WP Clinical translation and interpretation Deliverable: D4 ...€¦ · WP4 : WP Clinical translation and interpretation D4.2: Deliverable Third Year Report WP4 Version: 3v4 Date:

ITN-ETN 642612

Horizon 2020: The EU Framework Programme for Research and Innovation

MSCA-ITN-2014-ETN:

Marie Skłodowska-Curie Innovative Training Networks (ITN-ETN)

Work Package: WP4

WP Clinical translation and interpretation

Deliverable: D4.2

Deliverable Third Year Report WP4

Version: 3v4

Date: 31-Oct-18

MSCA-ITN-2014-ETN:– 642612, VPH-CaSE

WP4 : WP Clinical translation and interpretation

D4.2: Deliverable Third Year Report WP4

Version: 3v4

Date: 31-Oct-18

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DOCUMENT INFORMATION

IST Project Num MSCA-ITN-2014-ETN: – 642612 Acronym VPH-CaSE

Full title Virtual Physiological Human –

Cardiovascular Simulation and Experimentation for Personalised Medical Devices

Project URL http://www.vph-case.eu

EU Project officer Stanka Miteva

Work package Number 4 4 Title WP Clinical translation and interpretation

Deliverable Number 4.2 Title Deliverable Third Year Report WP4Third Year Report WP4

Date of delivery Contractual 31/10/2018 Actual 31/10/2018

Status Version 3v4 Final

Nature Prototype Report Dissemination Other

Dissemination Level

Public (PU) Restricted to other Programme Participants (PP)

Consortium (CO) Restricted to specified group (RE)

Authors (Partner) D Friboulet, AJ Narracott, JW Fenner

Responsible Author

Denis Friboulet Email [email protected]

Partner CNRS Phone

Abstract (for dissemination)

Research in VPH-CaSE has been driven by 14 Early Stage Researchers (ESRs), all but one of whom have been employed as PhD students. The individual projects are clustered under three topic headings, obtaining a natural dissemination focus through the activities of IRP11. Together they have been executed within a structure of 3 technical workpackages: WP2 – Simulation, WP3 – Experimental measurement and training, WP4 - Clinical translation and interpretation. This deliverable contains a report on the progress of the activities undertaken as part of WP4 (Clinical Translation and Interpretation), summarizing, clustering, and placing into context activities associated with the individual research projects, the VPH-CaSE training events (held at Sheffield (UK), POLIMI (Italy), CNRS (France), TU/e (Netherlands) and London (UK)) and events organised by local institutions and external organisations.

Keywords Final Progress Report, Virtual Physiological Human (VPH), Cardiovascular, Early Stage Researchers

The information in this document is provided as is and no guarantee or warranty is given that the information is fit for any particular purpose. The user thereof uses the information at its sole risk and liability. Its owner is not liable for damages resulting from the use of erroneous or incomplete confidential information.

Version Log

Issue Date Version Author Change

4 Jul 2018 1v0 Karen El-Arifi Initial Template

20 Sept 2018 2v0 Denis Friboulet Draft version

6 Oct 2018 2v1 Andrew Narracott Edits/summary of D4.1 status added

15 Oct 2018 2v2 Karen El-Arifi Edits of Tables

16 Oct 2018 3v2 Karen El-Arifi Edits of Tables

22 Oct 2018 3v3 John Fenner Additional text

31 Oct 2018 3v4 Karen El-Arifi Release version

http://www.vph-case.eu/




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Contents

1 Executive Summary ........................................................................................................................ 4

2 Contributors ................................................................................................................................... 5

3 Introduction ................................................................................................................................... 6

4 Summary of network-wide WP4 activities ..................................................................................... 7

4.1 Knowledge Transfer/Exchange ............................................................................................... 7

4.1.1 Horizontal strands of clinical translation ........................................................................ 7

4.1.2 Exchanges for VPH-CaSE technologies transfer and clinical applications ....................... 9

4.2 Toolbox Candidature ............................................................................................................. 13

4.3 Research Methodologies/Technologies ................................................................................ 13

4.4 Clinical Translation/Reporting .............................................................................................. 14

4.5 Translation through exposure of project outcomes ............................................................. 15

5 Summary and Discussion.............................................................................................................. 18

6 Conclusion .................................................................................................................................... 18

LIST OF TABLES

Table 1: Secondments and training events items discussed by the Steering Committee (Period 2) ..... 8

Table 2 : All Clinical secondments ........................................................................................................... 8

Table 3: Summary of internal exchanges on technologies and clinical applications (Period 2) ............. 9

Table 4: Summary of external exchanges on technologies and clinical applications – Period 2 .......... 11

Table 5: Methods or data prospectively shared in VPH-CaSE .............................................................. 13




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1 EXECUTIVE SUMMARY

Research in VPH-CaSE has been driven by 14 Early Stage Researchers (ESRs), all but one of which have been employed as PhD students. The individual projects are clustered under three topic headings (Fig1).

