Data Sharing With Collaborative Partners to Develop Computer Aided Detection for the Assessment of the Small Bowel Using MRI
Conditions: Small Bowel Disease, Gastrointestinal Diseases
Sponsor: University College, London

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Short Title:  
Anonymous Data Sharing for Small Bowel MRI 
 
Full Title:  
 
Data sharing with collaborative partners to 
develop Computer aided detection for the 
assessment of the small bowel using MRI.  
 
Prof. Stuart Taylor (Chief investigator) 1, 2 
Dr Alex Menys 1,3  
Dr David Atkinson 1,2 
Prof Dean Barratt 4 
Dr Shankar Kumar 2 
Dr Tom Watson 6  
Dr Ruaridh Gollifer 1,2 
Dr Heather Fitzke 1,2 
Dr Jennifer Steeden 6,7 
Dr Stuart Bloom 5 
Dr Anton Emmanuel 5 
1 Centre for Medical Imaging, University College London, 2nd floor Charles Bell House, 43-45 Foley 
Street, London W1W 7TY  
2 Imaging Division, University College London Hospital, 3rd Floor East, 250 Euston Road 
3 Motilent Ltd, 69 Wilson St, London, EC2A 2BB 
4 Centre for Medical Imaging Computing, University College London, 90 High Holborn, London, WC1V 
6LJ & Charles Bell House, 43-45 Foley Street, London W1W 7TY  
5 Department of Gastroenterology, University College London Hospital, 235 Euston Road, NW1 2BU 
6 Great Ormond Street Children’s Hospital, Great Ormond Street, London WC1N 3JH 
7 Great Ormond Street Institute of Child Health, University College London, 30 Guilford St, London 
WC1N 1EH 
 

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Chief Investigator contact Dr Stuart Taylor, University College London, 2nd floor Charles Bell House, 43-
45 Foley Street, London W1W 7TY Tel 07960 169 321. Email stuart.taylor1@nhs.net 
Table of Contents 
 
Overview ............................................................................................................................................. 3 
Background ......................................................................................................................................... 4 
Justification for the research .............................................................................................................. 4 
Clinical and patient demand ........................................................................................................... 5 
Clinical Impact ................................................................................................................................. 6 
Summary of Proposed Technology and Development plan ............................................................... 8 
Data Collection and Management .................................................................................................. 8 
Process for the sharing of anonymised datasets acquired as part of clinical practice. ................ 10 
Handling of datasets ..................................................................................................................... 10 
Data ownership and storage ......................................................................................................... 12 
Appendix 1.  - Protocol for software development by CMIC, UCL ................................................. 13 
Appendix 2 -VIGOR FP7 Protocol ...................................................................................................... 20 
 
 

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Definitions  
 
Personal Data: any information relating to an identified or identifiable living individual;  
 
Pseudonymised personal data means: 
 
‘...personal data [that] can no longer be attributed to a specific data subject without the use 
of additional information, provided that such additional information is kept separately and is 
subject to technical and organisational measures to ensure that the personal data are not 
attributed to an identified or identifiable natural person'  
[GDPR, Article 4]  
 
Anonymised data: data which does not relate to an identified or identifiable natural person or 
personal data that has been rendered anonymous in such a manner that the data subject is not or 
no longer identifiable.  
 
Data Protection Legislation: all applicable laws and regulations relating to the Processing of Personal 
Data as the same may be in force from time to time. Including, the Data Protection Act 2018 (DPA) 
and the General Data Protection Regulation (GDPR). 
Data Controller: a person which, alone or jointly with others, determines the purposes and means of 
the Processing of Personal Data. 
 

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Overview 
 
This document describes the protocol for the sharing of anonymised MRI and ultrasound small bowel 
datasets and associated fully anonymised clinical results with collaborators at UCL Centre for Medical 
Imaging (CMI) as part of parallel projects to develop computer software to quantify diseases of the 
small bowel using MRI. 
Background 
 
The department of Radiology at UCLH (along with many centres around the UK) has been running a 
clinical small bowel MRI service since 2005 and have several thousand datasets on its PACS along with 
a similar number of ultrasound datasets for patients often suspected of having Inflammatory Bowel 
Disease or other bowel disorders. The department of academic Radiology at UCLH has forged 
academic collaboration with several partners both at UCL and abroad to develop computer software 
to analyse these Imaging datasets, extracting quantitative information on bowel morphology and 
function. This document describes the process of anonymous data sharing with these collaborative 
partners. 
 
Justification for the research 
 
A growing number of diseases are being referred for assessment with Magnetic Resonance 
Enterography and/or enteric ultrasound including Crohn’s disease, constipation, dyspepsia, 
dysmotility disorders, Irritable Bowel syndrome and a range of neuropathic conditions with 
gastrointestinal involvement.  
By far the best characterised and most commonly referred condition that we routinely investigate is 
Crohn’s disease precipitated by an abnormal immunological response within the bowel wall leading 
to abnormal wall thickening, stricturing (narrowing), fistulation to adjacent organs and structures, 
abnormal motility and local sepsis.  The incidence is around 10 in 100,000 and in the UK for example 
there are 6000 new diagnoses of inflammatory bowel disease annually. Crohn’s patients experience 
times of disease quiescence punctuated by acute flares in inflammatory activity requiring medical 
intervention. Radiological imaging of the small bowel defines diagnosis, disease extent, biological 
activity and complications and is vital for timely and efficacious clinical management.  Several tests 
can image the small bowel but the conventional tests of barium follow-through and Computerised 
Tomography impart a significant radiation dose which is concerning since Crohn’s disease patients are 
relatively young and require repeated imaging over several years. The newer technology of small 
bowel MRI which does not impart ionising radiation is proving to be a safe, well tolerated and robust 
method of assessing the small bowel and is widely implemented in the UK and Europe. The use of 
ultrasound is complementary especially where focal disease has been localised with MRI and, like MRI, 
does not carry a radiation dose for the patient.  
 
MRI evaluates multiple disease related parameters including bowel wall thickness and signal return, 
contrast enhancement and pattern and bowel motility and is proving increasing reliable for disease 

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identification, staging, therapeutic guidance and assessment of treatment response.1, 2 Currently there 
are no tools that combine these parameters to provide robust and user friendly quantitative 
prediction of disease activity which severely limits uptake of this powerful tool in clinical practice. We 
propose to develop computer software to optimise and reliably quantify the information afforded by 
MRI, for the detection and staging of small bowel pathologies such as Crohn’s disease. We aim to 
provide tools for faster, safer, more accurate patient assessment and these may also aid in the 
understanding of disease aetiology.  
Importantly, MRI is now being clinically used at ULCH and other hospitals to explore gastrointestinal 
dysfunction (e.g. for abdominal pain, bloating and nausea). MRI in the use of CD is now well 
disseminated and great strides have been taken to objectively evaluate this data. In other conditions 
e.g. constipation and dyspepsia, diagnostic techniques are still lacking in clinical practice and 
automated methods, similar to those developed in CD would be highly advantageous. Furthermore, 
many observations made using MRI, for example the inverse relationship between motility and 
inflammatory activity, might be translated across to other imaging methods like ultrasound where 
dynamic imaging of the bowel structure and movement is easily performed and recorded. Using 
existing datasets collected at UCLH and partner hospitals, we could generate robust and compelling 
pilot data in this area to attract funding and drive larger studies.  
 
Clinical and patient demand 
 
Crohn’s Disease: 
Treatment of Crohn’s disease is divided into medical therapy or surgical intervention. In general 
biologically active disease is treated by medical therapy whilst surgery is undertaken in those with 
symptomatic “burnt out” fibrotic disease or in those who fail to adequately respond to medical 
therapy. Correct identification of these patients is the crux of optimum clinical management. Medical 
therapy is based largely on immunosuppressive medication. Although relatively effective, these drugs 
are expensive and not without significant side effects, some of them life threatening, notably sepsis 
secondary to immunosuppression, and malignancy. Rational use of immunosuppressive therapies in 
Crohn’s disease therefore is reliant on accurate identification of those patients with acute 
inflammation –so called “active disease” who are most likely to respond to the treatment. 
Unfortunately there is currently no reliable method to identify such patients. Clinical assessments 
based on patient symptoms, such as the Crohn’s disease activity index (CDAI), are relatively subjective, 
resource intensive (patient symptom data is collected for a whole week) and patients with inactive 
disease (such as those with chronic fibrotic strictures) often attract high scores. Biochemical markers 
such as ESR and CRP are useful adjuncts but again do not in themselves always differentiate reliably 
between active and chronic disease. Nevertheless, such imperfect standards of reference are the 
mainstay of both clinical and drug trial assessment of disease activity. 
MRI has the ability to non-invasively assess disease extent and activity. Specifically several parameters 
including wall thickness, T2 signal, contrast enhancement and enhancement pattern have all been 
linked to disease activity. Indeed our group has provided some of the most robust data to date.3 
Furthermore, Crohn’s afflicted bowel shows abnormal motility (peristalsis). One major advantage of 
MRI is its ability to acquire real time “cine” style imaging based on multiple image acquisitions at a 

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fixed anatomical point, enabling visualisation of motility.4 To date, assessment using MRI largely relies 
on subjective assessment by the reporting radiologists with poor inter and intra-observer agreement.5 
Extraction of quantitative information is very time consuming with little in the way of software 
automation, and thus is essentially limited to the research arena only. Enteric US is now increasingly 
used in the same way as MRI, providing information on bowel structure and function.6, 7 
We have consulted widely amongst user groups for our proposal including clinical and academic 
gastroenterologists (locally, and via the British society of Gastroenterology and European Crohn’s and 
colitis organisation [ECCO]), surgeons, clinical radiologists (locally and via the British Society of 
Gastrointestinal and Abdominal Radiology), Industry (Philips Medical Systems) and patient groups 
(patient forum of the national association of Crohn’s and colitis). We have identified a strong clinical 
need for a tool to reliably define the extent of Crohn’s disease, evaluate biological activity and 
facilitate safe and non-invasive assessment of therapeutic response. Several validated indices of 
disease activity are now available for the assessment of Crohn’s disease,8-11 but they are still too time 
consuming to use clinically. 
 
Functional gastrointestinal disease: 
 
A growing clinical demand exists for diagnostic tests in functional gut disorders. Up to 20% of the 
population may be classified as having irritable bowel syndrome (IBS) and as much as 50% of the 
gastroenterology workload presents with functional or unexplainable symptoms. This is 1) 
unsatisfactory for patients, 2) unsatisfactory for the clinician and 3) inefficient for the healthcare 
provider who invariably must request various tests. Based on recent developments in CD with CAD it 
is possible to extract a great deal more data from MRI scans of these patients. As MR has become 
more routine at UCLH, and many other hospitals we have seen an increase in ‘MR Physiology’ scans 
requested by clinical teams (a 20min MRI consisting of motility, anatomical and diffusion imaging) 
with no IV contrast. Since 2014, around 800 of these scans have been performed in mainly non-Crohn’s 
subjects, and development of quantitative technology to better evaluate functional bowel disease 
would be advantageous. 
 
 

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Clinical Impact 
 
Development of this robust computer aided diagnosis (CAD) system for assessing Crohn’s and other 
gastrointestinal disease extent and activity using medical imaging will have many meaningful impacts, 
the most important of which are: 
• 
Provide a diagnostic aid to radiologist, increasing accuracy and workflow efficiency. 
 
• 
Provide quantitative data on disease activity, facilitating use in clinical triage of patients, 
assessment of therapeutic response and use as a biomarker, or surrogate endpoint, in clinical 
trials of therapeutic agents. 
 
• 
Form the basis of software solutions applicable to other disease states such as disorders of gut 
motility including constipation, dyspepsia, post-surgical ileus, autonomic dysfunction, food 
intolerance and delayed gastric emptying. 
 
• 
Strengthen the role of MRI as a safe, well tolerated and effective method of assessing small bowel 
Crohn’s disease, obviating some of the need for invasive and potentially dangerous endoscopic 
procedures 
 
• 
Provide Insight into the mechanism of complex conditions using MRI that might be translated to 
other modalities like US, meaning greater availability for patients and potential cost savings for 
healthcare providers.  
 
• 
Through adding new collaborating sites (for example Great Ormond Street Hospital) observations 
made in adults might be replicated in children where the need for non-invasive, objective tests of 
gastrointestinal dysfunction are needed.  
 
 
 

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Summary of Proposed Technology and Development plan 
 
We have forged academic collaborative partnerships with  
• 
The Centre for Medical Imaging (CMI) and several European Countries with whom we have 
ongoing collaborative arrangements (Department of Radiology, AMC, Netherlands) << ONGOING 
>>  
• 
European centres in a  recently awarded European FP7 grant award to develop this software << 
THIS PROJECT WAS COMPLETED IN JANUARY 2015 >> 
 
Full details of the developmental protocols with these partners are provided in Appendix 1 (CMI); 
Appendix 2 (FP7 partners) 
In brief, the aims are too develop computer software to extract the bowel from the MRI dataset, 
measure various relevant parameters such as wall thickening, signal etc which reflect disease activity, 
create models of those parameters which best reflect disease activity and then validate these models 
against current clinical standards of reference (notably blood markers of inflammation such as CRP, 
endoscopic scores of disease activity, biopsy scores of disease activity and clinical questionnaire 
scoring system such as the Crohn’s disease activity index. We also developed accurate quantification 
of small bowel motility12-18 which may have clinical uses in other disease states, notably autonomic 
dysfunction and ileus.  
 
 
Data Collection and Management  
 
This standard operating procedure (SOP) applies to all NHS hospitals sharing data. Presently 
this is  
i) 
UCLH 
ii) 
Great Ormond Street Hospital, London 
 
Each site will give permission for data sharing as per this SOP via their usual regulatory/ data 
protection, research and development pathways and will appoint a local PI who will have 
responsibility for its implementation 
 

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The development of the software will require access to imaging datasets with concurrent clinical 
reference standards of disease activity such as endoscopy findings, histology results, blood tests and 
patient symptom questionnaires. 
Anonymised datasets acquired as part of an ethically approved research project ‘RESEARCH 
DATASETS’:  
We have two ongoing ethically approved UCLH studies investigating the use of MRI in small bowel 
Crohn’s disease and comparison with clinical standards of reference, notably endoscopic biopsy, blood 
test data and clinical symptom diaries. As part of these projects, patients agree to their anonymised 
data to be used for future work.  
Ethics ref: 05/Q0502/124  
Enteric and extra-enteric MRI manifestations of small bowel Crohn's disease: qualitative and 
quantitative histopathological correlation and assessment of disease activity with reference to surgical 
resection specimens 
Ethics ref: 09/H0714/62 (committee A) Defining the role of MRI as a marker of Crohn's disease activity-
Prospective Comparison to a clinical reference standard 
Ethical approval has been granted for both retrospective and prospective data sharing with our 
collaborators. 
<< THESE TWO PROJECTS COMPLETED IN JANUARY 2016 >> 
A third multisite study, METRIC (MR Enterography or ulTRasound In Crohn’s disease): Diagnostic 
accuracy for the extent and activity of newly diagnosed and relapsed Crohn’s disease: a multi-center 
prospective comparison of magnetic resonance enterography and small bowel ultrasound compared 
to a reference standard in those aged 16 and over, was completed in 2018. Funding and ethical 
permission has been received for an extended follow-up of a subset of METRIC patients (METRIC-EF), 
which is currently ongoing. Patients give permission for use of their anonymised data and imaging for 
future research (METRIC REC Ref: 13/SC/0394; METRIC-EF REC Ref: 18/LO/1930).  
A fourth multisite study, MOTILITY (Small bowel motility quantified by cine MRI as a predictor of long-
term response in patients with Crohn's disease commencing biological therapy; REC Ref: 
17/WM/0106) is also ongoing. Patients aged 16 and over commencing biological therapy are scanned 
at week 0 (baseline); 20-28 weeks (short term) and 1-year (long term) post-treatment. These patients 
can give permission to use of their anonymised data and imaging for future research at the time of 
consent. 
A fifth single site study, SB motility (Post-hoc analysis of dynamic magnetic resonance sequences to 
establish descriptive metrics for small bowel motility in vivo; REC Ref 11/LO/1634) is also ongoing at 
UCLH. Healthy participants and patients with a condition where dysmotility is postulated are 
scanned at one or more time-points to assess changes over time (e.g. following drug infusions, food 
ingestion or treatment). These participants can give permission to use of their anonymised data and 
imaging for future research at the time of consent. 

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Anonymised datasets acquired as part of clinical practice ‘CLINICAL DATASETS’: 
 
Many patients undergoing small bowel MRI or USS at UCH and other collaborating hospitals often also 
undergo additional tests as part of their usual clinical care which are recognised as good standards of 
reference against which we can validate our imaging findings. Notable examples are blood tests (eg. 
CRP), endoscopy and biopsy, and symptom questionnaires. Furthermore, many patients have normal 
examinations and these datasets are also very useful in software development to define a standard of 
normality. Suitable datasets will be found as follows: 
• 
Search of the PACS database to identify all small bowel examinations performed at collaborating 
hospitals 
• 
Use clinical sources freely available to hospital clinical staff via the CDR web system at 
collaborating hospitals to triage these patients into relevant clinical groups notably those who 
have normal small bowel examinations, and those with abnormal studies who have a relevant 
clinical standard of reference performed within 6-12 weeks (CRP level, endoscopy, biopsy, 
questionnaire) 
• 
Select a sample of relevant datasets for use in software development. The total number to be data 
shared with the FP7 consortium listed above will not exceed 75 (<< THIS DATA SHARING PROJECT 
IS NOW COMPLETED>>). The total number of datasets to be data shared with UCL will not exceed 
1,500 across collaborating hospital sites. The larger number shared with UCL reflects their need 
for a large database of normal examinations to train and test new algorithms and assess changes 
in imaging parameters over time.  
Handling of datasets 
 
• 
RESEARCH DATASETS: Only staff on the delegation log for the original research project will have 
access to any psudeo-anonymised datasets acquired as part of that research. This is consistent 
with ICH Good Clinical Practice and local Research Governance procedures.  
• 
CLINICAL DATASETS: Only staff with full or honorary contracts and part of the clinical team at 
collaborating hospitals will have access to the clinical data and un-anonymised datasets. This is 
consistent with the situation presently as such staff already can access both the PACS and hospital 
CDR as part of their usual clinical practice. 
• 
A full list of staff employed in preparing the datasets (and 2 page summary CV) will be kept for 
internal/external inspection. Only staff meeting the above criteria and approved by the chief 
investigator (Prof Stuart Taylor), will be permitted to prepare the datasets. At collaborating 
hospitals, the local PI will give approval 
• 
All chosen datasets will be fully anonymised before transfer using the anonymisation protocol 
approved by the data controller (i.e. research Sponsor or collaborating hospital) before any 
analysis or research is performed. No identifiable data (hospital number, DOB, name) will be left 
visible on the datasets. 

