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Viktoriya Antonova Simulation tools for mitral valve repair

1. Loading data Mitral valve parameters Material properties Visualization parameters Custom Color palette while showing the mitral valve model uud 00 Free edge 3Hfffb2 J Anterior leanet Posterior leaflet tx p The 3D finite element was generated Please find it in the Marginal chordae t pyFormex view screen n Basal chordae tend p 0446708_SV_hemodynamic_data thick_leafpos 0 25 4 Chordae tendineae None rdaetype truss Simulation parameters Noi leafant 117 poisson ratio leafant 0 Ch Export all of the ete ort to Ab inp fil kl leafant 11 0069 k2 leafant 84 8478 ki Borat parameters Exh o Seas on itio leafpos 0 355 enable6 True Posterid rp nr r 144 4848 kappa leafpos 0 0534 Custom Color palette while showing the mitral valve model None colorl amp ff0000 color2 ffff00 color3 ffffb2 color4 55aa00 color5 ffaa7f color6 aa55ff color7 4ccce6 Project None Script mv simulation 2014 05 27 py Cwd May Figure 51 MitralValvepyF Preview of FEA mitral valve model pop up Once the message appears a 3D finite element FEA mitral valve model is generated in the view window of pyFormex which is behind the application In order to see the FEA model one has to move the application screen or close it Example o
2. eeseeee 100 Figure 55 MitralValveDj Run server message seecccesesssccecsssnececseseneececseaaececseaeeecsseneeeeeeeaaes 102 Figure 56 MitralValveDj Figure 57 MitralValveDj Figure 58 MitralValveDj Figure 59 MitralValveDj Figure 60 MitralValveDj Figure 61 MitralValveDj Figure 62 MitralValveDj Figure 63 MitralValveDj Figure 64 MitralValveDj Figure 65 MitralValveDj Figure 66 MitralValveDj Figure 67 MitralValveDj Kor adiim e 102 Tabu ackseha esent abi prre oco AGE T quater Rated opi EH VR opt Fac tuia ud 103 Loading data talos iet nerdoed vocc Or Rei aaa EEEE ee eee 103 Mmitral valve parameters tab ssessssseseseseeeeeeeennnenennn nenne 104 Mmaterial properties tab eth oer ke rer one NER cera R E EROR 105 Simulation parameters tab ie LE yr ihe Er eren e teda edens 105 Welcome screen dete eiae ied ide qinse etiara retra tide tatus 106 Submit patient data screen oo ccccecesssssceeeceeeesesessseeeceeeessessesseaees 106 Verification of the file ExteNSiONS cssceceseceesscecsseceesseeeeseeeeesees 107 Linear elastic material model seen 108 Hyperelastic material model eese 108 List of submitted patient data entries 109 List of Tables Table 1 Summarized information of mitral valve FEA literature review een Table 2 Stakeholder analysis sa scccii
3. exeption of two which are strut Basal chordae are not included In 2009 the Norwegian research group of Prot et al models the geometry of the mitral valve using three dimensional echographic measurements from a porcine heart The shape of the annulus is a symmetric non planar ellipse They also perform an autopsy measurement from which the length of the annulus and distance from the annulus to the anterior and posterior leaflets are being extracted Innovative in their research is that they model a branched chordae network with branches staring from the middle point of the marginal chordae A total of twenty marginal and two basal chordae are modeled 29 In 2010 the same research group publishes a paper in which the mitral valve in healthy and pathological state is being examined Based on their own measurements for the deceased mitral valve they change the thickness of the anterior and posterior leaflets and implement different values for the cross section of the chordae tendinae 30 In another research of the same authors they show that the leaflets have 25 3 layers each with different material properties 31 In this study the effects of different material properties across the thickness of the mitral valve are investigated In 2010 Wenk et al construct a FEA model of the left ventricle that including the mitral valve too With the help of magnetic resonance imaging MRI they extract the geometry of the leaflets and thus different
4. Generated 3D dynamic model of the mitral valve appears in the view window in pyFormex Warning message pops up The model is in the right colors The model corresponds to the input parameters Generated 3D dynamic model of the mitral valve appears in the view window in pyFormex Warning message pops up The model is in the right colors The model corresponds to the input parameters Test Case ID TS0003 Test Case Name Export all of the parameters Operator has run the script Expected result Actual result Operator chooses TRC CSV and PGF files Operator enters mitral valve parameters Operator clicks on the Export all of the parameters button Authorization message pops up File system window appears JSON file with predefined set name is generated Authorization message pops up File system window appears JSON file with predefined set name is generated 75 Test Case ID TS0004 Preconditions Operator has run the script E dd Operator has in advance the JSON file Operator clicks on the Import parameters button BENNK LL Operator chooses the JSON file Expected result File system window appears Warning message pops up The JSON file is loaded and all of the parameters from it appears in GUI Actual result File system window appears Warning message pops up The JSON file is loaded and all of the parameters from it appears in GUI LET Test Case ID TS0005 Export to Abaqus inp file Operator has run
5. 42 pp 832 846 2004 D R Einstein K S Kunzelman P G Reinhall M A Nicosia and R P Cochran The relationship of normal and abnormal microstructural proliferation to the mitral valve closure sound J Biomech Eng vol 127 pp 134 147 2005 V Prot B Skallerud and G A Holzapfel Transversely isotropic membrane shells with application to mitral valve mechanics Constitutive modelling and finite element implementation Int J Numer Methods Eng vol 71 pp 987 1008 2007 K D Lau V Diaz P Scambler and G Burriesci Mitral valve dynamics in structural and fluid structure interaction models Med Eng Phys vol 32 no 9 pp 1057 64 Nov 2010 M Stevanella F Maffessanti C A Conti E Votta A Arnoldi M Lombardi O Parodi E G Caiani and A Redaelli Mitral Valve Patient Specific Finite Element Modeling from Cardiac MRI Application to an Annuloplasty Procedure Cardiovascular Engineering and Technology vol 2 pp 66 76 2011 S Schievano K Kunzelman M A Nicosia R P Cochran and R Daniel Percutaneous Mitral Valve Dilatation Single Balloon ver sus Double Balloon A Finite Element Study 2009 A Avanzini A computational procedure for prediction of structural effects of edge to edge repair on mitral valve J Biomech Eng vol 130 p 031015 2008 A Avanzini G Donzella and L Libretti Functional and structural effects of percutaneous edge t
6. Every tab has seven input fields two for the linear elastic material model and five for the hyperelastic Holzapfel material model 90 Anterior leaflet Posterior leaflet Parameters Young modulus GPa 117 Poisson radio 0 355 Hyperelastic anisotropic Holzapfel parameters C10 0 1245 D 0 0005 K1 11 0069 K2 84 8478 kappa 0 08 Figure 42 MitralValvepyF Material properties tab Anterior leaflet tab Anterior leaflet Posterior leaflet Linear elastic Parameters Young modulus GPa 117 Poisson radio 0 355 Holzapfel parameters C10 0 0502 D 0 003 K1 3 0207 K2 144 4848 kappa 0 0534 Figure 43 MitralValvepyF Material properties tab Posterior leaflet tab e Visualization parameters tab The visualization parameters tab contains seven input color fields Figure 44 91 Loading data Mitral valve parameters Material properties Visualization parameters Custom Color palette while showing the mitral valve model Annulus edge ff0000 Basal edge Free edge ffffb2 Anterior leaflet 55aa00 Posterior leaflet Marginal chordae tendinae Basal chordae tendinae Figure 44 MitralValvepyF Visualization parameters tab Exit system The x button on the right upper screen and the close button at the left down corner are the tools that can be used in order to exit the application Figure 45 MitralValvepyF Loading data Mitral valve parameters Material properties Visual
7. Mitral valve parameters text fields are defined in order to collect data for the thickness of the anterior and posterior leaflets number of basal and marginal chordae relative height of the basal chordae tendinae cross section of the basal and marginal chordae and also the type of the chordae tendinae for which a radio button has been implemented Figure 36 Leaflets Thickness of the anterior leaflet mm Thickness of the posterior leaflet mm Chordae tendineae Number of the basal chordae Number of the marginal chordae Relative height of basal chordae Cross section marginal cordae mm Cross section basal cordae mm Type of the chordae tendinae 0 25 0 25 05 04 0 23 Struss connectors Figure 36 Django mitral valve parameters tab 72 e Material properties a fieldset an HTML tool for the anterior and posterior leaflets were written Every fieldset contains a radio button in order for the user to be able to choose from linear elastic and hyperelastic material models Text fields were made for the parameters depending on the different material models Figure 37 A JavaScript code was implemented in order to show and hide the text fields Anterior leaflet Linear elastic Hyperelastic anisotropic Posterior leaflet Linear elastic Hyperelastic anisotropic Figure 37 Django material properties tab e Simulation parameters a text field for the friction coefficient and radio button fo
8. 1 3 1 2 HTML HTML stands for HyperText Markup Language and refers to the markup language for developing web pages A standard serving as a reference for the development of web pages in different versions it defines a basic structure and a code called HTML for defining the contents of a web page such as text images etc It is a standard by the W3C an organization dedicated to the standardization of almost all technologies related to the web especially with regard to writing and interpretation It is the language which web pages are defined on The HTML language development is based on referencing To add an external element to the page image video script etc this is not embedded directly in the page code but a reference of the location of that item is done using text blocks Thus the web page contains only text 36 while the web browser code interpreter has the task of uniting all the elements and consequently displays the final page As a standard HTML seeks to be a language that allows for any web page written in a particular version to be interpreted in the same way standard for any updated browser 3 1 3 CSS Cascading Style Sheets Cascading Style Sheets is a style sheet language used to describe the look and formatting of a document written in a markup language including several HTML and XML based languages such as XHTML or SVG Style information can be attached as a separate document or in the sam
9. chordae tendinae are fields of type slider in order to ensure that the user will enter integers The chordae type and the number of CPUs that will be used in the simulation on the cluster are radio buttons with predefined values The third tab group contains input information about the material properties of the leaflets The group has two sub tab groups about the anterior and posterior leaflets Every sub tab group contains two check fields one for the linear elastic and one for the hyperelastic Holzapfel material model Depending on the check field various numerical parameters can be entered Figure 26 Anterior leaflet Posterior leaflet Linear elastic Parameters Young modulus GPa 117 Poisson radio 0 355 Holzapfel parameters C10 0 0502 D 0 003 K1 3 0207 K2 144 4848 kappa 0 0534 Figure 26 GUI pyFormex Posterior leaflet material properties tab The fourth tab group contains button like fields with values corresponding to the colors of different parameters that are used for preview of the mitral valve finite element model Figure 27 Once clicked on the field a palette window pops up 61 Loading data Mitral valve parameters Material properties Visualization parameters Custom Color palette while showing the mitral valve model Annulus edge ff0000 Basal edge Free edge Anterior leaflet 55aa00 Posterior leaflet Marginal chordae tendinae staa55ff Loo mw 0 000 jJ ml i Uff a AM MEE
10. curve from literature pressure curve from literature atrial and ventricular pressure based on in vivo porcine measurements measured in vivo end diastolic and end systolic LV pressures effect of chordal replacement with sutures on valve stress the effects of annular dilatation on coaptation compare two types of annuloplasty ring prostheses support a study on altered leaflet collagen in response to increased leaflet stress analysis of the stress on mitral valve leaflets edge to edge repair compare different mitral annuloplasty prostheses analysis of healthy and pathological human mitral valves comparison between human and porcine data determine the effects of using different material properties across the thickness of the valve annulus shape effect and chordal force distribution fluid structure interaction investigating the behaviour of the normal and pathological mitral valve The Effect of Mitral Annuloplasty Shape in Ischemic Mitral Regurgitation Insights into Ischemic Mitral Regurgitation Model of the Left Ventricle With Mitral Valve 29 At the Figure 14 different FEA models of the mitral valve used in various research papers is depicted Fibrous Trigone Natural Chordae Anterior Leatiet marginal chordae N Y Secondary anterior chordae strut chordae PM Tendineae Tips Papillary Muscle Posterior Leaflet Points Figure 14 Mitral valve FEA models in r
11. data csv file 0446708 SV hemodynamic data csv Reconstructed leaflets geometry pgf file MV Echo case01 framell echo pgf Figure 40 MitralValvepyF Loading data tab e Mitral valve parameters tab 89 Mitral valve tab consists of 10 input fields containing the information about essential parameters necessary for the generation of the finite analysis model of the patient specific data Leaflets Thickness of the anterior leaflets mm 0 25 Thickness of the posterior leaflets mm 0 25 Chordae tendineae Number of the basal chordae 12 Number of the marginal chordae 28 Relative height of basal chordae 0 5 Cross section marginal chordae mm 0 4 Cross section basal chordae mm 0 23 Type of the chordae tendinae Simulation parameters Number of CPUs to be used by the cluster Friction coefficient 0 05 Figure 41 MitralValvepyF Mitral valve parameters tab e Material properties tab e truss connectors e4 6 8 Like select this allows selt The material properties tab contains information about the material models of the anterior and posterior leaflets It has two child tabs one for the material properties of the anterior leaflet Figure 42 and one tab for the material properties of the posterior leaflet Figure 43 Every tab contains check buttons which in the beginning are not active Once the check button is active depending on the chosen material model parameters can be changed
12. open mitral valve during diastole which is used as an initial configuration for the prediction of the valve in closed state The length of chordae tendinae is automatically set The model includes the basal and marginal chordae fourteen in total The papillary muscle heads are manually specified 39 In 2013 Pouch et al publish a research about semi automated mitral valve morphometry where the authors study the occurring stresses They construct the geometry of the mitral valve from ultrasound data Real time 3D transesophageal echocardiography 3D TEE and volumetric images of the mitral valve are segmented at mid diastole for two patients The first patient is healthy and the second one has severe ischemic mitral regurgitation They model a total of sixty four chordae while the papillary muscle heads are represented by points 40 The research group of Rim et al studies the effect of patient specific annular motion on dynamic simulation of the mitral valve in 2013 The geometry of the mitral valve is obtained from 3D TEE for two subjects a healthy one and another which has mitral regurgitation The leaflets and the annulus are segmented from the ultrasound data The PM tips are modeled as continuously deforming The chordae tendinae are represented as line elements from the 27 papillary muscle heads to the edge nodes of the mitral valve leaflets From the 3D TEE data the authors extract the annulus geometry at peak systole and end di
13. posterior leaflet marginal chordae and basal chordae Every color can be changed by clicking on in A color palette pops out and the color can be selected from it Figure 47 94 Select Color Basic colors Custom colors e 60 Red 255 255 Green 255 S 255 Blue 0 S Add to Custom Colors Cancel v OK Figure 47 MitralValvepyF Visualization parameters color palette pop up The MitralValvepyF application has five buttons with different functionalities exporting all of the input parameters import of mitral valve parameters generation of the 3D finite element analysis model and generation of input Abaqus file The buttons are situated at the left bottom corner Figure 45 e Export all parameters button The Export all parameters button makes possible to save all of the input parameters in JSON file By clicking on the button a pop up window appears In it a place where the file will be saved as well as a specific name can be chosen Figure 48 95 Save file as nx Look in lim home user Thesis PyFormex May lt a B CJ computer D 0446708 SV_hemodynamic_data csv fh user 0446708 SV PM Ann ALL Leaflets frame 6 12 trc bau json D mv simulation 2014 05 27 py D MV Echo case01 framell echo pgf D probal inp D probal request D D D DDO properties json vicky json wow request File name Patient12 02 06 2014 Files of type All files xy Cancel Figure 48 Mi
