Page 1

VPH-DARE@IT - This project has received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no FP7-ICT-2011-9-601055.

IN THIS ISSUE Editorial Project Focus • Deliverable Reviews

Partner Profiles • Empirica - Communication and Technology Research • ESI Group

Action Line Focus • Yiannis Ventikos - UCL

People • Matteo de Marco - USFD • Toni Lassila - USFD

Research Highlights

• Advanced imaging protocol design and feasibility studies in volunteers

Events

Project coordinator: The University of Sheffield Contact person: Professor Alejandro Frangi Tel: +44 114 222 6071 Email: contact@vph-dare.eu

w w w. v p h - d a r e . e u

Newsletter Issue III - MARCH 2015


Newsletter Issue III

editorial

VPH-DARE@ IT

Editorial Welcome to the third issue to the VPH-DARE@IT newsletter! We are fast approaching the end of the second year of the project and we, in the PMO in Sheffield are busy preparing for the upcoming reporting period and review meeting. Preparations for these key milestones are already well underway in the project management office, with dates already in the diary for our second review meeting in Brussels. The review will take place on Tuesday 26th and Wednesday 27th May 2015, and preparations for this key milestone will be the focus of our 4th General Assembly meeting in Rotterdam in March 2015. The project has progressed well since the kick off in April 2013, and one of the strengths of the consortium is the quality of the deliverables produced and submitted to the European Commission. In this issue, project manager, Matthew Henry and reviewers Dr. Rainer Thiel and Prof. Jyrki Lötjönen tell us about the quality control procedures in place to ensure that the quality of the research output is consistent and maintained across the consortium. There has been a lot of activity since the last issue of the newsletter, and in this issue we hear from project partners on the activities taking place in the different workpackages. Prof. Yiannis Ventikos at UCL provides an update on the progress in Action Line 2, and Prof. Sebastian Kozerke at ETHZ tells us about the Advanced Imaging protocol design and feasibility studies taking place in workpackage 2. We also hear from project partners ESI and Empirica about their roles in the project, and we meet new members of the team, Dr.Toni Lassila (Research Associate) and Dr Matteo de Marco (Research Associate) at the University of Sheffield. We also catch up with Prof Alejandro Frangi who gave a keynote lecture about the project at the recent Alzheimer’s Research UK Yorkshire Network Scientific Meeting, hosted by Prof.Annalena Venneri at the University of Sheffield. We would like to thank all of our contributors for taking the time to talk to us about the work they have been involved in during the last 6 months. We have a lot coming up in the next few months, our 4th General Assembly and 2nd review meeting being two of the key challenges in the coming months. We hope you enjoy this issue of the newsletter, and as always, if you have any views, comments or suggestions for future issues, please do not hesitate to contact us: contact@ vph-dare.eu, we would love to hear from you! Aisling Cooling

VPH-DARE@IT Communications Officer Centre for Computational Imaging & Simulation Technologies in Biomedicine (CISTIB) Department of Electronic and Electrical Engineering The University of Sheffield Pam Liversidge Building Mappin Street Sheffield, S1 3JD T: +44 114 222 6071 E: a.cooling@sheffield.ac.uk

w

w

w .

v p

h

- d

a

r e

.

e

u


Deliverable Reviews By Professor Jyrki Lötjönen (VTT), Dr. Rainer Thiel (EMP), Dr. Matthew Henry (USFD) A key output from VPH-DARE@ IT is a number of deliverables, some of which will be publically available. To ensure these deliverables are of the highest quality and meet with the European Commission’s requirements, we have an internal quality-control (QC) process in place. Here, we highlight the importance of the process and how it adds value to each deliverable and the project as a whole. The QC process covers all aspects of producing deliverables. Each deliverable is subject to 3 levels of quality control prior to submission to the European Commission. These levels are: 1) An initial review of the deliverable by the Work Package Leader to be completed within 10 working days. 2) An internal peer review process by two of the project’s researchers who have not been involved in its preparation. This review is to be completed at least 3 weeks before the deliverable due date. 3) A final check by the PMO to ensure consistency with other project deliverables. The Project Management Office (PMO) will provide reminders to deliverable authors and their respective Work Package Leaders to identify suitable internal reviewers at least 3 months in advance of the first draft being available for review. The initial draft of the deliverable should be completed at least 6 weeks prior to the final submission date. Deliverable authors are to use the Deliverable template, the latest version of which is available in the Documents Manager on EMDesk. Once the deliverable has been reviewed and revised accordingly, the PMO will upload a copy to EMDesk and submit a copy to the European Commission for acceptance. The QC process is an important feature of the project and was highlighted in the Period 1 Review by the independent reviewers, who remarked that it ‘constitutes one of the strong parts of the project’. When writing a deliverable for an EU project, authors should keep in mind the target audiences for whom the document is written. There are basically two main target groups: 1) independent reviewers set by the European Commission (EC) 2) scientists and other people interested in the topic, either from within or outside the project. MAR 2015

V PH - DA R E @ I T P ro j e c t

N ew sl e tte r I ssu e I I I

3


VPH-DARE@ IT

Independent reviewers Deliverables are the main source of information for the EC to assess whether the project has progressed as planned, i.e., as promised in the description of work (DoW). Independent reviewers perform the work on behalf of the EC. In summary, they are asked to evaluate the following aspects: progress towards objectives set in the DoW, progress of each individual work package, progress towards each milestone and deliverable specified in the DoW, relevance of the plans for the next period, use of resources, management, collaboration between beneficiaries, roles of beneficiaries, impact and exploitation (especially on SMEs), dissemination, involvement of potential users and stakeholders, and finally, links with other projects.