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• 
Regions of interest will be placed on the datasets (for example areas of wall thickening) but no 
further clinical evaluation of the datasets will be undertaken.  
• 
Each dataset will be given a unique identification number (UID). The key to this number will be 
stored temporarily on a separate standalone password protected Trust computer while the 
relevant clinical data is collated by a member of the clinical team. This key linking the UID to the 
pseudo-anonymised (RESEARCH DATA) OR un-anonymised (CLINICAL DATA) held on the Trust 
system will be deleted before the data is transferred. This process will be performed according to 
Information Commissioners Office guidance in such a manner that the data subject is not or no 
longer identifiable. For example, through utilisation of hashing or salting; processing data in 
batches to preserve k-anonymity and re-coding continuous outcomes as binary or categorical such 
that the subject cannot be identified by a combination of variables.  
• 
The chief investigator will personally approve any researchers who are permitted controlled 
access to identifiable data (including pseudo-anonymised data). All such staff will hold full or 
honorary contracts with the research Sponsor organisation or hospital site. Identifiable (including 
pseudo-anonymised) patient data will never leave the research Sponsor organisation or hospital 
site. This system is compliant with General Data Protection Regulations and local Research 
Governance procedures. Local collaborating hospitals will provide similarly secure arrangements 
for storage of their shared datasets. Data transferred to UCLH from collaborating hospitals will 
comply with NHS data protection regulations, for example the use of secure NHS email (see 
below).  
• 
Selected fully anonymised datasets will be stored on a password protected hard drive for 
transportation from collaborating hospitals. The chief investigator and local PI will approve those 
staff who will have access to the password. The password will only be released via secure email 
systems (ie NHS.net email systems) and never physically kept with the hard drive. If possible, 
secure PACS IEP systems can also be used to transfer the scan data to UCLH for analysis. 
• 
Transposition of MRI datasets on the hard drive will only be via manual hand over or courier 
services. Standard postal services will not be used 
• 
Correlative clinical data acquired as part of routine clinical practice (notably blood test results, 
endoscopic findings, questionnaires, histology data) will be collated where relevant. This data will 
be fully anonymised by collaborators at the donating hospital (members of the clinical team) and 
thereafter identified to researchers only by the unique study number assigned to each MRI 
dataset. Relevant data will have been collected within 12 months of the small bowel MRI. 
• 
The key to this number for UCLH data will be kept on a separate standalone password protected 
UCLH computer in a locked office at UCH (250 Euston Road). Local collaborating hospitals will 
provide similarly secure arrangements for storage of the key for their clinical data. Of note, a 
different password will be used than that for the MRI datasets to additional security. The chief 
investigator or local site PI will personally approve any local researchers who have controlled 
access. All such staff will hold full or honorary contracts at the donating hospital and be part of 
the clinical team. This system is compliant with data protection regulations. The source un-
anonymised patient data will never leave the donating hospital  

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• 
Anonymised clinical data will be sent to collaborative partners via pass word protected datasheets 
using secured hospital (nhs.net) or university email systems only. The password will only be 
released by the chief investigator or designated researcher in a separate email, also using secure 
email systems 
 
Data ownership and storage 
 
• 
The datasets will remain the property of the donating hospital 
• 
Datasets may be analysed with third party commercial algorithms to aid with research or 
validation. Examples would include Osirix, Horos and other imaging platforms or specific image 
analysis tools like GIQuant from Motilent. Under no circumstances will identifiable patient data 
be transferred to third parties for storage and all data will remain the property of the donating 
hospital.  
• 
Where third party commercial algorithms that require use of online platforms are utilised - this 
will be performed with a specific agreement/contract to ensure that data ownership and storage 
obligations are met. Only fully anonymised datasets - that cannot be linked back to the original 
data subject - will be analysed online. Although use of fully anonymised data falls outside of the 
scope of GDPR – appropriate steps will be taken to limit access to data (e.g. platforms hosted on 
ISO 27100 compliant servers in the UK with end-to-end encryption, 2-way authentication and 
restricted access; ability to download data restricted by user access level which is reviewed in a 
regular basis.  
• 
All data sharing (including any commercial aspects) has been agreed by Dr Susan Kerrsion in UCLH 
R&D. In particular a FP7 consortium agreement will be constructed to govern data sharing with 
the FP7 consortium. UCLH is formally listed as a subcontractor in the FP7 agreement << THIS 
PROJECT IS NOW COMPLETED>> 
• 
As part of the FP7 agreement, all datasets supplied to collaborative partners will be subject to the 
same data protection rules as at UCLH. Notably anonymised electronic data will be stored on 
password protected computer. As noted above NO un-anonymised data will be released to any 
collaborator. The FP7 consortium has appointed an external expert (Prof. Andrea Laghi, Rome), 
who will ensure ethical standards are maintained at all times. In addition an external advisory 
committee has been developed (see Vigor protocol, Appendix 2) << THIS PROJECT IS NOW 
COMPLETED>> 
• 
Both projects with CMI and the FP7 consortium (completed) are scheduled to run for 10 years. All 
shared data will be destroyed or returned to the donating hospital within 6 months of the projects 
finishing. 
 
 

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NOW COMPLETE 
Appendix 1. - Protocol for software development by CMI, UCL  
 
There are three main aspects to the computational work: data handling and visualisation, image 
processing to extract parameters including novel assessments of bowel motility, and a model to 
calculate the disease activity index from these image parameters. 
The UCL/H Comprehensive Biomedical Research Centre (CBRC) is currently funding two software 
developers within the UCL Centre for Medical Image Computing (CMIC) to produce an Insight Toolkit 
(ITK) based viewing package. ITK is an open source platform supported by US Federal funds and widely 
accepted internationally [http://www.itk.org/]. The UCL package is initially intended for neurological 
imaging but will be extensible to other types of medical images. We will use this framework to develop 
the tools necessary for loading, viewing and aligning (registering) MR bowel images from a range of 
different MR sequences. A tool will be implemented within this framework to allow radiologists to 
select regions of interest that include the Crohn’s affected area. Within these regions the bowel wall 
will be semi-automatically segmented on the different images. <<NOW COMPLETE>> 
Using this bowel wall segmentation, image parameters will be calculated, these could include; bowel 
wall thickness, signal intensity on T2 weighted images, intensity changes following contrast injection 
(absolute values and curve shape), pattern of enhancement and motility. <<ONGOING>> 
Motility in Crohn’s and other disorders of the GI tract such as pseudo obstruction, coeliac disease and 
radiation enteritis is restricted compared to normally functioning bowel and can be visually observed 
when time series images are played as a ‘cine’. Motility imaging combined with manual scoring has 
been shown to aid in Crohn’s detection.19 We aim to develop a new quantitative assessment of motility 
as part of our tool. We have used an EPSRC Platform grant to CMIC to pump prime pilot work in 
extracting motility information from MR cine images. The pilot method uses an adaptation of an optic 
flow registration algorithm to include intensity changes.20 Intensity changes are included in an attempt 
to account for bowel through-plane motion. Our quantitative motility parameter includes both these 
intensity changes and the local change in volume derived from the registration motion field. Volume 
change was chosen because it should be insensitive to locally rigid displacements caused by respiratory 
motion. The figure below shows a single frame from a cine series (left) with the affected thickened 
bowel wall highlighted by a red arrow. In our pilot quantification map (right), the affected bowel wall 
appears blue indicating little motion (red arrow) compared to healthier regions showing normal 
motility (green arrow). This pilot work demonstrates that we can obtain quantitative motility 
information, though the optimum choice of parameters and their usage remains to be determined. 
Furthermore the method has been tried on two datasets so far. 

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The motility and other image-derived parameters need to be combined in the optimum way. We will 
use linear regression analysis to build a model that can predict disease activity. In the model training 
and validation, we will use measures of Crohn’s activity derived from both the standard CDAI score, 
histopathological acute inflammatory scores from surgical resections and biopsies and biochemical 
measures. The application of the technique to other disorders of the small bowel such as dysmotilty 
syndromes, non-specific abdominal pain, radiation enteritis and coeliac disease etc will also be 
explored in suitable cohorts undergoing clinically requested MR enterography. 
We propose three overlapping development phases. First a software system that uses MRI data 
acquired on standard, commercially available systems. Second, new MR protocols adapted and 
optimised for obtaining parameters relating to small bowel disease. Third, extensions to the software 
to include the capabilities of the new MR protocols and to incorporate feedback from clinical 
evaluation.   
Our goal is a software tool that is easy and effective to use. The less user intervention required the 
better, but priority will be placed on getting a complete pipeline functioning first, even if this requires 
more manual interaction than is ideal or subjective visual scoring. The later development phases will 
be used to refine the software and to adapt MR techniques to give us more relevant or accurate image 
parameters. 
 
Work Package 1. The viewing tool  
A viewing tool currently under development in CMIC will be extended to allow the visualisation of 
images from multiple MR contrast types simultaneously. This will require standard techniques to 
handle data with different voxel sizes and slice positions. In addition, the ability to view time series 
(“cine”) images will be incorporated. Functionality will be added to allow the radiologist to select a 
point in an affected region of bowel in a volume and then reformat  so that the image slice is 
perpendicular to the local axis of the bowel (the bowel wall should then appear approximately circular 
in the image). Functionality will be added for radiologists to provide scores manually based on 
observations, e.g. presence or absence of the “comb sign” or abscesses. 
Disease 
healthy bowel 

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Work Package 2. Bowel Wall Segmentation 
The disease affects the bowel wall and many of the image based parameters will have to be extracted 
from this region. Ideally 3D surfaces that define the inner and outer edges of the wall would be found 
from one volume and copied to the different MR images. Subsequently the image parameters would 
be extracted from pixels that were located between these surfaces. The challenges are to define the 
surfaces, select only abnormal bowel and handle the partial volume effects associated with 
propagating these surfaces to images that may intrinsically have been acquired at a different slice 
orientation, slice thickness and with a gap between slices. Furthermore, the bowel twists and turns 
and often does not have a perpendicular intersection with the imaging planes leading to partial volume 
effects and the appearance of a thicker wall. 
The contours overlaid on the figure in the Technical Background section show that a simple edge 
detection algorithm can find the inner and outer walls, though its reliability and accuracy has yet to be 
tested. We will use techniques such as edge detection, region growing and thresholding to aid 
segmentation of  the bowel wall on a few slices where, after reformatting, the wall appears 
approximately circular (WP1). This semi-automatic segmentation will use the MR sequence that shows 
the best wall contrast and has voxels which are close to isotropic (equal length on all sides). With 
segmentations on a few adjacent slices, this will enable surfaces to be defined and their intersection 
with images from other contrast types computed. These intersections will be displayed as 2D ROIs on 
the other images and the radiologist given the opportunity to make position adjustments.    
In summary, at this stage of development, the radiologist has to perform the following steps; locate a 
point in an abnormal region of bowel wall, rotate the volume to display bowel “end on”, segment on 
a few slices the inner and outer wall (which will appear approximately circular and thus easy to 
segment manually or with region growing algorithms), check and adjust 2D ROIs that will then be 
automatically displayed on the other images. 
Work Package 3. Registration and Motility Quantification  
We will continue to develop the novel motility assessment outlined in the Technical Background with 
the aim of providing a quantitative measure which we hypothesise will be a key component in the 
prediction of disease activity. This motility quantification will be validated by comparison with a 
radiologist scoring system, e.g. 1 paralysis, 2 hypomotility, 3 normal, 4 hypermotility (see WP 7).  
Our use of local volume change in the motility assessment is expected to be independent of respiratory 
motion. However, the other image parameters are derived from standard MRI protocols including a 
variety of breath hold image sequences, most commonly Fast Imaging with Steady state Precession, 
Half Fourier Acquisition Single Shot Turbo spin Echo and Volumetric Interpolated Breath hold 
Examination before and after intravenous gadolinium injection. Such data suffers from motion 
artefact, notably from breathing, patient movement and peristalsis of the bowel. In order to reliably 
collate quantitative data from differing image sequences it is necessary to accurately co-register the 
datasets.  We will apply image registration technology developed by applicants in the UCL CMIC 
group. In brief these methods include fluid registration21 and its adaptation to sequences with different 
image contrasts,22 and a fast implementation of the B-spline non-rigid registration algorithm that 
incorporates biomechanics. This is a challenging topic and some residual mis-registration may remain. 

16 
 
For this reason, in WP 1 we have allowed for manual ROI adjustments by the radiologist and we will 
explore incorporation of biomechanical models of tissue deformation. 
 
Work Package 4. Parameter quantification  
Following image registration (WP 3) and identification of region of interest (WP 2) quantitative 
parameters from the affected bowel wall will be derived Parameters of interest include, bowel wall 
thickness, motility (WP 3), signal intensity on T2 weighted images, contrast enhancement (absolute 
value and curve shape) and pattern of enhancement.   
Wall Thickness: With the inner and outer wall ROIs already in defined in WP 2, this can be calculated 
in a straightforward way and an average for the slice provided. 
Contrast uptake: Multiple parameters can be calculated from contrast uptake curves (areas, slopes, 
timings etc). Recent work suggests the early uptake is correlated with disease23 and we will initially use 
the slope of enhancement as a parameter. 
T2 intensity: As with wall thickness, this is easy to find given the ROIs. It may also be necessary to 
identify an additional region of normal bowel to act as a reference. 
Motility: Described in WP 3. 
Pattern of enhancement or “layering”: Standard image processing methods of texture analysis will be 
used to quantify the pattern of enhancement. 
Other parameters: Crohn’s is associated with multiple characteristics on images. In addition to those 
above, other characteristics include fistulation, abscesses, luminal stenosis and the “comb sign” 
(increased mesenteric vascularity). Initially we will provide the facility for these to be manually scored 
and if necessary, a more quantitative assessment will be performed in WP 9. 
 
Work Package 5. Model interfacing  
The software tool will be augmented to output the image derived parameters in a consistent fashion 
and to enable the organised collection of this data from multiple patients. The statistical modelling will 
be performed in external software (see WP 6) and the model parameters and weights provided for the 
viewing software. Modifications to the viewer will be made so that on a given patient the model can 
be used with the pre-determined weights to display the predicted disease activity score. 
  

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Work Package 6. Software evaluation and optimisation  
 
i) 
We will use MRI datasets from 18 patients undergoing surgical resection for small bowel 
Crohn’s disease.1 Within this there are 60 regions of interest anatomically exactly matched 
between the MRI and histopathological sampling of the specimen. A validated transmural 
score of acute inflammation (AIS) has been assigned to each histological slice. In detail, 
patients underwent pre-operative MR enterography using a 1.5-T static magnet (Avanto; 
Siemens, Erlangen, Germany) with the manufacturer's body and spine array coils. Axial and 
coronal half-Fourier rapid acquisition with relaxation enhancement (RARE) and true fast 
imaging with steady-state precession (TRUEFISP) images of the small bowel were acquired, 
together with coronal fat-saturated half-Fourier RARE images. Coronal volumetric 
Interpolated Breath-hold Examination (VIBE) acquisitions were performed at 30 seconds 
after injection of 10 mL gadopentetate dimeglumine (Magnevist; Berlex Laboratories, 
Montville, NJ). The resected bowel was retrospectively identified on the preoperative MR 
images and multiple regions of interest (median 3, range 1-5 per patient) placed within the 
bowel, documenting their exact distances to nearby fixed anatomic landmarks (eg ileo 
caecal valve, fistula opening etc). The surgical specimens were imaged with MRI and 
regions of interest on the pre-operative MR were co-located on the specimen MRI by 
reference to the fixed anatomical landmarks.  Using the annotated specimen MR as a 
guide, pathological sampling was taken at sites matched exactly to the MRI regions of 
interest. A transmural histopathological acute inflammation score (AIS) was ascribed to 
each of the sample sites by two experienced gastrointestinal pathologists according to the 
method of et al:15 This grades AIS with a maximum of 13 based on mucosal ulceration 
(grade 0-3), oedema (grade 0-3), and quantity (grade 0-3) and depth (grade 0-4) of 
neutrophilic infiltration.24 Crucially, these histopathology slices include the whole 
thickness of the bowel wall and provide full information on cellular inflammation and 
disease activity - effectively the best standard of reference achievable against which to 
test the MRI parameter quantification. 
ii) 
We will assemble a sample of up to 75 MRI datasets with correlative terminal ileal 
endoscopy and biopsy data. Each biopsy will be scored for acute inflammation (from 1 to 
5) and matched to the MRI dataset. In detail, all patients will have undergone the small 
bowel MRI protocol described above and endoscopic terminal ileal biopsy within 4 weeks 
(median 5 days) of the MRI. The location of the biopsies is recorded with reference to the 
distance from the ileo-caecal valve-a fixed anatomical land mark identifiable on both 
endoscopy and MRI datasets. An endoscopic biopsy acute inflammatory score (eAIS) based 
on typical morphological features of Crohn’s disease described in guidelines published by 
the European Crohn’s and Colitis Organization25 is applied to the biopsy data. 
iii) 
 A sample of up to 200 normal small bowel MRI datasets will be assessed to define the 
range of normality for all parameters. 
iv) 
 A prospective study of MRI in the assessment of disease activity has been ethically 
approved is already underway. 100 MRI datasets validated against contemporary CDAI (i.e. 

18 
 
current clinical standard), CRP (blood marker of inflammation) and calprotectin (stool 
marker of inflammation) will be collated. In detail, prospectively recruited patients with 
known Crohn’s disease and undergoing small bowel MRI as part of normal clinical practice 
complete a symptom diary card the week before their MRI for calculation of the CDAI. In 
addition a blood sample for CRP measurement is taken on the day of the MRI, together 
with a stool sample for calprotectin level. Calprotectin is a biochemical marker of intestinal 
inflammation.26  
v) 
Ethical permission to perform small bowel MRI in 75 patients with known or highly 
suspected small bowel Crohn’s disease has been obtained. Each patient will have 
endoscopic and histological scoring of disease activity as described above 
 We will correlate our software quantified MRI or US scores of inflammation against each subcategory 
of activity reference individually i.e. 
i) 
Histopathological (surgical specimen and biopsy data)-scored for acute inflammation 
ii) 
Biochemical (CRP and stool calprotectin)-continuous data with higher values reflecting 
increased activity 
iii) 
Endoscopic inflammation scores 
iv) 
Clinical (Crohn’s disease activity index) - a continuous score with score >150 indicating 
active disease.  
The statistical modelling will use external software such as SPSS or MATLAB (Statistics Toolbox). We 
will perform linear regression to generate the weights for the image parameters, analyse the predictive 
power of the parameters and perform leave one out cross-validation. 
We have multiple possible parameters and multiple standards of reference (histological, biochemical 
and clinical) to define weights in the statistical modelling. Statistical methods such as back elimination 
are available for choosing parameters and we will also use our clinical judgement and knowledge of 
underlying disease mechanisms to identify the optimum combination and weighting of parameters 
best predicting acute inflammation. 
The software will thus be flexible to the variety of markers of disease activity used in clinical practice. 
Indeed it is anticipated the software modelling will differ depending on the type of reference standard. 
We will thus provide users with options as to whether the software quantifies according to a clinical 
(CDAI, biochemical CRP, calprotectin) or histological standard of reference 
 
Work Package 7. Software clinical evaluation  
Sections of bowel will be given a clinical score for motility and this will be compared with the numerical 
values derived in WP 3 (start of year 2). When the complete tool has been built and trained, we will 
determine the incremental benefit to radiologists of our tool by comparison with non CAD assisted 
reporting. Notably efficiency will be tested by measuring radiologist reporting times for quantitative 
evaluation of disease activity in 50 datasets with and without the CAD software.  The accuracy of the 

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interpretation in assessing disease activity with and without CAD will be tested against the defined 
standards of reference listed above and defined using standard ROC methodology. Usability of the 
software will be assessed through questionnaires to end users. Indirect evaluation will also take place 
through monitoring the extent of usage at UCH and the number of external software downloads 
Work Package 8 MR Sequence Adaptations  
We will investigate protocol modifications that help with the parameter extraction, for example 
removing any slice gaps or changing resolution. 
We will also investigate the use of newer or alternative MR sequences to provide data more specific 
for Crohn’s other enteropathies and provide images better suited to parameter extraction. We will 
apply MR techniques that can measure motility more directly such as tagging, and methods such as 
diffusion imaging that are sensitive to changes in water diffusion at the cellular level and flow in the 
microvasculature. The inflammatory process is linked to changes in blood supply, cell swelling and 
increased cell count. These all affect the bowel wall diffusion signal and we will adapt sequences and 
protocols to extract the most useful information for Crohn’s patients.  
 