14. saved in internal memory of the operating device Getting started Getting Started section explains how to get MitralValvepyF The section presents briefly system menu Installation The source code of the application can be downloaded from http tinyurl com MitralValvepyF It is a Python file that can be loaded in the pyFormex program The only thing that is necessary to be done after loading the script in pyFormex is to run it 88 System menu MitralValvepyF is a tabbed application which consists of four tabs Figure 39 There is tab for loading the patient specific data files and a tab in which essential parameters of the mitral valve can be entered The third tab contains the material models for the anterior and posterior leaflets of the mitral valve In the last tab user preferences about the colors in which the 3D finite element analysis model are available MitralValvepyF Loading data Mitral valve parameters Material properties Visualization parameters Figure 39 Tabs of MitralValvepyF e Loading data tab The Loading data tab Figure 40 consists of three fields in which files can be chosen In the first file field a TRC file can be loaded in the second field CSV file and the third one PGF file All of the files are required in order for the application to work correctly Please load the patient specific data Mitral valve geometry trc file 0446708 SV PM Ann ALL Leaflets frame 6 12 trc Hemodynamic
15. selects to load the mitral valve parameters The system allows the user to select the json file The system reads the json file The system loads the parameters in the graphic user interface in pyFormex The system puts predefined values for the mitral valve parameters 49 if they are not present in the json file e The system warns the user that he needs to choose some of the radio buttons in the material properties tab ENS re Preconditions User opened and ran the pyFormex script User loaded patient specific data The user defines the geometry of the mitral valve o Thickness of the anterior and posterior leaflets Number of basal and marginal chordae tendinae Relative height of the basal chordae tendinae Cross section of the marginal and basal chordae tendinae Type of the basal and marginal chordae tendinae truss or connector The user defines the material properties of the anterior leaflet o Theusercan choose to use linear elastic model o Theusercan choose to use hyperelastic model Holzaphel The user defines the material properties of the posterior leaflet o Theusercan choose to use linear elastic model o Theusercan choose to use hyperelastic model Holzaphel The user defines the simulation parameters o Friction coefficient o Time step The user defines how many computers will calculate the Abaqus simulation on the cluster The user chooses with what colors the system should show him the preview of the generated mitr
16. 007 the same group incorporates the different thickness of the leaflets at the area adjacent to 24 their free edge It is important to note that they model the FEA simulation with 52 chordae but still the geometry of the mitral valve is symmetric as in all of their previous research In 2005 Lim et al use 12 transceiver crystals placed in the mitral valve in order to better capture the boundary conditions and to obtain a more realistic geometry of the mitral valve Their mitral valve model is asymmetrical with a twisted saddle shape mitral annulus geometry 26 They model only marginal chordae with uniform thickness and also represent the leaflets like a single surface without distinguishing the anterior and posterior leaflets In 2008 Votta et al use a new approach to define the mitral valve geometry They apply ultrasound data to extract the annulus and papillary muscle motion The end diastole valve configuration when open is chosen because the pressure there at that moment is minimal Transthoracic real time three dimensional echocardiography has given them the opportunity to manually select points on the annulus and then interpolate the data with a sixth order Fourier function in order to get the continuous annular profile 27 The geometry of the leaflets is modeled as in their previous research 14 18 28 They implement a different thickness of the anterior and posterior leaflets and model 58 chordae all of which are marginal with the
17. 010 P Burlina C Sprouse D Dementhon A Jorstad R Juang F Contijoch T Abraham D Yuh and E Mcveigh Patient Specific Modeling and Analysis of the Mitral Valve Using 3D TEE pp 135 146 2010 C A Conti M Stevanella F Maffessanti S Trunfio E Votta A Roghi O Parodi E G Caiani A Redaelli P Milano N Ca and G Hospital Mitral Valve Modelling in Ischemic Patients Finite Element Analysis from Cardiac Magnetic Resonance Imaging CNR Institute of Clinical Physiology Pisa Italy pp 1059 1062 2010 A E W Van Loosdregt A E W Van Loosdregt B Sc R Amini D Ph and M M Sacks Toward developing a finite element model of the mitral valve Towards developing a finite element model of the mitral valve no July pp 1 10 2011 A S Jassar C J Brinster M Vergnat J D Robb T J Eperjesi A M Pouch A T Cheung S J Weiss M a Acker J H Gorman R C Gorman and B M Jackson Quantitative mitral valve modeling using real time three dimensional echocardiography technique and repeatability Ann Thorac Surg vol 91 no 1 pp 165 71 Jan 2011 A Quaini S Canic G Guidoboni R Glowinski S R Igo C J Hartley W A Zoghbi and S H Little A Three Dimensional Computational Fluid Dynamics Model of Cardiovasc Eng Technol Regurgitant Mitral Valve Flow Validation Against in vitro Standards and 3D Color Doppler Methods vol 2 no 2 pp 77 89 2012 Q W
18. HM Basal chordae tendinae Figure 27 GUI pyFormex Visualization parameters tab Predefined values for each parameter are integrated in the graphic user interface For the hyperelastic Holzapfel model the values are taken from the paper of Wang et al 38 The main function that creates the graphic user interface and its functionalities is createDialog In Figure 28 a diagram of the functionality of the script provided by the buttons is shown createDialog Import parameters Export parameters Export to Abaqus Preview FEA mitral valve button loadJson button saveJson inp file saveInp model previewFea askFilename acceptData acceptData acceptData 0 open model json load askNewFilename abaqus drawMV warning open waming dialog updateData json dump Figure 28 pyFormex Structure of the button functions 62 In the createDialog function four buttons are defined Every button is represented by a function The first button is Import parameters and the function that correspond to it in the script is loadJson Once the user clicks on this button askFilename function is called and thus they can choose a JSON file which contains mitral valve parameters The user needs to have the file in advance Such a file can be generated by the pyFormex script Django application or simply written by the users themselves Once the file is chosen then the script opens it and loads th
19. Simulation tools for mitral valve repair Viktoriya Antonova Supervisors Dr ir Matthieu De Beule Prof dr ir Benedict Verhegghe Counsellors Tim Dezutter dhr Philippe Bertrand Master s dissertation submitted in order to obtain the academic degree of International Master of Science in Biomedical Engineering Department of Electronics and Information Systems Chairman Prof dr ir Jan Van Campenhout Faculty of Engineering and Architecture UNIVERSITEIT Academic year 2013 2014 GENT Abstract As the second most common heart disease the mitral valve regurgitation has been subject of many researches through the years With the improvement of the technology resources more and more computer simulations that regard the dynamics and effect of different repair techniques of the mitral valve are done In order to produce a patient specific mitral valve model there are many steps that should be performed Every step requires time and knowledge about different software products There is a need of a software tool that combines big part of the steps and makes the process more efficient In this study two demonstration tools that save time and resources are constructed A web based application is developed which when installed on a server can be reached by every computer with internet In the application a patients specific data can be loaded as well as various mitral valve parameters can be chosen The application is designed to keep recor
20. affects the fluid flow as well Governing equations are usually defined and solved in order to see the result of the simulation 22 2 Literature review While speaking of the FEA modeling in respect to the mitral valve one can distinguish different methodologies applied to the geometry and the used material models In the early days of FEA modeling researchers used simplified and idealized geometries while in the past decade more and more patient specific and complex geometry models are being applied Also in the construction of the material models utilized in the past only linear elastic properties were used while today a much greater variety of FEA models exists which describe the behavior of the biological materials by making use of more realistic non linear constitutive model 2 1 Geometry of the mitral valve A realistic and accurate reconstruction of the mitral valve geometry is hard to obtain even nowadays The complex morphology of the MV and the difficulty in measuring and examining it make the modeling of the geometry very hard During the years different approaches of obtaining the geometry were used from an idealized general shape to more a patient specific one using the available technologies like computer tomography and echocardiography In general in the first published paper on the matter in 1993 Kunzelman et al the obtained data is reconstructed to 3D model of the mitral valve including the annulus leaflets chor
21. al commissure 4 Posterolateral commissure Posterior Posterior Chordae annulus tendineae Medial papillary muscle Lateral papillary muscle Figure 5 Side view of the healthy mitral valve 5 1 2 1 Macroscopic analysis The normal mitral valve consists of two leaflets anterior aortic and posterior mural The posterior leaflet has two indentations that generally form three segments There are two nomenclatures Duran 6 and Carpenter 7 which divide the leaflets in different zones Nowadays the most widely used one is the Carpenter nomenclature in which every leaflet is divided by 3 zones as you can see on Figure 6 The zones at the anterior leaflets are A1 for the most lateral segment near to the anterior commissure A2 for the central one and A3 for the medial segment near to the posterior commissure Anterior Posterior commissure commissure Anterior leaflet A1 n Na Posterior leaflet Figure 6 Carpenter s nomenclature 8 13 Important role of the function of the mitral valve plays the branching chordae tendinae network which extends from the mitral leaflets to papillary muscles Commissures Anterior Papillary Anterior Strut Posterior Posteriof Muscle l Chord Chord Posterior Marginal Commissural Anterior Intermediate Chord Chord Marginal Chord Chord Figure 7 The ventricular side of a porcine mitral 9 In general three types of chordae tendinae can be distinguished margina
22. al valve FEA model 50 SS EN as MEMMMEMNMEZMNMN Preconditions User opened and ran pyFormex script User defined the mitral valve previously The user selects to save the mitral valve parameters The system give chance to the user to choose where and with what name to save the mitral valve parameters The system saves the mitral valve parameters The system loads the parameters in the graphic user interface in pyFormex The system puts predefined values for the mitral valve parameters if they are not present in the json file Generating the input file for Abaqus simulations Description Generating the inp file which can be further used in order to make simulations in Abaqus Preconditions User opened and ran pyFormex script User defined the parameters of the mitral valve User loaded the patients specific data 51 The user selects to generate the inp file The system give chance to the user to select where and with what name to save the inp file The system warns the user that request file will be also generated The system generates and saves the inp file The system generates and saves request file Preview of the mitral valve generated FEA model Preview of the mitral valve FEA model Preconditions User opened and ran pyFormex script User defined the parameters of the mitral valve User loaded the patient specific data e The user selects to view the mitral valve FEA model e The system gener
23. ang and W Sun Finite element modeling of mitral valve dynamic deformation using patient specific multi slices computed tomography scans Ann Biomed Eng vol 41 no 1 pp 142 53 Jan 2013 P Burlina C Sprouse R Mukherjee D DeMenthon and T Abraham Patient specific mitral valve closure prediction using 3D echocardiography Ultrasound Med Biol vol 39 no 5 pp 769 83 May 2013 84 40 41 42 43 44 45 46 47 48 49 50 51 52 A M Pouch C Xu P A Yushkevich A S Jassar M Vergnat J H G lii R C Gorman C M Sehgal and B M Jackson Semi Automated Mitral Valve Morphometry and Computational Stress Analysis Using 3D Ultrasound vol 45 no 5 pp 903 907 2013 Y Rim D D McPherson K B Chandran and H Kim The effect of patient specific annular motion on dynamic simulation of mitral valve function J Biomech vol 46 no 6 pp 1104 12 Apr 2013 K May Newman and F C Yin Biaxial mechanical behavior of excised porcine mitral valve leaflets Am J Physiol vol 269 pp H1319 H1327 1995 K May Newman and F C Yin A constitutive law for mitral valve tissue J Biomech Eng vol 120 pp 38 47 1998 D R Einstein K S Kunzelman P G Reinhall R P Cochran and M A Nicosia Haemodynamic determinants of the mitral valve closure sound a finite element study Med Biol Eng Comput vol
24. astole In order to obtain dynamic annular motion they apply time varying nonlinear nodal displacement of the nodes across the annulus 41 In Table 1 summarized information for most of the reviewed papers is shown 28 Kunzelman et al Votta et al Prot et al Einstein et al Wenk et al 1993 1995 1996 1997 1998 2002 2007 2008 2009 2011 2007 2008 2009 2010 2003 2007 2011 2010 2012 Table 1 Summarized information of mitral valve FEA literature review Research group Year Geometry Material Loading Tasks models asymmetric leaflets different thickness on the posterior and interior leaflet porcine heart asymmetric leaflets no basal chordae no branched chordae Ultrasound and Transthoracic real time three dimensional echocardiography human symmetric branched chordae three dimensional echographic measurements basal and marginal chordae symmetric branched chordae in vivo data non symmetric basal and marginal chordae no branching magnetic resonance images sheep linear orthotropic collagen fibres leaflets hyperelastic anisotropic chordae hyperelastic isotropic leaflets hyperelastic anisotropic chordae hyperelastic isotropic leaflets hyperelastic isotropic chordae tension only cables leaflets hyperelastic transversely isotropic chordae cable element formulation pressure curve from literature pressure
25. ates the FEA mitral valve model e The system shows the user a 3D dynamic model of the mitral valve in predefined colors 52 4 2 Software design Software design is the last activity to be performed before the development of the software In the software engineering today there is a standard way to visualize the design of the system using Unified Modeling Language UML The UML offers a way to visualize system s blueprints in a diagram Appropriate use of UML notation is essential part in creating a complete and meaningful model For more information about the basic notations in UML please follow the link http www tutorialspoint com uml uml basic notations htm In this section the system architecture and activity diagrams will be defined with the help of UML Software design is based on previously developed pyFormex script for generation of input file for Abaqus and generation of mitral valve finite element analysis 3D model The chosen mitral valve parameters to be implemented will be mentioned 4 2 1 System architecture The system architecture is a conceptual model describing the structure and the behavior of the system In the Figure 17 a UML diagram of the system architecture is shown lt lt system gt Mitral valve service GUI Miitral valve pyFormex application E File system Ga Operator Mitral valve web application perators web J ERES 4 browser HTTP Figure 17 Syste