Newsletter Issue III

Not all these issues are expected to be covered in each deliverable, but it is good to keep in mind that identifying links to the bigger picture is important, as well as describing the topic of the deliverable. In addition, it is important to remember that reviewers cannot be experts on all the possible topics covered in each deliverable arising from such a big project. Therefore, the text should be written in such a way that people with common knowledge of science and engineering are able to comprehend the message without the need for extensive background reading. All authors who have acted as reviewers for journal papers know that reading fluent text leads to a more positive review of a manuscript. Scientists and other people interested in the topic These people read deliverables in order to learn information about the topic, and this audience appreciates a well-structured and well-written document. The majority of the VPH-DARE@IT deliverables are confidential which means that they are intended to deliver information just to the project team, in addition to independent reviewers. However, some deliverables are public which means that anyone interested in the project and topic area can access them. This aspect makes it important to have supreme quality and give a good impression of our work. The internal review process has been set up in the project with the aim of checking that the quality of deliverables meets the needs of our main audiences. Authors of deliverables may think that their deliverable is just there to meet contractual obligations but that is only a part of the picture. To maximise motivation and other benefits, authors could consider the writing process as the first step towards a scientific publication, which will be of interest to most of team members.

Dr. Matthew Henry VPH-DARE@IT Project Manager / WP10 Leader Centre for Computational Imaging & Simulation Technologies in Biomedicine (CISTIB) Department of Electronic and Electrical Engineering Mappin Street Sheffield, S1 3JD T: +44 114 2229736 E: m.henry@sheffield.ac.uk

ww ww ww . . v v p p h h - - d d a a r r e e . . e e u u


partners

March - 2015

Empirica - Communication and Technology Research (EMP) By Klaus Pi Piesche iesche

What is empirica? empirica was founded in 1988 in Bonn, Germany, Germaany, the birthplacee of Beethoven. But unlike him, empirica did not leave for Vienna and today it is a leading European rresearch institutee in eHealth concepts, policies, strategic development, technolo ogy assessment aand business development and is participating in five clinical and socio-economic impact, technology PULUS,VPH-Sha are,VPHOP, and NMS Physiome. VPH-related projects:VPH-DARE@IT, DISCI DISCIPULUS, VPH-Share, p in the VPH arena and through g co llaboration with the clinical, research and industrial Buildingg on its expertise collaboration partneer in the Discipu ulus project, drafting the research roadmap for the communities, Empirica was a leading partner Discipulus thaat will be used to o provide an integrative framework for Personalised, realisation of the Digital Patient Initiative that Predictive, and Integrative Medicine. tudies of complex eHealth RTD developments and Empirica regularly undertakes assessment aand evaluation st studies o healthcare, inclu uding developing exploitation strategies and business ICT-enabled systems and solutions applied to including Mr. Klaus Piesche Researcher Empirica - Communication and Technology Research (EMP) Oxfordstr. 2 D–53111 Bonn Germany T: +49 228 9853050 E: info@empirica.com

MAR 2015

V PH - DA R E @ I T P ro j e c t

N ew sl e tte r I ssu e I I I

5


Newsletter Issue III

VPH-DARE@ IT

plans, usually as international project leaders. It has also undertaken research on eHealth strategy development and implementation by EU States, on market trends, including establishing the EC database of good practice case studies, and has performed foresight exercises. An acclaimed EU impact assessment of eHealth solutions (eHealth IMPACT) was published in 2006.

The role of empirica in VPHDARE@IT Empirica coordinates the evaluation and exploitation work package (WP9) and plays a role in dissemination and community building activities. Furthermore, empirica provides both clinical and socio-economic expertise on evaluation and impact assessment, patient safety, eHealth concepts and framework, and will liaise with external experts and the European Commission.

Key Activities •

• •

• •

Assessment Framework Approach and Indicator Development of VPH-DARE@ IT Health Technology Assessment (HTA) Clinical impact assessment and socioeconomic cost-benefit assessment Integrating and Exploiting the Environmental Dimension in VPH-DA RE@IT Market Analysis Exploitation and Business Planning

Key people Dr. Rainer Thiel: is the leader of workpacka workpackage age ket Analysis aand nd 9 (Technology Assessment, Market search on clini ical Exploitation). Rainer leads the research clinical ogy and socio-economic impact and technolo technology ree, assessment in the VPHOP, MD-Paedigr MD-Paedigree, and VPH-SHARE projects, and now fuses his experience into VPH-DARE@IT. As a memberr of nternational, he Health Technology Assessment International, on and econom mic has been publishing about validation economic assessment frameworks for thee application of echnologies aand nd innovative and disruptive health technologies ICT infostructures. nce Dr.Veli Stroetmann: With all off her experien experience ipal Investigat tor as project coordinator and Principal Investigator eatly contributes contributtes in various eHealth projects,Veli greatly to WP9 not only with her knowledge, but also with completely new trains of thought regarding integrating and exploiting the possible projects’ outcomes. Dr. Karl Stroetmann: Being empirica’s grand seigneur of economic impact assessment, Karl contributes many ideas on conceptual and policy issues to VPH-DARE@IT, especially in the socioeconomic area when it comes to indicator development. For over 20years, his research has focused on the application of IT in the health sector. Christianne Lavin: Christianne is our student assistant. If there would be a Master of Literature

w w w w w w. . v v p p h h - - d d a a r r e e . . e e u u


partners

March - 2015

Ressearch, Christianne would mostt surelyy graduate Research, withh highest honours.With her back kground d in applied background biol logy she is a vital contribution to empir ica’s team. biology empirica’s Kla aus Piesche nsultant at Klaus Piesche:: is a junior research co consultant emp pirica. His responsibilities in the proje ect are to empirica. project carr ry out research on Business Modelling g, Big Data carry Modelling, Ana alysis and Health Technologyy Analysis Ass sessment. Assessment.

say that he enjoys the atmosphere of many peoplee from all over Europe working together, discussing, wholeheartedly arguing over the big picture as well as over apparently non-relevant details (which ever so often later prove to be quite essential).

