Millions of European citizens suffer from diseases of the intestines with 700 000 cases diagnosed as the autoimmune condition, Crohn's disease. This chronic condition is characterised by alternating periods of increased and reduced disease activity. It is therefore important to regularly assess the stage of the disease in order to adjust the treatment accordingly. Frequent and sometimes invasive examinations are necessary to monitor response. VIGOR++ aims to replace such examinations by combining advances in image analysis, modelling and interactive visualisation to create a personalised model of the gastrointestinal (GI) tract. The ultimate goal is to accurately predict the colonoscopy and histopathology data and the associated indices of disease severity.

Objectives include:

• Adapt existing image analysis algorithms to accurately measure descriptive properties of GI wall tissue.
• Create patient specific imaging tools to quantitatively assess the status of Crohn’s disease.
• Develop visualisations of all aspects of the GI tract model.
• Conduct rigorous testing to ensure a clinically usable system.
• Establish a new care pathway for accurate, non-invasive and cost-effective examination of the GI tract for Crohn’s disease.
• Disseminate knowledge and ICT tools by actively engaging fellow academic disciplines, industry and inflammatory bowel disease patient associations across Europe.

By adopting a ‘software as a service’ (SaaS) platform, VIGOR++ aims to make its tools accessible on any browser.

Policy Context

The project is part of the Virtual Physiological Human (VPH) framework established by the EC that investigates the human body as a single complex system. The VPH framework has already delivered descriptive, integrative and predictive knowledge regarding human (patho-)physiology. Still, VPH is the ‘grand challenge’ for many disciplines at the interface between ICT and the biosciences. Effectively, it sustains a system of shared resources formed by federations of disparate but integrated computer models regarding mechanical, physical, and biochemical functions of the human body.  The VPH framework is expected to alter health knowledge, thereby creating a new basis for research and opening new opportunities for healthcare provision.

Description of target users and groups

VIGOR++ targets several clinical, academic and industrial representatives. VIGOR++ has stimulated such association by creating an Interest Group that is kept up to date through project e-alerts, and will be consulted on any project issue requiring a broader consensus or set of viewpoints. Interest Group members as well the members of the Advisory Committee are actively encouraged to input ideas and to comment on the work under development. It is expected that some members of the Interest group can become early adopters of the VIGOR++ tools. Clearly, the close involvement into the project makes them well positioned for undertaking the exploitation of the project results. Specifically, the consortium has close interaction with representatives from the following sectors:

• Pharmaceutical companies looking to perform more efficient clinical trials by using accurate, quantitative descriptors of therapy effect and thereby reducing costs.
• Physicians (e.g. radiologists, gastroenterologists, general practitioners) who aim to improve the quality of quality of life of their patients by offering minimally invasive diagnostic procedures, improved treatment, and minimised length of stay in hospitals.
• Patient groups such, as European Federation of Crohn's & Ulcerative Colitis Association (www.efcca.org), who are represented in VIGOR++’s Advisory Committee and encourage scientific research into Crohn's and Colitis causes and treatment.

Description of the way to implement the initiative

VIGOR++ has undertaken extensive research and development of ICT tools for the analysis, modelling and simulation of human physiology and disease processes of the GI tract. The developed ICT tools are being used to build patient-specific computer models to sustain personalised healthcare. Such tools are widely favoured by physicians and other medical disciplines for improved diagnosis and follow-up. The approach is unique in that it enables quantitative assessment of diseases of the GI tract.

The methods developed in the project enable the creation of personalised GI tract models, which facilitate improved detection of Crohn’s disease and drives an index of Crohn’s disease severity. The models can lead to a non-invasive procedure for estimating the disease index.

Multiscale data acquisition including laboratory, MRI, colonoscopy and microscopy (histopathology) data from Crohn’s disease patients are used in the development of accurate prediction models as integrated ICT tools. These tools include a normal representation of the GI tract that facilitates detection of abnormalities, ability to grade disease severity, and influence clinical disease management.

VIGOR++ combines proven image analysis techniques to identify regions of interest and register the MR images to compensate for patient movement. In addition, descriptive properties of Crohn’s disease activity are measured in images. The features obtained are the basis of the modelling and classification tasks.

Pattern recognition techniques are subsequently applied to detect and rate abnormalities, so that a combined and quantitative, clinical disease severity index can be accurately established.

A visualisation software toolbox has been designed to enable interactive visualisation of GI wall tissue properties. It features techniques for concurrent visualisation of the clinical patient data as well as the properties measured by image analysis and classification.

Testing is underway to ensure both accuracy and usability in a clinical setting. The clinical benefit of the VIGOR++ system is demonstrated in a study in which the tools are tested regarding the performance to predict Crohn’s disease status, i.e. the conventional indices as well as the combined index.

A study is planned to establish the effect of therapy based on the measures generated by the VIGOR++ tools. Such a study effectively forms the of pinnacle of the work, since it is one of the largest unsolved problems of imaging research to be able to assess therapy by means of quantitative markers. This should drive further research regarding prevention of Crohn’s disease in risk populations and identification of predictors (or biomarkers) of early onset of disease.