Figure 1 – the research projects are clustered according to 3 headings (i) Cardiac tissue function and cardiac support; (ii) Cardiovascular haemodynamics – pathology and intervention; (iii) Image based

diagnosis and imaging quality assurance

Together these have been executed within a structure of 3 technical workpackages:

WP2 – Simulation

WP3 – Experimental measurement and training

WP4 - Clinical translation and interpretation

This deliverable contains a report on the progress of the activities undertaken as part of WP4 (Clinical Translation and Interpretation), summarizing, clustering, and placing into context activities associated with the individual research projects. Importantly it includes the impact of the VPH-CaSE training events (held at Sheffield (UK), POLIMI (Italy), CNRS (France), TU/e (Netherlands) and London (UK)) and events organised by local institutions and external organisations.

Maximising the impact of results and the sustainability of the methodologies obtained from the simulation and experimental techniques developed as part of WP1 and WP2 effort, has required close




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collaboration across the disciplines. Additionally, clinical aspects have helped to place the research in context, whilst the industrial contribution has clarified opportunities for exploitation as well as economic and regulatory constraints to translation. Of course within the biomedical area, it is also important to be mindful of ethical responsibilities to individuals who provide data or tissue for use in research.

This report begins by reviewing the tasks associated with this Workpackage, followed by a summary of overall network progress beyond activity reported previously in D4.1. As reported in D4.1 it was challenging to address the clinical and interpretation emphases of WP4 during the 1st year of the ESR projects, because the research initially focussed on development and understanding of fundamental techniques, equipping the ESRs with the necessary tools to address their individual areas of research. The progress reported in this deliverable demonstrates the significant increase in activity in the area of WP4, particularly in the context of clinical secondments undertaken by the VPH-CaSE ESRs.

2 CONTRIBUTORS

CNRS; Denis Friboulet

USFD; Andrew Narracott, John Fenner

Contributions from all partners for local reporting of WP4 activities




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3 INTRODUCTION

The science within the VPH-CaSE European Training Network (ETN) has evolved around basic and applied research in the field of Medical Devices and Cardiovascular Science, with a focus on cardiac tissue function/support, haemodynamics, imaging and QA (ie quality assurance). Our approach has relied on two main paradigms identifiable as (i) in-vitro and in-vivo experimentation (experimental science), and (ii) modelling and simulation (computational science). Translation of this basic and applied research to the clinic is also a contributor to this research, helping to deliver tangible content to the Science and Technology agenda for VPH-CaSE.

The core of this network has been formed by 14 Early Stage Researchers (ESRs). Their individual research projects (IRPs) have been described at length in the VPH-CaSE deliverable D1.4 (ESR 1st year reports). Deliverable D1.4 also contains the results obtained by each ESR during the first year of their employment.

These individual projects have operated under the auspices of 3 main workpackages in VPH-CaSE:

WP2 – Simulation

WP3 – Experimental measurement and imaging

WP4 - Clinical translation and interpretation.1

This deliverable D4.2 contains a report on the progress of the activities undertaken as part of WP4 since the delivery of D4.1. The accompanying deliverables D2.2 and D3.2 contain comparable reports for WP2 and WP3.

WP4 brings together the elements of the IRPs covering translation of results and techniques, both modelling and experimental, to address specific clinical (WP 4.1-4.3) and industrial (WP 4.4-4.5) needs. The effort in this WP is, by its nature, more application specific than in WP2 and WP3, and part of the objective is to provide concepts and skills that are valuable for a future career in the clinical, industrial and academic sectors. Activities in this WP are (quoting from the description of work):

Task 4.1: Knowledge transfer/exchange

Coordinate horizontal strands of clinical translation through the Steering Committee and secondments, organizing frequent multidisciplinary discussions bringing together all actors (Imaging physicist, post-processing engineers, applied mathematicians, industry) to ensure the optimal transfer of technologies supported by VPH-CaSE toward clinical applications.

Task 4.2: Toolbox candidature

Detect and list methods within the network that could ultimately be turned into toolboxes integrating newly developed data post-processing technologies within open software (e.g. Osirix), that can facilitate common research activities in the field of US and CMR analysis, and transfer to the clinical research environment.