20 
 
 
Appendix 2 -VIGOR FP7 Protocol NOW COMPLETE 
 
 
 
 
PART B 
COLLABORATIVE PROJECT 
 
Table of Contents  
CONCEPT AND OBJECTIVES, PROGRESS BEYOND STATE-OF-THE-ART, S/T METHODOLOGY AND WORK PLAN .. 22 
CONCEPT AND PROJECT OBJECTIVE(S) ........................................................................................................................ 22 
Concept ....................................................................................................................................................... 23 
S&T objectives ............................................................................................................................................. 27 
PROGRESS BEYOND THE STATE OF THE ART ................................................................................................................. 31 
State-of the-art in diagnostic procedures for the GI tract .......................................................................... 31 
State of-the-art in ICT tools for modelling the GI tract ............................................................................... 35 
Advantages over traditional techniques and main innovations ................................................................. 40 
S/T METHODOLOGY AND ASSOCIATED WORK PLAN ..................................................................................................... 41 
1.3.1 Overall strategy and general description ........................................................................................... 41 
Timing of work packages and their components ........................................................................................ 45 
IMPLEMENTATION ................................................................................................................................................ 47 
MANAGEMENT STRUCTURE AND PROCEDURES ............................................................................................................ 47 
The management structure layers .............................................................................................................. 47 
Methods of monitoring and reporting progress ......................................................................................... 51 
Conflict resolution procedures .................................................................................................................... 53 
BENEFICIARIES ...................................................................................................................................................... 53 
Delft University of Technology (TUD).......................................................................................................... 53 
University College London Hospitals ........................................................................................................... 54 
Eldgenössische Technische Hochschule Zürich (ETHZ) ............................................................................... 56 
Zuse Institute Berlin (ZIB) ............................................................................................................................ 57 
Biotronics3D Limited ................................................................................................................................... 58 
Academic Medical Centre, University of Amsterdam ................................................................................. 60 
Vodera Limited ............................................................................................................................................ 61 
CONSORTIUM AS A WHOLE ..................................................................................................................................... 62 
Overview of the consortium ....................................................................................................................... 62 
Subcontracting ............................................................................................................................................ 63 
Other countries ........................................................................................................................................... 63 
RESOURCES TO BE COMMITTED ................................................................................................................................ 63 
RTD .............................................................................................................................................................. 64 
Management ............................................................................................................................................... 65 
IMPACT ................................................................................................................................................................. 66 

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STRATEGIC IMPACT ................................................................................................................................................ 66 
Expected impact I (on patients) .................................................................................................................. 66 
Expected Impact II (on clinicians) ................................................................................................................ 66 
Expected Impact III (on healthcare systems) .............................................................................................. 67 
Expected Impact IV (on the pharmaceutical industry) ................................................................................ 68 
Expected Impact V (on the European industry and academic institutions) ... Error! Bookmark not defined. 
Relevant European research projects ......................................................................................................... 70 
PLAN FOR THE USE AND DISSEMINATION OF FOREGROUND KNOWLEDGE........................................................................... 70 
Dissemination of project results ................................................................................................................. 71 
Exploitation of project results ..................................................................................................................... 74 
Involvement in the exploitation of results .................................................................................................. 75 
Management of intellectual property ......................................................................................................... 77 
ETHICAL ISSUES ..................................................................................................................................................... 79 
 
 
 
 

22 
 
Concept and objectives, progress beyond state-of-the-art, S/T methodology 
and work plan 
Concept and project objective(s) 
Gastrointestinal (GI) disorders affect millions of people of all ages.1 What is more, inflammatory 
bowel diseases (IBDs) are a huge healthcare problem in the Western World, affecting over 1 million 
European citizens alone, 700,000 of whom suffer from Crohn’s disease2. Research in Crohn’s disease 
is particularly challenging due to its nature, which complicates a straightforward assessment of the 
severity. 
In fact, there is a widespread debate on how to extract quantitative, pathology related measures as 
well as how such measures should be interpreted for many diseases. This complexity has increased 
the demand for related ICT tools. Physicians require advanced tools to improve the detection and 
visualisation of abnormalities, to enhance the communication between fellow doctors, and to 
quantitatively assess the outcome of interventions. Delivering such tools can lead to early diagnosis, 
improved treatment, reduced clinical risks associated with interventions and eventually, hopefully, 
prevention of disease. 
In this project, we aim to develop a set of ICT tools to fulfil these prospects. The methodological 
advances this project entails, and the clinical evaluation study we propose, will add to the gaining 
momentum for a paradigm shift that paves the way for proving the clinical feasibility of new 
techniques. In order to demonstrate the nature of the tools and their applicability, we chose to drive 
the development by validating them on the most common type of inflammatory bowel diseases: 
Crohn’s disease. 
The VIGOR++ project aims to create a personalised GI tract model, which facilitates improved 
detection of Crohn’s disease and drives an index of Crohn’s disease severity. 
The proposed technology builds on multiscale information from patients, including laboratory, MRI, 
colonoscopy and microscopy (histopathology) data. A novel integration of existing models is 
employed to predict features on the molecular to cellular scale (microscopy/colonoscopy) from 
descriptive properties at the organ to patient scales (MRI/laboratory). 
The benefits are early diagnosis, improved therapy planning and a better quality of life for patient. 
The techniques are integrated in the 3Dnet™ Suite environment , to make them immediately 
available in a clinically usable environment. Notably, tools could be rapidly commercialized and 
delivered as an optional toolbox to clinical sites. 
 
1 For example, colorectal cancer is the second most common cancer in Europe. Source: International Agency for 
Research on Cancer (IARC), http://www.iarc.fr 
2 European Federation of Crohn's & Ulcerative Colitis Association (www.efcca.org). 

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Concept 
The introduction of cross sectional imaging modalities had a dramatic impact on healthcare by 
facilitating detailed exploration of the human body. In fact, it revolutionised the way in which many 
conditions are diagnosed and treated. The ability to examine in detail structures inside the body, 
without resorting to surgery, has allowed clinicians to diagnose problems and plan corrective 
procedures with a minimum of risk. 
Currently, a favoured step forward is to complement the traditional techniques by approaches that 
integrate observations with models for prediction. Such an approach is also promoted by the 
European Commission in the eHealth domain striving to promote a shift from population-centred to 
person-centred systems and from reactive to preventive healthcare. Specifically, it is envisioned that 
modelling and simulation is adopted to understand the complexity of human physiology and predict 
human response to therapies. What is more, virtual human organs may be used to understand the 
impact of patient variability on these predictions. 
Virtual Physiological Human 
Predictive models have already been successfully applied in the clinical practice, e.g. finite element 
models to predict the risk of bone fracture and molecular pathway modelling in the design of new 
drugs. Computer aided detection (CAD) of disease is a comparable, interdisciplinary technology 
integrating radiological practice into digital image processing and machine learning techniques. CAD 
systems analyse digital images for typical, physiological appearances and, alternatively, to highlight 
suspicious sections (potential diseases). Typically, the performance of the predictive models is 
significantly influenced by the quality of the used images, conditions of the examination, disease 
subtype and scale. The design of these decision support systems is complex since conventionally a 
large database with appropriate reference cases is needed to take account of such variations. 
Unsurprisingly, an evolving trend can be observed towards personalised healthcare, based on 
computer models that are robust for patient specific circumstances. The computer models 
effectively extend standard biomedical signal and imaging systems, when invasive measurements 
are not available, not preferred or not feasible. A crucial challenge to facilitate such extension is to 
appropriately relate features from observable biological scales to model parameters that accurately 
predict requested properties of other scales. 
The proposed project is part of the Virtual Physiological Human (VPH) framework3 that aims to 
investigate the human body as a single complex system. The VPH framework has already delivered 
extensive 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 is expected to dramatically alter health knowledge, thereby creating a new 
basis for research and opening new opportunities for healthcare provision. 
 
3 
 STEP Research Roadmap. Seeding the EuroPhysiome: A roadmap to the Virtual Physiological Human, Apr. 
2006. 

24 
 
The VIGOR++ project targets a valuable addition to the VPH framework by providing ICT tools for a 
personalised model of the Gastrointestinal (GI) tract. The models will enhance the understanding of 
inflammatory bowel diseases, in particular Crohn’s disease. The acronym of the project (VIGOR++) 
reflects the need of patients suffering from diseases of the GI tract to “be lively and active". The 
term also denotes the energy, capability, and dynamism of the consortium as a whole. It may be 
noticed that hardly any research focuses on the gastrointestinal tract in the context of the Virtual 
Physiological Human (VPH) objective, despite the large prevalence of diseases such as IBD4. 
Gastrointestinal Tract 
The GI tract (also called digestive tract or alimentary canal) is the system of organs that takes in 
food, digests it to extract energy and nutrients, and expels the remaining waste. A simplified 
illustration of the GI tract is given in Figure 1.  
 
The oesophagus is a long muscular tube, which moves food from the mouth to the stomach.  
 
The stomach, situated at the top of the abdomen, can hold up to about 1500 ml of food. In the 
stomach, acid and other digestive juices are added to the ingested food to facilitate breakdown of 
proteins, fats and complex carbohydrates into smaller, more absorbable units.  
 
A valve at the entrance to the stomach from the oesophagus allows the food to enter while 
withholding acid-laden food to "reflux" back into the oesophagus.  
 
The small intestine is about 4.5 to 6 metres in length and is where the majority of the absorption of 
the nutrients from food takes place. The small intestine is made up of three sections: the duodenum, 
the jejunum and the ileum.  
 
Another valve separates the small and large intestines to keep the bacteria-loaded colon content from 
re-enter the small intestine.  
 
In the large intestine, excess fluids are absorbed and firm stool is formed. The colon may absorb a 
limited amount of nutrients.  
GI diseases account for the highest number of bed days for surgical and endoscopic procedures in 
countries like England, which illustrates their importance.5 
 
4 According to EC briefings for ICT-2009.5.3a:P “The selection of proposals targeting clinical applications other 
than cancer and cardiovascular diseases will be given preference in case of proposals with tied scores at the 
evaluation stage”. 
5 Source OPCS-4 Intervention Classification Charter in England, 2000/01. 

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25 
 
 
Figure 1 Graphic representation of the GI tract. 
Application domain: Crohn’s Disease 
This project concerns the prediction and early diagnosis of a family of idiopathic and chronic 
conditions known as Inflammatory Bowel Diseases (IBD), in particular Crohn’s disease6. The high 
incidence and prevalence make that IBD are a huge healthcare problem in the Western world. In 
fact, over 1 million European citizens alone are affected, 700,000 of whom suffer from Crohn’s 
disease. IBD can begin at any age, but adolescents and young adults between the ages of 15 and 35 
are most susceptible. The condition affects both men and women equally. Current evidence suggests 
that both genetic and environmental factors contribute to the aetiology. IBD are characterized by an 
inflammation of the bowel wall due to an abnormal response in the body’s defence mechanism. 
Several types of IBD are distinguished by distinct genetic profiles, different clinicopathological 
features, including different locations affected within the GI tract, diverse histological patterns of 
inflammation and the relative importance of various symptoms such as abdominal cramps, 
diarrhoea, fever and weight loss. For instance, Crohn’s disease can affect any part of the GI tract 
from mouth to anus whereas ulcerative colitis, another common IBD, is confined to the colon. Also, 
Crohn’s disease may consist of patches of diseased and healthy tissue, whilst ulcerative colitis 
usually has a more uniform distribution. Crohn’s disease can also lead to the development of 
strictures where the diseased bowel becomes narrowed and to fistulae as a result of severe ulcers 
breaking through the bowel wall to form abnormal connections with other parts of the body such as 
the bladder or the skin. 
Crohn’s disease is characterized by a chronic relapsing and remitting course, i.e. periods of 
exacerbations are alternated by episodes of diminished disease activity. Accordingly, the mere 
 
6 
B. B. Crohn, L. Ginzburg, and G.D. Oppenheimer. Terminal ileitis, 83rd Annual Session of the American 
Medical Association, 1932. 

26 
 
presence of the disease must be distinguished from active disease, which can occur at varying levels 
of severity. The changes in disease activity are not necessarily correlated to changes in symptoms7. 
Exactly this complexity makes Crohn’s disease a challenging topic for a GI VPH project. 
Colonoscopy in combination with the assessment of biopsy samples is considered the reference 
standard for diagnosis of IBD. However, the procedure is invasive and requires extensive bowel 
preparation which is poorly tolerated by most patients. Also, the technique primarily gives 
information on superficial abnormalities (limited to direct visual inspection of the bowel lining or 
tissue samples from the inner bowel layers only), without much information on the intestinal wall or 
extra-intestinal disease, both of which are very important in Crohn’s disease. As a consequence, 
radiological imaging techniques have become important for evaluating disease activity in Crohn’s 
disease by providing information about the bowel lumen, bowel wall and extra enteric soft tissues 
(see section B1.2.1). 
Grading of Crohn’s disease severity is important to determine treatment strategy and to quantify the 
response to treatment. Ideally, an activity score should be objective, reproducible, quantifiable, non-
invasive and comprehensive. In clinical practice, this assessment can be made by the Crohn’s Disease 
Activity Index (CDAI)8, laboratory investigations and/or endoscopy (scored in Crohn’s Disease 
Endoscopic Index of Severity (CDEIS)9. However, none of these methods are infallible. The CDAI is a 
clinical index that incorporates subjective elements and therefore partly reflects patients’ perception 
of disease severity. Alternatively, blood markers can be unchanged in the presence of active 
disease10. The CDEIS score requires endoscopy, which is considered a very invasive procedure by 
most patients. Moreover, none of these indices include aspects of transmural and extra intestinal 
disease activity. Recently, D’Haens11 proposed a scoring system for histological abnormalities in 
biopsy specimens, but that measure focuses solely on microscopic aspects of Crohn’s disease. 
Table 1 summarizes the limitations for the described disease indices. The complex nature of Crohn’s 
disease hinders the development of an improved index. VIGOR++ aims to set a new standard by 
 
7 Cellier C, Sahmoud T, Froguel E, Adenis A, Belaiche J, Bretagne JF, Florent C, Bouvry M, Mary JY, Modigliani R. 
Correlations between clinical activity, endoscopic severity, and biological parameters in colonic or 
ileocolonic Crohn's disease. A prospective multicentre study of 121 cases. Gut. 1994;35(2):231-5. 
8 Best WR, Becktel JM, Singleton JW, Kern F, Jr. Development of a Crohn's disease activity index. National 
Cooperative Crohn's Disease Study. Gastroenterology 1976 Mar;70(3):439-44. 
9 Mary JY, Modigliani R. Development and validation of an endoscopic index of the severity for Crohn's disease: 
a prospective multicentre study. Groupe d'Etudes Therapeutiques des Affections Inflammatoires du Tube 
Digestif (GETAID). Gut 1989 Jul;30(7):983-9. 
10 Cellier C, Sahmoud T, Froguel E, Adenis A, Belaiche J, Bretagne JF, Florent C, Bouvry M, Mary JY, Modigliani R. 
Correlations between clinical activity, endoscopic severity, and biological parameters in colonic or 
ileocolonic Crohn's disease. A prospective multicentre study of 121 cases. The Groupe d'Etudes 
Therapeutiques des Affections Inflammatoires Digestives. Gut 1994 Feb;35(2):231-5. 
11 D'Haens GR, Geboes K, Peeters M, Baert F, Penninckx F, Rutgeerts P. Early lesions of recurrent Crohn's disease 
caused by infusion of intestinal contents in excluded ileum. Gastroenterology. 1998 Feb;114(2):262-7. 

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delivering a disease index that fulfils all the needs. A clever combination of existing image analysis 
and pattern recognition drives its development. 
Table 1 Synopsis of Crohn’s disease indices. 
Index\requirement: 
Objective 
Reproducible 
Quantifiable 
Noninvasive 
Comprehensive 
CDAI 
- 
+/- 
- 
+ 
- 
CDEIS 
+/- 
+ 
- 
-- 
- 
D’Haens 
+/- 
+ 
- 
-- 
- 
VIGOR++ 
+ 
+ 
+ 
+ 
+ 
S&T objectives 
The project lies squarely within the remit of the call for proposals by addressing the objective ICT-
2009.5.3 "Virtual Physiological Human" (VPH) in the ICT work programme 2009-2010.12 In particular 
it addresses the Target Outcome a) which states: 
Development of patient-specific computer based models and simulation of the physiology of 
human organs and pathologies. The models should be multiscale by integrating relevant aspects of 
anatomy and physiology across different levels (from molecular and cellular to tissue and organ 
levels). The emphasis should be on the integration of existing models rather than on development of 
new models. The use and benefits of the models must be demonstrated for a specific clinical need 
covering prediction of disease, prediction of treatment outcome and/or early diagnosis. Any organ 
or pathology could be targeted as clinical application. Access to existing computing facilities external 
to the consortium could be supported. 
The VIGOR++ project is about research and development of ICT tools for the analysis, modelling and 
simulation of human physiology and disease processes of the GI tract. It will use the ICT tools 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 
uniqueness of our approach is that it enables quantitative assessment of diseases of the GI tract. 
Consequently, it is expected that the tools will be very valuable to, for instance, pharmaceutical 
companies: clinical trials can be much more efficient by having accurate, quantitative descriptors of 
therapy effect and so reduce the high cost.  
Figure 2 graphically depicts the concept on which the project text builds. Crohn’s disease patients 
are the starting point as well as the end point of a working cycle. Multiscale data acquisition 
including laboratory, MRI, colonoscopy and microscopy data from these patients supports the 
development of 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 
 
12 ftp://ftp.cordis.europa.eu/pub/fp7/ict/docs/ict-wp-2009-10_en.pdf 

28 
 
management. The clinical benefit will demonstrated in a study in which the tools are assessed 
regarding the performance to predict Crohn’s disease status: application and validation. Moreover, a 
preliminary study will be performed in which the effect of therapy will be established. Ultimately, it 
is expected that the tools can be readily commercialized which we consider a crucial ingredient to 
dissemination. A more detailed description of the VIGOR++ concept is shown on Figure 4. VIGOR++ 
aims to predict features on the molecular to cellular scale (microscopy/colonoscopy) from 
descriptive properties at the organ to patient scales (MRI/laboratory). 
 
 
Figure 2 A top level description of the VIGOR++ concept. 
The vision of the project is 
VIGOR++ will create a ‘normal’ model of the GI tract that drives accurate detection and grading of 
Crohn’s disease, so that the management of the disease becomes personalized, patient friendly, and 
effective. 
Table 2 defines the key objectives of the project and what drives the consortium that we have 
assembled. No single country in Europe has the resources and competences required to attempt to 
satisfy this. It is here that the value of collaboration as part of the Framework Programme becomes 
directly relevant. 
Table 2 S&T objectives, challenges and tangible results for VIGOR++. 
S&TObjective 
Challenges addressed 
Tangible results 

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1. IMAGE ANALYSIS 
Adaptation of existing image 
analysis algorithms to accurately 
measure descriptive properties of GI 
wall tissue. 
What are the appropriate 
algorithms for accurate 
measurement of a wide variety of 
relevant features in multimodal 
images? 
A toolkit for analysis of all image 
data. 
Related Work Package: WP3 (MS4). 
2. MODELLING 
Creation of patient specific 
instruments to quantitatively assess 
the status of Crohn’s disease. 
How can we create a multiscale, 
‘normal’ representation of the 
gastro-intestinal tract, based upon 
which clinical decisions can be 
made? 
Can of-the-shelf pattern recognition 
techniques be adopted to sustain 
classification of disease severity? 
A multiscale, ‘normal’ 
representation of the GI tract to 
support detection of abnormalities. 
A tool to accurately detect and rate 
abnormalities in a quantitative 
manner. 
Related Work Package: WP4 (MS5). 
3. VISUALISATION 
Effective visualisation of the 
versatile aspects of the GI tract 
model. 
What are the appropriate 
visualisation techniques to depict 
the multiscale features of the GI 
tract? 
A computer model of the GI tract 
that allows easy inspection of 
descriptive features of Crohn’s 
disease. 
Related Work Package: WP5 (MS6).. 
4. SYSTEM ARCHITECTURE AND 
INTEGRATION 
Perform rigorous testing to truly 
guarantee that a clinically usable 
system is created. 
What are the limits regarding 
characteristics of the input data with 
which the system can cope? 
What are the characteristics of user 
friendly interfaces that help 
physicians navigate and inspect 
abnormalities by means of the 
designed tools? 
A clinically usable software 
environment in which all the 
developed ICT tools are 
appropriately integrated. 
Related Work Packages: WP6 (MS8, 
MS9). 
5. CLINICAL APPLICATION 
Establish a care pathway for 
accurate, non-invasive and cost-
effective examination of the GI tract 
for Crohn’s disease. 
Do the delivered ICT toolboxes 
sustain accurate assessment of 
Crohn’s disease?  
Can the efficacy and efficiency of 
treatment be improved by 
introducing ICT tools? 
Patient specific guidance 
recommendations for Crohn’s 
disease care, regarding normative 
scores, periodic monitoring and 
treatment. 
Related Work Packages: WP7 
(MS10). 