The Challenge for empirica Thhe most challenging part of the The pro oject for empirica is to get project a picture on how dementia is cu rrently diagnosed in different currently co untries and to input this into countries an impact assessment model wh hose environmental variables whose cha ange steadily. change

“on a technical level, it is highly Wee spoke to Klaus about his rolee impressive to see how the team tries in the the project and when asked d to reduce the immanent friction wha at he found most interestingg what losses in such a big project” abo out the project, he said thatt about gett ting to know the differentt getting peo ople involved in the project hass people bee en very interesting. He went on to say that “on on a been The team’s involvement in VPH-DARE@IT will tech hnical level, it is highly impressive to see seee how the technical allow empirica to establish itself in another clinical team m tries to reduce the immanent frictio on losses in friction community. As recent projects allowed for contact community such h a big project. I really do believe that tthis project, with key clinical experts in osteoporosis, now expert withh all the expertise of the consortium me embers, will members, knowledge on neurodegenerative diseases further havee an impact on the wellbeing of Europea an citizens citizens” European citizens”.. feeds and broadens the understanding of socioWo orking with the different people involv ved in the Working involved pro oject clearly appeals to Klaus and he w went on to project

“I really do believe that this project, with all the expertise of the consortium members, will have an impact on the wellbeing of European citizens”

MAR 2015

V PH - DA R E @ I T P ro j e c t

economic impact assessment and user needs in clinical, research and industrial communities. With all this in hand, empirica hope to be able to deliver even better support when it comes to exploitation of the VPH-DARE@IT results.

N ew sl e tte r I ssu e I I I

7


Newsletter Issue III

partners

VPH-DARE@ IT ESI Group By - Mustafa Megahed

What is ESI ESI Group is a pioneer and world-leading provider of digital simulation software for prototyping and manufacturing processes that take into account the physics of materials. ESI Group has developed an entire suite of coherent, industry-oriented applications to realistically simulate a product’s behaviour during testing, to fine-tune the manufacturing processes in synergy with the desired product performance, and to evaluate the environment’s impact on product usage.

With the collaboration of nearly 1000 highlevel specialists worldwide, the company and its global network of agents provide sales and technical support to customers in more than 30 countries. Within the health care sector ESI’s Multiphysics suite of tools CFD-ACE+ is widely used to model different pathologies and micro devices used in diagnostics and drug delivery.

Expertise ESI’s CFD and Multi-physics Centre of Ex-

Dr. Mustafa Megahed Researcher ESI Group ESI Group Headquarters ESI Group 100-102 Avenue de Suffren 75015 Paris, France E: mme@esi-group.com

w w w . v p h - d a r e . e u w w w . v p h - d a r e . e u


March - 2015

partners

cellence (CoE) focuses on the development of novel simulation techniques for advanced applications. Typically, these cutting-edge solutions are pursued in collaboration with partners from industry and research organizations. Team members have different scientific and engineering backgrounds, which ensure the multi-disciplinary expertise required to solve technological challenges.

The role of ESI in VPH-DARE@IT We talked to Dr. Mustafa Megahed about the role of ESI in VPH-DARE@IT, and how they became involved in the project. Mustafa told us that several collaborations were pursued with some of the project partners. The modelling work required for VPH-DARE@IT analysis seemed like a good extension to the existing collaborations building on tools already proven and in use towards next generation multi-scale modelling tools. ESI was involved in some of the first discussions about scope and selection of possible methods to approach the challenge. The main contribution of ESI to VPH-DARE@ IT is the simulation of fluid-structure interaction processes in the human brain. The objective is to gain a better understanding and a reliable, patient specific prediction of the influence that different factors may have on fluid flow and the interaction between different compartments and how that might affect the development of dementia disease. The main challenges in this endeavour stem from the multi-physics nature of the problem. These aspects in particular relate to the interaction of blood, CSF, and human tissue, which is porous in nature. Simulating this interaction necessitates the coupling of fluid flow with elastic and multi-

MAR 2015

∙

V PH - DA R E @ I T P ro j e c t

compartmental poroelastic materials, where the latter are governed by the so-called MPE theory developed by UCL.

Key People Members of the CFD and Multiphysics Centre of Excellence are involved in this large project. The principle investigators are: Dr. Joerg Willems, has a background in numerical analysis and has previously worked on multiscale problems e.g. related to flow in porous media. Currently, he is collaborating with colleagues from other ESI offices to integrate the simulation tools relevant for VPH-DARE@IT in a coupling platform. Dr. Mustafa Megahed, has more than 25 years of experience in the development of numerical algorithms and modelling. He is currently focussing on the interaction of pulsation blood flow with CSF in perivascular vessels. The interaction between the blood, the tissue and the freely available CSF leads to a form of CSF pumping the cause of which is being studied numerically.

Contributions to the project The contribution of ESI to VPH-DARE@IT is in the coupling of different physical aspects relevant for simulating processes in the human brain. To achieve this ESI develops a platform that facilitates the interaction of otherwise independent simulation tools. For this the platform adopts a plugin strategy, which is particularly suitable as it allows the coupling of different solvers without having to go through an expensive and error-prone process of reengineering. The different physical processes that will be coupled in this effort are fluid flow, elasticity and multicompartmental poroelasticity. The overall coupled solution is targeted to be performed on computational do-

∙

N ew sl e tte r I ssu e I I I

9


Newsletter Issue III

partners

VPH-DARE@IT IT news VPH-DARE@

mains resulting from MRI scans. In parallel to the extremely ambitious platform development effort, existing tools are applied to investigate different details such as perivascular vessels. We asked Mustafa what he found most interesting about being part of VPH-DARE@IT. He told us that in his opinion, “the most interesting aspect about being part of VPH-DARE@IT is the collaboration with researchers and practitioners from various disciplines. This combined with the prospect that the outcome of this mutual effort may in fact significantly improve the quality of life of manyy “Bringing together

people across Europe and around the globe is extremely fascinating and motivating”.

The Challenge Mustafa went on to say that being part of a large interdisciplinary project is certainly one of the main challenging and motivating aspects. “Bringing together ideas from people with different backgrounds is in my opinion an essential ingredient for a successful outcome of such a broad collaboration. Putting our contribution in the overall framework such that collaborators gain the maximum output from our work is probably the biggest chaideas from people

with different backgrounds is in my opinion an essential ingredient for a successful outcome of such a broad collaboration.”

w

w

w .

v p

h

- d

a

r e

.

e

u


March - 2015

partners

llenge. Meeting this task necessitates the successful communication across disciplines, which can be rather complicated and rewarding at the same time”.