26. ation section explains in general terms the system and the purpose for which it is intended System overview MitralValveDj is web based application which allows collecting patient specific data for the mitral valve The application provides electronic version of form in collecting mitral valve parameters The application saves the collected data to a database MitralVelaveDJ operates on personal computers with any operating system Organization of the manual The user s manual consists of four sections General Information System Summary Getting Started and Using The System General Information section explains in general terms the system and the purpose for which it is intended 100 System Summary section provides a general overview of the system The summary outlines the uses of the system s hardware and software requirements system s configuration user access levels and system s behavior in case of any contingencies Getting Started section explains how to get MitralValveDJ and install it The section presents briefly the system menu Using The System section provides a detailed description of system functions System summary System Summary section provides a general overview of the system The summary outlines the uses of the system s hardware and software requirements system s configuration user access levels and system s behavior in case of any contingencies System configuration MitralValveDj o
27. branches Vena cavae Left atrium Left ventricle Right atrium Right ventricle Systemic arteries Systemic veins Im Oxygen poor CO rich blood Oxygen rich CO poor blood Capillary bed of all body tissues where gas exchange occurs Figure 1 Blood circulation in human body 1 The heart has four valves In order to regulate the blood flow mitral aortic tricuspid and pulmonary valve Figure 2 If working properly the valves act like one way valves which allow the blood to flow from one chamber to another or to flow out of the heart in one direction SIDE VIEW TOP VIEW Cross Section Cross Section Tricuspid Valve Mitral Valve Mitral Valve Coronary Sinus Left Coronary Artery Pulmonic Aortic Valve Valve Pulmonic Valve Tricuspid Valve Right Coronary Artery Aortic Valve Figure 2 Heart valves 2 The bicuspid or also known as mitral valve consists of two cusps and is located between the left atrium and left ventricle The tricuspid valve has three leaflets and is located between the right atrium and right ventricle The aortic valve also has three leaflets and is located between the left ventricle and the aorta The pulmonary valve consists of three leaflets and is located between the right ventricle and the pulmonary artery The valves open and close to allow blood flow Their dynamics depend on the activity of the heart muscle i e when the ventricles are relaxed
28. cense v2 allowing their use in free software projects jQuery like other libraries offers a number of features based in JavaScript that would otherwise require a lot more code With the functions of this library great results are achieved in less time and space 3 2 pyFormex pyFormex is a Python based program which allows the user to generate and manipulate large and complex geometric models of 3D structures It has a single and consistent environment which provides many features that usually can be done by other CAD systems but none of them offer all of these features in single software The core idea of pyFormex is that the 3D geometry of the models can be obtained from mathematical description through interactive generation of its subparts and their consequent assemblage Commonly pyFormex is used to create 3D models from medical scan images Predefined operations help for the pre and post processing of the finite elements analysis models 53 A possibility of incorporating a graphic user interface makes the use of pyFormex easier PyFormex is a free program under GNU license 38 3 3 Django Django is an open source web framework open source which is written in Python and follows the paradigm known as Model Template View It was originally developed to manage several news oriented sites of the World Company of Lawrence Kansas and was released to the public under a BSD license in July 2005 Django s primary goal is to facilitate
29. chran C Chuong W S Ring E D Verrier and R D Eberhart Finite element analysis of the mitral valve J Heart Valve Dis vol 2 pp 326 340 1993 K S Kunzelman D W Quick and R P Cochran Altered collagen concentration in mitral valve leaflets biochemical and finite element analysis Ann Thorac Surg vol 66 no 6 Suppl pp 198 205 Dec 1998 82 17 18 19 20 21 22 23 24 25 26 27 28 K Kunzelman M S Reimink E D Verrier and R P Cochran Replacement of Mitral Valve Posterior Chordae Tendineae with Expanded Polytetrafluoroethylene Suture A Finite Element Study J Card Surg vol 11 no 2 pp 136 145 1996 K S Kunzelman M S Reimink and R P Cochran Annular dilatation increases stress in the mitral valve and delays coaptation a finite element computer model Cardiovasc Surg vol 5 no 4 pp 427 34 Aug 1997 K S Kunzelman M S Reimink and R P Cochran Flexible versus rigid ring annuloplasty for mitral valve annular dilatation a finite element model J Heart Valve Dis vol 7 pp 108 116 1998 F Maisano a Redaelli G Pennati R Fumero L Torracca and O Alfieri The hemodynamic effects of double orifice valve repair for mitral regurgitation a 3D computational model Eur J Cardiothorac Surg vol 15 no 4 pp 419 25 Apr 1999 E Votta F Maisano M Soncini A Redaelli F M M
30. d the simulation of complex physiological and biological systems The variety of problems that it can be applied to has grown enormously The element in the name of finite element analysis means that the structure usually is divided into elements defined by points that are called nodes Then the governing equations are calculated for every element and when one looks at the elements as a whole there is an approximation of the solution for the simulated problem The key aspects while modeling a FEA are the geometry the material properties and the boundary conditions 1 6 3 Computational fluid dynamics CFD The computational fluid dynamics CFD is a branch of fluid mechanics that uses numerical methods and algorithms to solve and analyze problems on the flow of substances Computers are used to perform millions of calculations required to simulate the interaction of the liquid and the gases with complex surfaces The method involves definition of the geometry as well as the volume occupied by the fluid is divided into discrete cells the mesh Boundary conditions and conservation equations are also defined After solving the equations the result is visualized 21 1 6 4 Fluid structure interaction FSI Fluid structure interaction FSI is the interaction between a fluid flow and a moving or deforming structure The fluid flow applies forces on the adjacent structure which results in deformation of the structure This deformation
31. dae tendinae and the papillary muscles There the geometry of the mitral valve is obtained from porcine heart in open position The leaflets are with given uniform thickness the chordae tendinae are defined as straight single lines and the papillary muscle heads are represented as a single point to which the chordae tendinae are attached 15 The FEA model of the mitral valve from this research is used for several studies by the same authors 16 17 They utilize it to investigate the annular dilatation increase of the stress in the mitral valve and delays of the coaptation 18 as well as to compare the flexible versus rigid ring annuloplasty for mitral valve annular dialation 19 In these studies they assume the symmetry of the valve in order to 23 reduce the computational time Also a non branching chordae network is assumed In 1997 in the study by Kunzelman et al the FEA model of the mitral valve is no longer symmetric and basal chordae tendinae are taken into account 18 A second research group that reconstructs mitral valve in 1999 in Italy was the group of Maisano et al They investigate the hemodynamics of the normal MV and examine the effect of repair for mitral valve regurgitation 20 For this study a simplified model of the MV in open and static position without representing the chordae tendinae is used The shape of the annulus is also simplified to a circular one similar to an annuloplasty ring In 2002 the same Italian res
32. del saving and loading of input parameters request a input file for simulations Submission of patient specific data visualization of 3D FEA model saving and loading of input parameters request a input file for simulations High quality programming code and good documentation for it Potentials and deficiencies Expert in surgery lacks technical knowledge Different background knowledge Differences in working processes Commercialising the product Implications and conclusions for the project Could be conservative so refusing new technologies wide range of patient specific problems makes it difficult to find a common solution Wide range of research topics makes it difficult to develop a common solution Essential for developing and maintains of the applications Knowledge of market potential The main identified stakeholders are the medical doctors surgeons researchers students developers and industry The expectations of the first two stakeholders are very similar in terms of their implications and conclusion for the project The deficiencies are also similar for the first 42 three stakeholders The industry is also present in the table since it should it should always be considered when working on the project even in the early stages 4 1 2 Requirements specification Requirements specification consists of functional non functional and environmental requirements Th
33. ds of all uploaded data and to generate a file that later can be used in the second produced application The second application that was created gives an opportunity to the user through its graphic user interface to load patient specific data files as well as files with mitral valve parameters The application generates a preview of the mitral valve finite element analysis model and makes an input file for Abaqus With the help of the graphic user interface the user saves time preparing different simulations and eliminates the need for having previous knowledge of the used software Acknowledgements would like to express my gratitude to those who made this thesis possible am very thankful to my promoters Dr Matthieu De Beule and Prof Benedict Verhegghe for sharing their vast expertise and guiding me in completion of this thesis work as well as for the opportunities they have provided me with would also like to thank PhD student Tim Dezutter and Evangelos Mantadakis for their collaboration while developing the software tools Last but certainly not least also owe gratitude to Dr Phillippe Bertrand who shared his clinical knowledge and expertise Table of Contents PRISE GAC oon ca ws get p ultitbp eaaa aa aa anv dae ich lba dla M DA MU M D Dru M a FON DR NU 1 Acknowledgements rrt trii eR vare nS NR Ee FERRY E dan FE Roe ve ERASE 2 Table of CONTENTS M aonana E E a E EE a ERa 3 List Of FIBUPES ginra ian terrae FERE RRE s
34. e data In order for the data from the JSON file to load in the GUI a dialog updateData function is used Also a warning message is created here to remind the user that he needs to activate one of the checkboxes in the Material properties tab The second button in the GUI is Export parameters which is responsible for saving all of the entered mitral valve parameters in JSON file This is possible because of the function saveJson This function contains a function for accepting the entered data acceptData a function which makes dialog window in which the user is asked whether to save export the parameters ack Moreover there is a function askNewFilename which asks where and with what name the file should be saved The next step is to open the file and write the mitral valve parameters in JSON format The third button is Export to Abaqus inp file and the function that is behind it is savelnp In this function there are three main functions acceptData model abaqus The first reads and accepts the input data from the dialog and makes it available for the other functions The functionality of the functions model and abaqus were previously developed by other student and they are integrated in this script The function is responsible for generating the finite element model It takes the PGF file and loads the valve geometry The PGF file contains information about the mesh s nodes and connectivity of the anterior and
35. e 10 you can see the difference between a normal MV and a MV with regurgitation Enlargement of the left ventricle can lead to dilation of the annulus displacement of the papillary muscles rupture of the chordae tendinae All of these abnormalities of the MV can lead to decreased cooptation between the leaflets and leakage of blood Normal Mitral Valve Mitral Regurgitation Apex 4 Displacement of j the posteromedial Anterolateral Posteromedial i id papillary muscle papillary muscle papillary muscle T Area of ischemic distortion D Mitral regurgitation Figure 10 A Normal MV B Mitral valve regurgitation 11 The treatment of MR depends on the patient specific problem their symptoms causes of the MR and also presence of other medical conditions People with mild or moderate MR may not require any specific treatment Once the MR is severe and chronic surgical repair or replacement can be performed 1 4 Mitral valve replacement When the MV has end stage disease and MV replacement is needed the native valve is surgically replaced by a mechanical or bioprosthetic valve The replacement valve is most 17 effective modality and gold standard treatment for mitral regurgitation Although it is very durable the replacement valve is also a foreign material for the body and a patient with mechanical valve should take anticoagulation medicines throughout all their life The biological valves can b
36. e HTML document In the latter case general styles could be defined in the header of the document or in a particular label by a lt style gt attribute 3 1 4 JavaScript JavaScript commonly abbreviated JS is an interpreted programming language a dialect of the ECMAScript standard It is defined as object oriented prototype based imperative weakly typed and dynamic It is mainly used in form client side implemented as part of a web browser enabling improvements in the user interface and dynamic web pages but there is a way side JavaScript Server side JavaScript or SSJS Use in external to the web applications such as PDF documents desktop applications mostly widgets is also significant JavaScript was designed with syntax similar to C although names and adopts conventions from the Java programming language It is important to note that Java and JavaScript are not related in terms of semantics and purposes 37 All modern browsers interpret JavaScript code embedded in Web pages To interact with a web page the JavaScript language provides an implementation of the Document Object Model DOM 3 1 5 jQuery jQuery is a JavaScript library which simplifies the way to interact with HTML documents manipulate the DOM handling events developing animations and add AJAX interaction with art websites jQuery is free open source software has a dual licensed under the MIT License and the GNU General Public Li
37. e finite element modelling from ultrasound data a pilot study for a new approach to understand mitral function and clinical scenarios Philos Trans A Math Phys Eng Sci vol 366 no 1879 pp 3411 34 Sep 2008 E Votta F Maisano S F Bolling O Alfieri F M Montevecchi and A Redaelli The Geoform Disease Specific Annuloplasty System A Finite Element Study Ann Thorac Surg vol 84 pp 92 101 2007 83 29 30 31 32 33 34 35 36 37 38 39 V Prot R Haaverstad and B Skallerud Finite element analysis of the mitral apparatus annulus shape effect and chordal force distribution Biomech Model Mechanobiol vol 8 no 1 pp 43 55 Feb 2009 V Prot B Skallerud G Sommer and G a Holzapfel On modelling and analysis of healthy and pathological human mitral valves two case studies J Mech Behav Biomed Mater vol 3 no 2 pp 167 77 Feb 2010 V Prot and B Skallerud Nonlinear solid finite element analysis of mitral valves with heterogeneous leaflet layers Computational Mechanics vol 43 pp 353 368 2009 J F Wenk Z Zhang G Cheng D Malhotra G Acevedo Bolton M Burger T Suzuki D a Saloner A W Wallace J M Guccione and M B Ratcliffe First finite element model of the left ventricle with mitral valve insights into ischemic mitral regurgitation Ann Thorac Surg vol 89 no 5 pp 1546 53 May 2
38. e from animal origin usually from porcine heart The biological valves have better haemodynamical performance than the mechanical ones although the blood flow is not completely physiological The disadvantage of the biological valves is their comparatively low durability with an average of 10 15 years Because of this drawback they are mostly used among elderly people 1 5 Mitral valve repair Studies in recent years shown that mitral valve repair is more successful than replacement with a better survival rates 12 In the last decade many different techniques for MV repair have been developed depending on the patient specific problem The surgeon may need to shorten the leaflets length replace or relocate some of the chordae tendinae fix the annulus shape reposition the papillary muscles or just fix the hole in the leaflet At the next figures you can see the most commonly used mitral valve repair techniques Figure 11 Open commissurotomy 13 18 Figure 11 shows the open commissurotomy procedure The mitral commissurotomy is aimed at opening up the corners of the valve for a proper whole size and adequate coaptation of the valve leaflets Figure 12 Annuloplasty 13 At Figure 12 the annuloplasty repair technique is depicted A surrounding device called annuloplasty ring is implanted in order to pull the leaflets together and to facilitate coaptation and re establish proper mitral valve function Edge to edge repair tec
