiles in a disturbed flow region of the adult porcine aorta." Procl Natl Acad Sci USA 101 (2004): 2482-87. 2. Civelek, M, E Manduchi, RJ Riley, CJ Stoeckert, and PF Davies. Chronic endoplasmic reticulum stress activates unfolded protein response in arterial endothelium in regions of susceptibility to atherosclerosis. Circ Res 105, no. 5 (2009): 453-461.

*Corresponding author: amalia.de-luca08@imperial.ac.uk

26

Multicompartmental Poroelasticity for the Multiscalar Modelling of CSF Production and Circulation in the Brain
John C. Vardakis, Brett Tully, Yiannis Ventikos* Institute of Biomedical Engineering and Department of Engineering Science, University of Oxford, Oxford, OX1 3PJ UK

Abstract
Hydrocephalus is a neurological disorder connected with abnormal flow of the cerebrospinal fluid (CSF) and is characterised by an active distension of the cerebral ventricles. It has no known cure and current treatment techniques exhibit an unacceptably high failure rate [1, 2]. A key complication associated with studying the transport of CSF, for this condition and others, stems from the fact that this water-like fluid does not act in isolation: exchange of water and ions between CFS spaces and the vasculature is continuous and apparently coupled with arteriole/capillary fluxes and possibly with cell channel fluxes. A detailed investigation of multiscalar, spatio-temporal transport of fluid between the cerebral blood, CSF and brain parenchyma is conducted. Specifically, the use of Multiple-Network Poroelastic Theory (MPET) to model the cerebral tissue is coupled with a threedimensional representation of the CSF open flow domain within a patient-specific cerebroventricular system (Figure). Anatomically accurate Choroid Plexuses are investigated as there is little doubt that CSF is primarily produced here [3]. Currently, an accepted depiction of a choroid plexus can be loosely defined as a highly vascularised entity, consisting of leaky plexus capillaries [4]. An ensuing investigation into these plexuses is established, owing to their presence at different sites within the cerebral ventricles. Finally, select surgical interventions (Third Ventriculostomy) are applied to this ventricular model, along with a simple incorporation of aquaporin water channels [5]. Figure: Geometry of a human ventricular system (VS) showing key anatomical features The novelty and most appealing feature of this modelling platform is that it allows for a natural incorporation of all transport processes from the microscopic scale of the aquaporins all the way to large ventricular or arterial spaces. This is accomplished by allowing for the assigning of different properties to specific discretised computational cells, but also for providing the facility to capture exchange processes, at all scales, either using resistance/transport constants, or, where the information is available, by using process-specific sub-models that are naturally embedded in the MPET framework. References
[1] Drake, J., Kulkarni, A., Kestle, J. (2009). Endoscopic third ventriculostomy versus ventriculoperitoneal shunt in pediatric patients: a decision analysis. Child's Nervous System. 25 (4), 467-472. [2] Tuli, S., Alshail, E., Drake, J. (1999). Third Ventriculostomy versus Cerebrospinal Fluid Shunt as a First Procedure in Pediatric Hydrocephalus. Pediatric Neurosurgery. 30, 11-15. [3] Oreskovic, D., Klarica, M. (2010). The formation of Cerebrospinal Fluid: Nearly a hundred years of interpretations and misinterpretations. Brain Research Reviews.64, 241-262 [4] Abbott, J (2004). Evidence for bulk flow of brain interstitial fluid: Significance for physiology and pathology. Neurochemistry Intl. 45 (4), 545-552 [5] Brian, O. K., Tom, P., & Wang, D. (2010). Aquaporins: relevance to cerebrospinal fluid physiology and therapeutic potential in hydrocephalus. Cerebrospinal Fluid Research, 7(15), 1-12

Keywords: Aquaporins, Choroid Plexus, Hydrocephalus, Poroelasticity * Email address: yiannis.ventikos@eng.ox.ac.uk (Prof. Yiannis Ventikos)

27

A Computational Model of Thrombus Development Malebogo N. Ngoepe, Timothy J. Bowker, Yiannis Ventikos*
Fluidics and Biocomplexity Group, Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford, United Kingdom

