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Newsletter Issue V - April 2016

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 • Clinical Scenarios

Partner Profiles • Combinostics • IRCCS Fondazione Ospedale San Camilo

Platform Focus • Advancement in Patient Care Platforms and Citizen Platforms • Advancement in The Research Platform

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People • Susheel Varma (USFD)

Exploitation • New Insole System • Philips Commercialisation of VPH-DARE@IT Technology

Event Review • ICT 2015 • ECR 2016

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Project coordinator: The University of Sheffield Contact person: Professor Alejandro Frangi Tel: +44 114 222 6071

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Email: contact@vph-dare.eu

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Newsletter Issue V

editorial

VPH-DARE@ IT

Editorial Welcome to the fifth issue of the VPH-DARE@IT newsletter! Since the last issue the project has been focused on the implementation of the clinical scenarios defined in the Málaga meeting (16th-18th September 2015). These scenarios are driving the project efforts shifting the focus from research and discovery, to technical integration; advanced personalisation; and incorporation of lifestyle and environmental risk factors. As a consequence, the maturity of the project platforms has been increasing, pointing them in direction of product development while at the same time, promising exploitation opportunities are progressing. Thank you for all of your contributions to this issue of the newsletter! It is great to hear about the research being undertaken by our partners and the progress towards product development and exploitation. There have also been many great dissemination activities, contributing to an increased awareness of Dementia research in Europe and the contribution of VPH-DARE@IT. In this issue of the newsletter, we hear from • Our new partners Combinostics and Funcazione Ospedale San Camilo • Philips commercialisation of VPH-DARE@IT technology • Decision support platform for early differential diagnosis and disease evolution assessment • Platform for Clinical Research and beyond…

Mr. Juan Arenas Márquez

Portfolio Manager Centre for Computational Imaging & Simulation Technologies in Biomedicine (CISTIB) Department of Electronic and Electrical Engineering The University of Sheffield Mappin Street, Sheffield S1 3JD United Kingdom T: +44 (0) 114 222 0166 E: j.arenas@sheffield.ac.uk

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VPH-DARE@IT Year 3 Review

By Juan Arenas

After the RP2 review, the project had several meetings to analyse the best way to address the recommendations received. As a summary, the recommendations were pointing the need to change the focus of the project from research and discovery to technical integration and platform developments paying special attention to 1) the integration of mature components; 2) the incorporation of lifestyle and environmental factor; 3) the extension of the personalisation. These were in order to improve the risk assessment at pre-symptomatic stages and the early and differential diagnosis at symptomatic stages, delivering the promised platforms Clinical Research Platform (WP7), and Patient Care platforms (Citizen Platform and Patient Care Platform in WP8). As a result, the project started a process to identify clinically relevant platform scenarios that would contribute to those goals, with the collaboration of all WPs and partners. At the Málaga GA, in September, twenty-five clinically relevant scenarios were presented by project partners, and this list was narrowed down to eleven scenarios before the end of the meeting. These final scenarios have been used to align project efforts during RP3 to fulfil the reviewers’ recommendations and project goals. All the selected scenarios were designed

to make use of the project platforms (CRP and PCP) to guarantee they contributed to increasing the maturity of them. The implementation of the different scenarios required the project partners to: 1) Coordinate the implementation of the clinical scenarios; 2) Extend data collection, annotation, curation and publication activities; 3) Accelerate integration of mature tools and external components; 4) Compose and verify scenarios workflows; 5) Monitor, execute and validate the scenarios workflows by the means of the project platforms; 6) Post process and analyse results of selected scenarios. In numbers, this effort will support the analyses for the majority of the 6,000 patient available in the platform, by the execution of +15,000 workflow instances, which requires +200.000 CPU hours to generate a large set of additional features - a subset of which would be incorporated into the patients care platforms (biomarkers) to demonstrate how the reviewers’ recommendations have been implemented by the project.

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People

Susheel Varma

USFD / The University of Sheffield Background and Research I am the Translation Technology Officer / CTO of CISTIB (www.cistib.org), a Software Sustainability Institute Fellow and the Clinical Research Platform Work Package Leader for €18m EC-funded VPH-DARE@ II project. I have been the Scientific Workflows Coordinator for the successful €15m EC-funded VPHShare project and have been intimately involved in the collaborative development of software, services and workflows to help translate biomedical and clinical research into clinical practice for over 6 years. I have been involved in developing software platform architectures, the development and deployment of all technical projects, including developing and deploying large-scale data analysis pipelines on HPC and Cloud computing infrastructures. As part of the VPH-DARE@IT initiative, I have also coordinated the scientific and technical delivery of over 25 projects at various levels of maturity and targeted multiple clinical domains. As part of my doctoral work at the Kroto Research Institute, I was involved in building FLAME, an open source Flexible Large-scale Agent Modelling Environment and also contributed to building the opensource Cancer, Heart and Soft Tissue Environment, CHASTE. What is your specific role in VPH-DARE@IT? I lead the Clinical Research Platform (WP7) development within the project.The Clinical Research Platform is enabled by a comprehensive data/metadata infrastructure for data integration & semantic query service, and by a highly flexible and scalable scientific application workflow system for data analytics and interpretation, supports all of our technical WPs to develop and integrate tools and dataset and help drive the project’s Clinical research scenarios to tackle dementia. What do you find most interesting about the VPH-DARE@IT project? I’m thrilled to be working as part of large diverse pan -European team to tackle Dementia. Inspiring conversations and discussions among colleagues and those moments when you know you have helped solve a tricky problem for someone is what I most enjoy and find interesting within the VPH-DARE@IT project. Of course there are good days and bad days, but the goals of the project seem almost within grasp and that drives us forward. What do you as a Workpackage Leader find most challenging about working in VPHDARE@IT? Due to the broad scope of our project, the require-