39. e functional requirement defines the functions of the system or in other words what the system is supposed to do The non functional requirements define how the system is supposed to be The environmental requirements which software should be installed in order the demonstrators to work 4 1 2 1 Functional requirements FUN 001 The application shall allow the user to upload patient specific data which further will be used in modeling the FEA mitral valve FUN 002 The application shall allow the user to change the chosen parameters of the FEA mitral valve model FUN 003 The application shall allow the user to view the preview of the mitral valve FEA model pyFormex FUN 004 The application shall allow the user to view all their requests in a list Django FUN 005 The application shall allow the user to save all of the input parameters that are used to model the FEA mitral valve FUN 006 The application shall allow the user to request the input file for further use in Abaqus pyFormex FUN 007 The application shall allow the user to load the input parameters from a file 43 4 1 2 2 Non functional requirements e Usability requirements USA 001 The application shall have a user manual e Other requirements OTH 001 The application shall not accept or store any kind of patient information 4 1 2 3 Environmental requirements Environmental requirement during deployment of the software e System side requi
40. e relative height of the basal chordae cross section of marginal and basal chordae The last field is a radio button field with two choices for each type of chordae tendinae Note that all of the fields are required and if any of them is missing enter data an error message will appear e Material properties tab The material properties tab consists of two radio buttons one for the material model of the anterior leaflet and one for the posterior Every radio button consists of two options one for the linear elastic properties and one for the hyperelastic Holzapfel model When checking the linear elastic option two numerical fields are whown one for the Young modulus and one for the Poisson ratio Figure 65 107 Anterior leaflet e Linear elastic Parameters Young modulus GPa 117 Poisson radio 0 355 Figure 65 MitralValveDj Linear elastic material model If a hyperelastic option is active a table with five numerical fields shows up The fields represent the parameters necessary for the Holzapfel model Figure 66 Posterior leaflet Linear elastic Hyperelastic anisotropic Holzapfel Paamee i p i p kem 0 0502 1444848 0 0534 Figure 66 MitralValveDj Hyperelastic material model e Simulation parameters tab The simulation tab consists of two fields The first one is a float field concerning the friction coefficient and the second one is a radio button with three options regarding the number of computer
41. earch group designs a new more accurate model of the mitral valve with which they examine the stresses during systole and diastole in order to obtain their distributions on the leaflets after edge to edge repair of the mitral valve regurgitation 21 In this study they also represent the chordae tendinae as straight lines connected from the free margin to the papillary muscles Also in 2002 the American research group of Salgo et al studied the effect of the annular shape on leaflet curvature They produce a model of the closed mitral valve without taking into account the chordae tendinae 22 In 2003 the research group of Einstein et al uses the geometry model of the mitral valve previously done by Kunzelman to implement the nonlinear anisotropic hyperelastic material model 23 and later in 2005 to produce the first non linear fluid coupled computational model of the mitral valve 24 In 2005 the Italian research group of Maisano et al produces a new mitral valve geometry model They use the literature data to define the geometry with idealized leaflets and free margin defined by a sinusoidal function 25 Thus they modeled three cases the first model has a circular annulus the second model a D shaped annulus representing the implantation of a typical annulus ring and the third model modified shape prosthesis Along with that they also model forty chordae tendinae with a constant section and fixed papillary muscles head Later in 2
42. egdcsdsedaudeacazacceacoayvdacues gadegusduvocaseeueccatisyvbacees 38 33 DJANGO E 39 4 Software development process ccccesesssssscececeescsesessesececeescessesesaeeeceeeesseeseaeseeeeeeseeeseeseaeeas 40 41 Software requirements e rrt irte tea db ee Eb a a 41 4 2 Software design cei Re e e d EL TERI EO E aa ao 53 2 3 Implementation ccs i have RA ee t e hot br eatur oy ee eene 58 44 Merficatioiieuseroatobis d nsu eaa an a Sy sen eins aegis Nada es QU SN NIS A Sakae VT ES EMQUE 74 2 5 Maifitetiance iin o Eee pe o Rer edet egeat Eee Re re a aa A ASSE Ead eaa EN eua 78 5 Conclusions limitations and future perspectives esssesseseeeeeeeenennnenne nennen 80 Belerencbs nea pp a too pd E Edd e a oett qul da dope req igi qupd e uat aa ara Ree bab a E 82 Appendices nee tee eet tte veu ria enis E 87 Appendix A pyFormex application user manual esssseeseseeeeeeeeer nennen ennemis 87 General INFORMAL lone bie peret iga nde alivio sole Vr Orb s E Rb I esl aiU UN EA a eorr URN TM NUS 87 SystemsutmmaLly 2 od ede eei ot cis eaa aces eui ot tee degere e De Ld eaae eeu E Ene naaa eH Pea dde A eaae eve d dote t dei dad 88 Getting started i enne eto e en temi e ese ete vitiose ee deret eret 88 Using tlie ssystem sii oue esce ie Ete Wea pete E ERR e eco dad ee oe aee a eee eo eine EE Dogs 93 Appendix B Django application user manual esses eene eene nennen nnne 100 Geriera
43. enerate and store INP and REQUEST files The REQUEST file shall be automatically generated in order for the operator to have the possibility to submit the simulation on the cluster immediately 4 2 2 2 Activity diagram for mitral valve web application Load patient Enter mitral valve ire ri apo specific data parameters valve parameters Operator System Store patient Accept the specific data Generate and entered data TRC file CSV file store JSON file PGF file Figure 22 Activity diagram web application Generate a JSON file In mitral valve web application the operator shall have possibility to load patients specific data files as well as to enter mitral valve parameters Moreover the operator shall be able to request export of all of the mitral valve parameters Then the system shall accept the entered data store the patient specific data files TRC CSV and PGF files and generate and store the JSON file 4 2 3 Mitral valve parameters The design of the software is based on the previously developed pyFormex script which has functionalities to generate an input file for Abaqus as well as to generate 3D finite element model of the mitral valve Taking into account the developed software and the literature review some essential parameters of the mitral valve were chosen to be implemented The chosen 57 parameters are thickness of the anterior and posterior leaflets number of basal and marginal chordae tendinae relati
44. erated and searches for the place in it where the information for the material properties is written After finding the proper lines the script adds new lines with the parameters necessary for the Holzapfel model The material properties of the chordae tendinae are hard coded in the script The material data is taken from uniaxial tensil tests performed by Kunzelman 54 The next button in GUI is Preview FEA mitral valve model The function behind it is previewFea and it s responsible for visualization of the 3D finite element model of the mitral valve The first step that is performed by the function is to accept the input data then to execute the function model which was explained previously Once the function model generates the FEA model a drawMV function is called and the patient specific mitral valve model is drawn in the pyFormex window The colors utilized are the one that the user picked in the visualization tab A warning message appears that the model can be seen behind the GUI These were the main functions used in the pyFormex script There are more that were written but their functionality is just supportive and they are not explained here 64 4 3 2 Django The python web framework Django is designed to make common web development tasks fast and easy to complete The Django application is developed under Linux Debian Jessie release Web browsers Mozilla Firefox 17 0 9 and Google Chrome 35 are used for visualiza
45. esearch papers by A Kunzelman et al 15 B Kunzelman et al 18 C Salgo et al 22 D Maisano et al 21 E Votta et al 27 F Prot et al 29 G Conti et al 34 H Burlina et al 39 Rim et al 41 30 2 2 Material models of the mitral valve The microstructure of the mitral valve shows that the leaflets and the chordae tendinae tissue are constructed from cells and fibrous tissue Because of various orientations and types of the fibers the behavior of the tissue is nonlinear transversely isotropic and elastic The leaflets of the mitral valve have different material properties along the radial and circumferential direction while in the third direction they exhibit certain similarities All that leads to a transversely isotropic behavior of the mitral valve leaflets In the past years a lot of improvement has been made considering material models for the mitral valve despite the comparatively scarce availability of sources of material data mathematical models and also easy implementation the different material models In the first FEA model of the mitral valve 1993 Kunzelman et al implement linear elastic model for the leaflet tissue In order to find the elastic moduli in the radial and circumferential direction they perform a uni axial tensile test 15 The same methodology is used during the years for many other studies 18 25 28 In 1995 May Newman et al make a biaxial test of excised porcine mitral valve leaflets in
46. f generated 3D FEA model is shown at Figure 52 Figure 52 MitralValvepyF Example of generated 3D FEA mitral valve model 98 The FEA model can be rotated and seen from different angles by using the mouse buttons e Import parameters Import parameters button makes possible to choose existing JSON file with mitral valve parameters and loading the information from it in the graphic user interface of the application automatically After clicking on the button a pop up window appears From this window a specific JSON file can be loaded Figure 53 m Open existing file tox Look in i home user Thesis PyFormex May lt gt a B EJ m Computer D bau json D Patient12 02 06 2014 json ft user D properties json D vicky json Filename t Open Files of type json v Cancel Figure 53 MitralValvepyF Import parameters button pop up window If the import of the mitral valve parameters is successful a confirmation message will appear Figure 54 Note that if the JSON file is imported correctly you still need to activate the 99 checkboxes for the desired material properties of the anterior and posterior leaflets in the Material properties tab The mitral valve parameters was successfully imported Please remember to choose the material properties of the leaflets OK Figure 54 MitralValvepy Import parameters button message window Appendix B Django application user manual General information General Inform
47. ged into the system User has the files in advance The user selects a trc file containing the geometry of the mitral valve The user selects a csv file containing hemodynamic data The user selects a pgf file containing generated mitral valve leaflet geometry mesh s nodes and connectivity The system validates that the user selected all the files The system stores the patient specific data The system assigns an id for the submitted patient specific data 46 Saving all of the parameters in json file Description To request a mitral valve simulation by submitting input parameters needed for the generation of the finite element model of the mitral valve simulation and saving them in json file which could be used later in pyFormex script Preconditions User is logged into the system User selected a patient specific data e The user selects a patient specific data entry The user defines the geometry of the mitral valve o Thickness of the anterior and posterior leaflets Number of basal and marginal chordae tendinae Relative height of the basal chordae tendinae Cross section of the marginal and basal chordae tendinae Type of the basal and marginal chordae tendinae truss or connector The user defines the material properties of the anterior leaflet o Theusercan choose to use linear elastic model o Theusercan choose to use hyperelastic model Holzaphel The user defines the material properties of the posterior leafle
48. he operator shall interact with the Mitral valve pyFormex via graphic user interface GUI and with Mitral valve web application via web browser and HTTP protocol 4 2 2 Activity diagrams Activity diagrams represent activities that occur during the process flows in the system Explanation about the notations used in this section can be found at http sourcemaking com uml modeling business systems external view activity diagrams The diagrams are divided by activity diagrams for Mitral valve pyFormex script and activity diagrams for Mitral valve web application In the diagrams below by Operator the author means any of the predefined actors medical doctor surgeon researcher student developer 54 System is a summarizing term depending in which section is used can mean Mitral valve pyFormex script or Mitral valve web application 4 2 2 1 Activity diagrams Mitral valve pyFormex script e Load a JSON file Operator Requestto load mitral valve S JSUN parameters System Load the input Read a JSON file parameters in GUI Figure 18 Activity diagram pyFormex Load a JSON file In order to load the JSON file first the operator shall submit request for it and then choose a JSON file from the file system Then the system shall read the JSON file and load the mitral valve parameters in the graphic user interface dialog e Generate a JSON file Operator Load patient Enter Load mitral jos specific data val
49. hnique is visualized at Figure 13 Suturing of the anterior and posterior leaflets creates a double orifice mitral valve The suturing can be performed with sutures or implanted clip 19 Qe ITE Mul Vlt jy Me NA Wy Figure 13 Edge to edge repair 14 1 6 Computational techniques used in the clinical practice 1 6 1 Added value The pressure stresses strains and shear rates are important when considering damage or rupture of the tissue and also are involved in various biological processes Fluid dynamics and the information about the shear stresses along the leaflets of the mitral valve can give useful information about the hemodynamics of the mitral valve This information is hard to obtain in vivo or in vitro because of the complex 3D shape of the mitral valve and also the high resolution that is needed Therefore computer simulations are a useful tool that can help to understand the patient specific problem With the help of imaging and the data that can be extracted from it the computer simulations could be more realistic and will aid doctors and researchers in their decision making 20 1 6 2 Finite element analysis FEA The finite element analysis method FEA is designed for use on computers and allows solving physical problems associated with complicated geometries on differential equations It is used to design and improve the mechanical behavior of products and industrial applications as well as to ai
50. igned to be user friendly and has four tabs which contain different data Figure 34 The JavaScript code was implemented in order provide interactions between the tabs Welcome div bosilek Logout Patient data gt Submit new patient data Loading data Mitral valve parameters Material properties Simulation parameters Patient specific data Mitral valve geometry trc file Choose File No file chosen Hemodynamic data csv file Choose File No file chosen Reconstructed leaflets geometry pgf file Choose File No file chosen Export all of the parameters Figure 34 Django submit patient data template The defined tabs are e Loading data tab enables the user to choose the patients specific files The user has possibility to load TRC file from which later the pyFormex application can extract the geometry of the mitral valve A PGF file that contains information for the mesh s nodes and connectivity of the anterior and posterior leaflets The CSV file contains the patient specific transvalvular pressure The fields are defined as type file with a 71 specific name and id Figure 35 If the user appears Mitral valve geometry trc file Choose File 0446708_S 6 12 tre Hemodynamic data csv file Choose File No file chosen enters an invalid file a message will Reconstructed leaflets geometry pgf file Choose File No file chosen Figure 35 Django loading data tab