Abstract
The haemostatic system ensures that the circulatory system remains intact. If the balance maintained during the process of coagulation is disrupted, the resulting pathology could be thrombosis if the procoagulant system is favoured and haemophilia if the anticoagulant system dominates. At times, it is desirable to induce a clot. The aim of some of the treatment methods employed for aneurysms is to induce a clot in the aneurysm, interrupting flow to the sac and restoring it along its original path. The main challenge with inducing a clot is that thrombus development is dependent on the specific patients blood composition, haemodynamic environment and endothelial cells. A computational model which is able to predict thrombus growth in a specific patient would therefore be a desirable tool for interventional planning. A two-dimensional model which incorporates fluid flow and coagulation reactions was developed. An idealised artery of radius r = 10mm was chosen as the region of interest. To initiate the process of coagulation, tissue factor, an integral membrane protein, is expressed along a damaged portion of the vessel wall. This results in the formation of a small amount of thrombin. Once the thrombin concentration for a given computational cell reaches a threshold value of 1pM, the cell assumes porosity and permeability values designated to the clot region (0.75 and 110-12m2 respectively). This distinguishes the growing clot region from the rest of the fluid domain. The clot region then expresses tissue factor and is able to support some of the reactions which have been known to occur on platelet surfaces but not in the rest of the fluid domain. The eventual result of the interaction between the fluid zone and the biochemical reactions is amplification in the amount of thrombin generated. Anticoagulant proteins present ensure that the system is regulated and early qualitative results show typical behaviour in the amount of thrombin formed. Figures 1 illustrates the growing clot in the idealised artery and its impact on the flow field. Future work will focus on implementing the model in realistic three-dimensional geometries.

Figure 1: The growing clot porosity (top) and its impact on the flow field (bottom)

Keywords: thrombus, patient-specific, biochemical coagulation models

*Corresponding author. Dept:+441865283452, Wadham:+441865277944 Email address: yiannis.ventikos@eng.ox.ac.uk (Prof. Yiannis Ventikos)

28

Establishment of Magnetic Resonance Elastography at the Clinical Research Imaging Centre (CRIC) Paul Kennedya*, David Gowb, David Donaldsonc, Angus Hunterd, Fredericke van Wijcke, Edwin van Beeka, Neil Robertsa
Clinical Research Imaging Centre, The University of Edinburgh, Scotland Southeast Mobility and Rehabilitation Technology (SMART) Centre, Edinburgh, Scotland c Department of Psychology, University of Stirling, Scotland d Department of Sports Science, University of Stirling, Scotland e Institute for Applied Health Research and School of Health, Glasgow Caledonian University, Scotland
b a

Abstract

Magnetic Resonance Elastography was first described by Muthupillai et al. in 19951. It is a non invasive phasecontrast based technique that allows the direct visualisation and measurement of mechanical vibrations in the form of acoustic waves as they travel through a tissue. The mechanical waves are induced through an actuator which is placed on or near the organ under investigation. The actuator is affixed to a non magnetic rod which transmits the vibrations from a powerful loudspeaker. A waveform generator allows the modification of the frequency and amplitude of the induced mechanical wave. A conventional magnetic resonance imaging (MRI) sequence with the addition of a motion encoding gradient (MEG) along a specific direction is used. In the presence of the MEG any periodic motion of the spins will cause a phase shift in the MR signal. From this phase shift the displacement at each voxel can be calculated. Here we present the current stage of MRE development at CRIC. Ongoing projects include the introduction of an EPI based MRE sequence allowing rapid image acquisition. A similar sequence has been employed by a collaborating group in Charit University, Berlin2. A rapid acquisition sequence is necessary for cardiac and liver studies which require breatholding. A slower FLASH based sequence has been successfully compiled on the 3T MRI scanner and preliminary investigations have been carried out. A collaboration with the Southeast Mobility and Rehabilitation Technology (SMART) Centre, Edinburgh is also being developed. MRI already plays a significant role in diagnosis of residual limb pain3. We aim to expand on this and contribute to the improved design of individual prostheses using MRE. Applications in the Sports Science arena are also being pursued with Dr. Angus Hunter in the University of Stirling in collaboration with the Scottish Institute of Sport. References: 1: Muthupillai, R. et al. Science, 1995. 269: 1854-1857 2: Klatt, D. et al. Physics in Med. and Bio. 21:6445-6459 3: Henrot, P., Stines, J. et al. Radiographics, 2000. 20:219-235

Keywords: Magnetic Resonance Elastography, MRE, EPI, Stiffness, Muscle.