The Future

without extensive effort enabling the application of specialized tools for the problem at hand. In the case of VPH-DARE@IT these tools will include computational fluid dynamics (CFD), finite element analysis (FEA) multicompartmental poroelasticity (MPET).

A broader prospect The immediate pros“The outcome of this mutual effort may for ESI may be the fupect for ESI is a sucin fact significantly improve the quality ture engagement in sicessful implementation milar research efforts of a flexible couplingg of life of many people across Europe with a pronounced platform. This will and around the globe is extremely physiological emphasienable the implemenfascinating and motivating” ze, which traditionally tation of solutions has not been the focus required within VPHof our company, but nonetheless fits ESI’s core id S I DARE@IT and will take Fl Fluid-Structure-Interaccompetences of providing cutting-edge simulation solutions to the next generation solution, tion solutions. where components can be included or excluded

Influence of perivascular pulsation on CSF flow rate

MAR 2015

V PH - DA R E @ I T P ro j e c t

N ew sl e tte r I ssu e I I I

11 11


VPH-DARE@ IT

Multifactorial & Multiscale Modelling By Yiannis Ventikos In this issue, we get an update from Professor Yiannis Ventikos about the activities taking place in Action Line 2

Newsletter Issue III

Collaboration activities •

We have worked closely with ESI, establishing the necessary links between the UCL-based poroelastic code and the software that will be used as the simulation platform that will represent the transport processes in the cerebral environment.

We have had important discussions with the Sheffield team regarding the modelling of lifestyle and circadian influences, and how these very important concepts embed themselves with the platform headed by our partners in ESI.

Furthermore, our discussions with the Sheffield team have also prompted the prospect of using the novel poroelastic methodology within a different setting. We call this aspect of the work the “LifeV Project” and we hope that a mature version of the methodology will be coded in an open source, modern and modular environment.

Active collaboration between UEF and VTT (both WP4) to transfer global transcriptomics from UEF for stochiometrical metabolite modeling at VTT (first data submitted to the VTT in November 2014)

Interactions of WP4 with AL1 (particularly WP1) to derive clinical data (from WP1) for metabolomics analysis used as input in WP4.

Action Line Achievements •

We can highlight the testing of the coding of the MPET model in the finite element ement framework.

Further, we can highlight the development of an idealised first-principles representation esentation of the perivascular glymphatic system, where transport and clearance features are studied.

In WP4, we obtained the first results of metabolite modelling based on transcriptomics criptomics data with clustering data on gene level and investigation into clustering according to Braak stages

osphate Pathway In WP4, we extended the kinetic metabolic model to include the Pentose-Phosphate

Prof.Yiannis Ventikos Researcher University College London Department of Mechanical Engineering - The University of Sheffield Gower St London London, United Kingdom T: +44 20 7679 2000

w w

w w

w w .. vv p p h h -- d d aa rr ee

.. ee u u


Activities planned The following activities are planned for the next 6 months 1. Prototype release of 3D multiporoelastic brain model into ACE+ (WP5) 2. Preliminary report on microscale water transport findings based on in silico tools (WP5) 3. Circadian and lifestyle models of physiological and physical dynamics in normal subjects of dementia (WP5) 4. Database for relevant biomarkers and their interdependencies with environmental and lifestyle factors as captured by metabolic network model (WP4) 5. Methods for connectivity modelling and how they can be used for generating hypothesis to test mechanistic models (WP6) 6. Methods for risk-scoring of dementias(WP6) 7. Software tool implementing generative 3D+t spatiotemporal models of the ageing brain: virtual population for biophysical modelling (WP6)

Capilary Velocity

Publications Journal Articles Vardakis J C, Chou D,Tully B, Hung C C, Lee T H.,Tsui P-H.,Ventikos Y (submitted). Investigating Cerebral Oedema using Poroelasticity. Medical Engineering & Physics. Vardakis J C, Chou D,Tully B,Ventikos Y. The impact of nonlinear permeability on a Multicompartmental model of Poroelasticity. Annals of Biomedical Engineering, in preparation. Vardakis J C and Ventikos Y . A Novel Model of Hydrocephalus using Multicompartmental Poroelasticity. Journal of Computational Physics, in preparation. Szokol K, Heuser K,Tang W, Jensen V, Enger R, Bedner P, Steinhäuser C,Taubøll E, Ottersen OP, Nagelhus EA. Augmentation of Ca2+ signaling in astrocytic endfeet in the latent phase of temporal lobe epilepsy. Frontiers in Cellular Neuroscience, in press. Tang W, Szokol K, Jensen V, Enger R, Trivedi C, Hvalby Ø, Helm PJ, Looger LL, Sprengel R, Nagelhus EA. Stimulation-evoked Ca2+ signals in astrocytic processes at hippocampal CA3-CA1 synapses of adult mice are modulated by glutamate and ATP. The Journal of Neuroscience, in press. Pettersen KH, Lindén H,Tetzlaff T, Einevoll GT. Power Laws from Linear Neuronal CableTheory: Power Spectral Densities of the Soma Potential, Soma Membrane Current and Single-Neuron Contribution to the EEG. PLoS Comput Biol. 10(11):e1003928 (2014) Conferences and Workshops Vardakis JC, Chou D, and Ventikos Y, Understanding Hydrocephalus using a Multicompartmental Poroelasticity Model, The 18th International Conference on Finite Elements in Flow Problems (FEF2015), 16-18 March 2015,Taipei,Taiwan Vardakis JC, Chou D,Tully BJ & Ventikos Y, Multicompartmental Poroelasticity for the Integrative Modelling of Fluid Transport in the Brain, 9th European Solid Mechanics Conference (ESMC 2015), July 6 - 10, 2015, Leganés-Madrid, Spain. Frangi AF, Lassila T, Vardakis JC,Ventikos Y, Multiscale Modelling of Transport Phenomena in Biological Tissue, 4th International Conference on Computational and Mathematical Biomedical Engineering - CMBE2015, 29 June-1 July 2015, France. Vardakis JC, Chou D, Tully BJ & Ventikos Y, A CFD and FEM Approach to a Multicompartmental Poroelastic Model for CSF Production and Circulation with Applications in Hydrocephalus Treatment and Cerebral Oedema, 4th Micro and Nano Flows Conference UCL, London, UK, 7-10 September 2014 Vardakis JC, Chou D,Tully BJ & Ventikos Y, Exploring a Multicompartmental Poroelastic Model for the Integrative Modelling of Fluid Transport, 7th World Congress of Biomechanics, Boston, Massachusetts, July 6-11, USA