1 The other workpackages of the network relate to Management (WP1), Training (WP5) and Dissemination (WP6).




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Task 4.3: Research methodologies/technologies

Foster and make available clinical and practical training in Cardiovascular Imaging in order to acquire the knowledge of state-of-the art technologies from industrials partners, and understand challenges and clear expectation of the clinical community in terms of new research methodology and technologies.

Task 4.4: Clinical translation/reporting

Coordinate reporting of clinical translation activity to contribute to D4.1 and D4.2

Relevant milestones associated with these tasks have been achieved - MS2 – All ESRs recruited; MS3 – ESRs complete first year assessment, MS4 All network-wide training activities delivered, MS5 Exposure of project outputs, MS6 concerns completion of PhDs and contribution to D2.2, D3.2 and D4.2.

4 SUMMARY OF NETWORK-WIDE WP4 ACTIVITIES

The following section of this report provides a breakdown of WP4 activity by the associated workpackage task.

4.1 Knowledge Transfer/Exchange

4.1.1 Horizontal strands of clinical translation

The horizontal strands related to clinical translation have been mainly monitored through the Steering Committee which shapes and coordinates the two main global tools related to this topic, namely the secondments and the training activities.

Table 1 on the next page provides the list of items related to these two aspects that have been worked out during the successive meetings of the Steering Committee. Items up to and including SC9 have been previously reported in D4.1.




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Table 1: Secondments and training events items discussed by the Steering Committee (Period 2)

Ref. Dates Type Discussed items

SC10 14/12/2016 Phone

conference Secondments: Update of the secondment tables

SC11 09/02/2017 Phone

conference

Secondments: Update of the secondment tables Training: Training event 3 in Lyon (16-23 June 2017) update, program, travel plans and SB invites

SC12 03/04/2017 Phone

conference Secondments: Update of the secondment tables Training: Training event 3 in Lyon (16-23 June 2017) : program, travel plans

SC13 19/06/2017 Meeting at CNRS, Lyon

Training: • Participation of the PI to Power pitch + poster presentation of each ESR

Secondments • Recording on EU portal • Clinical placements • Planning doc/output report • Update of current status

SC14 10/10/2017 Phone

conference

Training: Preparation of Training event 4 in London (19-20 July 2018) : program, travel plans

Secondments : Update of the secondment tables

SC15 25/01/2018 Phone

conference

Training: Training event 4 in London (19-20 July 2018 update : agenda, Evaluation, sessions


SC16 15/03/2018 Phone

conference

Training: Training event 4 in London (19-20 July 2018 update : agenda, Evaluation, sessions


SC17 28/06/2018 Phone

conference

Training: • Training event 4 in London (19-20 July 2018 final update : organisation, agenda,

Evaluation, sessions, special issue in Medical Engineering and Physics Secondments : Update of the secondment tables

SC18 19/07/2018 Meeting at

UCL, London Secondments : Update of the secondment tables

SC19 13/09/2018 Phone

conference Secondments : Update of the secondment tables

Secondments

Thanks to the close ties that most beneficiaries have established with clinical institutions, each ESR was able to benefit from a clinical secondment. Through this exposure to a real clinical environment, it is anticipated that the ESR will be able to understand challenges and the expectations of the clinical community in terms of new research methodology and technologies. Table 2 provides the list of the clinical secondments that have now been undertaken for each ESR. This table highlights that most of this activity has taken place since the reporting point of D4.1 (November 2016), demonstrating that all ESRs have significantly increased their exposure to the clinical environment since the early stages of network activity, as anticipated in D4.1.

Table 2 : All Clinical secondments

Number Name Date Place

ESR1 Paolo Ferraiuoli 18 Sept 2018 Academic unit of Radiology, Sheffield Teaching Hosptial, UK

ESR2 Simone Ferrari 18 Sept 2018 Academic unit of Radiology, Sheffield Teaching Hosptial, UK

ESR3 Louis Fixsen 10 May to 31 Jul 2017 Catharina Hospital, Eindhoven, NL




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ESR4 Eric Chen 29 Jan 2018 University Medical Centre, Utrecht, NL

ESR5 Carlos Ledezma 17 Apr-15 May 2018 St. Bartholomew's Hospital, London, UK

ESR6 Mirko Bonfanti 16-23 Oct 2017 Royal Free London NHS Trust, UK

ESR6 Mirko Bonfanti 14-18 Jan 2018 University Hospital of Bern, Switzerland

ESR7 Susanna Migliori 2-10 Feb 2017 Policlinico Gemelli, Rome, Italy

ESR7 Susanna Migliori 29 May-2 Jun 2017 Royal Sussex County Hospital at Brighton, UK

ESR8 Ricardo Gómez Bardón 27-28 Aug 2018 Policlinico Gemelli, Rome, Italy

ESR9 Emilia Badescu 09-10-Jan 2017; 16-17 Jan 2017 University Hospital Saint-Etienne, France