30 
 
6. KNOWLEDGE DISSEMINATION  
Disseminate generated knowledge 
and ICT tools by actively engaging 
fellow academic disciplines, industry 
and IBD patient associations across 
Europe. 
Identify opportunities for 
commercial exploitation of 
developed technology. 
How can the results be 
communicated to create awareness 
among the different technical and 
clinical audiences but also the 
patients? 
How can the developed techniques 
be commercially exploited and 
create successful usable systems? 
High quality publications. 
Trained computer scientists and 
clinicians. 
Protected intellectual property. 
Foundations of exploitation plans 
for commercially promising 
products. 
Related Work Package: WP8 (MS12). 
Table 3 Advancing State of the art in VIGOR++ 
S/T Objective 
State-of-the-art 
VIGOR++ 
Adaptation of existing image 
analysis algorithms to accurately 
measure descriptive properties of GI 
wall tissue. 
Image analysis techniques are 
widely available for all sorts of 
measurement tasks.  
Dedicated image analysis algorithms 
for feature extraction. The features 
on which we focus are described in 
Table 5. 
Related Work Package: WP3 (MS4). 
Creation of patient specific 
instruments to quantitatively assess 
the status of Crohn’s disease. 
There are established techniques to 
statistically model normal variations 
in data and to recognize certain 
patterns. We know of no application 
to IBD. 
VIGOR++ will render a multiscale, 
normal representation of the GI 
tract upon which abnormality can be 
established and objectively 
assessed. Moreover, numerical 
modelling of disease severity is 
facilitated. 
Related Work Package: WP4 (MS5). 
Effective visualisation of the 
versatile aspects of the GI tract 
model. 
Existing techniques based on 
volume rendering are not suited for 
MRI data. 
The field of multiscale visualisation 
is still in its infancy. 
Dedicated visualisation algorithms 
for diagnosis and treatment 
planning of GI diseases focused on 
Crohn’s disease. 
Related Work Package: WP5 (MS6).. 

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Perform rigorous testing to 
guarantee that a clinically usable 
system is created. 
There are no clinically usable 
systems whatsoever to 
quantitatively assess IBD. 
An intuitive, clinically applicable 
system. 
Related Work Package: WP6 
(MS8,MS9). 
Establish a new care pathway for 
accurate, non-invasive and cost-
effective examination of the GI tract 
for Crohn’s disease. 
Currently employed diagnostic 
techniques for GI disorders are 
either not accurate or very invasive. 
Early attempts were made by the 
clinical partners to develop new 
tools for assessment of Crohn’s 
disease, but a complete, 
quantitative model was never 
involved. 
VIGOR++ will establish quantitative 
techniques for diagnosis and 
management of patients with 
Crohn’s disease. Increased quality of 
life is facilitated by early prediction 
of disease, more accurate, non-
invasive diagnosis techniques and 
instruments to measure the effect 
of treatment. 
Related Work Package: WP7 (MS10). 
Disseminate generated knowledge 
and ICT tools by actively engaging 
fellow academic disciplines, industry 
and IBD patient associations across 
Europe. 
Identify opportunities for 
commercial exploitation of 
developed technology. 
Currently, there are no quantitative 
techniques for assessment of IBD. 
VIGOR++ will deliver tools for 
objective analysis of Crohn’s 
disease. We expect a large interest 
in those tools by many parties.  
Widespread application is foreseen, 
e.g. pharmaceutical industry will be 
interested for efficiently conducting 
trials of GI medication. 
Related Work Package: WP8 (MS12). 
Progress beyond the state of the art  
Table 3 summarises the advances that VIGOR++ would bring about and in the subsequent sections 
we provide more details about the state-of-the-art and the advances proposed. Initially, we will go 
into methods for assessment of gastrointestinal diseases in order to accurately identify the clinical 
benefits that VIGOR++ must deliver (B1.2.1). Thereafter, state-of-the-art ICT tools for modelling the 
GI tract are described, so that the advantages to be gained over traditional techniques and main 
innovations are made explicit (B1.2.2). 
State-of the-art in diagnostic procedures for the GI tract 
Assessment of GI diseases conventionally consists of a careful review of a patient’s history, 
laboratory tests, supplementary diagnostic imaging procedures and histopathology.  

32 
 
At present cross sectional imaging techniques (CT, scintigraphy, ultrasonography, MRI and 
scintigraphy) are routine techniques to assess disease activity in IBD. These methods are replacing 
conventional barium methods (Barium meal/follow through, enteroclysis, Barium enema). The role 
of the video capsule is not sufficiently established yet, but availability, costs and other limitations 
curtail its present use. A synopsis and comparative analysis of imaging techniques for IBD is provided 
in Table 4: 
 
 

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33 
 
Table 4 Synopsis of imaging techniques for IBD. 
Invasiveness 
Radiation 
burden 
Spatial 
resolution 
Bowel 
surface 
visualisation 
Bowel wall 
visualisation 
IBD diagnosis 
sensitivity 
Laboratory tests 
Low 
None 
None 
None 
None 
Medium 
Barium meal/follow 
through 
Low 
High 
Good 
Medium 
Low 
Low 
Enteroclysis 
High 
High 
Good 
Good 
Low 
Medium 
Barium enema 
High 
High 
Good 
Good 
Low 
Low 
Ultrasound 
None 
None 
Low to good Medium 
Moderate 
Medium to 
high 
Scintigraphy* 
Medium 
Medium 
Low 
None 
None 
Medium to 
high* 
CT enteroclysis 
High 
Very high 
Good 
Medium 
Good 
High 
CT enterography 
(without enteroclysis) 
None 
Very high 
Good 
Medium 
Good 
High 
MRI with enteroclysis High 
Low** 
Good 
Good 
Good 
High 
MRI enterography 
(without enteroclysis) 
None 
None 
Good 
Good 
Good 
High 
Camera Pill*** 
Low 
None 
Good 
Medium 
None 
Not 
established 
Optical Colonoscopy 
Very High 
None 
Very good 
Very good 
None 
High 
Histopathology 
High 
None 
Very good 
None 
Good 
High 
* Only studied in moderate to severe disease. 
** Only ionising radiation during positioning of the nasojejunal tube. 
*** No systematic investigation. 
A systematic review or meta-analysis is considered the best available method for summarising the 
evidence on a certain topic. Systematic reviews involve searching for all relevant evidence, selecting, 
critically appraising, and quantitatively summarizing reported outcomes. Systematic reviews are 
accepted as the most reliable way by which large volume of research evidence can be managed. 

34 
 
The medical literature on imaging in IBD has recently been studied in detail by one of the partners13. 
This analysis included 33 studies selected from a search resulting in 1406 articles on CT, scintigraphy, 
ultrasound, and magnetic resonance imaging. The outcome from endoscopy, barium enteroclysis or 
small bowel follow-through, surgery and/or histopathology was accepted as the reference standard. 
Mean sensitivity estimates for the diagnosis of IBD on a per-patient basis were high and did not 
show significant differences between imaging modalities (89.7% for US, 93.0% for MRI, 87.8% for 
scintigraphy, and 84.3% for CT, respectively). Mean specificity estimates were 95.6% for US, 92.8% 
for MRI, 84.5% for scintigraphy and 95.1% for CT respectively; the only significant difference was 
observed between scintigraphy and US (p=0.009). 
The meta-analysis indicates that there were no large differences observed between imaging 
techniques in terms of sensitivity or specificity. Importantly, a method abstaining from ionising 
radiation is preferred. Moreover, MRI is preferred over ultrasound because ultrasound has a high 
observer dependency. Also, it is difficult to quantify ultrasound findings (especially important in 
evaluating treatment response). MRI is established as the most diagnostically accurate modality in 
many soft tissue organ systems. However, until recently its role in diseases of the small and large 
bowel was still developing largely due to technical shortcomings leading to longer procedure times 
with mediocre image quality. Recent technological developments in MRI (higher magnetic field, new 
acquisition protocols and coils) have overcome these limitations, resulting in an accurate non-
invasive small and large bowel examination technique without radiation exposure.14 
 
Figure 3 Images of one patient with Crohn’s disease: (a) T2 weighted image showing the distension of the ileum 
(white); (b,c) T1 weighted images prior to and after contrast injection; the enhancement in the area of 
increased wall thickening indicates active disease. 
The VIGOR++ project focuses on GI tract modelling on the basis of MRI facilitating a minimally 
invasive, safe and potentially more accurate approach. Ultimately, it is our objective to accurately 
predict the colonoscopy and histopathology data and the associated indices of disease severity (e.g. 
 
13 Horsthuis K, Bipat S, Bennink R, Stoker J. Ultrasonography, Magnetic Resonance Imaging, Scintigraphy, and 
Computed Tomography for diagnosis of inflammatory bowel disease: a meta-analysis of prospective studies. 
Radiology 2008; 247:64–79. 
14 Gourtsoyiannis N, Papanikolaou N, Grammatikakis J, Maris T, Prassopoulos P. MR imaging of the small bowel 
with a true-FISP sequence after enteroclysis with water solution. Invest Radiol 2000;35:707-711. 
 
 
 

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CDEIS, d’Haens score). This would render the current methods redundant, which is preferred given 
their invasiveness. Part of the development comprises the creation of a normal representation of 
the GI tract, as well as ICT tools to detect and rate deviations from normality. VIGOR++ will acquire 
laboratory, MRI, colonoscopy and microscopy (histopathology) data in order to develop the required 
ICT tools. Importantly, the colonoscopy and the histopathology data serve for the development of 
accurate prediction models, but the goal is to predict them from the other modalities (see Figure 4). 
` 
 
Figure 4 A detailed description of the VIGOR++ concept. 
State of-the-art in ICT tools for modelling the GI tract 
In the last 15 years, significant efforts have been made to build numerical patient models from 
multimodal images for surgical planning and image-guided surgery. The components on which the 
VIGOR++ project will make S&T contributions in relation to the state of the art are described below.  
Image analysis 
There is a wealth of techniques available in the literature on medical image analysis. Much research 
was conducted in the context of CT colonography (CTC). This relatively new technique concerns CT 

36 
 
imaging of the colon for the detection of colorectal cancer/polyps. Image analysis algorithms were 
created to register the scans made of a patient in prone and supine positions15.  However, research 
has particularly focussed on the so-called electronic cleansing of CT images, i.e. automated detection 
of faecal residue in the intestines. Electronic cleansing relies on the patient taking a contrast agent 
that “highlights” the residue, which may subsequently be detected by means of thresholding. More 
elaborate techniques were also proposed to cope with noise and contrast non-homogeneity16. All 
this colon segmentation work mainly focused on the inner surface of the colon wall (the lumen-
mucosal boundary). Outer wall segmentation from CT images remains an unsolved problem, due to 
the low contrast between attenuation values of the colon wall and the surrounding fat tissue.  
VIGOR++ will employ MRI to produce robust tissue discrimination and to quantify the features of 
Crohn’s disease. Automated measurement of such features in MRI images has not been investigated, 
to the best of our knowledge. Signal fluctuations in MRI emanate both from global (bias field) as well 
as local effects (non-homogeneities in bowel content) and this variation in signal value may preclude 
simple approaches (e.g. thresholding) for MRI data. Fortunately, sophisticated methods are available 
cope with those variations, which will be adopted in WP3 (see below). 
Radiologists assessing MRI data of patients suffering from Crohn’s disease typically look for signs of 
local bowel wall thickening17 (see above). The MRI findings of bowel wall thickening are analyzed 
and classified into several types based on the mural signal patterns18. Moreover, the dynamic 
response of the tissue to the inflow of blood is studied since a marked increase in signal intensity of 
actively diseased bowel results from enhanced perfusion and vascular permeability in inflammatory 
tissue19. 
All these aspects will be contained in properties measured on the candidate lesions for Crohn’s 
disease. 
 
15 P. Li, S. Napel,B. Acar, D.S. Paik, R.B. Jeffrey Jr.and C.F. Beaulieu, ”Registration of central paths and colonic 
polyps between supine and prone scans in computed tomography colonography: Pilot study” MED PHYS, 
31 (10): 2912-2923 Oct 2004. 
16 Serlie IWO, Vos FM, Truyen R, Post FH, van Vliet LJ. Classifying CT image data into material fractions by a scale 
and rotation invariant edge model. IEEE Trans Image Process. 2007;16(12):2981–2904.  
 
Serlie IWO, de Vries AH, , Nio Y, Truyen R, Stoker J, van Vliet LJ and Vos FM. Lesion conspicuity and efficiency 
of CT colonography with electronic cleansing based on a three-material transition model. AJR Am J 
Roentgenol. 2008;191(11): 1493-1502. 
17 Low RN, Sebrechts CP, Politoske DA, Bennett MT, Flores S, Snyder RJ, Pressman JH. Crohn disease with 
endoscopic correlation: single-shot fast spin-echo and gadolinium-enhanced fat-suppressed spoiled 
gradient-echo MR imaging. Radiology. 2002;222(3):652-60. 
18 Choi D, Jin LS, Ah CY, Lim HK, Hoon KS, Jae LW, Hoon LJ, Park H, Rae LY. Bowel wall thickening in patients with 
Crohn's disease: CT patterns and correlation with inflammatory activity. Clin Radiol. 2003;58(1):68-74. 
19 Brahme F, Lindstrom C. A comparative radiographic and pathological study of intestinal vaso-architecture in 
Crohn's disease and in ulcerative colitis. Gut. 1970;11(11):928-40. 

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We intend to extract morphological (shape), textural (stratification) and structural 
(vascularisation) features and use a combination of these features for the detection of 
abnormalities. In particular the following features will be examined (Table 5): 
Table 5 Example features to be examined in the project. 
Morphological 
Morphology of lumen (diameter, curvature), morphology of wall 
(average thickness, curvature), granularity of wall surface. 
Textural 
Layer detection, presence of fat, oedema, haemorrhage in wall and 
around wall. 
Structural 
Absolute wall enhancement and enhancement pattern in dynamic 
contrast enhanced MRI, lymph node enhancements. 
Modelling 
Automatic detection and classification of abnormalities from medical images by machine learning 
has received much attention. However, regarding the gastrointestinal tract such computer aided 
detection is limited to recognition of polyps/colorectal cancer in CT colonography. The most 
successful techniques20 are based on local shape features, particularly the local shape index and 
curvedness, which are computed after segmentation of the colon surface. Although very good 
results were obtained, these techniques still often fail to differentiate between polyps and residual 
material. Moreover, they rely on accurate segmentation of the colon surface, which is not always 
feasible, especially if there is much faecal remains (particularly in patients that did not take laxatives, 
which is preferred for patient compliance). 
The use of dynamic contrast enhanced (DCE) MRI has been advocated by an increasing number of 
investigators studying physiological processes in the human body. Quantification of DCE MRI data by 
means of pharmacokinetic models, proposed initially by Tofts and Brix 21, aims at calculating 
absolute measures that are directly related to the tissue physiology such as vessel permeability, 
blood flow, blood transit time through a tissue and extracellular volumes. Unfortunately, such 
compartmental analysis suffers from wide variability in output, which is a consequence of the large 
variety of models used 22. 
An alternative and potentially more robust method is to study the uptake curve shape and to relate 
this to pathological findings. This approach is based on the utility of qualitative observations of the 
 
20 Z. Wang, A. Liang, L. Li, X. Li, B. Li, J. Anderson, D. Harrington, Reduction of false positives by internal features 
for polyp detection in CT-based virtual colonoscopy, Medical Physics, 32: 3602-3615, 2005. 
21 Tofts PS, Brix G, Buckley DL, Evelhoch JL, Henderson E and Knopp MV. Estimating kinetic parameters from 
dynamic contrast enhanced T1-w MRI of a diffusible tracer: standardized quantities and symbols. J Magn 
Reson Imaging 1999; 10(3): 223–232. 
22Harrer JU, Parker GJ, Haroon HA, Buckley DL, Embelton K and Roberts C. Comparative study of methods for 
determining vascular permeability and blood volume in human gliomas. J Magn Reson Imaging 2004; 20(5): 
748–757. 

38 
 
time–intensity curves (TIC) generated from ROI’s chosen in lesions by radiologists 23. Moreover, it is 
confirmed by the simulations in Tofts et al.24, that data from curve shape analysis reflect 
physiological parameters (e.g., the capillary permeability). 
We propose to use techniques from statistical pattern recognition in order to define an objective 
score of Crohn’s disease severity in WP4. 
Initially, a statistical model will be created that mathematically describes the normal variation in the 
features emanating from patients without active disease. Subsequently, we intend to ‘train’ a curve 
shape classifier on manually annotated data to remove the dependency on arbitrary MRI parameter 
settings. Alternatively, unsupervised techniques, i.e. both principal and independent component 
analysis will be employed to analyse the prevailing curves shapes. This exploration will enable 
objective measurement e.g. the prevalence of certain curves shapes in different disease states, that 
will add to the features described initially (such as wall thickness and stratification pattern). 
The combination of multiple imaging features within a classification framework25 is expected to 
sustain classification accuracy levels similar to those achieved by trained professionals. A further 
novel direction in VIGOR++ will be to investigate combining MR data and laboratory data for more 
reliable and precise diagnostic performance. The combination of imaging and clinical biomarkers of 
disease activity will draw on the strengths of both methodologies and it is anticipated will add to the 
robustness of any predictive model.  The design of a classifier for quantifying Crohn’s disease 
severity will be treated as a regression problem rather than a traditional classification task. In other 
words, a weighted probability density function is fit to the feature data in which the weights derive 
from clinical indices of Crohn’s disease activity (CDEIS, CDAI). 
Interactive visualisation 
A major challenge will be to develop new methods, which allow the examination of GI wall tissue. 
Conventional volume rendering techniques are applied in CT colonography to visualise the colon’s 
inner surface. The current project requires the depiction of multiscale, spatially diverse data. 
Consequently, novel ways of mapping the data to create an intuitive visual representation are 
needed. The difficulty to do so particularly lies in depicting clinically important features while 
mapping onto a two-dimensional display. 
 
23 
van Rijswijk CSP, Geirnaerdt MJA, Taminiau AHM, van Coevorden F, Zwinderman AH and Pope TL. Soft-tissue 
tumours: value of static and dynamic gadopentate dimeglumine-enhanced MR imaging in prediction of 
malignancy. Radiology 2004, 233293–233502. 
24Tofts PS, Berkowitz B and Schnall MD. Quantitative analysis of dynamic Gd-DTPA enhancement in breast 
tumours using a permeability model. Magn Reson Med 1995; 33(4): 564–568. 
25 G. T. Papadopoulos, V. Mezaris, I. Kompatsiaris and M. G. Strintzis: "Combining Global and Local Information 
for Knowledge-Assisted Image Analysis and Classification", EURASIP Journal on Advances in Signal 
Processing, Special Issue on Knowledge-Assisted Media Analysis for Interactive Multimedia Applications, 
vol. 2007 (2007), Article ID 45842.   