Technology solution

Over the last 15 years, significant efforts have been made to build numerical patient models from multimodal images for surgical planning and image-guided surgery. VIGOR++ has been extending the state of the art in the fields of image analysis (Inner and outer bowel wall segmentation; DCE registration); modelling and classification (super pixel classification); and interactive visualisation (2D and 3D rendering). Further information on these technologies is provided online. The developed tools are integrated in the 3DNetMedical.com medical imaging cloud service, to make them immediately available in a clinically usable environment.

Technology choice: Proprietary technology

Main results, benefits and impacts

VIGOR++ has been developing tools that can offer Crohn’s disease sufferers the prospect of a non-invasive, radiation free, low-risk and accurate diagnostic environment. The procedure will result in disease management that is less disruptive to patients’ day-to-day lives and empower them via simple portals to play an active role in their care.

Benefits for clinicians include:

• Increased efficiency of diagnosis and integration with treatment planning;
• Ability to assess the disease progress and predict potential complications in a non-invasive way;
• Minimisation of the need for optical colonoscopy particularly for patients unable to tolerate sedation or bowel preparation;
• Automatic identification of results outside acceptable ranges;
• Support for shared decision making with patients;
• Quantification of medication efficiency.

Benefits for pharmaceutical companies
Currently, all pharmaceutical companies are in a very competitive race to develop the next generation of medication for IBD and particularly Crohn’s, as there is no known cure for the disease. Several promising types of medication are prescribed to treat Crohn’s (Aminosalicylates, Immunomodulators, Corticosteroids, Cyclosporine and Tacrolimus, Infliximab) but without sufficient long-term medical evidence. Their side effects are not fully known, but some of them even mimic IBD symptoms. It is expected that the ICT tools produced by VIGOR++ significantly increase the knowledge emanating from clinical trials for Crohn’s by offering effective ways to perform early assessment of drug action.

Benefits for healthcare systems
Increased cost of healthcare delivery puts pressure on cost reductions. The VIGOR++ tools can have a direct impact on hospitals by reducing the cost and disease management (increased throughput, reduction in length of stay) and by improving their return on investment of acquired technology (MRI scanners.). There is also an impact for national health systems, as the outcome will help them meet targets set (waiting lists etc.). Finally, health insurance companies are expected to benefit by reduced costs that can be passed to clients.

Benefits for European industry and academic institutions
To build a verified and validated physiological model of a human organ and an intervention planning system of clinical relevance is without doubt a highly challenging research objective, which certainly requires critical mass of knowledge, expertise, manpower, and dedication. VIGOR++ is an example of bringing together European multidisciplinary research excellence, in the fields of medicine (radiology, gastroenterology) and ICT (image analysis, pattern recognition, scientific visualisation). The envisaged research and VIGOR++ developments will certainly help establish know-how beyond the current state of the art in GI diseases and allow participants to leap frog competitive groups outside the EU.

Return on Investment
All partners have clear exploitation plans for their respective work. The project’s ROI comprises several elements such as savings for the healthcare partners, promotion of the expertise of the partners to future clients and students as well as revenue from the commercialisation of the ICT tools and launch of related consulting services.

Return on investment

Return on investment: €1,000,000-5,000,000

Track record of sharing

VIGOR++ from the outset had dedicated activities for communicating, sharing and transferring relevant knowledge about the technologies and clinical practices developed in the project to the European market of technology providers and end users.

The project has been represented in over 40 national and international events including the European Congress of Radiology (ECR) and the Annual Conference of the Radiology Society of North America (RSNA). It also organised its own annual workshops with the next one scheduled to take place on 9 May 2014 in London. The consortium members regularly publish their latest results in journal papers, and conference proceedings that can be downloaded from the project’s website. The project was featured in a Euronews Futuris documentary broadcasted in July 2013.

The team has also produced two key reports: the VIGOR++ technology roadmap and the intellectual property landscape report. The first should help organizations interested in conducting R&D to evaluate options within the appropriate market, clinical, technology and science trends. The second builds on the analysis of patents granted over the recent years will offer key insights to the consortium members wishing to understand who are their competitors, their country of origin and the particular classes/keywords they tend to be used most frequently.

Lessons learnt

Key lessons from the studies undertaken so far, include:

• MRI remains a strong candidate to solve the problem of accurately grading Crohn’s disease activity as it evaluates the bowel lumen, bowel wall and extra enteric soft tissues without the use of ionizing radiation. The reproducibility of MRI features is fair to good, with a good reproducibility for some commonly used features. Work in the project proved that MRI assessment of Crohn’s disease activity benefits from the usage of multiple MRI features. We came across cases where classification can be executed solely on MRI data, so that the invasive colonoscopy can be avoided.
• There is merit in continuing bridging the gap between 2D and 3D renderings, since 3D renderings definitely have the advantage of providing an overview at a glance, while 2D depictions often better serve detailed analyses. The new volume picking technique called WYSIWYP (“what you see is what you pick”) developed in VIGOR++, in contrast to previous work, does not require pre-segmented data or metadata and thus is more generally applicable. More experiments are planned to establish its usefulness in the context of additional medical imaging data.
• Considerable effort has been put into integrating the various software modules that implement algorithms into the 3DNetMedical.com cloud-based system. It has become clear that such solutions can lead to the creation of an ecosystem of clinicians, researchers and developers that would be impossible to achieve with traditional imaging software and hardware.

Scope: Pan-European