CSF/ISF pressure MAR 2015

V PH - DA R E @ I T P ro j e c t

N ew sl e tte r I ssu e I I I

13


VPH-DARE@ IT

Matteo De Marco USFD / University of Sheffield

Newsletter Issue III

Background and Research dings and more broadly I will be involved My name is Matteo De Marco and I am in a range of studies which will use large a Research Associate within the Deretrospective datasets for addressing repartment of Neuroscience at the Universearch questions related to the improvesity of Sheffield. While my undergraduate ment of early detection of dementia. background is in psychology, my postgraduate studies have explored the field of neuroscience (with a focus on neurodeWhat do you find most interesgeneration) more widely, incorporating ting about the VPH-DARE@IT elements of sport sciences, genetics and project? especially neuroimaging. As part of the Translational Neuropsychology team The idea of IT giving a significant contriled by Professor Annalena Venneri, my bution to diagnostic routines is innovatiave focused over research interests have ve, ve and might have the last 2 years on a decisive impact “This is a great opportunity to non-pharmacological on o the clinical setshed new light on the hierarchies of treatments for earlyting. However, what ti brain structure and function, their stage Alzheimer’s diI find most interesinteraction with individuals’ life style sease. Particularly, I ting in this project tii have investigated the choices and what their importance is is the exploratory in relation to disease.” ample field of cognitinature of this inna ve stimulation and the vestigation. In fact, ve mechanisms by which this form of inter interthe IT IT-dependent of data analyth d d t methods th vention can trigger meaningful changes in sis will have the chance to process a very brain structure and brain function. large set of variables, many of which are not normally used in clinical practice beWhat is your specific role in cause of their obscure interpretation. This VPH-DARE@IT? is a great opportunity to shed new light on the hierarchies of brain structure and I will be involved in multiple stages of function, their interaction with individuals’ data collection for the prospective stulife style choices and what their importandy, data analysis, and dissemination of fince is in relation to disease.

w w

w w

w w ..

vv p p

h h

-- d d

aa

rr ee

..

ee

u u


What do you as a researcher find most challenging about working in VPH-DARE@IT? I believe that a major challenging aspect of this project associated with my role will be adapting the specific interest of the research questions to the dynamics of the clinical setting. It will take effort to address the clinical needs of patients and, at the same time, acquire data while sticking perfectly to the research methodological guidelines.

search interests and, possibly, start new collaborations. I am looking forward to attending my very first General Assembly meeting in Rotterdam in March 2015.

How has working on VPH-DARE helped to develop your career?

Being part of the VPH-DARE@IT has offered me a number of opportunities. I have now the possibility of being involved for the first time in a multicentre project, enrich my CV, and expand my professional network on a worldwide scale. Moreover, the ambitious nature of this How do you find working as a part project will allow me to be part of a research of a large collaborative project? p which has the potential to have a laroutput I think that the internage impact on the study and “The ambitious nature of this tional dimension of the m management of neurodegeproject will allow me to be part of VPH-DARE@IT projectt ne nerative conditions, but, at is a great opportunity forr th same time, might also the a research output which has the my personal professional he me identify new interhelp potential to have a large impact growth, as I will have the es esting research avenues for on the study and management of chance to expand my rem future career. my neurodegenerative conditions.”

MAR 2015

V PH - DA R E @ I T P ro j e c t

N ew sl e tte r I ssu e I I I

15 19


VPH-DARE@ IT Toni Lassila USFD / University of Sheffield

Background and research

Newsletter Issue III

At some point during my university studies in Finland I realised that research was the one profession that truly interested me. I subsequently received my doctorate in mathematics from Aalto University in 2010. Since then I have worked more than three years as a post-doc at EPFL in Switzerland and moved to Sheffield in August 2014 to work as a research associate on VPH-DARE@IT. While my training is in the field of mathematics, I have always wanted to work on a topic that is connected to helping people and society on general, and healthcare-related projects like VPHDARE@IT are a great opportunity for that. For several years now I have been working on mathematical modelling and simulation of fluid dynamics in biomedical applications. This work has been mainly focusing on specific techniques that fall under the umbrella of “model order reduction”, which means taking a mathematical model that is very complex but describes the system being studied well, and trying to reduce it to something that is much faster to solve on a computer but still describes the system almost as well as the original model. In the past I have applied these tools to the simulation of the cardiovascular system, such as modelling the fluid dynamics in the left ventricle of the heart or studying the effect of the flow uncertainty and shape of the end-to-side anastomosis have on

w w

w w

coronary ary bypass graft performance.

What at is your specific role in VPHRE@IT? DARE@IT? I am currently working with Luigi Di Marco o at the University niversity of Sheffield to try to specify tthe he requirements rements ffor a model d l off the h systemic i ciri culation on and autonomous nervous system tthat hat will provide models rovide input to the poroelasticity mod dels of the brain being developed at UCL. Thiss is not unlike nlike what I have worked with in the ppast, ast, exceptt that this time the model needs to incorporate rate the effect of lifestyle factors and d is driven by an experimental study starting ea early arly 2015 as part of VPH-DARE@IT. Trying to bu build uild personalised nalised models that provide clinically ppreredictivee results is always challenging. Afterwa Afterwards ards we plan devean to move on to the problem of de eveloping a mathematical model for the synthesis, transport, clearance and accumulation of amyloid-β, the peptide thought to be mainly responsible for Alzheimer’s disease, and incorporating it into the fluid dynamics models. That is quite a daunting task, I must say.