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ments for workflow tool/service vary diversely between each workflow. Architecting an infrastructure that aims to be ‘everything for everyone’ is an incredibly difficult task, and is something we are pursuing with due diligence.Apart from minor interoperability issues between workflow tools; security, semantics, licensing, versioning and workflow complexity are some of the major challenges we face currently. How do you find working as a part of a large collaborative project? It is challenging and hard working in a large collaborative project, specifically as disperse and diverse as VPHDARE@IT. There are always a lot of tasks and deliverables that need to be accomplished with the help of, and for, other partners, that creates a good cadence within the project and drives us forward.This also helps us identify potential problems and research opportunities and cement collaborations. Have you attended any of the VPH-DARE@IT project meetings and if so, what benefits did you get from attending these events? I have attended two project meetings and they always provide a good overview of the project and the tasks undertaken by various partners within the project consortium. It is always good to put a face to a name you see or hear often in an email or teleconference. I have also had the opportunity to attend external dissemination events with project partners such as the ECR 2016 in Vienna and ICT 2015 in Lisbon and both were fantastic experiences for me and for the VPHDARE@IT project’s visibility as a whole.We were able to summarise the efforts within the project into key outputs, namely the Patient Care Platform, the Clinical Research Platform, the Novel Image Processing pipelines and novel bio-mechanistic modelling tools; all devoted to early diagnosis and/or differential diagnosis of Dementia. These meetings allowed us to put our research in the context of global public and private efforts to tackle the ever rising problem of Dementia and find effective mechanisms to translate our work into clinical practice How has working on VPH-DARE helped to develop your career? Working with world-class scientists and ICT professionals has allowed me to appreciate the enormity of the task to tackle Dementia and has helped me develop skills to manage interactions and collaboration within a disperse and diverse group and between a wide multidisciplinary range. I’m confident that this will strengthen my resolve to apply myself at the forefront of insilico medicine.

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Platform Focus Platform for Clinical Research and beyond… By Susheel Varma partner’s clinical decision support tool PredictND In the context of VPH-DARE@IT and the developed by another partner VTT/Combinostics.This work in WP7, what is the Clinical Research interoperability does not end there – the platform Platform and its purpose? is able to provide feature extractions of a multitude The Clinical Research Platform (CRP) being develoof internal and external tools executed on all of our ped as part of the VPH-DARE@IT project in WP7 datasets for PredictND, including executing an ad hoc aims to develop a “Clinical Research as a Service” single patient feature extraction using the same pipeline platform to enable clinical research scientists to for comparison with the feature knowledgebase. perform ad hoc and large-scale analysis and feature Which VPH-DARE@IT partners are involved extraction on heterogeneous dementia-related datain the work? sets and hopefully identify biomarkers for early and The platform infrastructure is largely developed at differential diagnosis of Dementia. the University of Sheffield, with content (data, tools Integral to the and workflows) provided by our partners in WP2 “Clinical Research as a CRP platform are (Philips Research), WP3 (UCL - SO), WP4 (ASD), Service” platform to enable the semantic and WP5 (UCL – Eng), WP6(ICL) and STH. The platform services for clinical research scientists to data provide the fundamental technological underpinning managing large to bring together such a disperse and diverse cadre of perform ad hoc and largestructured datatechnologists, scientists, domain experts and clinicians sets with faciliscale analysis” to help tackle the problem of Dementia. ties to annotate What is the current status of this work and and link datasets for how can it be exploited in the future? discovery and knowledge engineering. The platform also provides a distributed object file system to store The platform is almost complete with the next year related data items such as images and ancillary files. focussed on helping our partners develop new advanThe platform also provides capabilities to develop ced tools and workflows for their work. In addition, and deploy scientific tools as virtual machines wrapwe plan to curate more third-party scientific content ped as a web service for workflow orchestration. (tools, data and workflows) to allow our clinical reThe platform further provides a cloud and grid basearchers to explore new avenues and ask further sed workflow engine to allow clinical researchers to question on the data available within the platform. execute ad hoc and automated data The platform is already analysis pipelines at scale. The being extensively exploi“Clinical Research as a platform’s purpose is to provide ted by a large number an interoperable infrastructure Service plan to curate more thirdof European projects for our partners and dementia party scientific content (tools, data seeking to conduct large researchers beyond. scale data analytics on and workflows) to allow our clinical Who will use this platform? researchers to explore new avenues and heterogeneous datasets. Some of the problem The platform is intended for all ask further questions ” domains already being clinical researchers interested addressed via European in Dementia and scientific projects within the platform are – Cardiovascular Didevelopers interested in developing applications sease, Neurovascular Disease, Orthopaedics, Virology, around the datasets, tools and workflows available Cancer and Paediatric diseases. The platform is destiwithin the platform. A perfect example of the use ned to further support more biomedical and clinical case is the development and deployment of a new research domains beyond Dementia and potentially brain segmentation tool by our partners at Philips roll out as a platform for “Research As A SerResearch, where the platform is able to execute at vice”. scale on our prospective dataset to feed another Apr il 2016

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Platform Focus

Newsletter Issue V

Decision support platform for early differential diagnosis and disease evolution assessment (WP8) By Jyrki Lötjönen Diagnostics of dementing diseases is not simple: there are a high number of different diseases and other conditions that could explain existing symptoms, and there are a high number of different tests and other data that can be used in making decisions. Because clinicians still combine all this information in their minds, the quality of the decisions relies strongly on the expertise of the clinician in question. One implication of this complex challenge is that there is an average delay of 20 months from symptoms to diagnosis in Europe. One objective of the VPH-DARE@IT project is to develop tools and biomarkers that enable shortening this delay.