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A potential solution to this problem is the concept of importance-driven visualisation26, which has 
been successfully employed for the combined visualisation of multi-modal data27. Such an approach 
involves an ordering of features according to a measure of ‘importance’. Automatically, a region 
containing less important features is depicted by means of a less detailed visual representation 
and/or displaced in order to provide an unobstructed view of a more important region. The ordering 
to importance will be derived from the classifier to be developed (WP4). The importance 
information will also be used to guide so-called unfolding techniques to minimize distortions in 
important areas while allowing for more relaxed conditions in ‘contextual’ regions.  
Clinicians must accurately interpret and integrate findings in order to achieve diagnostic certainty. It 
is important that uncertainties in the data are made visible. For this recently developed methods28 
29 will be adapted and extended. Clearly, the goal is to create an integrated visualisation framework 
which allows intuitive study of the all available information in a unified manner. Techniques for 
visualising complex anatomies30 and physiological data in complex anatomies31 have been studied 
previously, but a comprehensive solution for the domain addressed here that meets the current 
clinical demand is certainly not available yet. We hypothesize that the proposed research in this 
direction offers the prospect of significant progress beyond the state-of-the-art.  
Importantly, the consortium regards patient education an obligation that may not be discarded. It is 
expected that patient education will be supported by the developed visualisation techniques. 
Patient education is becoming an increasingly important aspect of medical care. Illustrations can be 
a valuable aid in explaining diagnoses and treatments.32 Recent progress33 in the area of illustrative 
visualisation seeks to reproduce the expressiveness and comprehensibility of traditional illustrations 
 
26 I. Viola, A. Kanitsar, M. E. Gröller. Importance-Driven Feature Enhancement in Volume Visualisation. IEEE 
Transactions on Visualisation and Computer Graphics, 11(4):408-418, Jul. 2005. 
27 M. Burns, M. Haidacher, W. Wein, I. Viola, M. E. Gröller. Feature Emphasis and Contextual Cutaways for 
Multimodal Medical Visualisation. In Proceedings of EuroVis, pp. 275-282, May 2007. 
28 K. Pöthkow and H.-C. Hege, Uncertain Iso-contours, accepted with minor revision for IEEE Trans Visual 
Comput Graph; available under www.zib.de:/hege/iso_uncertainty.pdf 
29 M. Otto, T. Germer, H.-C. Hege, H. Theisel, Uncertain 2D Vector Field Topology, to appear in Comput Graph 
Forum, May 2010, available under www.zib.de/hege/ uncertain_vectorfield_topology.pdf 
30  A. Kuß, S. Prohaska, B. Meyer, J. Rybak, H.-C. Hege: Ontology-Based Visualisation of Hierarchical 
Neuroanatomical Structures, Visual Computing for Biomedicine VCBM 2008, Eurographics, pp. 177-184, 
October 2008 
31 S. Zachow, P. Muigg, T. Hildebrandt, H. Doleisch, and H.-C. Hege, Visual Analysis of Nasal Air Flow, IEEE Trans. 
Vis. Comput. Graph., 15:6 (2009), pp. 1407-1414. 
32 P. S. Houtsa, C. C. Doakb, L. G. Doakb, M. J. Loscalzoc. The role of pictures in improving health communication: 
A review of research on attention, comprehension, recall, and adherence. Patient Education and 
Counseling, 61(3): 173-190, May 2006. 
33 S. Bruckner, M. E. Gröller. VolumeShop: An Interactive System for Direct Volume Illustration. In Proceedings 
of IEEE Visualisation, pp. 671-678. Oct. 2005. 

40 
 
using advanced visualisation techniques. Perceptually effective visualisation techniques as well as 
methods to evaluate their effectiveness34 and will support this development. Such an approach 
makes it feasible to generate patient-specific depictions of particular pathologies which are easy to 
understand for laymen. Similar techniques may also be used to aid medical education and 
communication.35 
Advantages over traditional techniques and main innovations 
The primary objective of VIGOR++ is to deliver ICT tools for modelling GI tract physiology as well as 
disease processes. Our research focuses on aspects for which current diagnostic techniques provide 
no or very limited value: 
 
An appropriate indication of the extent of disease is currently not available. Colonoscopy sustains 
visualisation of the bowel wall mucosa thereby only allowing identification of superficial disease. 
Importantly, MRI visualises all bowel wall layers, enabling transmural assessment, including 
submucosa, muscularis mucosae, serosa. 
 
Similarly, the extent of extraluminal disease is not visualised, such as fistulas, abscesses and their 
spatial relation to normal anatomy, which is important for surgical planning.  
 
Inspection of the bowel proximally of a stenosis, which is impossible by means of colonosocopy. MRI 
facilitates robust assessment of the complete bowel, such as presence of prestenotic dilatation and 
length of the stenosis which impact directly on therapeutic strategy. 
 
A reference standard to quantitatively assess patient specific findings is currently lacking. 
 
Quantifying disease activity is not sustained, which is of utmost importance, however, for clinical 
management and for monitoring pharmacological studies. 
The VIGOR++ tools comprise patient-specific computer models for personalised and predictive 
healthcare. The novel results of the project include: 
1. An improved care pathway for Crohn’s disease that will increase accuracy and efficiency of 
diagnosis, whilst minimising cost and enhancing well-being of patients. 
2. Adoption of existing image processing algorithms for segmentation of and feature extraction from 
MRI datasets of Crohn’s patients. 
3. Creation of a multiscale normal representation of the GI tract. 
4. Automatically detection and quantification of abnormalities in the GI tract 
5. Novel visualisation algorithms and user interfaces  
 
34 A. Kuß, M. Gensel, B. Meyer, V. J. Dercksen, and S. Prohaska, Effective Techniques to Visualize Filament-
Surface Relationships, Comput. Graph. Forum. 10 pp., to appear June 2010, available at www.zib.de/hege/… 
35 F. Ritter, C. Hansen, V. Dicken, O. Konrad-Verse, B. Preim, H.-O. Peitgen: Real-Time Illustration of Vascular 
Structures. IEEE Transactions on Visualisation and Computer Graphics. 12(5): 877-884, Sep. 2006. 

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6. Techniques to assist doctors for accurate risk assessment and Crohn’s disease management. 
S/T Methodology and associated work plan 
1.3.1 Overall strategy and general description  
Work plan strategy 
The VIGOR++ work plan defines the execution of activities for the three-year duration of the project. 
It comprises management and exploitation work packages (WPs) that will act in concordance with 
technical work packages. The work plan comprises two main iterations. The first one is about the 
prototype development (M1-M22) and the second left for fine tuning (M23-36), see Figure 6. 
The work-plan has been broken down according to the following activities:  
WP1: Management 
WP1 will oversee the smooth running of the VIGOR++ project, ensure that the project objectives are 
met, take care that all deliverables are presented to the commission on time and, if necessary, 
corrective actions are made. The management framework is detailed in Section 2.1 of this project. 
WP2 Clinical Data Acquisition and Data Management 
WP2 will acquire and annotate clinical data from Crohn’s disease patients at several biological scales: 
laboratory, MRI, colonoscopy, microscopy (histopathology) data. The MRI acquisition method will be 
fine-tuned, liaising with other WPs (particularly WP3, WP4 and WP5). Moreover, a combined, clinical 
disease severity index will be defined that integrates existing disease indices. 
WP3 Image analysis 
WP3 combines existing image analysis techniques to identify regions of interest and register the MR 
images to compensate for patient movement. Moreover, descriptive properties of Crohn’s disease 
activity will be measured in both the MR and the microscopy images. The features thus obtained are 
at the basis of the classification task in WP4. 
WP4 Modelling and classification 
WP4 will develop a patient specific instrument to quantitatively assess the status of IBD disease. Of-
the-shelf pattern recognition techniques will be adopted to sustain the classification of the disease 
properties measured in WP3.  It will deliver a tool to detect and rate abnormalities, so that the 
combined, clinical disease severity index created in WP2 can be accurately predicted in quantitative 
manner.  
WP5 Interactive Visualisation 
WP5 will develop a visualisation software toolbox to enable interactive visualisation of GI wall tissue 
properties. The software package will feature established techniques for concurrent visualisation of 
the multiscale multiscale clinical patient data as well as the mathematical properties measured by 
WP3 and the classification delivered by WP4. 

42 
 
WP6 System Architecture and Integration 
WP6 establishes the overall system architecture and provides a clinically usable software 
environment in which all the developed ICT tools will be integrated. Moreover, care will be taken 
that developed system units are continuously tested, so that progress is monitored and proper 
integration across the WPs is ensured. 
WP7 Clinical Application and Validation 
WP7 evaluates the accuracy of all developed analysis, modelling and visualisation techniques and 
serves to demonstrate their clinical benefit. Specifically, the tools for assessing the patient’s disease 
status will be clinically validated, after which the techniques shall be clinically used to quantify the 
effect of therapy.  
WP8: Dissemination, Exploitation and New Applications 
WP8 provides the interface between the project and the outside world including academic, clinical, 
industrial communities, but particularly also the population of patients suffering from Crohn’s 
disease. A dissemination strategy was designed to ensure high visibility of developed ICT tools in the 
European and International arenas and support the translation of the project’s findings into 
successful products and services. 
The components showing their interdependencies 
The interaction among the work packages is depicted Figure 5. The main box distinguishes the 
technical WPs that will be performing the R&D tasks. Central to that are the work packages that 
generate quantitative, measurable features (WP3); classifiers weighting their relative importance 
and integrating them in measures of disease severity (WP4); and a GI tract normal representation 
and techniques for its visualisation (WP5). All development will be performed using data acquired 
and annotated by WP2. WP6 interacts with the three technical WPs (WP3, 4 and 5) to formulate and 
reinforce the overall system architecture. The validity of developed techniques will be clinically 
tested by WP7. The aforementioned work packages are interacting with the management (WP1) and 
dissemination/exploitation (WP8) work packages to ensure a consistent and effective delivery of the 
work plan. 

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Figure 5 Interactions among the WPs in VIGOR++. 
ICT details regarding system architecture and data integration 
The VIGOR++ tools will be integrated in the 3Dnet™ Suite36 environment that has been developed 
and commercialised by B3D. 3Dnet™ Suite is an open platform for medical image post processing. It 
represents the latest trends in the ICT market as it is deployed following a paradigm called Platform 
as a Service (PaaS); the whole delivery mechanism is online, via an advanced and innovative online 
scripting language dedicated to medical imaging. The platform is a collaborative framework for open 
innovation, available to academic and commercial developers for application designers to use 
existing tools (e.g. for data reading, filtering and standard visualisation), or add their own to create 
 
36 http://www.3dnetsuite.com 

44 
 
new applications. Hence, by making the new tools resulting from VIGOR++ available to the existing 
community of 3Dnet™ Suite developers the project will stimulate faster adoption.  
Risk analysis and associated contingency plans 
The main risks for a research project such as VIGOR++ relate to technological and clinical facets. 
Partner problems and agreement risks are not considered potential threats since there is strong 
agreement on the objectives and work description among the partners. This stems from the strong 
collaboration that already exists between several partners. We feel that the small size of the 
consortium gives the advantage of quick decisions and relatively easily aligned drive in the project. 
The project plans to actively maintain a risk assessment table so that the Steering Committee 
(Section B2.1) can take appropriate actions as soon as a potential threat seems to become reality. 
The risk analysis matrix is given in Table 6. 
Table 6 Risk analysis for the VIGOR++ project. 
Category Code 
Description 
Tasks 
involved 
Probability 
1-10 
Severity 1
-10 
Milestone 
concerned 
Contingency plan 
Internal Risks 
Clinical 
R.I.1 Inappropriate 
data acquisition 
(insufficient or 
incomplete). 
T2.1,2,4  1 
5 
MS2 and 
MS3 
Continued development 
based on existing data for 
which ethical approval was 
already obtained in other 
projects. 
Technical 
R.I.2 Performance 
requirements on 
ICT tools not 
met. 
Variable 
(mainly 
WP3-5) 
2 
4 
MS4, MS5 
and MS6 
Ensure enhanced 
performance facilitated by 
means of user interaction. 
Technical 
R.I.3 Not enough level 
of integration 
or/and 
incompatibility 
between 
components. 
Variable 
(mainly 
WP6) 
1 
6 
MS9 
Initial partial integration 
complemented by analysis, 
plans and implementation of 
complete integration within 
the defined architecture 
supervised by WP6. 
Managemen
t 
R.I.4 Partner under 
performing or 
leaving the 
project. 
Variable 2 
4 
Variable 
Enforced completion of 
current responsibilities. 
Involve project officer and 
AC. In the short term divide 
the work among other 
partners, and in the long 
term, replace partner. 

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45 
 
Managemen
t 
R.I.5 Lack of 
appropriate 
commitment of 
participants (e.g. 
delays in 
deliverables). 
Variable 3 
6 
Variable 
WP1 will call attention to the 
responsibilities of the 
partners and ensure that 
appropriate actions are 
taken. 
Managemen
t 
R.I.6 Ineffective 
dissemination 
and exploitation. 
Variable 2 
3 
MS11 and 
MS12 
Coordinated action by the 
WP-leader to encourage 
attention to the collaborative 
project ambitions. Intensified 
dissemination activities. 
Ensure that consensus is 
present about exploitation 
routes. 
 
External Risks 
External 
R.E.1 Dramatic change 
in user 
requirements 
Variable 1 
7 
Variable 
Careful assessment of user 
needs by WP6 and 7 
involving the Interest Group. 
Adaptation of the project’s 
requirements of ICT tools.  
External 
R.E.2 Changes in the 
regulatory 
framework 
Variable 
(mainly 
WP2,7) 
1 
6 
MS2,MS3 
and MS10 
Systematic handling of 
ethical and legal issues 
throughout the project by all 
WP’s. 
External 
R.E.3 Competition 
risks 
Variable 3 
2 
Variable 
A meticulous assessment of 
the current state of 
knowledge as well as the 
markets throughout the 
project. 
Timing of work packages and their components 
The tasks are visualised in Figure 6 as part of a Gantt chart. M22 marks the completion of the first 
iteration of the project. The prototype tools will be subsequently clinically tested and fine tuned. The 
technical WPs (WP3-5) are front-end loaded. The same applies for the data acquisition WP (WP2). 
The intensity of tasks in the integration (WP6) and clinical (WP7) is slightly higher towards the 
second part of the project. Finally, the management (WP1) and dissemination/exploitation (WP8) 
are balanced reflecting an even distribution over project’s lifetime. 

46 
 
 
Figure 6 Gantt chart depicting the tasks of each work package during the project. M22 denotes the completion 
of the first iteration. All work packages start at M1 and finish at M36. 
 
 

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Implementation 
Management structure and procedures 
The management structure of the VIGOR++ project is designed to be simple, flexible, democratic and 
efficient in achieving its aims. In fact, it must ensure that all the consortium members work together 
as a team to undertake an efficient and effective research programme. The management 
organisation is lean, consisting of a three-layered structure involving a clear assignment of 
responsibilities at each level (Figure 7 ): 
 
The work packages  
 
The Steering Committee 
 
The EC 
These three levels will operate during the project’s lifetime. The coordinator (TU Delft) is responsible 
for supervising all communication flows between the levels. Decision making is done at all levels. At 
level one the communication and decision making is done at WP level by WP participants and the 
WP leader. At level two, the Steering Committee (SC) is the decision making body, gathering 
representatives of all parties including the coordinator. At level three the communication and 
decision making is done between Coordinator (representing the SC) and the EC. 
 
Figure 7: The project management structure. 
The management structure layers 
Work packages 
The individual consortium partners are responsible for executing the tasks as described in this 
description of work. The coordinator will play a supportive role, maintaining a project-wide 
overview, promoting synergy, identifying possible inconsistencies and generally overseeing 
implementation. The coordinator is supported in his work by Work Package Leaders who are 
(a) 
(b) 
(c) 
 
…. 
 
B3D 
 
 
AMC 
 
 
EU 
i
i
 
Ad

48 
 
responsible for workflow, coordination and progress of research and development activities and 
specific project results of the work package, including the contained tasks.  
The work package leaders will report to the coordinator every six months for the purpose of efficient 
monitoring of the progress of the project. Although the consortium partners individually are 
contractors with the Commission and bound to the Grant Agreement, they also sign a consortium 
agreement, laying down the rules and obligations to each other. Financial risks such as a bankruptcy 
of SME contractors in FP projects are covered by a guarantee fund of the Commission, with which 
the previously collective financial responsibility of partners has been taking over by the Commission. 
The responsible personnel for the WPs are listed in Table 7. 
Table 7 Steering committee 
Work package 
 
Allocated to: 
WP1 (Coordinator) 
Dr. F.M. Vos (TUD) 
WP2  
Prof.dr. S.A. Taylor (UCLH) 
WP3 
Prof.dr.ir. L.J. van Vliet (TUD) 
WP4 
Prof.dr. J. Buhman (ETHZ) 
WP5 
Prof. dr. H.C. Hege (ZIB) 
WP6 
Dr. H. Hatzakis (B3D) 
WP7 
Prof.dr. J. Stoker (AMC) 
WP8 
Dr C. Kompis (VOD) 
Steering committee  
The Steering Committee (SC) consists of one representative of each consortium partner (see table) 
and is chaired by the coordinator. The SC takes the following types of decisions:  
 
Decisions related to the entry of new participants, the exit of existing ones and major shifts in tasks  
 
After quality assurance (QA) check of technical coordinator, decision to accept/reject deliverables  
 
Other decisions related to alterations in contract and budget  
 
Planned publications and other dissemination actions  
 
IPR issues 
 
Conflict resolution as detailed in the consortium agreement  
 
All other decisions affecting the project as a whole  

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Decisions can only be taken by means of a simple majority provided that at least 4 of the 7 partners 
are present and in case of a tie the coordinator will have a casting vote. Decisions concerning 
individual partners (default or acceding or leaving the consortium) can only be taken unanimously. 
All meetings shall produce minutes and include a list of formal decisions taken.  
Coordinator 
The project coordination performed by TU Delft is realised by two different entities and persons:  
1. The technical and overall coordinator of the project will be Dr. F.M. Vos, whose main responsibility 
is to ensure that the main goals of the project are pursued and to verify the quality of all 
deliverables resulting from the project.  
2. The non-technical project management is realised by Ms. T. Twickler of TUD’s Valorisation Centre 
who is responsible for the following tasks: 
 
Liaison with European Commission  
 
Submission of deliverables and annual progress reports  
 
Budget control, financial management and declarations/payments from/to consortium 
partners  
 
Progress control (deadlines, deliverables, milestones, MM efforts and expenditures etc.)  
 