ESR10 Gerardo Kenny Rumindo 3-Nov 2015; 6 Apr 2016; 18 May 2017; 19 Dec 2017

University Hospital Saint-Etienne, France

ESR11 Massimiliano Mercuri 15-17 Jan 2018 University Hospital of Bern, Switzerland

ESR11 Massimiliano Mercuri 19-23 Mar 2018 University Hospital of Bern, Switzerland

ESR11 Massimiliano Mercuri 23-27 Jul 2018 University Hospital of Bern, Switzerland

ESR12 Simone Ambrogio 6-10 Jun 2016 Sheffield Teaching Hospitals NHS Trust, UK

ESR13 Jeroen Feher 6-8 Jan 2016 Inselspital Bern, Switzerland

ESR14 Benjamin Kappler 8-22 Sep 2017 Catharina Hospital Eindhoven, NL

Training events

Training events have represented an excellent venue to expose the ESRs to a structured vision of the clinical challenges as well as their link to research methodology and technologies. The aspects related to these training events are described in section 4.3.

4.1.2 Exchanges for VPH-CaSE technologies transfer and clinical applications

VPH-CaSE has provided a rich ecosystem that naturally fosters ESR appreciation for the challenges of technology transfer and clinical awareness. Often this has resulted in exchanges beyond the planned secondments and training events planned by the Steering Committee. These task-specific exchanges have been monitored and are characterised as internal or external interactions.

Internal interactions

Internal interactions concern two or more entities participating within VPH-CaSE. These interactions are summarized in Table 3. This shows in particular the vitality in the internal exchanges and concerns almost every ESR.

Table 3: Summary of internal exchanges on technologies and clinical applications (Period 2)

# Date Partner Description

ESR1 May/June 2018 USFD, LIFETEC Organising and performing passive heart experiments at LIFETEC, to compare optical and ultrasound based strain estimation methods

ESR1 April/May/June 2018

USFD, LIFETEC, TU/e

Collaborated on experiments at Lifetec. Organised and performed passive heart experiments at LIFETEC, to compare optical and ultrasound based strain estimation methods

ESR2 6-9 June 2017 CNRS, USFD Discussion about future experiments regarding Ultrasound acquisitions

ESR2 6-9/06/2017 CNRS, USFD Visit CNRS and carried out experiments (Ultrasound acquisition). Discussion about future experiments




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ESR3 May/June 2018 TU/e, LIFETEC Organising and performing passive heart experiments at LIFETEC, to compare optical and ultrasound based strain estimation methods


USFD, LIFETEC, TU/e


ESR6 16-23/10/2017 UCL, UCLH

Clinical secondment at the Royal Free London NHS Trust. Attendance to several aortic interventions (open surgery and endovascular interventions) and discussion with clinicians

ESR6 14-18 Jan 2018 UCL, University hospital of Bern

Clinical secondment at the University Hospital of Bern with M. Mercuri (ESR11). Discussion with clinicians (radiologists, vascular surgeons, cardiologists) on the use of computational tools and simulations in the clinic

ESR6 14-18 Jan 2018 UCL, University hospital of Bern

Discussion with clinicians (radiologists, vascular surgeons, cardiologists) on the use of computational tools and simulations in the clinic

ESR6 15-17 Nov 2017

UCL, Therenva Discussions on cardiovascular modelling and simulations with experts and academics

ESR6 31 Jul - 2 Aug 2018

UCL, Therenva, Polimi, ANSYS

Preparation of the material for the virtual reality showcase at the Avicenna alliance meeting held at the EU parliament on the 4th of September 2018

ESR6 31 Jul - 2 Aug 2018

UCL, Therenva, Polimi, ANSYS, USFD

Industrial secondment at ANSYS, Lyon. Preparation of the material for the virtual reality showcase at the Avicenna Alliance meeting held at the EU parliament on the 4th of September 2018

ESR6 15-17 Nov 2017

UCL, Therenva, USFD

Academic secondment at the University of Sheffield. Discussions on cardiovascular modelling and simulations with experts and academics

ESR6 April-September 2018

UCL, Polimi Parametric study of BCs in CFD simulations of coronary arteries. Scripting to run CFX solver on UCL cluster

ESR7 31 Jul - 2 Aug 2018

UCL, Therenva, Polimi, ANSYS

Preparation of the material for the virtual reality showcase at the Avicenna alliance meeting held at the EU parliament on the 4th of September 2018

ESR7 April-Sep 2018 UCL, Polimi Parametric study of BCs in CFD simulations of coronary arteries. Scripting to run CFX solver on UCL cluster