Patient Care Platform In the EU FP7 project PredictAD (www.predictad.eu, 2008-2011), novel biomarkers and a clinical decision support tool combining all biomarker information were developed for diagnostics of Alzheimer’s disease. The decision support tool has been developed in a close collaboration with clinicians and uses the disease-state index and disease-state fingerprint technologies which enable comparing the patient data quantitatively and intuitively with previously diagnosed cases. In VPH-DARE@IT, the development of this patient care platform has been continued in two ways: 1) the tool has been extended to differential diagnostics of neurodegenerative diseases and 2) testing of new research-based biomarkers is enabled, especially the ones developed in VPH-DARE@IT.

When symptoms appear, a cognitive disease is often already at a relatively advanced phase. In Alzheimer’s disease, pathological processes start even decades before symptoms occur. Therefore, making a Figure 1 shows a screenshot from diagnosis even im“The decision support the current tool with a differential mediately after the tool has been developed diagnostics module. VPH-DARE@ first symptoms is in a close collaboration with IT is collaborating closely with the not enough. New clinicians and uses the diseasePredictND (www.predictnd.eu, cost efficient biostate index and disease-state 2014-2018) EU FP7 project which markers and care fingerprint technologies which integrates the tool shown in Figure pathways are needed to detect enable comparing the patient data 1 into clinical practice and validates persons at the quantitatively and intuitively with it in a prospective trial implemented in four European hospitals and previously diagnosed cases.” pre-symptomatic consisting of 800 patients. In addition, phase. This is relethe tool contains a comprehensive set vant also for developing new efficient pharmaof imaging quantification tools developed in the ceutical and life-style-based interventions becauPredictAD/PredictND projects for the analysis se they are expected to be most effective at the of structural magnetic resonance images and in early phase. Related to this, one objective of the the VPH-DARE@IT project for the analysis of VPH-DARE@IT project is to develop a web-bavascular burden. sed citizen platform which could potentially be used even at the pre-symptomatic phase for Regarding testing of new research-based bioscreening subjects at high risk. markers, VPH-DARE@IT is developing a cli-

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Figure 1. Screenshot from the clinical decision support tool.

nical research platform which implements tools for extracting various biomarkers, a part of the tools developed in the project. During the ongoing project year, the project has been developing technology which enables starting the workflows of the clinical research platform from the patient care platform and finally downloading the results back to the patient care platform. The workflows contain multiple tools for image quantification. The goal is that new biomechanistic modelling based biomarkers developed in the project could also be incorporated into the tool which would enable to test “The current version of them together with standard the citizen platform is a webclinical biomarportal containing one web- kers from neubased cognitive test and three ropsycholog y, simple games. imaging and cerebrospinal fluid.

Citizen Platform In addition to the work on the patient care platform, VPH-DARE@IT develops further the concept of the citizen platform and validates it in the VPH-DARE@IT prospective trial.The current version of the citizen platform is a web-portal containing one web-based cognitive test and three simple games. The project is also validating blood-based metabolomics biomarkers, de-

veloped in PredictAD, which could potentially be used for complementing the information from the cognitive test and games in the future. In VPH-DARE@IT we implement new functionalities to the portal, such as a visualisation module showing the progress of the patient, and we validate the results of the web-based cognitive tests against standard previously validated clinical measures acquired in the VPH-DARE@IT prospective trial.

Future perspectives A part of the patient care platform is already on track regarding commercialisation. A new partner, Combinostics Ltd, has recently joined the project and it has acquired a license from VTT for commercialising the technologies developed mostly in “The citizen platform PredictAD but containing also forms a highly interesting concept with a great pieces developed potential” in VPH-DARE@ IT. The clinical and commercial value of the novel biomarkers being developed in the project will become apparent later.The citizen platform forms a highly interesting concept with a great potential but the concept needs to be developed further and results validated carefully before it can be brought into public use.

Dr. Jyrki Lötjönen

Principal Investigator Combinostics Ltd Hatanpään valtatie 24 33100 Tampere Finland T: +358 50 346 3250 E: jyrki.lotjonen@combinostics.com

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Combinostics By Jyrki Lötjönen

Newsletter Issue V

What is Combinostics? Combinostics is a company which started its operations in November 2014 with the goal to develop and market advanced tools for data-driven diagnostics. Our initial focus is on dementia diagnostics but the technology is generic and can be used also in other diseases.

The Role of Combinostics in VPH-DARE@IT Dementia diagnostics is challenging due to several reasons. First, there is a multitude of underlying diseases and other conditions that may explain the symptoms observed. This emphasises

“Combinostics is a company which started its operations in November 2014 with the goal to develop and market advanced tools for data-driven diagnostics..”

the importance of differential diagnostics. Second, the amount of data acquired from patients is high and increasing; there is no single efficient biomarker available for diagnostics. Third, diseases causing dementias, such as Alzheimer’s disease, can have a very long period without any or only subtle symptoms making early diagnosis and consequently starting early interventions difficult. At this moment, this puzzle is solved for each patient based on the expertise of the clinician interpreting all available data. Combinostics aims to provide tools that could support clinicians making more objective and evidence-based decisions. These tools enable extracting efficient quantitative biomarkers from data, especially from imaging data, and combining all biomarker data for improved diagnostics by comparing it with previously diagnoses cases.

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partners

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How and when did you become involved in VPH-DARE@IT?

Who are the key people involved in the VPH-DARE@IT and what do they do?

Combinostics is a start-up company from VTT TechDr Jyrki Lötjönen continues leading WP8 after monical Research Centre of Finland. VTT has developed ving from VTT to Combinostics in the beginning of technologies for image quantification and for clinical the year 2016. Dr Jussi Mattila, the chief architect of decision support for many years. The EU FP7 prothe PredictAD tool, will supervise the software deveject PredictAD (www.predictad.eu, 2008-2011) was lopment in WP8. Dr Juha Koikkalainen will be involved a starting point for developing advanced tools for in the development of image analysis tools for vascudementia diagnostics at VTT. Combining these techlar burden (WP2). nologies with more traditional Virtual Physiological Human modelling approaches was What do you find one key idea of the whole VPHmost interesting DARE@IT project preparation. about VPH-DARE@ “Combinostics aims to provide VTT was involved in the prepaIT? tools that could support clinicians ration from the very beginning making more objective and The most interesting issue is and as Combinostics is comevidence-based decisions. ..” to work with the top partners mercialising the technologies in Europe on the exciting chadeveloped at VTT, it was natural llenge of dementias. that Combinostics joins the project.