51. isi sbeeeitsgeeetsthsbenvetaeesaeaaesveresate 5 Eko o EEE A E E E N mista E E E E 8 T Introductio Ec aipa aa an aaia aa ea aa aaaea Aia Eaa asia aea iiaa 9 1 1 Anatomy and physiology of the he art ccccccccccccecsssssssseeeceesesssesssseeeseeeessessneeaeeeeeeeens 9 1 2 Anatomy and physiology of the mitral valve essssesseeeeeeeerenenne nennen 11 1 3 Pathology of the mitral valve ccccccccsssssssscececeeeceesesseseseceeeesssesseaeseeeeeeseseseesseeeeeeeens 16 1 4 Mitral valve replacements a a aeaa 17 15 Mitral valve repair DER EE EE E ER Ue dei vat eis 18 1 6 Computational techniques used in the clinical practice eeesssseeeesess 20 2 literat re reVIeW i e eds remet eek ber ae d RES ERU ieee sin ode ER Xe SER re Ran ud 23 2 1 Geometry of the mitral valve nennen nennen nnne nnnn nns reser neni nnn nns 23 2 2 Material models of the mitral valve 31 2 3 Boundary conditions ssssssssesesseseeeeeeen nennen nennen neni oneni iieii ranas isses ener ii 32 2 4 Computational analysis of mitral valve repair eseseeeeeeeenenenn enne 33 2 5 Current research of mitral valve modeling in a spin off of Ghent University 33 PROCEED the thesis PONERET TEUER PEE 34 3 Overview of the used software technologies esee eene enne 36 CN NEM iier lan EIE UIS ND D TEL omms 36 3 4 DVEOFIDOX iic estesa davaceveteeceatesyediaue
52. itecture and requirements a Django application was developed The complete file tree of the Django project can be seen at the next figure 66 MV manage py MV april init py settings py urls py wsgi py mitral valve static mitral valve css basic style css js jJquery 1 9 1 js tab strip js templates admin base site htmi mitral valve base htmi login html pt data list html pt data submit htmi init py admin py forms py models py tests py urls py views py media 1 2 Figure 30 File tree of Django project The outer MV root directory is just a container for the project The python file manage py is a command line utility that lets the user to interact with the Django project The inner directory MV april contains the main python files necessary for the project The MV april init py is an empty file that tells Python that this folder should be considered as a Python package The MV april settings py file consists of the settings of the Django project MV april urls py contains the URL declarations for the Django project while MV april wsgi py contains an entry point for WSGl compatible web servers to serve the project The directory mitral valve is the main directory of the application and consists of files and two other folders In the directory mitral valve templates files regarding the template of the 67 Django application are stored In the folder mitral_valve static the CSS and JavaScript files a
53. itral valve parameters tab consist of ten input fields Thickness of the anterior and posterior leaflets the relative height of the basal chordae tendinae the cross section of the basal and marginal chordae and the friction coefficient are numerical fields The number of the marginal and basal chordae tendinae are slider fields in which only an integer value can be entered The number of CPUs to be used by the cluster field can be defined from a radio button which offers one of the three values to chosen from Material properties tab Material properties tab consists of two tabs referring to different material models for the anterior and posterior leaflets respectively In every tab there are checkboxes for the linear elastic and hyperelastic Holzapfel models Note that both of the checkboxes can be active in every tab but one should choose only one of them in order for the application to work correctly After a checkbox is clicked on the input fields of the checkbox become active In the case when the linear elastic checkbox is active two numerical fields become available while in the case when the checkbox for hyperelastic material model is activated five numerical fields about the parameters of the Holzapfel model become editable Visualization parameters tab The visualization parameters tab consists of seven color fields The parameters according to which the colors can be changed are annulus edge basal edge free edge anterior leaflet
54. ization parameters Please load the patient specific data Annulus and papilary muscle motion Hemodynamic data 0446708 SV hemodynamic data csv Mitral Valve geometry MV Echo case01 framell echo pgf Close Export all of the parameters Export to Abaqus inp file Preview FEA mitral valve model Import parameters Figure 45 MitralValvepyF input dialog 92 Using the system This section provides a detailed description of system functions e Loading data tab Loading data tab consist of three file fields The first file field is about loading a TRC file which contains information about the geometry of the mitral valve and the annular and papillary muscles The second file field loads a PGF file which contains the mesh s nodes and connectivity of the anterior and posterior leaflets The third file field loads CSV file which contains the patient specific transvalvular pressure The three file fields react like a button and one is clicked on some of them a pop up window appears In this window only a file with the chosen format can be seen At Figure 46 An example of a pop up after clicking on the TRC file field is showed Open existing file DX Look in fm home user Thesis PyFormex May lt oO EB EJ e Computer 0446708 SV PM Ann ALL Leaflets frame 6 12 trc fh user Filename data r5 Open Files of type trc Cancel Figure 46 MitralValvepyF Loading TRC file pop up window 93 Mitral valve parameters tab M
55. l primary chordae which are connected to the free edge strut secondary chordae which are inserted in layers to the rough zone of the anterior leaflets and basal tertiary chordae that extend from the papillary muscles and attach to the base of the posterior leaflet Anatomically usually in the healthy mitral valve the marginal chordae are thinner than the basal chordae while the strut are the thickest The main role of the marginal chordae is to maintain leaflet flexibility and governing proper valve closure while the main role of the basal chordae is to provide a constant connection between the annulus and papillary muscles 9 1 2 2 Microscopic analysis Normal mitral leaflets have four layers that can be seen in Figure 8 The layer marked with A is the Auricularis S is Spongiosa F stands for Fibrosa and V comes from Ventricularis 10 14 p rx RC per auo S E ie F V B PA C Figure 8 Histologic sections of normal mitral valve A Annulus and basal third of the leaflet B Middle third of the leaflet C Distal third of the leaflet The auricularis is a thin of loose connective tissue containing elastic fibers and collagen which is the main component of the annulus Spongiosa is a loose connective tissue with abundant proteoglucans few elastic fibers and few collagen fibers It extends along the entire length of the leaflet from the annulus to the free edge and is the main component of the free edge The fibrous c
56. l INFORMACION usse ene rrr eoa o AP Dep I D M ERI eI aM e sei v SARUM dd 100 System summary E MEER REM e MR X M METRI RR EER ER ERE ER PARARE e SURE ENERO 101 Getting started s ooo edited reca o dara psi stented a adem re Victus SUC ER D Rei dau a 101 Using thie system z etr eR REPE Fa Ne x Erw ru ive ve er edens 105 List of Figures Figure 1 Blood circulation in human body 1 15 ciet eoa r urat Sn n ao suena Rd ter ur yu cte area 9 Fig re 2 Heart valves 2 oo EE ERE UR ERE IRI RS 10 Figure 3 Wiggers diagram 3 rri ee i id E tn RR rese E eus vv va eeu AY Ue uns 11 Figure 4 Mitral valve a mitral valve in open position b mitral valve in close position 4 12 Figure 5 Side view of the healthy mitral valve 5 eseseseeeeeseeeeenerer nnnm 13 Figure 6 Carpenter s nomenclature 8 eessececssssececeessecececssasececseueeecseseneeceeseaaecesseaeeesesenneeees 13 Figure 7 The ventricular side of a porcine mitral 9 seeeessseseeenenennnerrnn nnn 14 Figure 8 Histologic sections of normal mitral valve A Annulus eseeeeeennen 15 Figure 9 Cross section of chordae tendinae cssccccssssscccecssnaccecssseeeeceeseeeececssnaeeeessaeeesesseneeees 16 Figure 10 A Normal MV B Mitral valve regurgitation 11 esesseeeeeerneenern 17 Figure 11 Open commissurotomy 13 esssseeseeseseseeeeeren enne nnne enne 18 Figure 12 Annulo
57. l are performed for both software demonstrators the web based application and the pyFormex graphic user interface Further in the text when not explicitly specified which demonstrator is referred it is implied that both are being referred 4 1 Software requirements Software requirements help the developer in designing quality software that meets the stakeholder s needs The steps performed are e Step1 Stakeholder analysis e Step2 Requirements specification functional and non functional e Step3 Use case specification 4 1 1 Stakeholders The first step is to identify the stakeholders All persons that are involved in the given problem must be considered In the Table a separate scheme of the stakeholders their relation to the project their problems and their expectations is shown 41 Stakeholder Medical doctors Surgeons Researchers Students Developers Industry Characteristics Strives for the best treatment of his patient Interested in user friendly and easy software tools that will help them to plan their surgery more efficient Interested in user friendly and easy software tools that will help them understanding better the mitral valve apparatus Involved in the development of the applications Interested in innovative products at low development costs Table 2 Stakeholder analysis Expectations Submission of patient specific data visualization of 3D FEA mo
58. lication Operator sees their entries Operator opens the uploaded files Operator opens the generated JSON file Operator deletes entry List with all of the submitted entries sorted by ID is shown System opens in the browser any file from the list if clicked on it System deletes the entry if this option is selected 77 Actual result List with all of the submitted entries sorted by ID is shown System opens in the browser any file from the list if clicked on it System deletes the entry if this option is selected 4 4 2 Traceability matrix The traceability matrix links the functional requirements of the system throughout the validation process The purpose of the matrix is to ensure that all of the requirements defined for the system are tested Table 3 Traceability matrix Functional FUN 001 FUN 002 FUN 003 FUN 004 FUN 005 FUN 006 FUN 007 Requirements EN RN en se T CNN ENS NN Esc MNA SR D ERN ee ee CONSEEEENEN C NN ee ee ee ccu MN RR SES n n ics t MS n ME E EN a LONE NS ANE RN RNC CN NC LECCE MEE HESSE E pu lm L 4 5 Maintenance The maintenance phase refers to the stage when the software is complete fully integrated and in use The developed software in this thesis represents a start for the establishment of 78 framework for modeling of mitral valve FEA models and is not complete and therefore not yet in commercial use Therefore the maintenance phase is out of the scope of thi
59. m architecture 53 The system shall have three components Mitral valve pyFormex script Mitral valve web application and File system The developed components shall be demonstrators of what is possible to be done for easy differentiating of the components they will be called Mitral valve pyFormex script Mitral valve web Django application Mitral valve pyFormex script shall be responsible for generation of the 3D finite element analysis FEA model of the mitral valve as well as for generation of input file for Abaqus Other functionality of this application shall be saving and loading patient input data In the mitral valve web application the operator shall have possibility to enter and save all of the input parameters necessary for the generation of the mitral valve model as well as the patient specific data In the file system the Mitral valve web application shall keep the three files TRC PGF CSV that the operator has previously uploaded and also a JSON file with all of the input parameters of the mitral valve After submitting a request from the operator for input file for Abaqus or saving the input parameters the Mitral valve pyFormex script shall save INP REQUEST and JSON file in the file system The REQUEST file is necessary in case the operator wants to run a simulation on the cluster An operator in such UML diagram could be any of the predefined actors medical doctor surgeon researcher student or developer which testing the system T
60. ments in which different types of parameters are defined The first tab group is related to the loading of the patient specific data files Three button like file fields are defined Every button opens pop up window in which the user can choose a file The script shows to the user only the files with the same extension as the file that should be loaded For example if the user chooses to load a TRC file the script will show them only the TRC files in the directory and will not give them possibility to change the extension of the shown files The second tab group contains different types of fields of all of the mitral valve parameters that can be changed by the user They are structured in three groups leaflets parameters chordae tendinae parameters and simulation parameters Figure 25 Leaflets Thickness of the anterior leaflets mm 0 25 Thickness of the posterior leaflets mm 0 25 Chordae tendineae Number of the basal chordae 12 5 Es Number of the marginal chordae 28 Relative height of basal chordae 0 5 Cross section marginal chordae mm 0 4 Cross section basal chordae mm 0 23 Type of the chordae tendinae e truss connectors Simulation parameters Number of CPUs to be used by the cluster e4 6 8 Friction coefficient 0 05 Like select this allows sele Figure 25 GUI pyFormex Mitral valve parameters tab 60 Numerical fields are used for most of the values The numbers of basal and marginal
61. metry trc file Please choose a file Hemodynamic data csv file Please choose a file Reconstructed leaflets geometry pof file Please choose a file Close X Export all of the parameters Export to Abaqus inp file Preview FEA mitral valve model Figure 23 GUI mitral valve pyFormex script The structure of the graphic user interface can be seen in the figure below en ae Visualization parameters Annulus edge color Basal edge color Free edge color Anterior leaflet color Posterior leaflet color Marginal chordae color Basal chordae color TRC file Loading patient data Material properties Thickness anterior leaflet float Thickness posterior leaflet float Number basal chordae integer Number marginal chordae integer Cross section basal chordae float Cross section marginal chordae float Relative height basal chordae float Type chordae string Number of CPUs integer Friction coefficient float Anterior leaflet PGF file Posterior leaflet CSV file AS Anterior leaflet linear elastic hyperelastic Young modulus integer Posterior leaflet linear elastic hyperelastic Young modulus integer Figure 24 Structure of the GUI in pyFormex 59 The shown scheme represents the structure of the input dialog note that it does not incorporate the standards of the UML language The four tabs are shown in blue and the two sub tabs in green Every tab group contains group ele
62. mitral valve FEA modeling Once the data is obtained it s further post processed in pyFormex With the help of pyFormex a patient specific FEA model is generated There is also a possibility to generate the input file for ABAQUS in which the patient s specific annular and papillary muscle motion is taken into an account Also a patient specific measured transvalvular pressure is integrated into the input file Once all of the data is implemented in the input file for ABAQUS closure simulation can be done The research group is also working on the graphic user interface in pyFormex and a web based application in order to help people without programming skills to interact with the available resources 2 6 Aim of the thesis The treatment of MR is a patient specific problem based on symptoms causes of the MR and also presence of other medical conditions Because of this medical doctors are sometimes 34 impeded to decide which method to use for the patient specific problem Currently there is no software tool available by which the doctors can simulate the desease of a given person experiment and thus find out which treatment will give the best results Also for the researchers that are interested in improving and developing new technologies there is a need for a user friendly and easy to use tool that can be utilized from anywhere in order to help them to better understand the hemodynamics of the mitral valve Such a system can improve