ESR7 31 Jul - 2 Aug 2018

UCL, Therenva, Polimi, ANSYS, USFD

Industrial secondment at ANSYS, Lyon. Preparation of the material for the virtual reality showcase at the Avicenna alliance meeting held at the EU parliament on the 4th of September 2018

ESR7 April-Sep 2018 UCL, Polimi Secondment at UCL. Parametric study of BCs in CFD simulations of coronary arteries. Scripting to run CFX solver on UCL cluster

ESR8 18 Feb – 3 Mar, 23 Apr – 5 May 2018

UCL, Polimi Secondments at UCL. Experimental studies on microfluidic phenomena occurring at the level of red blood cell flow in the oxygenator fibre bundle

ESR9 24-28/04/2017 CNRS, USFD Experiments for improvements for both vector velocity high-frame rate ultrasound methods and vortex phantom

ESR9 24-28/04/2017 USFD

Experiments conducted with Simone A.(ESR12) and Simone F. (ESR 2). Ideas of improvements for both vector velocity high-frame rate ultrasound methods and vortex phantom

ESR10 Feb-Apr 2017 CNRS, TU/e Comparison of mechanical model of the LV

ESR10 Apr 2018 CNRS, TU/e Discussion to improve the LV model of Creatis (CNRS)

ESR10 04/06/2018 CNRS, ANSYS Discussion on the limitations of the LV model of Creatis (CNRS)

ESR10 Feb-Apr 2017 TU/e Visiting researcher / academic secondment. Comparison of mechanical model of the LV

ESR10 Apr-18 TU/e Discussion about results on real data. Some suggestions to improve the LV model of Creatis (CNRS)

ESR10 04/06/2018 Ansys Industrial secondment. Discussion on the limitations of the LV model of Creatis (CNRS)

ESR11 15-17 Nov 2017

Therenva, UCL Discussions on cardiovascular modelling and simulations with experts and academics

ESR6, 11 15-17 Nov 2017

UCL, Therenva, USFD

Academic secondment at the University of Sheffield. Discussions on cardiovascular modelling and simulations with experts and academics

ESR12 Oct 2018 LTO, CNRS Test of the vortex phantom with advanced Vector Doppler Imaging implemented on a Verasonics system




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ESR14 May/June 2018 LIFETEC, TU/e, USFD

Organising and performing passive heart experiments at LIFETEC, to compare optical and ultrasound based strain estimation methods

ESR14 01/01/2016 till today LIFETEC, TU/e

Discussion with Marcel Rutten about future experiments. The VPH-CaSE training event provided the occasion to discuss the details of their research project with senior staff from LTO and USFD.

ESR14 01/01/2016 till today LIFETEC, UCL

Close contact with Vanessa Diaz and Carlos Ledezma (ESR5) about upcoming studies. Attended the Festival of Life organized by the University of Sheffield. Gaining experience with the outreach events, improving presentation skills

ESR14 01/01/2016 till today LIFETEC, UCL

Frequent discussions with Carlos Ledezma (ESR5) about electrophysiology, possible measurements and simulations. Attended d a presentation of the company, showing me different departments. Discussion about the project and the possibility to collaborate in the future.


USFD, LIFETEC, TU/e


External interactions

External interactions concern the participation of ESRs and PIs in external events or meetings involving participants from entities external to VPH-CaSE. The associated exchanges are summarized in Table 4. These interactions have allowed sharing of expertise between various experts (i.e. clinicians, imaging physicist, post-processing engineers, applied mathematicians, industry, etc.), including ESRs and PIs in VPH-CaSE related fields. Table 4 shows the wealth of these interactions.

Table 4: Summary of external exchanges on technologies and clinical applications – Period 2

# Date Institution Event Place

ESR1 Oct - Dec 2016 USFD Experimental Stress Analysis module Sheffield UK

ESR1 22/02/2017 USFD BSSM - Uncertainty Quantification in Digital Image Correlation Teddington, NPL

ESR1 3-7 Jul 2017 USFD DIC course, MatchID Ghent, Belgium

ESR2 15/01/2018 USFD LaVision PIV experiment Sheffield, UK

ESR2 06-12/05/2017 LTO, USFD, CNRS CNRS Lyon, France

ESR2 22-26/05/2017 USFD 2nd VPH Summer School Barcelona, Spain

ESR2 18-22/06/2018 USFD 3rd VPH Summer School Barcelona, Spain

ESR6 2-5 July 2017 UCL Congress of the European Society of Biomechanics Seville, Spain