What is the main contribution of Combinostics to the VPH-DARE@ IT project? The leadership of WP8 “Decision support platform for early differential diagnosis and disease evolution assessment” moved from VTT to Combinostics. Both VTT and Combinostics continue working on the clinical decision support platform.

What do you find most challenging about working in VPH-DARE@IT? Combinostics joined VPH-DARE@IT in the beginning of the year 2016 and we don’t have much experience from working in the project yet, but is likely that managing our time when combining the company’s intense product development with VPH-DARE@IT project work, will be the main challenge.

Dr. Jyrki Lötjönen

Principal Investigator Combinostics Ltd Hatanpään valtatie 24 33100 Tampere Finland T: +358 50 346 3250 E: jyrki.lotjonen@combinostics.com

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IRCCS Fondazione Ospedale San Camillo

The main goal of the study at IRCCS FOSC is Vascular conditions such as hypertension, to conduct a quantitative and comprehensive atherosclerosis, hypercholesterolemia, assessment of systemic risk factors (vascular, diabetes and hyperhomocysteinemia, cardiac and autonomic) as well as modifiable liamong others are established systemic festyle factors for cognitive decline and demenrisk factors for cognitive decline and tia. To address this issue a cross-sectional and dementia. Increasing evidence emerging a correlational observational study is currently from the literature suggests that other ongoing, in which structural and functional data conditions such as heart failure and describing the cardiovascular system are collecvalvular dysfunction, cardiac arrhythmia ted from a sample of 52 cognitively impaired and sympathovagal dysregulation, also play subjects, and 52 age-matched control subjects. a role in the pathogenesis of dementia. The influence of flow dynamic and cardiac outHowever, studies generally focus on a put on brain degeneration will be tested. specific aspect, in which only a subset of potentially relevant measurements is considered. A limiting factor of the current literature is the paucity of “ The main goal of the study at IRCCS FOSC is studies including both structural and to conduct a quantitative and comprehensive functional data from ultrasound (cardiac assessment of systemic risk factors (vascular, and carotid), Holter (electrocardiogram cardiac and autonomic) as well as modifiable and pressure) and body activity (daytime lifestyle factors for cognitive decline and activity, sleep). dementia.�

Pof. Annalena Venneri

Scientific Director Fondazione Ospedale San Camillo Ospedale San Camillo IRCCS Lido di Venezia Italy T. +39 (0)41 22 07 269

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“FOSC is a large neurological and neurorehabilitative hospital located in the island of Lido in Venice, Italy.” It has a unique location between the Adriatic sea and the Venetial Lagune. FOSC has 115 beds for inpatients and several outpatient clinics, including a memory clinic where this study is taking place.

The team at FOSC is interdisciplinary and includes: Professor Annalena Venneri (Scientific Director of IRCCS Fondazione Ospedale San San Camillo d): Principal Investigator (PI) and coordinator of the FOSC study. Dr. Francesca Meneghello (Neurologist of IRCCS Fondazione Ospedale San Camillo) who is involved in participant selection and management. She is in charge of the neurological evaluation and completion of the Clinical Report Form (CRF) for each participant. Dr. Giorgio Levedianos (Cardiologist of IRCCS Fondazione Ospedale San Camillo) is involved in collecting Cardiac Ultrasound measurements, 24-Hours Electrocardiogram (ECG) Holter and 24-Hours Blood Pressure (BP) Holter for each participant.

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Dr. Vincenzo Iaia (Neurologist of IRCCS Fondazione Ospedale San Camillo) is involved in collecting Carotid Ultrasound measurements for each participant. Dr. Elena Cosentino (Physiatrist of IRCCS Fondazione Ospedale San Camillo) is involved in collecting quantitative gait measurements for all participants while walking a fixed distance (10 m) along a delineated indoor walkway. Dr. Micaela Mitolo (Post-Doctoral Researcher of IRCCS Fondazione Ospedale San Camillo) is in charge of the overall logistic management of the study, manages recruitment of all participants, organization of the week schedule with all exams for each participant (including MRI and neuropsychological assessment), management of the relationship (in person and on the phone) with the caregivers of those people who are cognitively impaired, collection of demographic features and measures of height and weight for each participant, administration of the Lifestyle Questionnaire, testing for orthostatic hypotension, collection of data from the actigraph for 5 days and collection of data from the “diary of event” during the 24-Hours ECG Holter and during the 24-Hours BP Holter. She is also in charge of all data management, ensuring that data collected from the various measurements (ultrasound, holted, MRI) are properly downloaded and organized for transfer to the VPH-DARE@IT platform and for implementation of the behavioural databases.

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Exploitation

Philips Commercialisation of VPH-DARE@IT technology By Fabian Wenzel “It is therefore perfect timing that the model-based segmentation of sub-cortical brain structures developed and optimized in VPH-DARE@IT is ready for integration”

Newsletter Issue V

Rapid segmentation of brain structures In 2015, Philips launched IntelliSpace Discovery, a multimodality visualization and analysis platform that facilitates Research by enabling clinicians to more easily evaluate the latest quantitative analysis methods. IntelliSpace Discovery is integrated in the hospital’s IT infrastructure and can be accessed from almost any PC on the network using a standard webbrowser. Furthermore, research data can be managed by IntelliSpace Discovery after transfer from a PACS or scanner console. The first dedicated application package offered is the Research Oncology Suite for lesion tracking and advanced characterization. Moreover, it includes open programming interfaces that enable users to integrate their own analysis tools as plugins. “Now, based on positive customer feedback and requests, we have decided to add a neurology application package”, says Richard Ayres, responsible

for marketing of IntelliSpace Discovery. The functionality has been developed in VPH-DARE@IT’s work package on novel imaging and image quantification technologies. It consists of shapeconstrained deformable surface models that are able to quickly adapt to the shape of various individual brain structures as seen in T1-weighted MRI. Even though the underlying framework and an initial proof of concept have been made prior to VPH-DARE@IT, the project allowed functionality to be optimized, to be made robust, and to match requirements of clinical routine. “A typical radiologist, e.g. in a private practice, ideally would like to see volumes of brain structures in seconds,

Figure 1: Screenshot of model-based segmentation functionality after a first integration into Philips commercial Research platform “Intellispace Discovery”.