Co-organisation of project meetings (together with host partner), making minutes of 
meetings  
 
Preparing and implementing SC decisions on an administrative level  
 
Liaison with other European research projects (at the project management level)  
This division in tasks will take away the administrative tasks from the technical coordinator who on 
his turn can dedicate himself fully to the scientific and technological content development of the 
project. 
Participants will report man-hour expenditures and costs periodically to the project manager while 
maintaining a registration of same based on their own accounting principles within their own 
organisation. This information will be recorded in the administration system under responsibility of 
the project manager. 
Advisory Committee 
The Advisory Committee (AC) consists of high profile, senior external reviewers who give advice on 
the strategy and policy of the VIGOR++ project. The Committee has at least four members, 
appointed by the SC. The members will be experts in the fields that VIGOR++ covers and thus 
originate from industry, academia (EU based), investors and Government (national or EC). The 
Advisory Committee will be asked to provide input regarding the project’s progress and milestones. 
Table 8 collates the experts that have been invited to join the project’s Advisory Committee. 
Table 8 Advisory committee members 

50 
 
Name 
Organisation 
Country 
Expertise 
Sir Muir Gray 
National Knowledge 
Service 
UK 
Health databases. 
Chayim Bell 
EFCCA 
Belgium 
Patient representative 
Prof. Maria Petrou 
Informatics and 
Telematics Institute 
Greece 
Image Analysis and 
Pattern Recognition 
Prof. Eduard Gröller 
Technical University of 
Vienna 
Austria 
Computer graphics and 
Visualisation 
Dr. Michael Grahn 
Enteric  
UK 
Implementation of 
Medical Technology 
 
Sir Muir Gray has worked in public health for 35 years. He helped pioneer Britain's breast and 
cervical cancer screening programmes and was knighted in 2005 for the development of the foetal, 
maternal and child screening programme and the creation of the National Library for Health. He is 
former director of the National Knowledge Service for the NHS and responsible for the National 
Library for Health.  
Mr Chyim Bell is secretary of EFCCA and himself IBD patient. EFCCA's aim is to improve the well 
being of patients with inflammatory bowel disease by (1) working with and for the EFCCA Member 
National Associations and others throughout all of Europe; (2) facilitating the exchange of 
information and the promotion of cross-frontier activities; (3) effecting regular contact with the 
European authorities, doctors, health professionals and organisations and with others world-wide; 
(4) the encouragement of scientific research into Crohn's and Colitis (IBD) causes and treatment. 
Prof. Maria Petrou is the Director of the Informatics and Telematics Institute in the Centre for 
Research and Development, Hellas, in Thessaloniki, Greece. Her research interests include many 
topics on Image Processing, Computer Vision and Pattern Recognition, with applications (amongst 
others) in Biomedicine. She has more than 350 publications and numerous articles of journalistic 
nature, like book reviews and conference reports and co-authored two books. She has served in the 
Editorial board of several high impact journals and was a member of many (inter)national 
committees in her field. 
Prof.dr. Eduard Gröller’s research interests include computer graphics, flow visualisation, volume 
visualisation, and medical visualisation. He is heading the visualisation group at the Institute of 
Computer Graphics and Algorithms. He co-authored more than 140 scientific publications and serves 
on various program and paper committees, such as Computers&Graphics, IEEE Transactions on 
Visualisation and Graphics, EuroVis, IEEE Visualisation conference, Eurographics conference. He was 
paper-co chair of Volume Graphics 2005, IEEE Visualisation 2005 and 2006, and Eurographics 2006.  
Dr. Michael Grahn is Operations Director with Enteric, The Bowel Function Healthcare Technology 
Co-operative. Additionally, he is a Senior Lecturer in Biochemistry and has been working with the 
Academic Surgical Unit, Royal London Hospital, since 1987.  His particular interests lie in the 

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development and implementation of complex medical technologies in the treatment of colorectal 
disorders.  He also acts as a consultant to the European Commission and the UK Technology 
Strategy Board and has contributed to several medical publications. 
Methods of monitoring and reporting progress  
Communication 
At the kickoff meeting a number of slots will be dedicated to tutorials on the different technologies 
and clinical knowledge involved in the project. This ensures knowledge sharing and agreement on 
the terminology at the beginning of the project among the partners on top of our previous 
interactions and collaborations. Each partner will be responsible for maintaining particular topics in 
the fields of their competence and ensure knowledge sharing in those fields, within and across the 
relevant work packages. 
The internal communication will be straightforward and informal since all project partners know 
each other very well and they have met several times during proposal preparation. All project 
partners are or have been partners in framework projects before, and are well known with the 
procedures of communication and reporting. Information sheets, deadline recall, minutes of 
meetings and reports elements will be exchanged via Internet on a regular basis to reduce dead 
time. Moreover, the project's (web-based) collaboration space will also be used for internal 
dissemination of documents and knowledge. 
Project meetings 
A number of physical meetings is also envisaged, although the majority of the decisions may be 
taken after due consultation by phone or email. The levels, again, reflect the organisational 
structure: 
WP meetings target specific technique or co-operation issues arising from the particular tasks. WP 
meetings are held in small groups. The WP leaders will give a short summary of past work and then 
each group member will give a presentation of his achievements if necessary. WP meetings involving 
more than one participant will usually take place along with the general project meetings in order to 
save the consortium resources. 
General project meetings will be hold at the commencement and completion of the project, every 
six months during the project, and at the request of more than two project partners.  All meetings 
will be minuted and formally structured around the previous minutes, matters arising, and 
actions.  It will be the coordinator's responsibility to chair or to delegate chairing to another 
partner, depending on topic.  The meeting agenda will be dispatched to all participants from the 
appointed Chairman one month in advance of the meeting.  The most crucial meetings will be held 
face-to-face, but where it will not impinge on our success we will make use of phone conference 
facilities.  Informal communication between these meetings will be supported using the project‘s 
web pages and mailing lists. 
The general project meetings will be once a year attended by the Advisory Committee. 

52 
 
Steering Committee meetings take place twice every year and will coincide with the general project 
meetings. Such meetings will ensure that the project outcomes are verified and take into account 
the latest technological, clinical and market developments. Reports reaching the SC from WP’s via 
the PC will include deliverables, milestone reports and risk-related reports. The SC will also monitor 
the ethical issues within the project. 
Decision-making structure 
Decision-making shall be devolved to the appropriate organisational level, so that three categories 
of decisions are distinguished: 
Local decisions concerning day-to-day responsibilities of a work package are taken by the WP 
Leaders and participants with back up from coordinator. These decisions concern progress, quality 
and problems that are related to a particular WP and do not influence the project aim and plan, so 
they can be made within corresponding WP’s through local discussions and meetings organised by 
the WPL’s. 
Co-ordinated decisions affecting more than one work package shall be referred to the coordinator. 
The coordinator will then initiate a discussion among the leaders of the involved WP’s to reach a 
solution. Eventually, if a solution cannot be found through discussion, the problem will to be 
reported to the SC and the SC will make a final decision. 
Ultimate decisions related to strategic issues impacting on the project aims and overall progress 
planning and control are taken at the level of the SC. The EC Project Officer shall be notified and may 
request participation in the decision-making. This includes resolution of conflicts that cannot be 
dealt with by the Project Co-ordinator. 
Reviews and quality assurance 
Each WP leader will have to provide an intermediate progress report every 6 months to the 
coordinator. The report will be written on the basis of a regularly updated detailed plan. It will 
contain information about the technical progress, results obtained and compliance with the work 
program. These reports will be combined into one report which will be the basis for discussions at 
the Steering Committee meetings. Progress reports will include specific management accounting by 
the project manager that will show the budgeted, used and remaining personnel effort and costs. 
Progress on dissemination will be also included as a separate chapter in the annual progress reports. 
The progress of each WP and the outlook of the exploitation of the results will be critically reviewed 
and compared to the planning and criteria described in the work program. The coordinator is 
responsible for a first quality check of all deliverables and outcomes of the project. Drafts will be 
submitted to the SC for final approval. The assessment ensures that deliverables meet the project's 
requirements and are of high technical quality. Ultimate approval is done at EC level, through annual 
review meetings. A list and database of all deliverables and publications will be kept and updated by 
the coordinator and can be submitted to the Commission upon request.  
Any participant who encounters a problem which may cause a delay in the program will have to 
inform the coordinator and the corresponding WP manager immediately. The coordinator proposes 
solutions at the SC, or in case of urgency to hold a virtual SC meeting by email or telephone 

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conference. Any occurrence or conflict that could seriously affect the work will be reported to the 
Commission in order to have timely feedback on alternatives and solutions. 
Conflict resolution procedures 
The organisational structure is appropriate for the complexity and scale of the VIGOR++ project. 
Effectively, it provides built-in escalation and transparent conflict-resolution procedures. WP1 will 
maintain an archive of all project-external and internal technical documents and discussions. This 
will be used as a base for resolving any conflicts. Ultimate decisions about issues impacting on the 
project aims and overall progress planning and control are taken at the level of the Steering 
Committee. The EC Project Officer shall be notified and may request participation in the decision-
making. This includes resolution of conflicts that cannot be dealt with by the coordinator. 
Beneficiaries  
Delft University of Technology (TUD) 
Department carrying out 
the work: 
Image Sciences and Technology/Valorisation Centre 
Role in the project: 
Leader of WP1 (Project Management), leader of WP3 (Image analysis) and 
contributor to most other WP’s. 
Delft University of Technology, founded in 1842, is the oldest, largest and most comprehensive 
university of technology in The Netherlands. It offers a wide variety of education in Science, 
Engineering and Design. A total of 16.000 students are enrolled in one of its 14 bachelor programs 
(10.500 students) or in one of its 41 master programs (5500 students) including several Erasmus 
Mundus Masters. TU Delft has showed its responsibility towards society by focusing its research on 
four global themes: Energy, Environment, Infrastructures, and Health. It is partner in two recently 
granted KIC’s (Knowledge and Innovation Community) Environment and ICT. The Delft Health 
Initiative combines all health research at the TU Delft, spread over various faculties and 
departments. It holds a strong position in developing technology for healthcare in collaboration with 
partners in industry and academia. It focuses on imaging technologies from nano to macro, 
molecular technologies for diagnosis and treatment, computer modelling and digital image analysis, 
measurement techniques, as well as the engineering and design of new surgical instrumentation and 
implants.  
Key Personnel 
Dr. Frans M. Vos (1969) obtained Masters Degrees in medical informatics as well as in computer 
science at the University of Amsterdam, The Netherlands, in 1993. He performed his graduation 
work at Yale University (USA). In 1998 he obtained the Ph.D. degree at the Vrije Universiteit 
Amsterdam and subsequently he was a research fellow with the Department of Applied Physics of 
Delft University of Technology. He became assistant professor with Delft University of Technology in 
2003. Since 2000 he is also a staff member with the Department of Radiology at the Academic 
Medical Centre Amsterdam. Dr Vos is past treasurer of the Dutch Society for Pattern Recognition 
and Image Processing (2000-2007).  Since 2007 he is a member of the education board of the 

54 
 
Master’s program on Biomedical Engineering. His main research interests are in medical image 
processing and visualisation, particularly focussing on virtual colonoscopy, diffusion tensor imaging. 
He was able to acquire many research Grants from the Dutch Foundation for Scientific Research, 
Dutch Foundation for Technology and Philips Healthcare. He has been responsible for the 
development of many tools for CT colonography in Philips’ ViewForum workstation. He has 
supervised 10 Ph.D. students and 40 graduate students and authored and co-authored over 70 peer-
reviewed publications in the field of medical imaging. 
Professor Dr Ir Lucas J. van Vliet is Professor of Image Analysis at the Delft University of Technology, 
Director of the Delft Health Initiative, Chairman of the Department Imaging Science & technology, 
and Head of the Quantitative Imaging group. He obtained his Ph.D. degree cum laude in 1993 and 
was awarded a prestigious talent research fellowship from the Royal Dutch Academy of Arts and 
Sciences (KNAW) in 1996. In 1999 he was appointed Antoni van Leeuwenhoek professor. Professor 
van Vliet is past president (2003-2009) of the Dutch Society for Pattern Recognition and Image 
Processing (NVPHBV) and sits on the board of the International Association for Pattern Recognition 
(IAPR) and The Netherlands Advanced School for Computing and Imaging (ASCI). He is (co)author of 
more than 200 peer reviewed research papers, supervised 20 Ph.D. theses and is currently 
supervising another 12 Ph.D. students. He was visiting scientist at Lawrence Livermore National 
Laboratories (1987), University of California San Francisco (1988), Monash University Melbourne 
(1996), and Lawrence Berkeley National Laboratories (1996). He has initiated and acquired 
numerous competitive research grants through various funding agencies and public-private 
partnerships. 
Theresia Twickler, MSc, is Senior Project Manager in the Valorisation Centre. She has been 
managing projects with EU funding since the Third Framework Programme onwards together with 
supporting staff of assistants and financial officers at TU Delft. Her present portfolio contains an FP6 
project (15 partners), two FP7 projects (8 partners each), an Asia Switch project (with 7 partners 
from Asia including UNEP and UNIDO). She is involved as Liaison Officer on behalf of TU Delft in the 
Dutch Association of Universities, taking part in member state discussions on the preparation and 
evaluation of EU Framework Programmes. She is co-founder of the Dutch association of EU project 
managers (EUPMAN). 
 University College London Hospitals 
Department carrying out 
the work: 
Department of Gastroenterology 
Role in the project: 
Leader of WP2 (Clinical Data Acquisition and Data Management) and contributor 
particularly to WP7 (Clinical application) as well as several other WP’s. 
UCL is one of the UK’s top 4 medical schools whatever criteria are adopted. The associated hospital 
group is a dynamic foundation trust, and is one of only 5 in England to be awarded Comprehensive 
Biomedical Research Centre status by the National Health Service. It was recently designated as one 
of the UK’s first academic health science centres (based on demonstrating excellence in research, 
education and patient care).  UCL is Europe's second most productive partnership for biomedical 
science research (according to The Partnership for Science & Technology Studies), which accounts 

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for 65 per cent of all University activity. The Department of Gastroenterology at UCL and UCH is one 
of the biggest in the UK and has a very substantial research output as well as an impressive clinical 
reputation.  Specifically in the field of inflammatory bowel disease there are more than 1000 
current patients with the condition. There is excellent GI pathology back-up, and imaging support in 
the hospital is second to none in the UK. The institution has an extremely strong track record and 
international reputation in medical imaging. By way of illustration, a recent RAND Europe review of 
the UK (Thed van Leeuwen, Jonathan Grant. Report WR-368-68; April 2006) UCL was the only critical 
mass contributor to the field “Radiology, Nuclear Medicine, and Medical Imaging “, contributing 18% 
of HCPs in that field. It holds EPSRC/CRUK Imaging in Cancer Centre status. The Department of 
Imaging has attracted £16.9M grant funding (£4.4M principal applicants and £12.5M as co-
applicants) in the last 7 years and has published over full 120 peer-reviewed publications in the last 5 
years. A research 3T MRI facility is currently being installed. Prof Steve Halligan (dept chair) is NIHR 
senior faculty and the only Radiologist PI to date awarded a NIHR program grant. Important 
collaborations with pre-clinical partners particularly Centre for Medical Image computing (Prof Dave 
Hawkes) and Centre for biomedical imaging (Dr Mark Lythgoe) form an integral part of the research 
program of the unit.  
Key Personnel 
Prof. Alastair Forbes is professor of Gastroenterology at University College London and University 
College Hospital. He is Head of the Centre for Gastroenterology and Theme Leader for Research and 
Development.  He was Medical Director of Core (the Digestive Disorders Foundation) and is now 
Chairman of the Education Committee of the European Society for Nutrition and Metabolism 
(ESPEN).  He was previously consultant at St. Mark's Hospital (1992-2005), Dean of the St. Mark's 
Academic Institute, Honorary Secretary of the British Society of Gastroenterology, and Chairman of 
the British Association for Parenteral and Enteral Nutrition (2002-5).  His interests lie mainly in 
inflammatory bowel disease and nutrition, including laboratory work on intestinal regeneration.  
He has written more than 140 original papers, over 80 review articles, together with books, videos 
and CD-ROMs. 
Dr Stuart Taylor is one of just two HEFCE funded academic Radiologists in the UK. He is a Reader in 
ClinicalRadiology, University of London and honorary Consultant Radiologist, University College 
London NHS Foundation Trust. He currently sits on the NCRI Colorectal Surgical Subgroup, is 
Research Officer for British Society of Gastrointestinal and Abdominal Radiology, and is a member of 
the Royal College of Radiologists Research Committee and European Society of Gastrointestinal and 
Abdominal Radiology CT colonography and Educations Committees. He is the chairman of the 
Abdominal Imaging Section for the European Congress of Radiology (ECR) 2012. He leads the 
Department of Health Radiological Academic Clinical Fellows and Academic Clinical Lecturer 
Programme at UCLH/UCL. He was recipient of Radiology Editor’s Award for ‘reviewing with 
distinction’ 2007-2009, awarded to less than 10% of reviewers. He is the current Royal College of 
Radiologists travelling Roentgen Professor. He has published 20 book Chapters, invited reviews, 
guidelines and letters: and has 90 full peer review publications with an H index of 19. He has 
attracted over £3M Euros grant income as principal or co-applicant, including grants from the 
National Institute of Health Research and Health Technology Assessment Board. He currently heads 
the functional MRI research program at UCH and is lead for a new 3T MRI research facility. Current 

56 
 
research interests include the use of MRI, CT and ultrasound in the prediction of histological markers 
of disease activity in Crohn’s disease. He has published widely on the use of computer aided 
detection software in CT colonography. 
 Eldgenössische Technische Hochschule Zürich (ETHZ) 
Department carrying out the 
work: 
Computer Science 
Role in the project: 
Leader of WP4 (Modelling) and contributor to several other WP’s. 
 
ETH Zurich is the study, research and work place of 20,000 people from 80 nations. About 370 
professors in 16 departments teach mainly in the engineering sciences and architecture, system-
oriented sciences, mathematics and natural sciences areas and carry out research that is highly 
valued worldwide. As an internationally oriented institution of higher education and a nationally 
grounded one this forward-looking task is fulfilled in service to the Swiss nation. Twenty-one Nobel 
Laureates are connected with ETH Zurich. Maintaining and developing its top standing in the 
international competition among top universities is an important task of ETH Zurich. 
Key Personnel 
Prof. Dr Joachim M. Buhmann leads the “Machine Learning Laboratory” in the Department of 
Computer Science at ETH Zurich. He has been a full professor of Information Science and Engineering 
(Informatik) since October 2003. 
Born in 1959 in Friedrichshafen, Germany, he studied Physics at the Technical University Munich and 
obtained his PhD in Theoretical Physics with Professor Klaus Schulten. His doctoral thesis 
investigated pattern recognition problems in neural networks. He then spent three years as a 
research associate and as a research assistant professor at the University of Southern California, Los 
Angeles. In 1991, he joined the Lawrence Livermore National Laboratory in California. From 1992 to 
2003, he held a professorship of applied Computer Science (praktische Informatik) at the University 
of Bonn, Germany. 
His research interests spans the areas of pattern recognition and data analysis, including machine 
learning, statistical learning theory and applied statistics. Application areas of his research include 
image analysis, medical imaging, information security and bioinformatics. He is currently the 
president of the German Pattern Recognition Society (Deutschen Arbeitsgemeinschaft für 
Mustererkennung). He has been associate editor for IEEE Transactions on Neural Networks (1998-
2004), IEEE Transactions on Image Processing (2003-05) and IEEE Transactions on Pattern Analysis 
and Machine Intelligence (2004-08). 
Dr. Cheng Soon Ong is a research associate at the Machine Learning Laboratory of the Department 
of Computer Science at ETH Zurich. He completed his PhD titled "Kernels: Regularization and 
Optimization", at the Australian National University in 2005. He shortly held a postdoc position at 
the Statistical Machine Learning Group, in NICTA, Canberra, followed by longer ones at both the Max 
Planck Institute of Biological Cybernetics and the Friedrich Miescher Laboratory. Prior to his PhD, he 

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researched and built a search engine at Bahasa Malaysia Technologies at Mimos Berhad, Malaysia. 
He obtained his B.E. (Information Systems, 1999) and B.Sc. (Computer Science, 1997) from the 
University of Sydney, Australia. Since 2007, he has been action editor at the Journal of Machine 
Learning Research and advocates open source software through mloss.org. He is currently working 
on kernel methods and computational biology. 
Zuse Institute Berlin (ZIB) 
Department carrying out 
the work: 
Visualisation and Data Analysis Department (VDAD) 
Role in the project: 
Leader of WP5 (Interactive Visualisation). 
The Visualisation and Data Analysis Department (VDAD) of the Zuse Institute Berlin (ZIB), Berlin, 
Germany, currently consists of 4 research groups with about 25 researchers and 21 master students. 
The main research areas of the VDAD are interactive visualisation, geometry reconstruction and data 
analysis, especially for biomedical applications. Currently there are several ongoing research projects 
funded by the European Union, the DFG (German Research Foundation), BMBF (Federal Ministry of 
Education and Research), three Max Planck Institutes and companies. VDAD produces about 30 
reviewed publications per year in journals and international conferences and is quite active in the 
international research community on graphics and visualisation. Such activities include paper 
reviewing and conference chairing, program committee memberships for numerous international 
conferences, and conference organization. For example, EuroVis 2009 – Eurographics/IEEE 
Symposium on Visualisation, the largest European conference on data visualisation, was organised 
by the VDAD in Berlin. The ZIB is co-initiator and partner of the DFG Research Center Matheon which 
develops mathematics for key technologies, including visualisation, and which supports partners in 
industry, economy and science. VDAD has established four spin-off companies, all in the field of 
visualisation.  
Key Personnel 
Prof. Hans-Christian Hege is head of the Visualisation and Data Analysis Department at Zuse 
Institute Berlin (ZIB). After studying physics and mathematics, he performed research in 
computational physics and quantum field theory at Freie Universität Berlin (1984-1989). Then, he 
joined ZIB, initially as a scientific consultant for high-performance computing and subsequently as 
head of the Scientific Visualisation Department, which he started in 1991. His group 
performs research in visual data analysis and develops visualisation software such as Amira and 
Biosphere3D. He is cofounder of Mental Images (1986), Indeed—Visual Concepts (1999) (now Visage 
Imaging) and Lenné3D (2005). He teached as guest professor at Universitat Pompeu Fabra, 
Barcelona, as honorary professor at the German Film School (University for Digital Media 
Production), and as lecturer at the Freie Universität Berlin. His research interests include many 
branches in visual computing and applications in natural sciences, life sciences, and engineering. 
Hege co-authored more then 220 scientific publications and acted as a reviewer for numerous 
conferences and journals in the field. He also served at more then 40 international program 
committees (like IEEE Transactions on Visualizaton and Graphics, Computers & Graphics, ACM 
Siggraph, EuroVis symposium, IEEE Visualisation conference, Eurographics conference). He was 