What do you find most interesting about the VPH-DARE@IT project? The prospect of using magnetic resonance elastography and functional magnetic resonance

w p h d aa rr ee w .. vv p h -- d

.. ee u u


imaging to non-invasively determine both the structure and function of the brain in vivo is fascinating and provides a very strong experimental basis on which to build mathematical models. It also seems that accumulation of amyloid-β within the endothelium has a key influence on cerebral blood flow and that might be one of the key factors in the onset of Alzheimer’s disease. That to me is a great motivation to continue my work on the mathematical modelling techniques for blood flow in the arteries that I have pursued for the past several years.

What do you as a researcher fin nd most challenging about working in VP VPH-DAPH DA PH-DARE@IT? Forr me, it is understanding the clinical aspe aspects ects of deworked mentia and its causes. While I have worke ed on projects interests ject ts with strong clinical research interes sts before, they the ey have not looked at one specific clinical clinicaal question in such such all-encompassing way to sort of tryy to attack (imaging, thee problem from all angles at once (ima aging, modelling, simulation, software platforms for diagnosis). VPH-DARE@IT VPH H-DARE@IT is also the first project I have worsome ked d on which explicitly tries to model so me of the complex com mplex mechanisms of the human brain.

How do you find working as a part of a large collaborative project? This is the third large European project I have been involved in. They are always very challenging because there are many deadlines and deliverables and equally many opinions and personalities. It is interesting to observe how things progress in a kind of self-organised chaotic system of multiple independent actors - obstacles are met and then overcome, methodologies are tweaked and experiments undertaken, and in the end a kind of consensus scientific idea emerges

MAR 2015

V PH - DA R E @ I T P ro j e c t

from the primordial soup of all the individual contributions.

Have you attended any of the VPHDARE@IT project meetings and if so, what benefits did you get from attending these events? I attended the General Assembly Meeting in Manchester last September. There I had the opportunity to see and meet a lot of brilliant people with expertise in different topics. It allowed me to really appreciate the difficulty and importance of the problem.

How has working g on VPH-DARE helped to develop your career? For anyone looking to one day run their own European project it’s enlightening to see how such a complex multi-national project is managed on a day-to-day basis. From a scientific point of view the difficulty of even understanding, let alone modelling, something as complex as the causes and onset of Alzheimer’s disease really forces one to look at the clinical question and re-evaluate what I as an applied mathematician and modeller think is relevant. Being involved in VPH-DARE@IT certainly gives me more credibility when I try to convince people that mathematical modelling is not just a theoretical toy but an actual tool in future clinical studies, provided that fundamental clinical science is the driving force behind it.

“Being involved in VPH-DARE@IT certainly gives me more credibility when I try to convince people that mathematical modelling is not just a theoretical toy but an actual tool in future clinical studies”

N ew sl e tte r I ssu e I I I

17


Resear

VPH-DARE@ IT

Advanced imaging protocol design and feasibility studies in volunteers By Prof. Sebastian Kozerke One of the major pieces of work delivered in the last 6 months has been the development of the Advanced Imaging protocol design and feasibility studies in volunteers. In this issue, Prof. Sebastian Kozerke at ETH Zurich tells us about the work being undertaken in workpackage 2, what has been achieved to date and what work needs to be done.

Newsletter Issue III

What is MRSUB2? MRSUB2 is a set of advanced MRI scan protocols to obtain hemodynamic and microstructural information of the brain. The information will help in mechanistic model development and potentially provide new tools with improved sensitivity and specificity for disease staging and patient stratification. Beyond structural information, MRSUB2 will assess the stiffness and complexity of vasculature, perfusion and viscoelastic properties of brain tissue.

Implementation

Perfusion Fraction

Since the functionality offered with MRSUB2 is not part of standard MRI scan software, so-called patches have been developed to replace product MRI software components. Using dedicated programming tools provided by Philips, the vendor of the clinical MRI platform used here, and the image reconstruction framework developed by GyroTools, a Master patch has been created which implements the necessary extensions. Software development has been conducted according to rules and guidelines required for ethical approval to perform scanningg on volunteers and ppatients.

Testing Initial testing of the Master patch has been carried out on healthy volunteers recruited locally at ETH Zurich. The Master patch is distributed to Klinik Hirslanden and the University of Sheffield, which will scan sub-cohorts of the prospective patient population scheduled.

Diffusion

w

w

w .

v p

h

- d

a

r e

.

e

u


VPH-DARE@IT Partners During the development and data acquisition stage, Ralph Sinkus (King’s College London), Iain Wilkinson (University of Sheffield) and Isabel Wanke, Daniel Ruefenacht (Klinik Hirslanden) have been involved. Parts of the image reconstruction software development have been carried out by GyroTools, an SME partner based in Zurich. At a later stage, data will be made available to partners concerned with mechanistic modelling including the groups of Yiannis Ventikos (University College London) and Alex Frangi (University of Sheffield).

Prep T1,T2

8:30

3:00

MultiBand Diffusion

MultiVenc Flow

Diffusion Perfusion ODFs Kurtosis

6:00 MRE

Velocity MKE/TKE Pulsatility Transfer

Advanced MR Imaging Protocol

Current status The Master patch including methods for assessing stiffness and complexity of vasculature and perfusion has successfully been implemented and tested. The patch is available for Philips SW releases 3.2.2, 4.1.3 and 5.1.7 which are run by King’s College, ETH Zurich and Clinic Hirslanden.