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since time is money”, explains Dr. Fabian Wenzel, Senior Scientist at Philips Research in Hamburg. “Furthermore, our approach allows fast and intuitive interactive correction of results in case of severely abnormal anatomies or contrast, in which fully automated approaches generally fail”. At the beginning of VPH-DARE@IT, a single brain shape model was available. It covered 12 sub-cortical structures, including the hippocampus, and was optimized for scans from Philips MR scanners only. During the project, two further models have been created, extending the supported anatomies to 27 sub-cortical regions, the left and right hemisphere, and 12 bi-lateral cortical regions. Furthermore, adaptation was not restricted to Philips scanners anymore. These advances enabled various validation experiments with over 400 scans from multiple databases, which were necessary to proof functionality. Wenzel: “In VPH-DARE@IT, we have learned again that the validation of segmentation techniques is non-trivial, and that many pitfalls need to be considered when inspecting, assessing, and comparing quantitative results.” Due to clinical relevance, evaluations have been mainly focused on sub-cortical brain structures – which are the first to be integrated into the IntelliSpace Discovery platform, and for which segmentation requires about 30 to 45 seconds of processing time. “It is exciting to see that part of the work we have done in VPH-DARE@IT now finds its way to a first product”, denotes Wenzel. The software has also been shared with partners in the consortium for the creation of personalized physiological models (USFD) and for comparing different age-matched volumetric models based on data from the Rotterdam Scan Study (EMC).

“A typical radiologist, e.g. in a private practice, ideally would like to see volumes of brain structures in seconds, since time is money”, explains Dr. Fabian Wenzel, Senior Scientist at Philips Research in Hamburg.

Figure 2: Surface representation of the shape model for segmenting sub-cortical brain regions.

Ayres is looking forward to offering the brain shape model as part of a Neurology application in Intellispace Discovery. “Currently, we are completing specifications of the app based on customer requests.” However, he is confident that Clinical Researchers will soon be able to benefit from both the fast processing time as well as the fact that IntelliSpace Discovery offers batch processing functionality, enabling a convenient way for the automated analysis of study cohorts.

“VPH-DARE@IT’s Research Platform, in which the modelbased brain segmentation functionality is integrated as well, currently goes one step further and brings analysis functionality to the cloud. ” Also Philips is looking into cloud-based computing. Nevertheless, at this time, the hardware for IntelliSpace Discovery is supposed to be installed on site so that sensitive, personalized patient data is not exposed to public servers. Over the next years, Philips will offer more and more cloud-based tools and services, also for healthcare. So IntelliSpace Discovery’s integrated brain segmentation functionality may, one day, do the work at the same spot at which VPH-DARE@IT’s version is also running - somewhere in the cloud.

Dr. Fabian Wenzel

Senior Scientist Philips Research Philips GmbH Innovative Technologies, Röntgenstraße 24-26 Hamburg, D-22335 Germany E: fabian.wenzel@philips.com

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Exploitation New Insole System for Gait and Physical Performance Assessment By Miguel Velhote Correia

Newsletter Issue V

Brief description of the insole technology Kinematix is a company devoted to the development of innovative and disruptive solutions to extract knowledge from human body movement. Knowledge that can benefit anyone to improve their health conditions and physical performance. Its first product –WalkinSense – initially targeted to diabetic patients to avoid foot pressure ulcers, found several applications in the clinical field, from balance and stability assessment of stroke patients to gait monitoring of elderly subjects, as well as in sports such as football, rugby, golf and running and even in the footwear design industry, providing shoe recommendations for children in their early footsteps. Under project VPH-DARE@IT activities, WalkinSense evolved from a ankle and foot worn system to an in-shoe attached device easier to place and wear seamlessly and effortlessly by elderly people and/or non-cooperative patients. Considerable design and engineering efforts were focused on making the system the most comfortable and unobtrusive as possible. The insole includes force sensing resistors specially developed and proven to work under the harsh conditions of the foot insole, namely sweat

moisture, temperature and frictional stresses. An inertial measurement unit, integrated in the data logging and transmission module, provides information on the person’s lower limbs movements and gait-related characteristics. The accompanying computer software permits the acquisition and viewing of online gait and foot pressure data, during experimental scenarios, intuitively by both researchers and clinical staff.

Why these systems were developed and specifics of their role in the project Previous studies have found that many patients

“Kinematix is a company devoted to the development of innovative and disruptive solutions to extract knowledge from the human body movement.”