58 
 
paper co-chair of VMLS 2009, EuroVis 2009, Volume Graphics 2008 and 2007, TopoInVis 2007, 
VisMath 2002, 1997 and 1995. He is member of Advisory Board of the SciDAC Institute on Ultrascale 
Visualisation, Davis, USA; the Advisory Board, AFI/TFI, Sendai, Japan; the steering committee of 
section Graphical Data Processing of GI; and the steering group of Eurographics on Visual Computing 
for Biology and Medicine. Furthermore he serves as vice-speaker of the working group Visual 
Computing in Medicine of the German Association of Computer Science (GI). He is member of IEEE 
Computer Society, ACM (Association of Computing Machinery), GI (Gesellschaft für Informatik), DPG 
(German Physical Society), and CURAC (German Society for Computer- and Roboter-assisted 
Surgery). 
Dr. Steffen Prohaska is deputy head of the Visualisation and Data Analysis Department and is 
leading the Visualisation Systems group. He received his PhD in Computer Science from the 
Universität Potsdam in 2007. He also holds a diploma in physics from the Technische Universität 
Darmstadt. His main research interests are visualisation systems and the visual analysis of image and 
flow data. He published several refereed articles in these areas. He contributed to the scientific 
community as a member of the internal program committee of the Eurographics/IEEE Symposium 
on Visualisation. Dr. Prohaska is also leading the development of the visual data analysis system 
Amira/Avizo, which ZIB and two companies have been jointly developing. Together with the project 
managers at the companies, he is steering the system architecture and the integration of code 
contributed by approximately fifty researchers and software developers. 
Vincent Dercksen received his M.Sc. degree in technical informatics from Delft University of 
Technology, Netherlands, in 2003. Since then, he has been a research scientist and PhD student in 
the Visualisation and Data Analysis Department at the Zuse Institute Berlin (ZIB). His research topics 
include 3D geometry reconstruction and biomedical image analysis. 
Biotronics3D Limited 
Department carrying out 
the work: 
R&D 
Role in the project: 
Leader of WP6 (System Architecture and Integration), and contributor to several 
other WP’s. 
Biotronics3D Ltd was established in 2004 in London and opened an R&D centre in Cambridge in 
2009. The company develops and markets innovative components and complete medical software 
systems for the diagnostic imaging industry. Biotronics3D core technology known as 3Dnet™ Suite37 
offers fast distribution of images across the medical enterprise and has received FDA 510K market 
clearance and is CE marked. This servicing platform has allowed the company to enjoy a significant 
position in the international market of advanced medical imaging spanning Europe, North America, 
Japan and Africa and to sustain substantial growth. The company closed its first round of 
institutional investment in August 2008 (Longbow Capital). 
 
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Key Personnel 
Dr Harry Hatzakis is co-founder and CEO of Biotronics3D. He has spent all his professional working 
years in medical technologies in Europe and North America, progressing from R&D through Product 
Management to Strategic Global Marketing of Diagnostic Imaging Solutions. He has ample 
experience in global markets having successfully introduced several new lines of products. Harry 
studied Electrical Engineering as well as Medicine in Greece and Electrical Engineering at Imperial 
College, London. His current main research is in the field of the management, analysis and 
visualisation of medical images and their interface to Electronic Health Records. Examples of the 
recent projects he has been responsible for include a CONNECT project in 2005 from the London 
Development agency, a SMART R&D award from the UK department of Trade and Industry during 
2005-7, a CASE Award by EPSRC to support post graduate research in medical imaging during 2005-
7, the usability work package in FP6 MUTED and the MODiMaS project co-funded by EEDA (2009-
2011) developing subsystems to support clinical, administrative, research and patient services 
related to breast cancer. 
Dr Soeren Grimm is co-founder and CTO of Biotronics3D with more than 10 years of experience in 
devising and developing innovative products for the medical imaging market. He has contributed to 
the development of many start-ups in Europe and USA, including Tiani MedGraph AG, Austria and 
Viatronix Inc., USA. He holds a Ph.D. in Computer Science from Vienna University of Technology, 
Austria, and an MSc in Computer Science from the University of Tübingen, Germany. His interests 
include web technologies, computer graphics, scientific visualisation, computer architecture and 
especially medical visualisation. He has co-authored numerous scientific articles, is co-inventor of 
one issued and two pending patents, and acts as reviewer for many conferences and journals in the 
field. 
Rado Andriantsimiavona is a Senior Software Engineer at Biotronics3D. He has over 10 years 
experience in medical imaging, healthcare and science, in various positions from software 
engineering, academic research to business development for top tier institutions. In particular, he 
held positions at Renishaw (UK), SecureRAD (USA), Apple Europe (UK), Guy’s & St Thomas Hospitals, 
(UK), Philips Healthcare (Netherlands) and Metrovision (France). He has an MPhil in Interventional 
Cardiac MR Imaging, from King’s College London, an MSc in Digital Signal & Image Processing from 
Cranfield University and an Engineering Diploma in Mathematics, Computer Sciences & Biomedical 
Engineering, Université de Technologies de Compiègne, Compiègne, France. 
Laurence Bourn is a Senior Imaging Scientist at Biotronics3D with 12 years of industry experience in 
3D medical imaging. He has worked for a variety of European start-up companies in medical imaging 
including Voxar, 3mensio and Medis. He has a broad range of technical skills including volume 
visualisation on GPU/CPU, high performance code and cloud computing. Laurence studied 
Mathematics at Warwick University and has done postgraduate work at Liverpool and Edinburgh 
computer science departments. 

60 
 
Academic Medical Centre, University of Amsterdam 
Department carrying out 
the work: 
Department of Radiology 
Role in the project: 
Leader of WP7 (Clinical Data Acquisition and Data Management) and contributor 
particularly to WP2 (Clinical application) as well as several other WP’s. 
The Academic Medical Centre of the University of Amsterdam is one of the leading medical schools 
in the Netherlands. GI diseases are one of the spearheads of research and patient care. The 
department of Radiology of the Academic Medical Centre has extensive experience with the 
development and evaluation of imaging methods for GI diseases, especially of the small and large 
bowel (project leader Prof. Dr. J. Stoker). Emphasis is on imaging of (precursors of) colorectal cancer 
(colonography/virtual colonoscopy; molecular imaging), MRI in IBD, pelvic floor imaging and MR 
spectroscopy of liver steatosis. The department of Radiology has a close collaboration with the 
department of Gastroenterology in the development and evaluation of these imaging methods for 
GI diseases. Approximately 2000 patients with IBD are treated at the AMC. The department of 
Radiology has an extensive experience with multicenter collaborations. 
Key personnel 
Prof Dr Jaap Stoker is professor of Radiology with a special interest in abdominal radiology. He is 
abdominal radiologist, head of research at the department of Radiology, head of the abdominal 
imaging fellowship and chair of the Abdominal imaging chapter of the Radiological Society of the 
Netherlands. He has been member of the board of the Radiological Society of the Netherlands 
(2002-2005) and chair of the Annual Meeting of the Radiological Society of the Netherlands (2002-
2005). He is chair of the section Abdominal Radiology of the Radiological Society of the Netherlands 
(2005-2010). He was/is member (chairing one national guideline) of several national guideline 
workgroups on gastrointestinal diseases (including on inflammatory bowel diseases). He is author of 
over 180 peer reviewed papers (H-index 30) and 25 book chapters and is reviewer for several 
journals including Radiology. He is Editor of the Nederlands Tijdschrift voor Geneeskunde (Dutch 
Medical Journal) and member of the Signalling Committee Cancer of the Dutch Cancer Society. He 
has written many granted proposals in the field of development and evaluation of GI imaging (Dutch 
Organisation for Health Research and Development ZonMw (Dutch Research Council) and Dutch 
Cancer Society).  
Dr Manon Ziech is research fellow MR imaging in Crohn’s disease at the department of Radiology. 
She has performed several studies on MRI of the small and large bowel in Crohn’s disease and on 
MRI of perianal Crohn’s disease. The aim of these studies was to develop new methods in MRI in 
Crohn’s disease and evaluate the accuracy and patient acceptance. 
Dr Aart Nederveen is MR physicist at the department of Radiology. He is involved in several projects 
concerning development and evaluation of GI imaging, including MRI in Crohn’s disease (primarily at 
3T).  He has authored and co-authored over 20 peer-reviewed publications in the field of medical 
physics and bioinformatics and assists several PhD students. 

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Dr. Cyriel Y. Ponsioen was trained in Internal Medicine and Gastroenterology & Hepatology from 
1989-1998. He is currently a senior staff-member of the Department of Gastroenterology & 
Hepatology at the Academic Medical Centre in Amsterdam. From 1995-2000 he has devoted 40 % of 
his time to his PhD thesis titled “Etiologic and Clinical Studies in Primary Sclerosing Cholangitis 
(PSC)”, under supervision of Prof. Dr. G.N.J. Tijtgat. In the past five years he has been involved in 
several large-scale projects concerning Barrett’s esophagus research as well as several projects 
concerning PSC. Since 2006 he is principal investigator of a large scale project covering almost 50 % 
of the Dutch population (amounting to 8 mln inhabitants) titled: “Epidemiology and Natural History 
of, as well as Risk Factors for Primary Sclerosing Cholangitis and Primary Biliary Cirrhosis in Central 
Netherlands”. He heads, together with dr. Pieter C. Stokkers, the tertiary referral IBD-centre of the 
Academic Medical Centre in Amsterdam since 2007. Currently, he is principal investigator of a 
multicenter epidemiologic project studying the occurrence of intercurrent infectious enterocolitis in 
IBD. He has published more than 25 articles and has coached several PhD students. 
Vodera Limited 
Department carrying out the 
work: 
Collaborative R&D 
Role in the project: 
Leader of WP8 (Dissemination, Exploitation and New applications) and 
contributor to several other WPs. 
Vodera is an innovation accelerator company, specialising in bridging the gap which prevents 
emerging technologies from making significant contributions to business growth. This gap is often 
caused by badly defined system requirements, inaccurate estimates of needed resources or poor 
handling of intellectual property. Vodera was founded in 2006 and assists high-tech start-ups, 
technology corporations and universities create competitive advantage by rapidly developing new 
systems and solutions, commercialising technology breakthroughs and transferring knowledge 
across projects and business units. Vodera maintains close relationships with many experts from 
academia, industry, and government, who are an invaluable resource when it comes to analysis, 
scientific dissemination or commercial exploitation activities. Currently, Vodera is engaged in the 
Framework 7 projects FeedNetBack and RAPPORT, leading work packages related to roadmap 
development, exploitation and dissemination. The senior staff of the company has also worked in 
FP6 RUNES, WINNER, MAGNET and FP5 PAMPAS. 
Key Personnel 
Dr Costis Kompis is the Managing Partner of Vodera specialising in knowledge exchange, technology 
transfer and research strategy. He has over fifteen years of experience, the first part of which was 
devoted to ICT research and development and the second part to innovation management and 
technology commercialisation. He serves as manager of the Wireless Sensing Interest Group (WiSIG), 
as well as on a number of advisory committees for scientific research, engineering and economic 
development.  He has also helped organise and chaired numerous international workshops and 
meetings. His work has received several awards, including a Marie Curie Postdoctoral Fellowship, an 
EPSRC Realising Our Potential Award, a Nokia Invention Award, and the Ericsson First Award of 
Excellence in Telecommunications. He has a PhD in Computer Science, an MSc in Technology and 

62 
 
Innovation Management and an MEng in Electronic and Computer Engineering. He has also been 
trained in project management, intellectual property exploitation, technology roadmapping and 
contract law. 
Dr Vaia Sdralia is Partner of Vodera specialising in the design and engineering of communication 
networks and international market analysis. She has held R&D and product management positions 
with NEC Europe, Samsung Electronics Research Institute, ARRIS Interactive, the Information 
Security Group at Royal Holloway University of London and the Aristotle University of Thessaloniki 
where she worked on medical imaging applications. Vaia has published over forty papers, filed eight 
patents and sits on various committees and standardisation groups. She holds a PhD in Computer 
Science, an MSc in Telematics and a BEng in Informatics. 
Prateek Sureka is a Research and Innovation Manager of Vodera specialising on technology 
roadmapping and research commercialisation. He has worked at the University of Sussex as an 
online search specialist. Prior to that, he worked as computer network specialist. He has helped to 
organise several technological forums and focus groups. In a short stint of career he has represented 
the UK in major global business competition and has won other awards in business management and 
entrepreneurship. He holds an MSc in Technology and Innovation management and a BEng in 
Electronics and Telecommunication Engineering. 
Consortium as a whole  
Overview of the consortium 
The VIGOR++ consortium is a well balanced and highly interdisciplinary group of academic, clinical, 
and industrial partners with expertise to carry out novel R&D in the emerging fields of medical 
diagnosis and disease monitoring. In particular, the consortium comprises partners from medical 
research (2 Hospitals), ICT experts (3 Universities and 1 SME) and an industrial intermediary (1 SME) 
coming from all over the European Union. All partners have long experience in research and are 
used to working in collaborative R&D projects. We have been careful not to make the consortium 
too large in order to keep the activities focused and the communication overheads low. We want 
European quality and commitment but not too much internal communication. In fact, we believe 
that external dissemination is more valuable, than using our energy in disseminating between 
ourselves. As depicted in Table 9 each of the seven organisations in the consortium has clearly 
defined and complementary areas of responsibility and proven collaboration experience.  
Table 9 Consortium expertises (vertically) and project partners (horizontally); the color of the circles indicates 
the extend of expertise (black: extensive know-how; white: no know-how). 
Research area 
TUD 
UCLH 
ETHZ 
ZIB 
B3D 
AMC 
VOD 
Abdominal Radiology  
 
● 
 
 
 
● 
 
Image Processing and Analysis 
● 
 
● 
● 
● 
 
 
Pattern Recognition and Machine Learning 
● 
 
● 
● 
● 
 
● 

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Interactive Visualisation and Computer 
Graphics 
● 
 
● 
● 
● 
 
 
System architecture and integration 
 
 
 
 
● 
 
● 
Clinical Management of Crohn’s Disease 
 
● 
 
 
 
● 
 
Knowledge Exchange and Exploitation 
 
 
 
 
● 
 
● 
 
The formation of the VIGOR++ consortium targeted to ensure a good representation of the entire 
supply chain for medical imaging solutions. Therefore, we have within the team access to high 
quality medical data, expertise to generate practically usable models from it as well as expert users 
defining needs to be addressed. The medical data will be supplied by participants AMC and UCLH 
(Radiology Departments). The academic participants (TUD, ETHZ, ZIB) bring the necessary know-how 
regarding development and integration of image analysis, pattern recognition and scientific 
visualisation methods and have a strong experience in the biomedical field. B3D is experienced in 
translating academic research, integrating ICT components, creating practically usable systems and 
bringing these to the market. AMC and UCLH (Gastroenterology Departments) also bring know-how 
concerning management of Crohn’s disease. The planned clinical trials will determine the 
effectiveness of the resulting system and help the industrial participants (VOD, B3D) establish it as 
commercially viable option in the healthcare market. Both companies are very close to the target 
customers and correspondingly aware of their needs, enabling the consortium to spot quickly the 
opportunities offered by the application of new technology. 
Subcontracting 
Subcontracting is not envisaged in the project, except for the audit certificates to be provided by 
externally contracted auditors in case a partner receives more than €375.000 EC contribution.  
Other countries 
All but one participant are based inside the EU: ETHZ resides in Switzerland. 
Resources to be committed  
The financial plan is tailored specifically to the needs of the project. The person months in the WPs is 
fitting to complexity of the tasks to be conducted. Together with the equipment and the 
complementary resources shown here the financial plan is adequate – ensuring project success 
while not wasting resources and fitting the expected impact. The financial plan is tailored specifically 
to the needs of the project. The person months in the WPs is fitting to complexity of the tasks to be 
conducted. Together with the equipment and the complementary resources shown here the 
financial plan is adequate – ensuring project success while not wasting resources and fitting the 
expected impact. The overall budget is composed as follows: 

64 
 
 
Figure 8: Financial overview table. 
The total cost of the project is €3.923.620 and the total requested EC contribution is €2.988.090. 
Figure 9 depicts the total EU contribution on RTD activities per partner. 
  
 
Figure 9: Total EU contribution (%) regarding RTD activities per partner. 
RTD 
Staff 
The participants are both able to invest by means of co-financing the proposed research and to 
achieve return of the investment through revenue generated by the exploitation of the results in 
their products and services. The required effort in person-hours for each task was carefully 

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calculated by the professionals concerned once the detailed work plan was finalized at the tasks 
level. The partners will mostly employ PhD staff to carry out the work.  
Table 10 f effort (in person months) stratified by staff type (vertically) and partners (horizontally). 
TUD 
UCLH 
ETHZ 
ZIB 
B3D 
AMC 
VOD 
PHD student/research fellow 
72 
36 
36 
36 
0 
36 
0 
Postdoc/junior staff 
0 
0 
36 
0 
41 
0 
14 
Senior staff 
18 
4 
4 
4 
31 
4 
10 
Administration 
10 
0 
0 
0 
0 
0 
0 
Total 
90 
40 
76 
40 
72 
40 
26 
Travel 
We have allowed approximately €3,000 per 12 person months to cover the travel costs to attend 
project meetings and international conferences. Travel cost thus represents 2.94% of the total.  
Equipment resources 
This project will use conventional of-the-self computer hardware (laptop/desktop computers) and 
3rd party application software. As such requirements for equipment resources are limited. We have 
allowed approximately €2,500 per 36 person months to cover the equipment costs.  
Data acquisition  
We plan to conduct 150 MRI studies both at UCLH and AMC during the project. Therefore, part of 
the budget needs to be reserved since such imaging is currently not part of the regular care. MRI 
scanning cost per subject is estimated to be €250 at UCLH and AMC. The prospective colonoscopy 
collection at the AMC and UCLH concerns examinations that are performed as part of the patients’ 
regular care and therefore no additional funding will be required. However, the extensive 
histopathology assessment that is required falls outside regular funding, which cost is budgeted at 
€100 per subject (both at UCLH and AMC). Additionally, we budget €50 per study for subject 
recruitment. The total cost will be €30,000 = 75*(250 +100 +50). The generated MRI datasets will be 
used in addition to the existing studies that AMC and UCLH will supply.  
Management 
The Management budget is mostly reserved for the non-scientific management of the project. For 
this, a dedicated project manager is assigned to support the coordinator and the consortium in all 
non-scientific activities and outputs. The ten person months are reserved based on experience of TU 
Delft in the management of similar STREP like ICT funded projects: 3 MM per year + one extra MM 
at the end for final reporting. 
Clearly, the partners will be involved in ‘scientific’ management, e.g. the coordination of research 
activities. Such scientific management is integrated in the WPs. 