63. mputational analysis of mitral valve repair Because of improvements made in past years regarding the modeling of the geometry of the mitral valve and the applied material properties more and more researchers study the effects of the mitral valve repair techniques Investigation about the mitral annuloplasty ring size based on the patient specific data were made by Votta et al 28 and Stevanella et al 48 In 2009 Schievano et al compare the single balloon technique versus the double balloon one for percutaneous mitral valve dilatation 49 The edge to edge repair procedure was also simulated by Votta et al 21 and Avanzini et al 50 In 2011 Avanzini et al conclude that the stresses and transvalvular pressure gradient are similar to those after the surgical edge to edge procedure 51 Lau et al also study the edge to edge technique with the help of FSI model on the idealized geometry of the mitral valve in 2011 52 2 5 Current research of mitral valve modeling in a spin off of Ghent University Currently FEops a spin off from IBiTech bioMMeda a research group of Ghent University works in the framework of finite element modeling of the mitral valve The study is based on in vivo 3D TEE images from which the mitral valve geometry and annular and papillary muscle motions are extracted semi manually Figure 15 33 Annular and papillary muscles motion Finite element model k Closure simulation GUI Figure 15 Framework for
64. n elements of the web site are written The child templates can override the base html There are three child templates that were made for the submission of the patient data for the list with the submitted patient data and also template for the login of the user Styles of the pages were imported from Bootstrap 56 In the base html JavaScript files are also imported from the same source The first from the three templates is login html which is responsible for the template of the page with the login form Figure 32 Login Login Username div bosilek Password Jeeeeeeeee Login Figure 32 Django login template The second one pt data list html contains a HTML code representing a simple table in which the user can see list of the submitted patient data by id Except the id the user can see the date in which he submitted the data and can open any of the patient specific data files as well as the generated JSON file The user can also choose to delete some of the entries in the table Figure 33 70 Welcome div_bosilek Logout Patient data Add new patient data Table Submitted date files parameters TRC file June 4 2014 5 23 p m PGF file JSON file delete CSV file Figure 33 Django patient data list template The third child template file is pt_data_submit html which is responsible for the submission of the mitral valve parameters A POST method is used in the HTML form The template is des
65. n the browser the visualization of the file fields can be different Mitral valve geometry trc file Choose File 0446708 S 6 12 trc Hemodynamic data csv file Choose File No file chosen Reconstructed leaflets geometry pgf file Choose File No file chosen Figure 58 MitralValveDj Loading data tab 103 e Mitral valve parameters tab Mitral valve parameters tab consists of eight fields Two fields regard the leaflets and their thickness and the other fields are essential parameters of the chordae tendinae Figure 59 Leaflets Thickness of the anterior leaflet mm 0 25 Thickness of the posterior leaflet mm 0 25 Chordae tendineae Number of the basal chordae 12 Number of the marginal chordae 12 Relative height of basal chordae 05 Cross section marginal cordae mm 04 Cross section basal cordae mm 0 23 Type of the chordae tendinae truss connectors Figure 59 MitralValveDj Mmitral valve parameters tab e Material properties tab Material properties tab consist of two radio buttons one for the anterior leaflet and one for the posterior Figure 60 Each of the radio buttons consists of two options which are linear elastic or hyperelastic Holzapfel material models Depending on the material properties two parameters can be entered for the linear elastic and five parameters can be submitted for the hyperelastic model 104 Anterior leaflet Linear elastic Hyperelastic anisotropic Po
66. nFile FileField Figure 31 Database diagram Django Form An HTML form was created in mitral valve templates mitral valve pt data submit html In mintral valve forms py a class PtDataForm was made in which verification of the input parameters for the mitral valve were implemented In the ptDataForm also a validation for the extensions of the submitted files is done by the help of the functions clean trcfile clean pgffile and cleancsvfile This class is also responsible for storing the TRC PGF and CSV files in the mitral valve media directory A generation of the JSON file which contains all of the input parameters is also done there URLs Scheme of the URLs was made in the mitral valve urls py A pattern of URLs was defined and once the user requests a page Django goes through each pattern in order to find the first one that matches the requested URL If there is a match Django calls the given view that is defined in mitral valve views py There are defined views for the login and logout of the user view for the submission of the mitral valve parameters and also a view which shows to the user a list with all of the submitted patient data entries sorted by id 69 Template In the directory mitral_valve templates mitral_valve four different HTML files were made All of the files contain HTML code and also a Django template language The base html file consists of the base skeleton template in which all of the commo
67. o edge double orifice repair under cardiac cycle in comparison with suture repair Eng Med vol 225 pp 959 971 2011 K D Lau V D az Zuccarini P Scambler and G Burriesci Fluid structure interaction study of the edge to edge repair technique on the mitral valve J Biomech vol 44 pp 2409 2417 2011 85 53 54 55 56 B Verhegghe pyFormex C R Kunzelman KS1 Mechanical properties of basal and marginal mitral valve chordae tendineae 1990 Django architecture Online http mytardis readthedocs org en 2 5 architecture html functional architecture Bootstrap Online Available http getbootstrap com Available 86 Appendices Appendix A pyFormex application user manual General information General Information section explains in general terms the system and the purpose for which it is intended System overview MitralValvepyF is an application which allows the generation of a patient specific mitral valve input file for further use in Abaqus software The application provides possibility for loading patients specific data from files and changing the essential parameters of the mitral valve apparatus The application generates and saves input files for Abaqus software and also saves all of the entered parameters in format that can be reused later on It enables a preview of the 3D finite element analysis model of the mitral valve Organiza
68. ology 7th Edition Heart valve surgery Online Available http www heart valve surgery com heart surgery blog 2008 09 02 mitral valve annulus definition diagrams prolapse calcification treatment N Kumar M Kumar and C M Duran A revised terminology for recording surgical findings of the mitral valve J Heart Valve Dis vol 4 pp 70 75 discussion 76 77 1995 A F Carpentier A Lessana J Y M Relland E Belli S Mihaileanu A J Berrebi E Palsky and D F Loulmet The Physio Ring An advanced concept in mitral valve annuloplasty in Annals of Thoracic Surgery 1995 vol 60 pp 1177 1186 Mitral valve leaflets J P M Rabbah N Saikrishnan A W Siefert A Santhanakrishnan and A P Yoganathan Mechanics of healthy and functionally diseased mitral valves a critical review J Biomech Eng vol 135 no 2 p 021007 Feb 2013 P Fornes D Heudes J F Fuzellier D Tixier P Bruneval and A Carpentier Correlation Between Clinical and Histologic Patterns of Degenerative Mitral Valve Insufficiency Cardiovasc Pathol vol 8 no 2 pp 81 92 Mar 1999 Libreta de notas Online Available http libretadenotas93 blogspot be M HOWARD C HERRMANN Transcatheter Mitral Valve Implantation 2009 CTSNet Ede to edge repair Online Available http circ ahajournals org content 117 7 963 F7 expansion html K S Kunzelman R P Co
69. oned above finite element analysis computational fluid dynamics analysis and fluid structure interaction Currently most of the published studies examine the structure of the mitral valve In FEA analysis the blood flow through the mitral valve is neglected while in CFD analysis normally the deformation of the leaflets of the mitral valve is neglected and the focus is on the blood flow through the valve In contrast in FSI simulations both the structural deformation and the blood flow are captured In the FEA analysis the blood flow is simulated by applying pressure load curves which are usually based on medical data The authors mainly use the pressure difference between the left ventricle and the left atrium derived for the whole cardiac cycle 15 Some research groups like that of Maisano use a linear pressure curves 21 25 27 28 The groups of Prot and Kunzelman use more accurate transvalvular pressure profiles 17 43 47 The boundary conditions used in the modeling of the mitral valve are really similar and reflect the physiological aspects of the valve Usually the boundary conditions are applied at the annulus and the papillary muscles A typical assumption made in many studies is that the papillary muscles head are fixed Some more recent published papers investigate the dynamics of the annulus and the papillary muscles while applying more complex boundary conditions combined with loads 25 27 41 47 32 2 4 Co
70. onsists of bundle of collagen fibers which extend from the annulus The ventricularis consists of loose connective tissue that is rich in collagen fibers which extend to the chordae tendinae The distal third of the leaflets contains only fibrous and spongiosa Figure 8 C 15 Y C Li P CEP d B A i 3 L4 Figure 9 Cross section of chordae tendinae At Figure 9 two cross sections of chordae tendinae are shown The center cores of the chordae are composed of longitudinally oriented collagen bundles The core is surrounded by elastic fiber see the arrow at Figure 9 1 3 Pathology of the mitral valve Conditions like rheumatic fever calcium deposits forming around the mitral valve radiation treatment to the chest mitral valve prolapse infective endocarditis congenital heart abnormality etc can lead to abnormal function of the mitral valve The well known classification of the mitral valve disease names the different conditions mitral stenosis MS and mitral regurgitation MR Mitral stenosis means that the MV is narrowed and blood s passage from the left atrium to the left ventricle is obstructed If MR is present there is leakage of blood back to the left atrium when the ventricle contracts That ultimately leads to overworking of the heart since it impedes the pumping of enough oxygenated blood 16 Nowadays MS is not that common disease but MR is the second most common valvular disease in Europe In Figur
71. ontevecchi and O Alfieri 3 D computational analysis of the stress distribution on the leaflets after edge to edge repair of mitral regurgitation J Heart Valve Dis vol 11 pp 810 822 2002 l S Salgo J H Gorman R C Gorman B M Jackson F W Bowen T Plappert M G St John Sutton and L H Edmunds Effect of annular shape on leaflet curvature in reducing mitral leaflet stress Circulation vol 106 pp 711 717 2002 D R Einstein P Reinhall M Nicosia R P Cochran and K Kunzelman Dynamic finite element implementation of nonlinear anisotropic hyperelastic biological membranes Comput Methods Biomech Biomed Engin vol 6 pp 33 44 2003 D R Einstein K S Kunzelman P G Reinhall M A Nicosia and R P Cochran Non linear fluid coupled computational model of the mitral valve J Heart Valve Dis vol 14 pp 376 385 2005 F Maisano A Redaelli M Soncini E Votta L Arcobasso and O Alfieri An annular prosthesis for the treatment of functional mitral regurgitation Finite element model analysis of a dog bone shaped ring prosthesis Ann Thorac Surg vol 79 pp 1268 1275 2005 K H Lim J H Yeo and C M G Duran Three dimensional asymmetrical modeling of the mitral valve a finite element study with dynamic boundaries J Heart Valve Dis vol 14 pp 386 392 2005 E Votta E Caiani F Veronesi M Soncini F M Montevecchi and A Redaelli Mitral valv
72. order to get more accurate stress strain curves They perform the test of leaflet specimens in both principle directions Results from the test show that both anterior and posterior leaflets behave anisotropically the obtained stress strain relations are highly non linear They also find that in general in both principle directions the curves follow the same relation 42 Based on the results of this study later in 1998 the authors define a constitutive law describing the mitral valve material properties 43 After the publishing of the constitutive law by May Newman the first successful implementation for FEA analysis is performed by Einstein et al in 2003 23 Additionally one year later Einstein et al implement the first non linear material properties for mitral valve 44 45 31 Conti et al also utilize the constitutive law by May Newman to describe the material behavior of the leaflets 34 In 2005 the research group of Holzapfel publishes a paper in which they determine another non linear constitutive mode which in turn is implemented in 2007 by Prot et al in their FEA model of the mitral valve 46 This material model is again used in later publications 30 31 of theirs Later in 2008 the Holzapfel model is as well implemented in the FEA model of Votta et al 27 2 3 Boundary conditions Depending on the goal of study applied loads and boundary conditions are different There are three main analyses as menti
73. orking web browser should be open and an address 127 0 0 1 8000 should be entered in the address bar The MitralValveDj login screen appears Figure 56 Login Login Username div bosilek Password jeeeeeeeee Login Figure 56 MitralValveDj Login screen For a username and password please contact Viktoriya Antonova at Viktoriya Antonova ugent be 102 System menu MitralValveDj is a tabbed application which consists of four tabs Figure 57 In the first tab patients specific data files can be loaded in the second tab essential parameters of the mitral valve can be edited The third tab has user preferences about the material models of the anterior and posterior leaflets In the last tab parameters related to the simulation can be changed Loading data Mitral valve parameters Material properties Simulation paramters Figure 57 MitralValveDj Tab menu e Loading data tab Loading data tab consist of three file fields Figure 58 The first file field is about loading a TRC file which contains information about the geometry of the mitral valve and the annular and papillary muscles The second file field loads a CSV file which contains the patient specific transvalvular pressure The third one loads a PGF file containing the mesh s nodes and connectivity of the anterior and posterior leaflets If a file is chosen the name appears next to the field if not a message No file chosen will show Note that depending o
74. perates on computer platforms with any operating system The application requires installed Django framework 1 6 1 installed browser Mozilla Firefox 24 Google Chrome 30 and installed database SQlite 2 8 17 After installing all of the required software and running the server the MltralValveDj can be used immediately without any further configuration User access levels Only registered users can use the application Contingencies In case of power outage data are not saved in internal memory of the computer system Getting started Getting Started section explains how to get MitralValveDj and install it on the device The section presents briefly system menu 101 Installation and logging in The newest version of MitralValveDj can be downloaded from http tinyurl com MitralValveDj and it is in ZIP file which should be unzipped on the personal computer where the application will be used After unzipping the archive you should go to the directory MitralValveDj MV via the terminal and write the following code S python manage py runserver If the server runs correctly the message as shown at Figure 55 should appears in order to run the server Validating models 0 errors found June 04 2014 14 12 46 Django version 1 6 2 using settings MV april settings Starting development server at http 127 0 0 1 8000 Quit the server with CONTROL C Figure 55 MitralValveDj Run server message Once the server is w
75. plasty 13 ere ee rere hee rene diea ev ee asi Rose e das ere Ua aan 19 Figure 13 Edge to edge repailr 14 nette patrono ton Anco tdaadantdesegedecasbadscesbiquscedasdandeennds 20 Figure 14 Mitral valve FEA models in research papers by A Kunzelman et al 15 B Kunzelman et al 18 C Salgo et al 22 D Maisano et al 21 E Votta et al 27 F Prot et al 29 G Conti et al 34 H Burlina et al 39 Rim et al 41 seseseeeeenennnneenennn nnns 30 Figure 15 Framework for mitral valve FEA modeling eeeesseeeeeeeneeennnee enne 34 Figure dG Waterfall Model P 40 Figure 17 System architecture coe aeneae Pl reo epocha gru ERRE a AEE ira ed been Rue CUP aA 53 Figure 18 Activity diagram pyFormex Load a JSON file esessseeeeeeeeneeneennnen 55 Figure 19 Activity diagram pyFormex Generate a JSON file sss 55 Figure 20 Activity diagram pyFormex Preview of mitral valve FEA model 56 Figure 21 Activity diagram pyFormex Generate a input file for Abaqus sssseeess 56 Figure 22 Activity diagram web application Generate a JSON file 57 Figure 23 GUI mitral valve pyFormex script eese eene enne enne enn 59 Figure 24 Structure of the GUI in pyFormex eese ener nnns nne 59 Figure 25 GUI pyFormex Mitral valve parameters tab sese 60 Figure 26 GUI pyFo