ESR6 8-12 Jul 2018 UCL World Congress of Biomechanics Dublin, Ireland

ESR6 5-7 Sep 2018 UCL VPH Conference 2018 Zaragoza, Spain

ESR7 25 Mar 2017 POLIMI Marie Curie Alumni Association 2017 Annual Congress Salamanca, Spain

ESR7 4-5 April 2017 POLIMI 12th International Symposium on Biomechanics in Vascular Biology and Cardiovascular Disease

Rotterdam, The Netherlands

ESR7 2-5 July 2017 POLIMI XXIII Congress of the European Society of Biomechanics Seville, Spain

ESR7 8-12 Jul 2018 POLIMI 8th World Congress of Biomechanics Dublin, Ireland




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ESR7 4 Sep 2018 POLIMI

In vivo, in vitro, in silico: Why computer modelling is the next evolution of the healthcare sector

European Parliament, Brussels, Belgium

ESR7 5-7 Sep 2018 POLIMI VPH Conference 2018 Zaragoza, Spain

ESR8 25 Mar 2017 POLIMI Marie Curie Alumni Association 2017 Annual Congress Salamanca, Spain

ESR8 22-26 May 2017 POLIMI 2nd VPH Summer School Barcelona, Spain

ESR8 2-5 July 2017 POLIMI XXIII Congress of the European Society of Biomechanics Seville, Spain

ESR8 18-22 Sep 2017 POLIMI

XXXVI Annual School of the Italian National Group of Bioengineering: “E-Health and Digital Medicine” Bressanone-Brixen, Italy

ESR8 9-11 Oct 2017 POLIMI Blood Flow: Current State and Future Prospects Paris, France

ESR8 25-27 Jun 2018 POLIMI Sixth National Conference of Bioengineering - GNB 2018 Milan, Italy

ESR8 8-12 Jul 2018 POLIMI 8th World Congress of Biomechanics Dublin, Ireland

ESR9 06-09/09/2016 CNRS IEEE International Ultrasonics Symposium Washington DC, US

ESR9 Jan 2017 CNRS Saint Etienne Hospital Saint Etienne, France

ESR9 15/02/2017 CNRS Phillips Paris, France

ESR9 07/12/2018 CNRS Workshop on cardiovascular applications of medical ultrasound imaging Lyon, France

ESR12 06-12/05/2017 LTO, USFD, CNRS CNRS Lyon, France

ESR12 29/05/2017-02/06/2017 LTO National Physical Laboratory London, UK

ESR12 22-24/11/2017 LTO Institute of Cancer Research, London London, UK

ESR12 26/11/2017 - 1/12/2017 LTO RSNA 2017 Chicago, USA

ESR12 24/02/2018-04/03/2018 LTO ECR 2018 Vienna, Austria

ESR14 03/03/2016 LIFETEC Academic Medical Center Amsterdam, The Netherlands




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4.2 Toolbox Candidature

The exploitation of methods and/or data that could ultimately be used as toolboxes to facilitate common research activities in VPH-CaSE fields is always challenging since the ESRs tend to focus on developing and understanding fundamental techniques to address their individual areas of research. Nonetheless toolbox opportunities have been explored, and the list in Table 5 below thus summarizes the elements that could prospectively be shared.

Table 5: Methods or data prospectively shared in VPH-CaSE

ESR# Institutions DESCRIPTION

ESR1 USFD

Graphical user interface (GUI) developed in Matlab to capture synchronously images with stereo-cameras

Matlab scripts and functions coupled with Ncorr software to enable 3D strain computation using DIC method.

ESR2 USFD Optimized methods for numerical characterization of complex flow behaviours

ESR5 UCL

Custom made routines developed in Matlab for both the generation of populations of electrophysiological models and the propagation patterns over the left ventricle.

Electrical activity on the left ventricle data to apply the population of models methodology and to calibrate the electrical propagation model.

ESR6 UCL

CT scans to extract the vessel geometry for patient-specific model generation.

4D Flow MRI for flow visualization, 2D pc-MRI for flow quantification

Doppler ultrasound for blood flow quantification.

ESR7 POLIMI X-ray Angiography and OCT of patients undergoing PCI

X-ray Angiography and Optical Frequency Domain Imaging acquisitions of patients treated with Bioresorbable Vessel Scaffold

ESR8 POLIMI Computational tools which can help companies to design their devices in a more

methodological and accurate way.

Computational tools for multiphysics analyses for oxygenators design.