The next phase Currently, the hard and software components necessary for quantifying viscoelastic properties as developed by King’s College await integration. A key challenge faced relates to different MRI SW upgrade strategies at different sites. Since the University of Sheffield has upgraded their MRI system to SW release 5.1.8 recently, another software merging step is required during the next weeks. Once this step is completed and ethics approval is in place, patient recruitment can commence. Prof. Sebastian Kozerke Researcher The Swiss Federal Institute of Technology Zürich (ETHZ) ETH Zürich Prof. Dr. Sebastian Kozerke Institut f. Biomedizinische Technik ETZ F 94 Zurich, Switzerland T: +41 44 632 35 49 E: kozerke@biomed.ee.ethz.ch

MAR 2015

V PH - DA R E @ I T P ro j e c t

N ew sl e tte r I ssu e I I I

19 13


Events Events

VPH-DARE@IT at the Alzheimer’s Research UK Yorkshire Network Scientific Meeting 2014 By Monika Feigenbutz In October 2014, a community of scientists researching Alzheimer’s disease across Yorkshire, UK met at the University of Sheffield for a day of scientific networking. Professor Annalena Venneri’s (WP1) Translational Neuropsychology Group at the University of Sheffield hosted the annual meeting of the Alzheimer’s Research UK Yorkshire Research Network. When asked of the purpose and the importance of the event, Professor Venneri said: “The annual ARUK Network scientific and public meetings not only crucially support collaborations and scientific exchange required to drive our research forward, but also increase public awareness to help people understand moree Professors Annalena Venneri, Paul Ince and Stephen d Wharton (from left to right) hosted the ARUK Yorkabout this cruel condition that affects so many people. I am delighted Network Meeting at SITraN, University of Shed shire to be part of a team that is working hard to defeat dementia and ffield in October 2014. raise awareness through events like this.“ The meeting was well attended with over 40 researchers, clinicians and academics from across Yorkshire, attending the meeting to network and disseminate progress and results of Alzheimer’s research in the region. A broad range of Alzheimer’s research was presented from neuropathology and basic neuroscience to computational modelling, clinical and psychosocial aspects to applied interventions. Prof. Alejandro Frangi VPH-DARE@IT Coordinator, Professor Alejandro Frangi attended the meeting Project Coordinator and gave a keynote lecture about VPH-DARE@IT and Computational imaging and modelling for the understanding and diagnosis of dementias. Professor Frangi said: “The event was an opportunity to disseminate the vision and progress made in VPH-DARE@ IT to the community of Alzheimer’s researchers in Yorkshire. This community is very interdisciplinary with a mix of basic scientists, neuroscientists, social scientists, neurologists, psychiatrists, psychologists all with a broad knowledge of Alzheimer’s disease and other dementias who are open to learn from researchers in engineering and physical sciences that share their interest in combatting Alzheimer’s disease.” Members of the VPH-DARE@IT team also atten-ded the meeting and presented posters on theirr “The annual ARUK Network scientific and research in the project. public meetings not only crucially support Dr Rosa Sancho, representing Alzheimer’s Re-- collaborations and scientific exchange required search UK (ARUK), gave an update on fundingg to drive our research forward, but also increase opportunities and grant schemes pointing to cu-public awareness to help people understand

more about this cruel condition.”

w

w

w .

v p

h

- d

a

r e

.

e

u


rrent ARUK priorities including interdisciplinary research projects, training and capacity building, resources, drug discovery and supporting the 15 Alzheimer’s Research Networks. Translational research is a clear focus, bridging the gap between research and drug development. Dr Sancho welcomed that the additional funding for Alzheimer’s Research pledged by the government enables ARUK for the first time to encourage and support more research into the prevention of Alzheimer’s disease. The CISTIB research group from the University of Sheffield’s Department of Electronic and Electrical Engineering at SITraN. Alzheimer’s Research UK is the UK’s leading dementia research charity, funding research into the causes of dementia, diagnosis, preventions and treatments. They currently fund more than £22m of dementia research across the UK,, including over £500,000 of pioneering science in Yorkshire.. The event was an opportunity to This investment is being used to understand a wide range off n disseminate the vision and progress made complex problems, including the build-up of toxic proteins in in VPH-DARE@IT to the community of dementia and how best to diagnose the condition. Alzheimer’s researchers in Yorkshire. Dr Laura Phipps, Science Communications Manager att Alzheimer’s Research UK, said: d there is also an army of informal al carers wh who “Over 6,000 people in Sheffield are living with dementia and l find d a cure ffor d dementia ntia bbut also l work tirelesslyy to support loved ones. We are working hard to not only igma associated with this condition.” reduce the stigma

”FROM MECHANISMS TO PREDICTION AND INTERVENTION OF ALZHEIMER’S DISEASE”

7th KUOPIO ALZHEIMER SYMPOSIUM JUNE 11-13, 2015, KUOPIO, FINLAND www.uef.fi/kuopioadsymposium

THURSDAY, JUNE 11 Memory Day - Finnish session - Muistipäivä) I Haasteena työikäisen muistipulmat II Muistisairauksien ehkäisy ja kuntoutus

IMPORTANT DATES

Keynote Lectures Welcome Reception

Registration by May 10

Abstracts by April 30

Opening Symposium

FRIDAY, JUNE 12 Main Symposium I New insights into neurodegeneration II Diagnosis and prediction of Alzheimer’s disease: Update on biomarker studies III New advances in imaging IV Technology supported diagnosis and care Get-together Party and Posters

SATURDAY, JUNE 13 V Novel approaches towards prevention VI Population-based prevention studies VII Novel approaches in clinical treatment studies MAR 2015

V PH - DA R E @ I T P ro j e c t

Welcome to Kuopio ! CONTACTUS SymposiumSecretariat,7thKuopioAlzheimerSymposium UniversityofEasternFinland,Neurology POBox1627,FIͲ70211Kuopio,FINLAND Tel:+35850 3609123MaaritNärhi,Secretary Tel:+358403552695MariaPikkarainen,Exhibitor'sContact Tel:+358403552768AnnakaisaHaapasalo,ScientificSecretary/Abstracts Fax:+35817162048 neurology.symposium@uef.fi

N ew sl e tte r I ssu e I I I

21


VPH-DARE@ IT Publication Highlights 1.

Vardakis J C, Chou D, Tully B, Hung C C, Lee T H., Tsui P-H., Ventikos Y (submitted). Investigating Cerebral Oedema using Poroelasticity. Medical Engineering & Physics.

2.