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with some degree of cognitive impairment show evidence of gait disorders (Elble 2007). According to the review by Scherder et al. (2007), gait and gaitrelated motor disturbances are present in all subtypes of dementia, even in the early and preclinical stages, without exception. Furthermore, assessment of gait may contribute to differential diagnosis, since gait disturbances may differ among the various subtypes of (preclinical) dementia (Scherder et al. 2007). A wellfunctioning ability to sustain, shift, and divide attention between environmental and body function factors is thus essential for walking safely in everyday life (Cedervall et al. 2014). Increase in gait variability has previously been found in Alzheimer disease patients (Wittwer et al. 2014). The most promising therapeutic advances target the earliest phases of the dementia disorders, before brain tissue is irrevocably damaged or has been lost altogether. This means that early diagnosis of dementia disorders will be increasingly important. Improved diagnostic accuracy will allow better targeting of increasingly limited resources for the treatment of patients with cognitive impairment and dementia. In VPH-DARE@IT, WalkinSense II devices are available and can be used for the study of gait performance in dementia patients. An experimental protocol is designed with the intent to collected data from cohorts of patients with Alzheimer’s Disease, Vascular Dementia or Mild Cognitive Impairment and healthy

age-matched controls in dual-tasking scenarios similar to those of published studies, but with an additional methodological improvement consisting of measuring gait variability in more detail and more objectively with the help of gait sensors. This would lead to the development of gait-related biomarkers for differential diagnosis of dementia conditions, to be integrated in the project’s Clinical Research Platform.

Exploitation in other commercial and future research applications The insole technology is also being exploited in other commercial and research applications.WALKiNSENSE II has been tested for assessment of gait impairments in stroke patients and people who suffer from osteoarthritis. Based on the same technological hardware platform but with substantially different requirements and application scenarios, Kinematix is now developing TUNE – the first wearable consumer product from the company, targeting both casual and professional runners worldwide. TUNE is a simple, easy to use smart wearable that goes beyond measuring basic statistics such as pace or speed, but also measures each foot’s ground-contact time (GCT), heel-contact time (HCT) and symmetry. Runners often have imbalances that are the source of physical problems. If detected in time, most of them can be easily corrected with proper training. TUNE monitors both feet in-shoe and detects asymmetries, allowing to prevent injuries and run better.

Dr. Miguel Velhote Correia Researcher Rua das Oliveiras, 72, 1 Andar Porto 4050-448 Portugal T: +351 222 010 752 E: m.correia@kinematix.pt

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VPH-DARE@IT IT news VPH-DARE@

Events Review VPH-DARE@IT Attendance 2015-2016 Since the last newsletter VPH-DARE@IT has taken part in several events aimed at communicating our research to a wide audience. Below is the review of two key European Commission events we attended; ICT2 015 and ECR 2016. This only represent two events that form part of VPHDARE@IT communication activities. For more information on events please visit the project website and for a list of published research articles since the last newsletter please see the publications list at the back off this newsletter.

ICT 2015

Newsletter Issue V

The project presented a stall at ICT2015 in Lisbon Portugal 20th to 22nd October 2015. ICT involved both a conference and an exhibition which is based on three main themes; Connect, Innovate and Transform. The conference was focused on the new commission policies and initiatives around ICT. Sessions ranged from Horizon 2020 Work Program to themed parallel sessions. The exhibition ran in parallel to the talks with stalls showing the advanced research and activities that will have high potential impact on European industry and the life and well-being of European citizens. The exhibition also provided a display space for companies that have grown from funding provided by the EC, as well as explored the interaction of art and technology. Three partners presented the work of VPH-DARE@IT.Tomorrow Options (Kinematics), Teknologian Tutkimuskeskus VTT Oy and the University of Sheffield. We demonstrated all three platforms: The citizen platform, The Clinical Platform and the Research Platform. Kinematic also demonstrated the insole system that you can read more about in this newsletter. We supported our stall with videos and posters explaining how the platforms form a cohesive whole.We made use of social media to give real time updates and news from the event. Our stall allowed us to interact with fellow projects and the general public.The discussions explored both the specifics of the platforms and the project as whole with specific interest in both the clinical platform and its applications both in relation to dementia and other areas.The research platform’s infrastructure was another area that received interest.The event made use of social media presenting various feeds on large screens around the venue and VPH-DARE@ IT made good use of this raising our profile both of our stall and the project’s website. We feel the contacts and the output of the event helped us raise awareness of our project, both to the EC and the wider community.

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Events

ECR 2016

The European Congress of Radiology (ECR) is Europe’s largest event in medical imaging and serves as the annual meeting of the European Society of Radiology (ESR), the world’s largest radiology society with more than 62,000 members. Each year, the congress attracts more than 20,000 participants from all over the world from a variety of imaging-related fields, such as radiology, medical physics and radiography. At ECR 2016, the VPH-DARE@IT project held its very own session titled “The VPHDARE@IT Project: Delivering a clinical decision support platform for earlier dementia diagnosis”, to give congress attendees an opportunity to learn about the project’s aims, progress, results and the contribution made by medical imaging to the project. Six researchers from the VPH-DARE@IT consortium spoke at the session: Delivering a Clinical Decision Support Platform for Earlier Dementia Diagnosis on Saturday March 5, 2016.The session gave attendees an insight into the clinical platform being developed by the project, as well as the modelling approaches and imaging data being used to achieve the project’s objective of earlier dementia diagnosis. Talks were delivered on the clinical platform presented by Mark Van Gils (affilation). Exploring further into the project the research platform and the use of new techniques were presented by Susheel Varma (CISTIB, University of Sheffield) and Leandro Beltrachini (CISTIB, University of Sheffield). Susheel had the following to say about ECR; “The ECR was a fantastic experience for me and for the VPH-DARE@IT project’s visibility as a whole. We were able to summarise the efforts within the project into key outputs, namely the Patient Care Platform, the Clinical Research Platform, the Novel Image Processing pipelines and novel biomechanistic modelling tool; all devoted to early diagnosis and/or differential diagnosis of Dementia. The ECR allowed us to put our research in the context of global public and private efforts to tackle the ever rising problem of Dementia and find effective mechanisms to translate our work into clinical practice” Turnout was good and the speakers had a great opportunity to engage with attendees who had a number of relevant questions about the project. This continues to raise the profile of the project among our fellow researchers and healthcare professionals. ECR Website: https://www.myesr.org ICT 2015 Website: http://ec.europa.eu/digital-agenda/en/ict2015-innovate-connect-transform-lisbon-20-22-october-2015

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VPH-DARE@ IT

Publication Highlights Journals 1. L.Beltrachini,M.De Marco,Z.A.Taylor,J.Lotjonen,A.F.Frangi,and

Dispersion,” Phys Rev Lett, vol. 115, p. 094301,Aug 2015.