*Corresponding author. Tel.: +44 131 242 7774; Fax: +44 131 242 7773. Email address: s1064505@sms.ed.ac.uk

29

The Importance Of Modelling Bone-Implant Interface In Locking Plate Finite Element Models Alisdair MacLeodab*, Pankaj Pankajab, Hamish Simpsona
a

Edinburgh Orthopaedic Engineering Centre, The University of Edinburgh, UK b School of Engineering, The University of Edinburgh, UK

Abstract
Finite element modelling is being extensively used to evaluate the biomechanical behaviour of fractured bone treated with fixation devices. Appropriate modelling of the bone-implant interface is thought to be of primary importance for quality biomechanical prediction. The present study considers this interface modelling in the context of locking plates. The majority of previous studies assume the interface to be represented by a tied constraint or a fully bonded interface. Many other studies incorporate a frictional interface but ignore screw threads. This study compares the various interface modelling strategies. An idealised three-dimensional geometry of the tibial diaphysis was developed using a standard left composite tibia. A finite element study was conducted with varying screw-bone contact interactions: tied contact with the screw as a simplified cylinder; tied contact; frictional contact; frictionless contact. The study finds that interface modelling has significant impact on local behaviour within the bone, with the stress-strain environment close to the screws being altered. This means that different contact interfaces will have different predictions for screw loosening, bone damage and stress shielding. Globally, the load-deformation behaviour shows much less difference due to the interface conditions. The results demonstrate that the widely used tie constraint can be used effectively for finite element models where the only interest is the global load-deformation behaviour; however, the local behaviour cannot be accurately represented. Correctly predicting the performance of a construct around screw locations would be beneficial in preventing stress concentrations which lead to loosening or periprosthetic re-fracture, especially in osteoporotic bone.

b Figure: Strain contours around a) a tied contact interaction b) a frictional contact interaction

Keywords: Finite-element model; Screw-bone interface; Locking plate fixation; Tibia

*Corresponding author. Tel.: (+44) 01316505790 Email address: a.macleod@ed.ac.uk (Alisdair MacLeod)

30

Modelling to Capture the Mechanical Environment in the Femur Noel Conliska,b*, Pankaj Pankaja,b, Colin Howieb
b

School of Engineering, The University of Edinburgh, Edinburgh, UK Edinburgh Orthopaedic Engineering Centre, The University of Edinburgh, Edinburgh, UK

Abstract
Finite element (FE) modelling of the musculoskeletal structure requires appropriate input of the geometry of the system being considered, material properties of different components, loading regimes and boundary conditions (i.e. the manner in which the system is supported). This study focuses on the effect that boundary conditions have on the mechanical environment in the distal femur. The model geometry was based on the Standardised Femur [1]. Linear isotropic elastic material properties were assumed for cortical and cancellous bone. Two different boundary conditions were applied to the FE model. In the first the displacements at the mid-shaft of the femur were restrained in all three directions (Fig. 1a). The second model was created with no restraints applied to the femur itself; instead muscles and ligaments structures were attached to support the femur. Each of the muscle origin points that did not lie on the femur was assumed to be restrained at the location of its insertion point (Fig. 1b). Identical loads, corresponding to a single legged stance, were applied computationally at the femoral condyles to both models and the internal forces/deformations computed. In this instance muscles and ligaments were modelled as linear elastic connector elements with stiffness for each element based on a previous study [2]. Loading data corresponding to a single legged stance was obtained from telemetric implant studies to determine realistic in-vivo loads acting on the hip and knee joints [3]. These loads were then applied to the femur as distributed pressure loads rather than as concentrated point loads over realistic contact areas.

Figure: a) Fixed and b) Musculoskeletal boundary conditions The femur restrained at the mid-shaft produces significantly higher stresses along the shaft in comparison to the femur supported by muscle and ligaments structures. However this study also highlights that the stress distribution across the distal femur for both models is very similar suggesting that the fixed boundary conditions have minimal effects in regions close to load application. The implications of this work are that if the mechanical environment of the entire femur is required the boundary conditions need to be appropriately modelled to produce reliable results. However, if the mechanical stress/strain field close to the region of load application is required (e.g. to examine knee replacement components) simple restrained boundary conditions can provide acceptable results.