ESR10 CNRS Methodologies for patient MR imaging and to specify the patient specific

geometry and simulation input parameters

ESR12 LTO Experimental methodology for image capture and measurement – exemplified

with travelling ring vortex behavior

ESR13 ANSYS Extension for ANSYS Fluent software allowing multiscale modelling and coupling

of windkessel system models to 2D/3D numerical models. In addition, integrated tools will be made available to clinical partners affiliated to the project

VPH-CaSE Exposure of simulation results through accessible media such as 3D pdf, 3D

printing, VR

4.3 Research Methodologies/Technologies

While the internal and external interactions described in section 4.1.2 are flexible and task-specific, the training and access to research methodologies/technologies has been monitored on a global level through the deployment of the VPH-CaSE training activities (TA), since they are attended by all the ESRs.

All five training events: TA1 (in Sheffield by USFD), TA2 (in Milan by POLIMI) and TA3 (in Eindhoven by TU/e), TA4 (Lyon by CNRS) and TA5 (London by UCL) have been successfully organized, and the




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detailed content and outcomes of these events are available in the associated detailed reports (D5.2, D5.3, D5.4, D5.5 and D5.6). The WP4 aspects of TA1, TA2 and TA3 were reported in D4.1.

TA4 was held in Lyon by CNRS, June 2017. The event focussed mainly on the exploitation of VPH-CaSE research results including contributions from industrial partners, and aspects related to IPR, commercialisation, financing, marketing and sales. In particular, the following items were presented to the ESRs:

Planning of a clinical study: ethics, logistics and regulatory requirements

Preparing for an international job application

Launching a high tech start-up

Example of start-ups : E-ophtalmo (e-health services for eye care professionals), Predisurge (Preoperative planning by numerical simulation)

Quantitative image analysis in clinical trials: from applied research to business opportunities

Visits : CERMEP Imaging platform and EDAP Technomed company

TA5 was held in London by UCL, July 2018. This event took the form of a conference entitled: Frontiers of Simulation and Experimentation for Personalized Cardiovascular Management and Treatment. The main topics of the conference were the following:

Cardiac and vascular disease modelling.

Cardiac and vascular experimentation.

Medical devices.

Patient-specific modelling.

In-vitro experimental platforms for personalised treatment, device testing, surgical planning and disease diagnosis.

4.4 Clinical Translation/Reporting

The monitoring of WP4 activities and the current report has been compiled from the following material:

Steering Committee minutes

Secondment organization document (see Table 2)

Questionnaires about the specific interactions filled on a yearly basis by the ESRs and PI (see Table 3 and Table 4)

Reports issued as outcomes of the training events.

These inputs to WP4 monitoring have been maintained throughout the duration of the project.

Reporting of the VPH-CaSE projects in this document has been designed to avoid repetition (of other documents), providing a concise account of the methodologies and results of the individual research projects in a workpackage context. This will be disseminated to the VPH-CaSE Supervisory Board, providing an opportunity for Supervisory Board members to provide feedback from a clinical/industrial perspective.




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4.5 Translation through exposure of project outcomes

The inherent multi-disciplinarity of the VPH domain means that researchers need to be equipped with an ability to address novel, challenging research questions through assimilation of knowledge from a range of disciplines whilst maintaining adequate depth of skills in individual specialties. The ultimate goal of the research undertaken by the 14 VPH-CaSE Early Stage Researchers (ESRs) is to accelerate the process of personalised cardiovascular medical device design and the researchers are motivated by a desire to deliver work that has implications for improved patient care. However, this translational ambition requires not only the combined expertise of those developing the technologies (ie. the ESRs) but also engagement by clinical and industrial end-users, supported through an effective multi-disciplinary environment.

As the ESRs have progressed in their research they have become acutely aware that production of research solutions per se, does not readily translate to acceptance in clinical practice. Here, the industry partners have been particularly valuable as they provide expertise and insight into addressing the practical difficulties and requirements of delivering new technology to the clinic. A particular example within the consortium is Therenva with its goal of producing tools to support planning of transcatheter aortic valve implantation (TAVI). This encompasses a breadth of processes, including imaging modalities, application of image processing techniques to assess device placement and interaction with cardiovascular patient-specific physiology. TAVI neatly illustrates the challenges, placed in a highly relevant context.