A.Venneri,“Integration of CognitiveTests and Resting State fMRI for the Individual Identification of Mild Cognitive Impairment,” Curr Alzheimer Res, vol. 12, pp. 592-603, 2015.

15. M.K.Lupton,L.Strike,N.K.Hansell,W.Wen,K.A.Mather,N.J.Armstrong, et al.,“The effect of increased genetic risk for Alzheimer’s disease on hippocampal and amygdala volume,” NeurobiolAging,vol.40,pp.68-77, Apr 2016.

2. L. Beltrachini, Z. A. Taylor, and A. F. Frangi, “A parametric finite

element solution of the generalised Bloch-Torrey equation for arbitrary domains,” J Magn Reson,vol.259,pp.126-34,Oct 2015.

16. D. M. McGrath, N. Ravikumar, I. D.Wilkinson,A. F. Frangi, and Z.A.Taylor, “Magnetic resonance elastography of the brain: An in silico study to determine the influence of cranial anatomy,” Magn Reson Med, Sep 2015.

3. M. Bocchetta, E. Gordon, E. Manning, J. Barnes, D. M. Cash, M. Espak, et al.,“Detailed volumetric analysis of the hypothalamus in behavioral variant frontotemporal dementia,” J Neurol, vol. 262, pp. 2635-42, Dec 2015.

17. T. Natunen, M. Takalo, S. Kemppainen, S. Leskelä, M. Marttinen, K. M. Kurkinen,et al.,“Relationship between ubiquilin-1 and BACE1 in human Alzheimer’s disease and APdE9 transgenic mouse brain and cell-based models,” Neurobiol Dis, vol. 85, pp. 187-205, Jan 2016.

4. M. J. Cardoso, M. Modat, R. Wolz, A. Melbourne, D. Cash, D. Rueckert, et al.,“Geodesic Information Flows: Spatially-Variant Graphs andTheirApplication to Segmentation and Fusion,” IEEE Trans Med Imaging, vol. 34, pp. 1976-88, Sep 2015.

18. H.F.Rhodius-Meester,J.Koikkalainen,J.Mattila,C.E.Teunissen,F.Barkhof, A.W.Lemstra,et al.,“Integrating Biomarkers for UnderlyingAlzheimer’s Disease in Mild Cognitive Impairment in Daily Practice: Comparison of a Clinical Decision Support System with Individual Biomarkers,” J Alzheimers Dis, vol. 50, pp. 261-70, Nov 2015.

5. D. M. Cash, C. Frost, L. O. Iheme, D. Ünay, M. Kandemir, J. Fripp, et al.,“Assessing atrophy measurement techniques in dementia: Results from the MIRIAD atrophy challenge,” Neuroimage, vol. 123, pp. 149-64, Dec 2015.

19. T. Rog and A. Koivuniemi,“The biophysical properties of ethanolamine

6. D. Chou, J. C.Vardakis, L. Guo, B. J.Tully, and Y.Ventikos,“A fully

plasmalogens revealed by atomistic molecular dynamics simulations,” Biochim Biophys Acta, vol. 1858, pp. 97-103, Jan 2016.

dynamic multi-compartmental poroelastic system:Application to aqueductal stenosis,” J Biomech, Nov 2015.

20. A.Salminen,A.Haapasalo,A.Kauppinen,K.Kaarniranta,H.Soininen,and

7. M. de Groot, L. G. Cremers, M.A. Ikram,A. Hofman, G. P. Krestin,

M.Hiltunen,“Impaired mitochondrial energy metabolism inAlzheimer’s disease: Impact on pathogenesis via disturbed epigenetic regulation of chromatin landscape,” Prog Neurobiol, vol. 131, pp. 1-20,Aug 2015.

A. van der Lugt, et al.,“White Matter Degeneration with Aging: Longitudinal Diffusion MR ImagingAnalysis,” Radiology,p.150103, Nov 2015.

21. A.Salminen,P.Jouhten,T.Sarajarvi,A.Haapasalo,and M.Hiltunen,“Hypoxia

8. M. de Groot, M. Ikram, S.Akoudad, G. Krestin,A. Hofman,A. van

and GABA shunt activation in the pathogenesis ofAlzheimer’s disease,” Neurochemistry International, vol. 92, pp. 13-24, JAN 2016 2016.

der Lugt, et al., “Tract-specific white matter degeneration in aging:The Rotterdam Study,” Alzheimers & Dementia, vol. 11, pp. 321-330, MAR 2015 2015.

22. T.Sarajärvi,M.Marttinen,T.Natunen,T.Kauppinen,P.Mäkinen,S.Helisalmi, et al.,“GeneticVariation in δ-Opioid ReceptorAssociates with Increased β- and γ-Secretase Activity in the Late Stages of Alzheimer’s Disease,” J Alzheimers Dis, vol. 48, pp. 507-16, 2015.

9. M. De Marco, F. Meneghello, D. Duzzi, J. Rigon, C. Pilosio, and A. Venneri, “Cognitive stimulation of the default-mode network modulates functional connectivity in healthy aging,” Brain Res Bull, vol. 121, pp. 26-41, Mar 2016.

23. S. Sedaghat, L. G. Cremers, M. de Groot, E. J. Hoorn,A. Hofman,A. van der Lugt, et al.,“Kidney function and microstructural integrity of brain white matter,” Neurology, vol. 85, pp. 154-61, Jul 2015.

10. M. De Marco and A.Venneri,“’O’ blood type is associated with

larger grey-matter volumes in the cerebellum,” Brain Res Bull, vol. 116, pp. 1-6, Jul 2015.