References
1. Viceconti, M. (2003). Journal of Biomechanics, 36, 145-146. 2. Phillips ATM, Med Eng Phys, 2009, 31:673-680. 3. Bergmann, G. 2008; Available from: www.orthoload.com

Keywords: Femur, TKA, musculoskeletal, finite element, *Corresponding author. Tel.: +7775332506. Email address: n.conlisk@ed.ac.uk (Mr Noel Conlisk)

31

A biomechanical study on the effect of fracture intrusion distances in three-part trochanteric fractures treated with Gamma nail and sliding hip screw Jerome M. Goffina*, Pankaj Pankajb, A. Hamish Simpsona
a

Edinburgh Orthopaedic Engineering Centre, The University of Edinburgh, Edinburgh, UK b School of Engineering and Electronics, The University of Edinburgh, Edinburgh, UK

Abstract
We compared the biomechanical performance of the Gamma nail and the sliding hip screw used for the fixation of 3-part trochanteric fractures (31-A2.1 in the AO classification) using finite element analysis. We varied the size of the medial fragment based on clinical data. We show that, as the size of the medial fragment increases, the peak stresses in the lag screw of the sliding hip screw are considerably higher than in the lag screw of the Gamma nail. We also show that, as the size of the medial fragment increases, a greater volume of cancellous bone is likely to yield and therefore more likely to be involved in the cut-out of the lag screw. When the size of the medial fragment exceeds 35% of the width of the femur, the volume of bone susceptible to yield dramatically increases when a sliding hip screw is used. In conclusion, we have identified a subtype of fracture (31-A2.1 with large medial fragments) for which there could be smaller risks of cut-out if an intramedullary nail was used instead of the sliding hip screw. Our findings suggest that future clinical trials investigating fixation of unstable proximal fractures should include the size of the medial fragment as a covariable and be powered to evaluate whether intramedullary devices are superior to sliding hip screws for this subset.

Keywords: finite element analysis, osteosynthesis, cut-out

*Corresponding author. Tel.: +44 (0)131 242 6465. Email address: jerome.goffin@uclmail.net

32

Photogrammetry as a Cost Effective Geometric Reconstruction Technique: Investigation of Reliability and Suitability for Bioengineering Use Stephen Broderick, Barry Doyle, Michael Walsh*
Centre for Applied Biomedical Engineering Research (CABER), Mechanical, Aeronautical & Biomedical Engineering, and the Materials and Surface Science Institute, University of Limerick, Ireland

Abstract
The imaging method of MRI, CT and ultrasound are well established in the medical and biomedical field. However, they are not without their disadvantages. Ultrasound can be noisy and requires contact for images. CT requires contrast dye and exposes the patient to radiation. While MRI is expensive and requires long acquisition times. The goal of this study is to examine if photogrammetry can be used for medical imaging in a surgical environment. Photogrammetry is the use of image data from cameras to triangulate corresponding points from 2D space into 3D positioning. The benefits of this method in medical imaging during surgery are its ease of use, low cost, rapid data acquisition, non contact and flexibility within a surgical environment. The method was tested using a rubber model of an Abdominal Aortic Aneurysm (AAA) with known dimensions. Images were taken of the AAA model and processed to obtain the point cloud data of the model. This was compared to the geometrically to the computer data of the rubber model. This was repeated two more times to examine variability in the method. As well as variation in geometry using this method, the geometries were also examined using common biomedical metrics in Computation Fluid Dynamics (CFD) and Finite Element Analysis (FEA). This was also compared to the computer data of the rubber model, to examine how well the reconstructions represented the numerical solutions and if the same conclusions could be made from such reconstructions. Approximately 50% area was within 1% of the control geometry, with the proceeding 25% area below 2% error. On average the worst error was in the 4-5% error but only was occupied by 2% area. General trends were represented in the FEA and CFD with peak values lower than the control geometry. However with FEA, 85% area was within 10% of the control value, while with CFD, 95% area was within 10% of the control value.

0%

5%

(a)

(b)

(c)

Figure: (a) the reconstruction process of the rubber model from images to 3D data, (b) the error distribution of one of the unwrapped cases, (c) examples of wall shear stress magnitude distribution (top) from CFD and Wall stress from FEA (bottom) unwrapped.