Vardakis J C, Chou D,Tully B,Ventikos Y. The impact of nonlinear permeability on a Multicompartmental model of Poroelasticity. Annals of Biomedical Engineering, in preparation.

3.

Vardakis J C and Ventikos Y . A Novel Model of Hydrocephalus using Multicompartmental Poroelasticity. Journal of Computational Physics, in preparation.

4.

Szokol K, Heuser K,Tang W, Jensen V, Enger R, Bedner P, Steinhäuser C,Taubøll E, Ottersen OP, Nagelhus EA. Augmentation of Ca2+ signaling in astrocytic endfeet in the latent phase of temporal lobe epilepsy. Frontiers in Cellular Neuroscience, in press.

5.

Tang W, Szokol K, Jensen V, Enger R, Trivedi C, Hvalby Ø, Helm PJ, Looger LL, Sprengel R, Nagelhus EA. Stimulation-evoked Ca2+ signals in astrocytic processes at hippocampal CA3-CA1 synapses of adult mice are modulated by glutamate and ATP. The Journal of Neuroscience, in press.

6.

Pettersen KH, Lindén H,Tetzlaff T, Einevoll GT. Power Laws from Linear Neuronal Cable Theory: Power Spectral Densities of the Soma Potential, Soma Membrane Current and Single-Neuron Contribution to the EEG. PLoS Comput Biol. 10(11):e1003928 (2014)

7.

Di Marco LY, Venneri A, Farkas E, Evans PC, Marzo A, Frangi AF. Vascular dysfunction in the pathogenesis of Alzheimer’s disease – A review of endothelium-mediated mechanisms and ensuing vicious circles. Journal of Alzheimer’s Disease (Submitted 18 Jan 2015)

8.

Di Marco LY, Farkas E, Martin C, Venneri A, Frangi AF. Is vasomotion in cerebral arteries impaired in Alzheimer’s disease? - A review study. Neurobiology of Disease [In preparation]

9.

Schmidt-Richberg A, Ledig C, Moren RG, Molina-Abril H, Frang AF, Rueckert D, (2014) Learning biomarker models for progression estimation of Alzheimer’s disease, Medical Image Analysis, Sumbitted)

10.

Cash DM, Rohrer JD, Ryan NS, Ourselin S and Fox NC. (2014) Imaging endpoints for clinical trials in Alzheimer’s disease, Alzheimers Research & Therapy

Deliverables and Milestones completed D 4.2

ASD

Detailed workflow specification and component roadmap for high-throug put image analysis of large-scale studies

D 8.3

VTT

Design specifications and requirements for a dementia-specific metabolic network model

M 2.2 EMC

Normal ageing brain models – Initial phenomenological model and links to mechanistic modelling framework

D 7.1

USFD Architectural framework design and interoperability

D 9.1

EMP

D 10.3 USFD

VPH-DARE@IT Health Technology Assessment conceptual framework First periodic progress report, including public summary of each work for publication

MS102 USFD Appointments to Scientific Advisory Board Completed w

w

w .

v p

h

- d

a

r e

.

e

u


Events

Upcoming events

• SPIE Medical Imaging Conference 2015 - Orlando, Florida, United States 21 - 26 February 2015 http://spie.org/medical-imaging.xml

• ECR 2015 - Vienna, 4-8 March 2015

http://www.myesr.org/cms/website.php?id=/en/ESR_ECR_news.htm#30494

• International Symposium on BIOMEDICAL IMAGING - New York - USA, 16-19 April 2015 http://biomedicalimaging.org/2015/

• Dementia Challenge 2015 - London, UK, 2nd June 2015 http://www.dementia-challenge2015.co.uk/event-home

• 7th Kuopio Alzheimer Symposium - Kuopio, Finland, 11 - 13 June 2015 http://www.uef.fi/kuopioadsymposium

• AAIC15 - Washington DC, USA, 18 - 23 July 2015 http://www.alz.org/aaic/

In the next issue... • Action Line 1 Focus • Partner Profiles: Hirslanden Klinik

Philips Medical Systems

• Periodic Review 2 To ensure that we capture all the important issues from across the research arena, we invite you to send us your ideas, comments and suggestions for future editions to contact@vph-dare.eu. Non-VPH-DARE@IT participants interested in receiving this newsletter can subscribe via the VPH-DARE@IT website at www.vph-dare.eu

Acknowledgment This project has received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no FP7-ICT-2011-9-601055

MAR 2015

V PH - DA R E @ I T P ro j e c t

N ew sl e tte r I ssu e I I I

23


VPH-DARE@IT Partners USFD The University of Sheffield VTT ESI

VTT Technical Research Centre of Finland ESI Group S.A

ASD EMP

ASD Advanced Simulation & Design GmbH Empirica Gesellschaft für Kommunikations– und Technologieforschung mbH

UIO

Universitetet i Oslo

EMC Erasmus Universitair Medisch Centrum Rotterdam HIRS Hirslanden Klinik PMS

Philips Medical Systems Nederland BV

ETHZ Eidgenössische Technische Hochschule Zürich KCL King’s College, London PRH STH

Philips Technologie GmbH Sheffield Teaching Hospital NHS Foundation Trust

UCL

University College London

UEF Itä-Suomen yliopisto UMA University of Maastricht TO ICL

Kinematix Imperial College of Science, Technology and Medicine

EIBIR EIBIR Gemeinnützige Gmbh zur Förderung der Erforschung der Biomedizinischen Bildgebung UOXF The Chancellor, Master and Scholars of the University of Oxford

This project has received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no FP7-ICT-2011-9-601055 VPH-DARE@IT Virtual Physiological Human: DementiA Research Enabled by IT Project coordinator: Alejandro Frangi - The University of Sheffield Timetable: April 2013 to March 2017 VPH-DARE@IT Project University of Sheffield Sir Frederick Mappin Bldg, Mappin Street S1 3JD Sheffield, UK + 44 114 222 6071 contact@vph-dare.eu www.vph-dare.eu

VPH-DARE@IT Newsletter Issue 3  
Read more
Read more
Similar to
Popular now
Just for you