24. A.Schmidt-Richberg,C.Ledig,R.Guerrero,H.Molina-Abril,A.Frangi,D. Rueckert,et al.,“Learning Biomarker Models for Progression Estimation of Alzheimer’s Disease,” PLoS One, vol. 11, p. e0153040, 2016.

11. A. Haapasalo, M. Pikkarainen, and H. Soininen, “Alzheimer’s disease: a report from the 7th Kuopio Alzheimer symposium,” Neurodegener Dis Manag, vol. 5, pp. 379-82, Oct 2015.

25. C. H. Sudre, M. J. Cardoso,W. H. Bouvy, G. J. Biessels, J. Barnes, and S. Ourselin,“Bayesian model selection for pathological neuroimaging data applied to white matter lesion segmentation,” IEEETrans Med Imaging, vol. 34, pp. 2079-102, Oct 2015.

12. J.Koikkalainen,H.Rhodius-Meester,A.Tolonen,F.Barkhof,B.Tijms,

A.W.Lemstra,et al.,“Differential diagnosis of neurodegenerative diseases using structural MRI data,” NeuroImage:Clinical,vol.11, pp. 435-449, // 2016.

26. J. C.Vardakis, D. Chou, B. J.Tully, C. C. Hung,T. H. Lee, P. H.Tsui, et al.,

“Investigating cerebral oedema using poroelasticity,” Med Eng Phys,vol. 38, pp. 48-57, Jan 2016.

13. T. Laiterä, M. I. Kurki, J. P. Pursiheimo, H. Zetterberg, S. Helisalmi,T.

Rauramaa,et al.,“The Expression ofTransthyretin andAmyloid-β Protein Precursor is Altered in the Brain of Idiopathic Normal Pressure Hydrocephalus Patients,” J Alzheimers Dis, vol. 48, pp. 959-68, 2015.

27. P. S. Weston, R. W. Paterson, M. Modat, N. Burgos, M. J. Cardoso, N.

14. S.A. Lambert, S. P. Näsholm, D. Nordsletten, C. Michler, L. Juge, J.

28. P.S.Weston,I.J.Simpson,N.S.Ryan,S.Ourselin,and N.C.Fox,“Diffusion

Magdalinou, et al.,“Using florbetapir positron emission tomography to explore cerebrospinal fluid cut points and gray zones in small sample sizes,” Alzheimers Dement (Amst), vol. 1, pp. 440-446, Dec 2015.

M. Serfaty, et al.,“Bridging Three Orders of Magnitude: Multiple Scattered Waves Sense Fractal Microscopic Structures via

imaging changes in grey matter inAlzheimer’s disease:a potential marker of early neurodegeneration,” Alzheimers Res Ther, vol. 7, p. 47, 2015.

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Deliverables D1.4

Report on prospective data acquisition and evaluation studies (WP1) D1.5 Initial report on validation with prospective data (WP1) D2.10 Algorithms and libraries for extracting biomarkers of vascular dementia from MR data (WP2) D2.5 MR acquisition & processing techniques report (WP2) D2.6 Report on software library for adaptation of anatomical brain models to subject-specific brain scans (WP2) D2.7 Integrated analysis of multi-modal brain scns (WP2) D2.8 Pipeline design and implementation for the construction of personalised brain models for fluid transport simulations (WP2) D2.9 Initial clinical data relating regional CBV/CBF values in dementia patients to apparent stiffness values (WP2) D2.11 Algorithms and libraries for construction of normative models of brain tissue image intensity etc. (WP2) D3.3 Workflow implementation and streamlining for highthroughput image analysis of large-scale studies (WP3)

D4.4

Model of lipid membrane-Aβ interaction of progression to AD (WP4) D5.6 Circadian and lifestyle models of physiological and physical dynamics in normal subjects & dementia (WP5) D5.7 Preliminary release of coupled biophysical-metabolic modelling framework and software pipeline (WP5) D5.8 Prototype release of subject-specific 3D multiporoelastic brain model workflow and software pipeline (WP5) D6.5 Ageing brain models in normal ageing and disease: virtual population for biophysical modelling (WP6) D7.4 Second prototype of the VPH-DARE@IT research platform WP7 D8.4 Specification of clinical platform (WP8) D9.4 Initial Health Technology Assessment Report (WP9) D9.5 Annual exploitation report (WP9) D.10.6 3rd six-monthly progress report (WP10) D10.7 Third periodic progress report, including public summary of each work for publication (WP10)

Events

Upcoming events

• ISBI (International Symposium on BIOMEDICAL IMAGING) 2016 Prague, Czech-Republic, 13-16 April 2016

http://biomedicalimaging.org/2016/

http://www.alz.org/aaic/overview.asp

• AAIC16 - Toronto, Canada, 24-28 july 2016 • •

WBIR (International Workshop on Biomedical Image Registration), Las Vegas, Nevada, 1st July 2016 http://wbir2016.doc.ic.ac.uk/

EMBL Conference- Lifelong Learning in the Biomedical Sciences EMBL Heidelberg, Germany, 5 - 7 July 2016 http://www.embl.de/training/events/2016/LLL16-01/

In the next issue... • • • •

Outcome of Lido Cohort Study A Clinician’s Perspective Large Data Management On The Research Platform Outcome of Year 3 Review

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

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VPH-DARE@IT Partners USFD The University of Sheffield VTT VTT Technical Research Centre of Finland ESI ESI Group S.A ASD Advanced Simulation & Design GmbH EMP 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 Philips Technologie GmbH STH Sheffield Teaching Hospital NHS Foundation Trust UCL University College London UEF Itä-Suomen yliopisto UMA University of Maastricht TO Kinematix ICL 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 FOSC Fondazione Ospedale San Camillo COMBINOSTICS Combinostics Ltd

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 5  
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