Keywords: Photogrammetry, Cost effective, Reconstruction, Validation

*Corresponding author. Tel.: +353-61-202367; Email address: Michael.Walsh@ul.ie

33

A Computational Simulation of MRE through Patient Specific Diseased Arterial Geometry Lauren Thomas-Sealea*, Dieter Klattb, Ingolf Sackb, Pankaj Pankajc, Neil Robertsd, Peter Hoskinsa
Department of Medical Physics, The University of Edinburgh, Edinburgh, UK MR Elastography Group, Charit Universittsmedizin Berlin, Berlin, Germany c School of Engineering, The University of Edinburgh, Edinburgh, UK d Clinical Research Imaging Centre, The University of Edinburgh, Edinburgh, UK
b a

Abstract
The assessment of the rupture risk of atherosclerotic plaque is commonly made using a measurement of lumen reduction, either by angiography or ultrasound. However it is known that this is an imperfect criterion, and that other features related to the composition, the stiffness of the plaque constituents and the mechanical stresses within the plaque, may be more relevant. Magnetic resonance elastography (MRE) is a novel method of imaging tissue stiffness. Phase contrast MRI measures the tissue deformation in response to a harmonic shear wave induced by an external actuator. An image of stiffness, known as an elastogram, is created by applying an inversion algorithm to the complex wave images. MRE through arterial geometry can be simulated using finite element analysis (FEA). A frequency response analysis yields a complex wave image at the excitation frequency of the applied shear wave. Synonymous with the complex wave image gained from experimental MRE; this serves as the input data for the wave inversion algorithm which yields an elastogram. The aim of this study is to run a preliminary simulation of MRE through a finite element model of patient specific diseased arterial geometry. The 3D FEA geometry was created from a set of MR images through a diseased carotid bifurcation. The vessel geometry was embedded in a block of tissue to replicate the transmission of MRE shear waves in-vivo. A harmonic shear load was applied to the surface of the tissue above the vessel, and a frequency response analysis was simulated at the corresponding excitation frequency. A 2D matrix of the complex deformation results were taken and transformed into an elastogram using the algebraic Helmholtz wave inversion algorithm. An elastogram shall be presented through a cross section of the carotid geometry at an excitation frequency of 200Hz.

Keywords: Atherosclerosis, Elastography, MRI, FEA *Corresponding author. Tel.: +44 131 2426307 Email address: L.E.J.Thomas@sms.ed.ac.uk (Mrs Lauren Thomas-Seale)

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The Importance Of Biomechanical Modelling In Abdominal Aortic Aneurysm RuptureRisk Prediction Barry Doylea,b*, Peter Hoskinsb, Tim McGloughlina
Centre for Applied Biomedical Engineering Research (CABER), Department of Mechanical, Aeronautical and Biomedical Engineering, and the Materials and Surface Science Institute, University of Limerick, Limerick, Ireland. b Medical Physics, The University of Edinburgh, Edinburgh, UK.
a

Abstract
Approximately 500,000 new cases of abdominal aortic aneurysm (AAA) are reported worldwide each year, resulting in about 8,000 AAA-related deaths per year in the UK alone. The current approach to AAA management and treatment relies heavily on size, primarily diameter. However, it is now well established that the biomechanics of the disease play an important role in rupture-potential, as failure will occur when the local wall stress exceeds the local wall strength. Several alternative rupture-risk parameters have been suggested over the years, such as the centreline asymmetry of the aneurysm and a finite element analysis rupture index (FEARI) which couples the numerically-predicted wall stress to the mechanical wall strength. In this study, 52 cases of AAA (repaired, n=42 and ruptured, n=10) were retrospectively analysed and compared for rupture-risk based on asymmetry and the FEARI. 3D reconstructions were created using Mimics (Materialise) and wall stress determined using ABAQUS (Simulia). All wall stress results were deemed to be independent of the mesh size when the difference in peak wall stress was 2% from the previous mesh size. Results indicate that maximum wall stress () was 51% higher in the ruptured cases (=0.89 v 0.57 MPa, P=0.018). Asymmetry was 33% higher in the ruptured cases and more significantly correlated to maximum wall stress than maximum diameter in both the repaired group (P=0.002 v P=0.032) and the ruptured group (P=0.033 v P=0.174). FEARI was also 60% higher for the ruptured group (1.04 v 0.65, P=0.02). Our numerical methods to determine rupture-prediction have been validated using with patient-specific AAA phantoms in various experimental set-ups and also in several clinical cases. The findings and methods reported here could help contribute to the better understanding of AAA rupture-risk prediction and with further work and rigorous validation, may someday find their way into the clinicians toolkit.