Such an example highlights that in silico simulation data must be configured to be accessible to clinicians and presented in a clear manner, otherwise it will never be adopted and will fail to deliver on its true potential. Consequently, VPH-CaSE reviewed the landscape relevant to the research of the network and identified a pathway that might facilitate communication across all of its research topics. An approach was proposed that revolves around data conversion between file formats such as csv, obj and pdf. The latter offers ready access to, and interactive interpretation of, 3D simulation data by virtue of 3D PDF2 in the standard Adobe Acrobat pdf reader. Exemplification through several case studies was investigated, encompassing fluid dynamics, medical device design and clinically informed simulation. The process begins with production of simulation results, followed by conversion between file formats, adopting established and standardised tools where possible. Many of the projects in VPH-CaSE use ANSYS software as the primary simulation tool, and consequently it was possible to report numerous examples of exposure of simulation results using this method. Several clinically relevant case studies were constructed to demonstrate exposure of VPH-CaSE research outputs and these are described in D6.1. Additionally, the brief of VPH-CaSE also includes design and development, and an example in this area was explored too. The particular examples, more fully reported in D6.1 are:

Case study #01: Heart attack – the use of simulation results to inform stent placement

Case study #02: Aortic coarctation – simulation of blood flow to confirm the need for intervention

Case study #03: Aortic Dissection – simulation of aortic blood flow for improved understanding of the impact of pathology

Case study #04: Concept for a complex flow phantom – communication of design concepts in a medical device

2 https://en.wikipedia.org/wiki/PDF




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The final year of VPH-CaSE (2018) offered numerous opportunities for promotion of VPH-CaSE research with opportunities to demonstrate the accessibility of this approach. Three particular events were targeted, illustrating exposure of VPH-CaSE outputs to a range of audiences, namely:

1. Title: By the deep, by the mark

Venue: Somerset House

Date: Feb – Apr 2018

Audience: General public

Attendees: In excess of 20,000 visitors

2. Title: Hearts and how to heal them

Venue: UCL, London

Date: 18th July 2018 18:30-20:30

Audience: Mixed - public, students, school children, scientists etc.

Attendees: Approx. 30 visitors

3. Title: Avicenna Alliance conference, Brussels

Venue: EU Parliament

Date: 4th Sept 2018

Audience: Mixed – industry, clinicians, scientists, engineers, politicians

Attendees: 80-100 people

These events were well received, benefitting from the exposure that our ESRs have had to the three sectors of the network – academic, clinical, industrial. Network secondments and training events have been crucial here. A recurring theme has been to look beyond the immediate focus of the research to appreciate the wider landscape within which it fits and to consider how translation might take place. Within VPH-CaSE we have designated this as a challenge in communication that is best addressed by pushing our ESRs into non-specialist environments and forcing them to engage with interested non-experts. Our outreach programme has had particular value, especially since each ESR was committed at the beginning (2015) of the project, to multiple outreach events across the duration of their




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research. With such efforts, we do not suggest that VPH-CaSE has accomplished the journey to clinical and industrial translation, but we do argue that we have equipped our ESRs with the skills and confidence to go out and communicate more effectively so that a translational focus is embedded within their mindset. The process of preparing research outcomes for exposure has required the VPH-CaSE ESRs to consider their research from diverse perspectives, preparing them well for the defense of their thesis and providing broad communication skills relevant to career paths across the industrial, clinical and academic sectors in which the network has operated.




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5 SUMMARY AND DISCUSSION

Over the course of this project, the ESRs have been introduced to various aspects of clinical and industrial translation. This was intended to raise ESR awareness that research can be more effective if it is mindful of translation, clinical and industrial endpoints. The role of industry and the clinic in determining the focus of research questions has been highlighted, and this is evident within the project planning that is clear within each IRP.

Through the collaborative nature of the Marie Curie network it has been possible to expose the ESRs to a wide range of clinical areas and research methodologies that would not have been possible with a purely local training approach. A particular example of this is the range of facilities made available to ESRs during all the training events. Secondments have also provided an effective mechanism for ESRs to engage with clinical contacts from other network partners.

The consortium is aware of the importance of ensuring that WP4 activities, in particular, were sustained and increased throughout the third period of the project. This not only involved training and secondments but was more widely supported by opportunistic exchanges (internal and external) as well as more structured routes involving dissemination and outreach. Together they have strengthened a sustainable approach to the clinical translation and interpretation activities of the Network.

Good experimentation has been an underlying principle that underpinned VPH-CaSE effort, and it was a feature of each of the three clusters that span the Network. The experimental work of TU/e and LTG in respect of heart physiology and measurement has been particularly valued for the insights provided on physiology and its capacity to inform and validate the simulation models. Expertise elsewhere across the Network has included various forms of imaging, analysis and 3D printing. Opportunities for instrumentation design, development, data acquisition etc. have been plentiful, which collectively offered sophisticated tools for improved understanding and model validation. The latter was a recurring theme in VPH-CaSE, because only through rigorous validation can evidence be provided that instils confidence for use of computational tools by the industrial and clinical end users.

6 CONCLUSION

The work reported shows significant progress of experimental efforts in VPH-CaSE over the final year of the ESR projects. An increasing collaboration and synergy between the different IRPs as a result of continued training and secondments as agreed by the VPH-CaSE steering group has been demonstrated.




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