76. posterior leaflets Then the function uses the CSV file to load the patient specific transvalvular pressure and the TRC file to reconstruct the whole mitral valve geometry as well as the annular and papillary muscle motion Then model generates the basal and marginal chordae tendinae taking into account the entered parameters from the user The last function used in savelnp function is 63 abaqus which is responsible for the generation and save of the input file for Abaqus The function generates in a correct format the geometry of the mitral valve elements and nodes set the material properties of the leaflets and chordae tendinae then makes sections and assigns them The function incorporates the pressure loads annulus and papillary muscles movement and defines the ODB output and the steps Changes in the functionality of the function are made in the initial previously written script An option is added in the functionality of the aboqus function which allows the user to choose from linear elastic and hyperelastic Holzapfel material model for the leaflets of the mitral valve With the help of if else statements and manual operations the right format of the Holzapfel model was generated in the input file PyFormex is under development and still doesn t support automatically implementation of Holzapfel material model If the user chooses hyperelastic material properties for some of the leaflets the script opens the INP file after it is gen
77. r the number of used CPUs were made Figure 38 Friction coefficient 0 05 Number of CPUs to be used in the cluster 94 26 78 Figure 38 Django simulation tab Buttons also were defined by type submission in order to export all of the submitted parameters 73 4 4 Verification In this phase a testing is performed as well as traceability matrix is done 4 4 1 Testing The testing is performed for both of the applications Below tables with all of the performed tests can be seen Test Case ID TS0001 Load patient specific data Operator has run the script Operator loads and runs the script in pyFormex Operator goes to Loading data tab Operator chooses TRC CSV and PGF files Expected result A pop up window with possibility of choosing a files shows There is option to choose specific file with proper extension The system shows the name of the chosen file in the dialog window Actual result A pop up window with possibility of choosing files shows There is option to choose specific file with proper extension The system shows the name of the chosen file in the dialog window Le 74 Test Case ID TS0002 Test Case Name Preview of mitral valve FEA model Operator has run the script Expected result Actual result Operator chooses TRC CSV and PGF files Operator enters a mitral valve parameters Operator chooses colors for the preview Operator clicks on the Preview FEA mitral valve model button
78. re stored The directory media consists of the patient specific entries that the user submits which are arranged by dependence on the number of such submissions Each folder of these consists of the submitted TRC CSV and PGF files and the generated JSON file As shown above the file system of mitral valve Django application is wide and in this section only essential files and some of their content will be discussed In order to have an application consistent with the requirements and the used technology a few steps were performed e Amodel was defined A form was created URLs scheme was made Views were written A template was designed Model A model was defined in mitral_valve model py and it contains the fields in which the user can load the patient specific data TRC PGF and CSV files as well as a function which deletes user entries of patient specific data Once the model was done synchronization with the database was performed and a database table was automatically created The database diagram at Figure 31 shows the organization of the information in the project There is a user which has id username and password that are kept in the database The database keeps record also of the patient data that is submitted by the user 68 id AutoField username CharField authenticationMethod Charfield AN id AutoField submitted_user ForeignKey sub date DateTimeField trcfile FileField paffile FileField csvfile FileField jso
79. rements o Operating system Debian jessy release Web application python django 1 6 1 o o Other software pyFormex 0 9 1 o Database SQlite 2 8 17 e Client side requirements o Operating system Linux debian Windows XP 7 8 o Web browser Mozilla Firefox 24 Google Chrome 30 4 1 3 Use cases A use case is a description of the steps or activities to be undertaken to carry out a process The characters or entities that participate in a use case are called actors In the context of software engineering a use case is a sequence of interactions that take place between a system and its actors in response to an event that initiates an actor s principal on the system itself The use case diagrams are used to specify the communication and behavior of a system by interacting with users and or other systems In the use cases described below 44 under Operator the author means that the actor can be any of the listed medical doctor surgeon researcher student or developer testing the system 4 1 3 1 Use cases Django application NEN C cca Esos NENNEN e The user types his username and his password e The system checks if the username and password is correct o If correct logs the user into the system o If wrong the user is notified that he typed the wrong username password re ieee S Theaniomigthewserouttomthespesfon 00 e The system logs the user out from the application 45 NEN re Preconditions User is log
80. ressure against atrioventricular valves atrioventricular valves are forced open 2 As ventricles fill atrioventricular valve flaps Nc AN yA X H i di hang limply into ventricles TN WS V N er Chordae tendineae 3 Atria contract forcing INN TN N X additiona blood into Nu UNE N I Ventricle e ventricles JANI CS r E nant muscle Atrium Cusp ot atrioventricular valvo a Venticles contract hs atrioventricular forcing blood against fC atrioventricular valve cusps f Atrioventicular valves close Papillary muscles contract and chordae tendineae tighten preventing valvo flaps from everting into atria Atrioventricular valve closed b Figure 4 Mitral valve a mitral valve in open position b mitral valve in close position 4 The mitral valve has a complex structure and the normal function of the mitral valve requires proper coordination between all of its components On Figure 5 the elements of a healthy mitral valve are depicted The MV has two thin asymmetrical leaflets anterior and posterior leaflets They are attached to the left ventricle at the annulus fibrous ring The anterior leaflet is larger than the posterior but the latter having longer attachment to the annulus The chordae tendinae are string like structures that connect the free edge of the leaflets with the two papillary muscle heads 12 Anterior annulus Anterior leaflet Anteromedi
81. rmex Posterior leaflet material properties tab seeseeesssess 61 Figure 27 GUI pyFormex Visualization parameters tab enne 62 Figure 28 pyFormex Structure of the button functions ssssessssseseseseeee eene 62 Figure 29 Standard Django architecture 55 cssccccsssscececssnececsssseeecssseeeececseaaeeeeseaeeeessseeeeees 66 Figure 30 File tree of Django project c cccccccecsessssecececeesssessnneeececeescessesseseeeceeeesssesseaeeeeeeseseeeeees 67 Figure 31 Database diagram Django sess ennemis en neni nnn nnns enne 69 Fig re 32 Django login template ssa 5 ein eio eoe ended eie dites 70 Figure 33 Django patient data list template eene enne enne enne 71 Figure 34 Django submit patient data template essere enne enne 71 Figure 35 Django loading data tab ccccccccccccssssssssececececscsessaeseeeeeesceesesseaeseeeesessseseeaeeeeeeseseeesees 72 Figure 36 Django mitral valve parameters tab c cccccccccsssssssssceeeceeeceesesseaeeeceeseessesssseeeeeeeseeeeees 72 Figure 37 Django material properties tab ssssssssessseseeeeeee nennen enne nennen enne 73 Figure 38 Django simulation tab ccccccccccccecssssssnecececeeessessaeeeeeeeesceeseeseeeeeesesssesssaeaeeeeseseeeees 73 Figure 39 Tabs of MitralValvepyF c cccccccccccssssssnsecececeeessessaeseseceesceesesaeseeeeeeseessesssaeeeeeesesseeees 89 Figure 40 MitralValvep
82. s project 79 5 Conclusions limitations and future perspectives The objectives of the study were to develop a graphic user interface of existing code under pyFormex and to make a web based application with the Django framework The main goals were to create user friendly demo applications which allow every user to generate a patient specific 3D finite element analysis model of a mitral valve and to give easy way of making an input Abaqus file A web based application under Django framework was developed which allows the user to save patient specific data files and generate a file with all of the input parameters of the mitral valve The second application is developed under pyFormex and allows the user to load input parameters from a file previously generated by the one of the two applications This application is also responsible for the generation of the 3D finite element analysis model of the mitral valve as well as for the generation of input file for Abaqus One of the first limitations of the study to be mentioned is that the two applications work independently The web based application is useful because can be reached from every computer that has internet on it but doesn t have the functionality that the other application provides The pyFormex application needs to be run under Linux and the user cannot work on it via internet easily In the future the two applications can be run on a server and automatically coupled This will allo
83. s that will be used in order to solve the simulation e Export all parameters button 108 At the right bottom corner of the Submit new patient data window there is a button Export all of the parameters Once it is clicked on the system will show whether there is some error and if not will bring up the welcome screen If the system brings up the welcome screen it means that the three files TRC PGF CSV were saved in the database and JSON file with all of the input parameters has been generated Note that the JSON file can be loaded in MitralValvepyF e List of the submitted patient data entries As mentioned above in the welcome screen there is a table with all of the submitted patient data entries sorted by ID Figure 67 Welcome div bosilek Logout Patient data Add new patient data Table I Submitted date Patient specific Mitral vovtjiction files parameters TRC file 1 JJune 4 2014 5 23 p m PGF file JSON file delete CSV file Figure 67 MitralValveDj List of submitted patient data entries In the table there is a possibility to open and see every file previously loaded for the patient specific data as well as the JSON file There is a delete button which will delete the entry 109
84. sestiesesecarehisiadennwnnlancteniebecasceateautpeobsnucys leneuinnedanuacpcceeeboeeensa derek Table 3 Traceability matrix 1 Introduction This chapter consists of a description of the heart anatomy and general function of it followed by the anatomy and physiology of the mitral valve The chapter continues with the pathology of the mitral valve and the current treatment methods At the end of the chapter a brief overview of the computational techniques used in the clinical practice is made 1 1 Anatomy and physiology of the heart The heart is placed in the medial of the thorax With the size of a fist and a mass up to 350 grams it is an essential organ without which our body can t live The main function of the heart is to pump blood through the vessels to all parts of the body This is possible thanks to the four chambers and the four valves in the heart The left and right atriums are receiving chambers and left and right ventricles are discharging chambers The blood circulates in the body through the pulmonary and systemic circuit Figure 1 The right side of the heart pumps deoxidized blood to the lungs where the blood gains oxygen and goes back to the left side of the heart From the left side of the heart the blood is pumped through the systemic circuit to all of the body parts where it loses oxygen and gains carbon dioxide Capillary bed of lungs where gas exchange occurs Pulmonary arteries Pulmonary veins E Aorta and
85. sterior leaflet Linear elastic Hyperelastic anisotropic Figure 60 MitralValveDj Mmaterial properties tab e Simulation parameters The Simulation parameters tab consists of two fields as shown in Figure 61 Friction coefficient 0 05 Number of CPUs to be used in the cluster 94 06 78 Figure 61 MitralValveDj Simulation parameters tab Exit system To exit the system logout from it Using the system After login in the system a welcome screen shows In this window a list of submitted patient specific data and parameters can be found There is a button Add new patient data which leads to the window in which patient data can be submitted In Figure 62 only a welcome screen of newly registered user is shown because there are no submitted patient data yet 105 Welcome div bosilek Logout Patient data Add new patient data Table You did not submitted any patient data from your account Figure 62 MitralValveDj Welcome screen Once the Add new patient data is clicked Submit patient data screen appears Figure 63 Welcome div bosilek Logout Patient data gt Submit new patient data Loading data Mitral valve parameters Material properties Simulation parameters Patient specific data Mitral valve geometry trc file Choose File No file chosen Hemodynamic data csv file Choose File No file chosen Reconstructed leaflets geometry pgf file Choose File No file chosen E
86. t o Theusercan choose to use linear elastic model o Theusercan choose to use hyperelastic model Holzaphel The user defines the simulation parameters o Friction coefficient o Time step The system validates that the user typed the correct kind of data The system saves the parameters in a json file The system assigns an id for the submitted request of a mitral valve simulation model The system collects the following data o the json file o patient specific data trc csv pgf 47 4 32 Use cases pyFormex script NEN GO a Preconditions Installed and working pyFormex 0 9 1 User has the pyFormex script in advance The user opens the program pyFormex The user selects the script code The user runs the script Use Case ID D L e O UU e The user selects to close the graphic user interface e The user selects to close the pyFormex program 48 NEN re Preconditions User opened and ran the pyFormex script User has the files in advance The user selects a trc file containing the geometry of the mitral valve The user selects a csv file containing hemodynamic data The user selects a pgf file containing generated mitral valve leaflet geometry mesh s nodes and connectivity Loading of the mitral valve parameters from json file Description Loading the mitral valve parameters from json file which was previously generated by Django application User opened and ran pyFormex script The user
87. the work of the medical doctors and researchers The future ability to simulate any problem and also simulate any treatment will save time and might also permit process impact The aim of the present thesis is to make a demo for a graphic user interface GUI for the existing mitral valve modeling script in pyFormex Another goal is to make web based application using the Django framework With the help of a GUI in pyFormex each interested user will have the opportunity to load different patient specific data to change chosen parameters considering the mitral valve geometry and also to implement different material properties for the leaflets and chordae tendinae without any programming knowledge With the help of Django a web based basic version will be made and every user will have access to the framework remotely 35 3 Overview of the used software technologies 3 1 Programming languages 3 1 1 Python Python is an interpreted programming language which emphasizes a very clean syntax and encourages readable code It is a multi paradigm programming language since it supports object oriented imperative programming and to a lesser extent functional programming It is an interpreted language uses dynamic typing and is multiplatform It is managed by the Python Software Foundation It has an open source license called Python Software Foundation License which is compatible with the GNU General Public License from version 2 1
88. the aortic and pulmonary valves close and the mitral and tricuspid valves open in order to allow blood flow from the atria to the ventricles In this period the atria contract allowing income of blood to the ventricles diastole 10 Isovolumic relaxation Ejection Rapid inflow Diastasis Atrial isses Isovolumic contraction Aortic valve Aortic pressure Pressure mmHg g Atrial pressure Ventricular pressure d 130 b Ventricular volume B 90 gt 50 Electrocardiogram Phonocardiogram Diastole Figure 3 Wiggers diagram 3 When the ventricles contract systole the mitral and tricuspid valves are closed The aortic and pulmonary valves open to allow blood flow through the blood vessels 1 2 Anatomy and physiology of the mitral valve The mitral valve MV or bicuspid valve is the only bi leaflet valve in the heart It is situated in the left side of the heart between the left atrium and the left ventricle During diastole the blood fills the left atrium and raises the pressure there Once the pressure is higher than the pressure in the ventricle the mitral valve opens and the blood is directed to the ventricle At the end of the diastole atrial contraction occurs and the blood is transferred in the left ventricle Then the mitral valve closes which prevents a reversal of the blood flow Figure 4 11 Direction of Blood returning to PR j blood flow the heart fills atria putting p