Figure: (A) Method of determining asymmetry from AAA centrelines. (B) the FEA-predicted wall stress contours for a AAA case with peak stress indicated the with black dot. (C) Regions of the AAA that relate to specific wall strengths. Wall stress can then be coupled to wall strength to determine the FEARI.

Keywords: aneurysms, patient-specific modelling (PSM), rupture-risk

*Corresponding author. Tel.: +353 61 2026309, +44 131 2426307 Email address: Barry.Doyle@ul.ie (Dr. Barry Doyle)

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CONTACT LIST
Name Adrian Ionescu Ajit Yoganathan Alistair McLeod Amalia De-Luca Anis Shuib Barry Doyle David Hardman Hamish Simpson Hao Gao Henrik Gollee Ian Marshall Igor Sazonov Janet Powell Jason Xie Jeff Bamber Jennifer Richards Jerome Joffin Joaquim Peiro John Vardakis Jonathan Gillard Jrgen Braun Kateryna Spranger Lauren Thomas-Seale Malebogo Ngoepe Manosh Paul Mark Taylor Neil Roberts Nikhil Sindhwani Noel Conlisk Pankaj Pankaj Paul Kennedy Perumal Nithiarasu Peter Hoskins Philip Riches Philip Rowe Philippe Young Prashant Valluri Ralph Muller Rhodri Bevan Simon Maxwell Stephen Broderick Tim McGloughlin Vronique Peiffer Xiaoyu Luo Affiliation Swansea NHS Georgia Tech, USA Edinburgh University Imperial College Edinburgh University Edinburgh University & University of Limerick Edinburgh University Edinburgh University Glasgow University Glasgow University Edinburgh University Swansea University Imperial College Swansea University ICR, Sutton Edinburgh University Edinburgh University Imperial College Oxford University Cambridge University Charit, Berlin Oxford University Edinburgh University Oxford University Glasgow University Southampton University Edinburgh University Materialise Edinburgh University Edinburgh University Edinburgh University Swansea University Edinburgh University Glasgow University Glasgow University University of Exeter & Simpleware Edinburgh University ETH Zurich Swansea University Edinburgh University University of Limerick University of Limerick Imperial College Glasgow University Email adrian.ionescu@wales.nhs.uk ajit.yoganathan@bme.gatech.edu a.macleod@ed.ac.uk amalia.de-luca08@imperial.ac.uk a.shuib@ed.ac.uk barry.doyle@ul.ie d.hardman@sms.ed.ac.uk hamish.simpson@ed.ac.uk hao.gao@glasgow.ac.uk h.gollee@mech.gla.ac.uk ian.marshall@ed.ac.uk i.sazonov@swansea.ac.uk j.powell@imperial.ac.uk x.xie@swansea.ac.uk jeff@icr.ac.uk jenny.richards@ed.ac.uk jerome.goffin@uclmail.net j.peiro@imperial.ac.uk john.vardakis@eng.ox.ac.uk jhg21@cam.ac.uk juergen.braun@charite.de kateryna.spranger@eng.ox.ac.uk s0954267@sms.ed.ac.uk malebogo.ngoepe@gmail.com manosh.paul@glasgow.ac.uk m.taylor@soton.ac.uk neil.roberts@ed.ac.uk nikhil.sindhwani@materialise.be n.conlisk@ed.ac.uk pankaj@ed.ac.uk s1064505@sms.ed.ac.uk p.nithiarasu@swansea.ac.uk p.hoskins@ed.ac.uk philip.riches@strath.ac.uk philip.rowe@strath.ac.uk philippe.g.young@exeter.ac.uk prashant.valluri@ed.ac.uk ram@ethz.ch r.bevan@swansea.ac.uk smaxwell@staffmail.ed.ac.uk stephen.broderick@ul.ie tim.mcgloughlin@ul.ie v.peiffer09@imperial.ac.uk xiaoyu.luo@glasgow.ac.uk

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