89. the creation of complex websites Django emphasizes re use connectivity and extensibility of components rapid development and the principle of not repeating oneself DRY Do not Repeat Yourself Python is used in all parts of the framework even in settings files and data models 39 4 Software development process Two demonstrator of software tools are developed during the work on this project The first one is developed in pyFormex and the second one is a web based application developed using of Django Their functionalities allow the user to load patient specific data and to enter values for input parameters that are essential for the generation of mitral valve finite element model Modules of the demonstrators will generate 3D patient specific mitral valve models generate an input file for Abaqus and also will allow the user to save or load files with information about all of the input parameters The development of the demonstrators is following the so called Waterfall model In this model the software development is divided in five stages Software requirements Software design Implementation Testing Maintenance Figure 16 NN Min aan NN Figure 16 Waterfall model The last stage of the model the so called Maintenance is out of the scope of this project because it refers to the stage when the software is fully ready and already in use from the users 40 All of the stages of the waterfall mode
90. the script Operator chooses TRC CSV and PGF files Operator enters a mitral valve parameters Operator clicks on the Export to Abaqus inp file button Operator chooses the name for the INP file Expected result File system window appears Warning message pops up INP file is generated REQUEST file is generated Actual result File system window appears Warning message pops up INP file is generated REQUEST file is generated INL oos 76 Test Case ID Test Case Name Expected result Actual result Test result Test Case ID Test Case Name Expected result TS0006 Submit patient specific data Operator logs into the mitral valve web application Operator clicks on the Add new patient data button Operator enters values for the input parameters and uploads patient specific data files Operator clicks on the Export all of the parameters button JSON file is generated If some of the values is not in required range the system shows a notification If some of the uploaded files is not with correct extension the system shows a notification JSON file is generated If some of the values is not in required range the system shows a notification If some of the uploaded file is not with correct extension the system shows a notification TS0007 View submitted data Operator s account exists and is active Operator submits at least one patient specific entry Operator logs into the mitral valve web app
91. they make segmentation at midsystole using different axis and rotational template with eighteen long axis In each one of the eighteen axes they identify two annular intersection points The anterior and posterior commissures are identified also The coaptation zone between the anterior and posterior leaflets is captured across the entire extend of the mitral valve 36 26 Quaini et al 2012 produce a three dimensional computational fluid dynamics model CFD of the mitral valve flow with the aim of validation against in vitro standards and 3D color Doppler methods They model the chambers of the heart as idealized cylinders with a circular and rectangular orifice A 2D spectral Doppler transducer and a 3D color Doppler transducer are used to access trans orifice flow 37 Wang and Sun published a paper in 2012 about the modeling of mitral valve dynamic deformation using patient specific multi slice CT scans There they segment the scans from middle diastole after mitral valve opening and before closure and middle systole after mitral valve closure and before opening From the CT scans they obtain the geometry of the left ventricle mitral valve chordae tendinae papillary muscles and chordae intersection points Their model has 21 chordae tendinae 38 Burlina et al use 3D echocardiography to predict a patient specific mitral valve closure in 2013 After the automatic segmentation the authors refine the geometry into a 3D model of the
92. thickness for the anterior and posterior leaflets are implemented Since the chordae tendinae can t be captured by MRI they are approximated from anatomic images Twenty four marginal and eight basal ones with different material properties are modeled The points where the chordae tendinae connect to the papillary muscles are modeled to distribute the load instead of concentrating them in single points 32 The geometry of the mitral valve is successfully extracted from 3D Transesophageal Echocardiography 3D TTE in 2010 by Burlina et al They obtain it in open position and predict the configuration at end systole 33 Conti et al 2010 investigate the mitral valve modeling in ischemic patients where they obtain the mitral valve geometry from cardiac magnetic resonance data and thus build three models one for a healthy mitral valve and two representing the mitral valve regurgitation associated with the ischemic disease They reconstruct the mitral valve model by segmentation of the imaging data 34 In 2011 the research group of Inge et al models the geometry of the mitral valve by obtaining the data from 3D microCT CT stands for Computer Tomography They place 20 onyx glass bead markers in ovine heart In this way after segmentation the leaflets and the chordae tendinae are being constructed 35 The same year Jassar et al publish a paper about mitral valve modeling using real time three dimensional echocardiography where
93. tion of the application The used database is SQLite 3 8 4 The final version of Python was also installed 2 7 5 After choosing and installing the database and the web browsers a Django 1 6 1 was installed The full documented application can be found on the CD that comes with this document or at the web address https www dropbox com s m1w3geeu197xyix MitralValveDj zi Once all of the software is up and running a Django project is made In Django the difference between project and application is that a project is a collection of applications and configurations for a given Web site while an application is the Web application that excecutes certain actions and interacts with the users Once the project was made an application was created The Django framework automatically generates the initial files that are needed to have a working application The application follows the standard Django architecture which can be seen in Figure 29 65 Web Browser Caching URL Dispatch Framework eee Figure 29 Standard Django architecture 55 The URL dispatcher urls py maps the requested URL to view a function and consequently calls it The view function views py performs the requested action The model models py defines the data and interacts with it The data is stored in database After performing the requested task the view function takes the result and returns it through the template to the web browser Following these arch
94. tion of the manual The user s manual consists of four sections General Information System Summary Getting Started and Using The System General Information section explains in general terms the system and the purpose for which it is intended System Summary section provides a general overview of the system It outlines the uses of the system s hardware and software requirements system s configuration user access levels and system s behavior in case of any contingencies Getting Started section explains how to get MitralValvepyF The section presents briefly the system menu 87 Using The System section provides a detailed description of system functions System summary System Summary section provides a general overview of the system The summary outlines the uses of the system s hardware and software requirements system s configuration user access levels and system s behavior in case of any contingencies System configuration MitralValvepyF operates on computer platforms with Linux operating system It is compatible with Ubuntu 10 or higher Fedora 13 or higher Debian 7 or higher releases The application requires installed software pyFormex 0 9 1 or higher version After having pyFormex up and running the application doesn t require any further configuration User access levels Everyone can use the application and registration is not needed Contingencies In case of power outage data are not
95. tralValvepyF Export all parameters button pop up Export to Abaqus inp file button The Export to Abaqus inp file button takes the loaded patient specific data file as well as all of the input parameters and generates an input Abaqus file The application also generates a REQUEST file automatically The REQUEST file is used for simulations on the bumper cluster of UGent Once the button is clicked on a pop up windows appears asking for confirmation Figure 49 Q Export this model in Abaqus input format and request file needed for the cluster Figure 49 MitralValvepy Export to Abaqus inp file pop up window 96 After approval another pop up window comes out asking where and with what name to save the INP file The pop up window is similar to the one at Figure 48 Once the INP and REQUEST files are made a confirmation message shows up Figure 50 A The mitral valve simulation was successfully exported OK Figure 50 MitralValvepy Successful generation of INPUT file message e Preview FEA mitral valve model button The Preview FEA mitral valve button takes all of the loaded patient specific data files as well as the input parameters and generates a 3D finite analysis model of the mitral valve Once the button is clicked on and the 3D model is generated a pop up message appears Figure 51 97 E pyFormex 0 9 1 0X File Settings Viewport Camera Actions Script App Geometry Formex Surface Tools Jobs Help pb
96. ve height of the basal chordae cross section of the basal and marginal chordae type of the chordae tendinae and friction coefficient With the help of these parameters various pathology states as well as reconstruction techniques can be simulated 4 3 Implementation After defining the software requirements and design the implementation phase was completed The demonstrators were done on a personal computer under Linux Jessie operating system A pyFormex 0 9 1 Django 1 6 1 and SQlite 2 8 17 were used as well as web browsers Google Chrome 30 and Mozila Firefox 24 4 3 1 Mitral valve pyFormex script Mitral valve pyFormex demonstrator was developed under pyFormex program version 0 9 1 The mitral valve pyFormex script is recorded in a Python file A previously developed by other student code was used as well Extension of the code was done by implementing a graphic user interface GUI New material models for the anterior and posterior leaflets were included The full documented script can be found on the CD that comes with this paper work or at the web address https www dropbox com s 1w44v6fla60a77n MitralValvepyF py Considering the software requirements and the software design a tabbed GUI is developed Figure 23 a screenshot from developed GUI can be seen 58 MitralValvepyF Loading data Mitral valve parameters Material properties Visualization parameters Please load the patient specific data Mitral valve geo
97. ve parameters chia Accept the Generate JSON entered data file Figure 19 Activity diagram pyFormex Generate a JSON file 55 If the operator loads patient specific data and mitral valve parameters and request to save them the system shall accept the data and generate and store it in a JSON file e Preview of mitral valve FEA model Load patient Enter Load mitral Ricoto specific data valve parameters valve FEA model Operator Accept the Generate mitral entered data valve FEA model Figure 20 Activity diagram pyFormex Preview of mitral valve FEA model If the user loads the patient specific data files and mitral valve parameters and then submits a request for a preview of the mitral valve FEA model the system shall accept the data and generate a 3D FEA model Mitral valve parameters here refer not only to the parameters involved in the generation of the geometry of the mitral valve but also to the colors in which the operator wants the model to be e Generate the input file for Abaqus Load patient Enter Load mitral Request input file specific data valve parameters for Abaqus Operator Generate and Bccept the store INP and entered data REQUEST file Figure 21 Activity diagram pyFormex Generate a input file for Abaqus 56 Once the user submits the patient specific data files and the mitral valve parameters and request input file for Abaqus the system shall accept the data Moreover the system shall g
98. w the user to upload all of the patient specific data files enter the input parameters for the mitral valve and after submitting them to get the generated input file for Abaqus and images from the generated 3D model in the same application All that can be done through the web application Verification of the input parameters and extension of the file is made only in the Django application This is a limitation of the pyFormex graphic user interface that could be improved in the future If both of the applications were coupled together there would be no need for this because the pyFormex would use the valid parameters entered in the Django application In the future with improvements in the extracting methods for patient specific data a functionality that generates the TRC PGF and CSV files can be added 80 There is a future possibility for the application to be used also for investigation of the effect of different repair techniques 81 References 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 Tooloop Online Available http www tooloop com picture of blood circulation in the human body picture of blood circulation in the human body 2 Cardiothoratic surgery Online Available http www cts usc edu hpg valvesoftheheart html Wiggers diagram Online Available http en wikipedia org wiki Wiggers diagram Marieb Human Anatomy and Physi
99. xport all of the parameters Figure 63 MitralValveDj Submit patient data screen e Loading data tab Loading data tab consists of three file fields in which TRC CSV and PGF files can be load After clicking on the Choose File button a pop up window appears and the files can be chosen If a file is not selected a message No file chosen next to the file field will appear If a file is loaded its name will appear The MitralValveDj application makes verification for the file extension and if not a right file is selected an error message is shown Figure 64 and will lead to an empty Submit new patient data form Note that all of the file fields are required 106 Loading data Mitral valve parameters Material properties Simulation parameters trcfile File is not TRC Patient specific data Mitral valve geometry trc file Choose File No file chosen Hemodynamic data csv file Choose File No file chosen Reconstructed leaflets geometry pgf file Choose File No file chosen Export all of the parameters Figure 64 MitralValveDj Verification of the file extensions e Mitral valve parameters tab Mitral valve parameters tab consists of eight fields The first two fields are float fields concerning the thickness of the anterior and posterior leaflets The next two fields are integer fields corresponding to the number of basal and marginal chordae tendinae The next three fields are float fields about th
100. yF Loading data tab eene 89 Figure 41 MitralValvepyF Mitral valve parameters tab esseeseseseeneneeeenenenennn enne 90 Figure 42 MitralValvepyF Material properties tab Anterior leaflet tab sssessse 91 Figure 43 MitralValvepyF Material properties tab Posterior leaflet tab sss 91 Figure 44 MitralValvepyF Visualization parameters tab sesseseseseeeenennemnnnnnn nnne 92 Figure 45 MitralValvepyF input dialog ssessssesseeeeeeeeeee eren nenne nnne nennen nnn nnne nennen 92 Figure 46 MitralValvepyF Loading TRC file pop up window eeeeeeennnnenrn nn 93 Figure 47 MitralValvepyF Visualization parameters color palette pop up sssss 95 Figure 48 MitralValvepyF Export all parameters button pop up eeeennnnm nnn 96 Figure 49 MitralValvepy Export to Abaqus inp file pop up window eeeeeeeeeees 96 Figure 50 MitralValvepy Successful generation of INPUT file message seeeeee 97 Figure 51 MitralValvepyF Preview of FEA mitral valve model pop up eeeeeennene 98 Figure 52 MitralValvepyF Example of generated 3D FEA mitral valve model 98 Figure 53 MitralValvepyF Import parameters button pop up window eeeeeennnee 99 Figure 54 MitralValvepy Import parameters button message window

Viktoriya Antonova Simulation tools for mitral valve repair

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