66 
 
A small budget is dedicated to the logistics of the (6) project meetings (€10,000). Furthermore, the 
costs of the Advisory Committee are set are set to € 1,200 per committee member for 3 meetings, 
including travel, living allowance and a maximum daily fee (total: €18,000). Moreover, a dedicated 
budget of €10,000 was planed for the dissemination workshops covering organisation, travel cost of 
guest speakers and panelists. As such, the total management cost is only 4.63% of the total project 
cost.  
 Impact 
Strategic impact  
VIGOR++ contributes to all 5 expected impacts described for Objective ICT-2009.5.3 Virtual 
Physiological Human.  Below we show how each of these impacts will be realised. 
Expected impact I (on patients) 
More predictive, individualised, effective and safer healthcare 
Inflammatory bowel diseases, such as Crohn’s disease, constitute a major burden for society, both in 
monetary costs and in suffering of patients and their relatives. Crohn’s disease can affect any part of 
the gastrointestinal tract, from the mouth to the anus, but primarily concerns the small bowel and 
the colon. Symptoms do not necessarily correlate with disease activity, which complicates 
treatment. What is more, treatment is associated with substantial side effects and cost. Frequent 
examinations are necessary to monitor response. The ageing society and the altering living habits 
add to this burden. Currently, approximately 700,000 patients are affected in Europe alone and 
increasing.  
Those patients will be served directly by the project results by integrating detailed, quickly accessible 
and readily updateable information. The project tools will bring advanced ICT systems to disease 
management offering to patients with Crohn’s disease the prospect of a non-invasive, radiation free, 
low-risk and accurate diagnostic environment. The VIGOR++ tools will not only result in disease 
management that is less disruptive to patients’ day-to-day lives but will also empower the patients 
via simple portals to play an active role in their care. Consequently, the project will have a significant 
economic impact by reducing patient’s time out of work given that IBD affects many people at a very 
productive age. At the same time public and private health insurance organisations would face 
significantly reduced costs.  
Expected Impact II (on clinicians) 
Accelerated developments of medical knowledge discovery and management, development of 
devices and procedures using in-silico environments 
The associated work plan gives a clear view on the collaboration for knowledge discovery, 
management and implementation. It is especially designed to allow fast setup of highly 
interdisciplinary research and to foster the partner’s mutual understanding of each other’s research 
area – leading to more multidisciplinary research excellence. Importantly, the developments are 

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driven by clearly identified clinical needs. Hence, the project will create impact by delivering a 
plethora of benefits for clinicians using the envisaged ICT tools including: 
 
Increased efficiency of diagnosis. 
 
Integrated support for diagnosis and treatment planning  
 
The ability to assess disease progress and predict potential complications both objectively and 
personally. 
 
Minimisation of the need for optical colonoscopy particularly for vulnerable patients, such as elderly 
patients, patients with another serious illnesses, and patients who are unable to tolerate sedation or 
bowel preparation (e.g. due to allergy or psychological reasons).  
 
Automatic identification of results outside acceptable ranges. 
 
Support for ‘shared decision’ making with patients. 
 
Quantification of medication efficiency (type and doses). 
 
Tools for quantitative assessment of potential drug interactions 
Notably, the latter two benefits concern direct VIGOR++ impacts on medication related issues: 
correct medication is of vital importance because of the high prevalence and the chronic, lifelong 
nature of IBD. 
Expected Impact III (on healthcare systems) 
Improved interoperability of biomedical information and knowledge 
Many Crohn’s patients are diagnosed in their teenage years or early twenties. Patients need life-long 
support from the health services to enable them to achieve the best quality of life they can within 
the constraints of their illness since no cure has yet been found. At the same time people are more 
mobile than ever. Information about an individual’s symptoms and treatment must be readily 
available independent of location. The project will improve the interoperability of medical 
information and knowledge by overcoming the main difficulties with the Crohn’s disease 
management within healthcare systems which can be summarised as: 
1. Management by a multidisciplinary (and geographically distributed) team is required.  
2. Self-management requires support by rapid access to specialist services  
3. Care needs to be personalised and customised to the individual patient.  
4. Treatment moves from hospitals to the community where a ‘super’ nurse plays a key role. 
Increasing complexity of the involved medical imaging.The VIGOR++ system yields new knowledge 
related to the GI tract by delivering ICT models for personalized assessment of the organ that are 
combined with clinical evidence and associated information. The project will ensure that all essential 
information to manage a patient with IBD is easily accessible in a clearly presented form at the point 

68 
 
of care. The integrated presentation of IBD patient information and analyses of such information is 
what makes the project unique: it is the key to improved care.  
Increased cost of healthcare delivery puts pressure on cost reductions.38. We expect that the project 
will 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.).39 Finally, health insurance companies are expected 
to benefit by reduced costs which can be passed to clients.  
Expected Impact IV (on the pharmaceutical industry) 
Increased acceptance and use of realistic and validated models that allow researchers from different 
disciplines to exploit, share resources and develop new knowledge 
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 disease (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. The project can address a frequently acknowledged risk in Crohn’s treatment: the 
mismanagement of drug intervention due to missing data. 
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. For instance, does the new drug do what is expected, and, is there objective, 
quantitative evidence on its effectiveness? These decisions can have a direct impact on the cost 
reduction of bringing the new drug to the market. It should be noticed that even small 
improvements in accuracy in clinical trial outcomes can translate into savings of millions of euro in 
development and to faster time-to-market. Consider also that pharmaceuticals R&D spending could 
continue to grow at more than 12% per year. The estimated average cost of bringing a new drug to 
market is $1.7bn (approx. €1.2bn).40 The role of medical imaging in clinical trials has increased 
rapidly in recent years both due to the enormous technical advances in the field and the mounting 
evidence that it helps answer key questions that arise during the development and evaluation of 
 
38 Healthcare is already accounting for around 9% of EU GDP, 
39 The cost of IBD to the UK NHS has been estimated at about £720 million per annum, based on the prevalence 
and an average cost of £3,000 per year per patient. However, half of all annual direct healthcare costs from 
IBD relate to the inpatient management of a minority of patients who need intensive medical or surgical 
intervention. 
40 Paul Clewlow, Drugs in transit, Chemistry and Industry, April 2004  

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medical products.41  We believe that there is a significant size market for systems like VIGOR++ for 
IBD in clinical drug trials. A recent market report from Decision Resources found that the market for 
agents to treat IBD totalled more than £0.6bn (approx. €0.85bn) in 2001 and is expected to increase 
to £1.2bn (approx. €1.7bn) by 2011. During the course of the VIGOR++ project, factors influencing 
pharmaceutical sales will include the expanded use of Infliximab and the launch into the market of 
other biologic agents, which carry a high price tag. We expect that successful outcomes from the 
VIGOR++ project (including the disease index, the software environment and the technology 
roadmap) will absolutely appeal to pharmaceutical companies looking to develop or test new drugs 
in relation to diseases of the GI tract. 
Expected Impact V (on the European industry and academic institutions) 
Reinforced leadership of European industry and strengthened multidisciplinary research excellence 
in supporting innovative medical care 
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, man-power, 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 are only feasible with extensive European 
cooperation: the critical mass in terms of skills in this area is simply unavailable at national level. It 
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.  
Image processing and visualisation often focuses on extracting more information from acquired 
images. This is mostly accomplished by processing the images with additional knowledge of an 
underlying model and jointly visualising registered images with more information, which is especially 
important for processes that concern multiple scales. The imaging industry is certainly strengthened 
by providing image processing and visualisation ICT tools that smoothly integrate with biomedical 
modelling such as developed in VIGOR++.  
The research outcome is going to be evident via the application of sophisticated tools for 
segmentation, feature extraction, classification and visualisation. The research activities will 
strengthen Europe’s technology base and ensure its leadership in ICT, help drive and stimulate 
product, service and process innovation and creativity through ICT use and ensure that ICT progress 
is rapidly transformed into benefits for Europe’s citizens, businesses, industry and governments in 
the field of Crohn’s disease. The proposed approach which involves an open software architecture 
with accurately documented and well defined interfaces for the developed tools, creates a strong 
backbone for attacking other physiologic simulation research questions. 
 
41 According to Dr. George Mills, Director, Division of Medical Imaging and Radiopharmaceutical Drug Products 
at the FDA: “Modelling based on imaging is a key technology for assessing, accelerating the development 
of, and guiding the use of, new therapeutic options.”  

70 
 
Relevant European research projects 
Numerous prior and ongoing EU projects are relevant to the S&T domain of VIGOR++. Focusing on 
the topics across the related application domains at EU level, we find at least the next ongoing 
projects to be relevant. 
The VPH concept has a precursor initiative, the EuroPhysiome, which reflects a grouping of 
researchers connected to the International Union of Physiological Sciences (IUPS) at the European 
level. This grouping represents a wish for a stronger and more co-ordinated representation of 
European research on the international scene. The STEP Coordination Action developed the VPH 
roadmap (STEP: a Strategy for the EuroPhysiome). The GIOME project is the GI part of the Physiome. 
The modelling of the anatomy and function of the digestive system has provided a platform for the 
development of scientific and educational tools, and diagnostic medical devices, for understanding 
the pathophysiology and pharmacology of symptoms and pain. Success stories from this 
development are multimodal and functional imaging probes and stimulation techniques that are 
now being commercialised by European start-up companies and used for clinical drug trials and 
diagnostic and prognostic clinical studies. The Renal Physiome project is a French-led international 
collaboration that develops a virtual kidney. 
VPH related work was undertaken as part of FP6. @neurIST (IP) aimed to develop an IT 
infrastructure for the management of heterogeneous data associated with the diagnosis and 
treatment of cerebral aneurysms. (Project dates: 02/06 - 01/10) and ACGT (IP) Advancing Clinico-
genomic trials on cancer: Open Grid services for improving medical knowledge discovery The ACGT 
project aimed to develop a GRID platform to support and stimulate further exchanges of both clinic 
and genetic information, with a particular focus on breast cancer treatment. (Project dates: 02/06 - 
01/10). The Living Human Project simulated the muscles and skeleton needed to animate the virtual 
body. ImmunoGrid is another project that built a computer model of the human immune system 
using grid technologies. It integrates processes at molecular, cellular and organ levels. The LHDL 
(Living Human Digital Library) project developed interactive digital library services so as to make 
easier to share and to access collections of complex biomedical data relative to the musculoskeletal 
system. 
Lately, a significant boost for VPH research was given by the VPH Initiative as part of Call FP7-ICT-
2007-2.  
Although none of the above projects focuses on GI tract or diseases related to Crohn’s, VIGOR++ will 
closely monitor their work and take as much as possible advantage of the knowledge generated by 
them.  
Plan for the use and dissemination of foreground knowledge 
Professional management and protection of the results of the project are fundamental, and 
therefore we have dedicated sufficient effort to Knowledge and IPR management. This is in the form 
of a separate work package (WP8) that implements these activities. This dedicated work package will 
assume responsibility for the management of intellectual property and other aspects of innovation, 
since this requires a co-ordinated approach. The WP8 leader specializes in exploitation of scientific 
research, is close to the target audiences and aware of their needs, which enables the consortium to 

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quickly spot the opportunities offered by the application of new technology. The foundation for the 
proposed strategy is a synthesis of a sophisticated research to deliver relevant ICT tools, a good 
understanding of the market dynamics, mutually agreed expectations regarding exploitation, and a 
joint planning.   
Dissemination of project results 
The dissemination and exploitation of knowledge is a key ingredient for a successful research 
project. Such transfer of outcomes is not a process which begins when research is complete, but one 
which runs from the first days of a project to its completion and beyond. Consortia are often 
unaware of the interests of other stakeholders and often use very different language and concepts. 
It is the ambition of VIGOR++ to prevent such confusion that hinders knowledge transfer, for 
instance by a high visibility in media as well as in scientific forums, which will stimulate 
communication with potential users. VOD brings in VIGOR++ the unique combination of contacts at 
the cutting edge of technology transfer, research and practical business experience. The target 
audiences for VIGOR++ dissemination are shown in Table 11. This classification underpins the 
rationale for different activities to achieve knowledge/technology transfer to different target 
audiences, such as: annual workshops, the project‘s scientific publications (papers and deliverables) 
and press releases, the Annual Workshops, Advisory Committee,  the technology roadmap, the 
project’s web portal and the Interest Group. 
Table 11 Target audiences for VIGOR++'s dissemination and exploitation activities. 
Target audience 
Why to them? 
What is for them? 
Physicians (e.g. radiologists, 
gastroenterologists, general 
practitioners). 
To obtain feedback so that the 
design and functionality of the 
system may be improved. 
Increased efficiency of Crohn’s 
disease management by means of 
the VIGOR++ tools. 
Pharmaceutical industry. 
It is the fastest growing market for 
medical image processing 
techniques. 
Increased efficiency of clinical trials. 
Manufacturers of medical imaging 
equipment such as MRI scanners 
and post-processing workstations. 
Potential mediators to pass the 
VIGOR++ tools to end users and 
stimulate adoption of methodology. 
A competitive advantage gained by 
fast support adoption of 
sophisticated tools. 
IBD Patients groups. 
The ultimate user. 
Improved quality of life, minimally 
invasive diagnostic procedures, 
improved treatment, and minimised 
length of stay in hospitals. 
Academics. 
Image processing, pattern 
recognition and scientific 
visualisation are important research 
topics in universities. 
Extension of research into new 
fields inspired by novel VIGOR++ 
technology. 

72 
 
Software engineers.  
May give feedback regarding the 
project’s software design. 
Acquire knowledge regarding new 
implementation designs. 
The opportunity to hear first about 
new tools. 
Students. 
The VIGOR++ topics are taught 
extensively in universities. 
Comprehensive knowledge of state-
of-the-arts techniques such as 
delivered by VIGOR++ significantly 
enhances their career 
opportunities. 
VIGOR++ partners. 
To benefit from other partner’s 
expertise and skills. 
Knowledge, contacts and tools 
sharing. 
 
It frequently happens in collaborative projects that so much information is unavailable for everyday 
use because it is fragmented. Hence, WP8 will handle the information that is distributed, e.g. via 
mailing lists and made available on the project's external website. It will ensure that such 
information is readily accessible, updated regularly, and stored appropriately. Specifically, WP8 will 
keep tract of all project publications, suggest conferences and journals to aim for and keep track of 
submissions, attend professional events and suggest and support a partner’s participation.  
The project aims to participate in several conferences, exhibitions and industry fairs to showcase its 
intermediate and final results and discuss them with interested participants. These occasions will 
also serve to demonstrate prototype systems, enabling early feedback as well as outreach. 
Targeted conferences in which the project partners will be seeking to promote VIGOR++'s results 
include: Medical Image Computing and Computer Assisted Intervention Conference (MICCAI), IEEE 
International Conference on Image Processing, International Conference on Pattern Recognition, 
IEEE Visualisation Conference, and International Symposium on Gastroenterology.  
Moreover, we aim to publish the project’s results in highly esteemed journals, such as Radiology, 
IEEE Transactions on Medical Imaging, Medical Image Analysis Journal, IEEE Transactions on Pattern 
Analysis and Machine Learning, IEEE Transactions on Visualisation and Computer Graphics, 
Gastroenterology, Computer Graphics and Applications. 
To foster a high level of dissemination among the targeted end-user groups VIGOR++ results will be 
demonstrated in relevant exhibitions and congresses: RSNA - Radiological Society of North America, 
ECR - European Congress of Radiology, and SIR - Society of Interventional Radiology. 
Furthermore, organisations such as the European Crohn's and Colitis Organisation (ECCO), the 
European Patient Forum, and UK’s Health Technologies Knowledge Transfer Network will be 
approached so as to communicate the aims and results of the project as appropriate. Moreover, the 
consortium maintains strong links with pharmaceutical companies (e.g. GSK, Pfizer, UCB), clinical 
research organisations (e.g. Timaq) and manufacturers of medical imaging equipment (e.g. Philips, 
Siemens). In order to have a more direct impact on practitioners and industry, VIGOR++ will organise 
four important additional dissemination activities. 

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Interest Group 
It is envisaged that several clinical, academic and industrial representatives will have an ongoing 
association with the project. VIGOR++ will stimulate such association by creating an Interest Group 
that will be 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 shall be 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, we have had close interaction with representatives from Philips 
Healthcare and GSK who expressed a strong interest in joining the Interest Group during the 
preparation phase of this project. 
Contributions to academic curricula 
An increasing number of medical and engineering students have become interested in the topic of 
medical imaging. Simultaneously, medical imaging problems are posing enormous challenges, so 
that a high and increasing demand exists now for academically trained, technically skilled personnel. 
TUD, ETHZ and ZIB have a longstanding scientific and commercial relationship with various industrial 
participants and are prime providers of qualified staff. The scientific excellence and technical skills 
built through the VIGOR++ project will be incorporated as case studies in various courses. Moreover, 
it will influence the university curricula of the academic participants for the benefit of the student 
communities at those universities, and eventually for the benefit of industries employing those 
students.   
Contributions to standards  
VIGOR++ will deliver methods for objective, comprehensive and quantitative measurement of 
Crohn’s disease severity. Therefore, it will set a new standard for existing disease indices (e.g. CDAI, 
CDEIS), which are all limited regarding those aspects. 
There are also important implications with regards to adopting such disease indices in patient 
records. For example in UK’s NHS, the National Care Records Service (Connecting for Health) aims to 
create a nationwide computerised store of each person’s medical information. However, it is 
unrealistic to expect this electronic patient record system to contain all the necessary details in the 
foreseeable future. Creating an IBD Management framework “is a medium-term and future proof 
solution for the over-worked, repeatedly distracted gastroenterologist. And the patient, their 
general practitioner and the IBD nurse benefit, too”.42 
The VIGOR++ tools will be integrated in the 3Dnet™ Suite environment that has been developed and 
commercialised by B3D. 3Dnet™ Suite is an open platform for medical image post processing. It 
represents the latest trends in the ICT market as it is deployed following a paradigm called Platform 
as a Service (PaaS); the whole delivery mechanism is online, via an advanced and innovative online 
scripting language dedicated to medical imaging. The platform is a collaborative framework for open 
 
42 Rose J, Dunne I, Grainger SL.  An electronic patient record for inflammatory bowel disease: helping patients 
and doctors. Gut 2001;(Suppl 1)48:A87. 

74 
 
innovation, available to academic and commercial developers for application designers to use 
existing tools (e.g. for data reading, filtering and standard visualisation), or add their own to create 
new applications. Hence, by making the new tools resulting from VIGOR++ available to the existing 
community of 3Dnet™ Suite developers the project will stimulate faster adoption.  
Dissemination workshops 
The knowledge delivered by the project will be disseminated through workshops, to be hosted by a 
member of the consortium in conjunction with the annual project reviews. The workshops target to 
broaden the participants' appreciation for and interest in the field of the VPH, and in particular to 
extend their knowledge of the VIGOR++ tools and their application on Crohn’s disease diagnosis and 
treatment. The target audience of the workshops will include radiologists, gastroenterologists, 
pharmaceutical industry representatives, specialised nurses, patient group representatives, 
manufacturers of medical imaging equipment as well as medical imaging software engineers. 
Exploitation of project results 
The performance of an R&D project such as VIGOR++ can be judged externally based on outcomes 
such as: 
1. Papers (and citations) 
2. Prizes 
3. Patents 
4. Invention disclosures 
5. Higher degrees awarded 
The nature of the work in VIGOR++, which will result in ICT tools and proof-of-concept medical 
diagnosis systems for the healthcare and pharmaceutical industry, demands that the research team 
operate in a commercially responsible way from the outset, aware of the need to respond to the 
evolution of the external state-of-the-art. There are in fact several commercial reasons for getting 
the partners involved in this research project. Some of them are: 
 
need to innovate on existing products or develop new ones 
 
need to uptake R&D results in order to give our organisations that competitive edge, increasing our 
patient care (for the hospitals) or sales (for the companies) 
 
desire to access new customers or new markets 
 
already performing our own internal research in related areas and want to deepen our knowledge and 
know-how in that particular field of research 
 
value the prestige associated with being part of an important transnational research project 
 
want to build lasting cooperation with other R&D organisations at European level 

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bring funding to conduct further research and technology development 
WP8 will have the responsibility of preparing the project’s Technology Roadmap and subsequently 
Exploitation Plan after reviewing the partners’ capability to exploit the results of the project with 
respect to exploitation rights as outlined in the Consortium Agreement. The Exploitation Plan will 
define the project’s target markets and carry out a thorough analysis in order to identify business 
conditions and opportunities, and also to establish potential commercial routes for the project’s 
results. Like most key technologies, the above cannot be seen in isolation. We understand the 
interactions with complementary technologies and we will take into account the complex 
circumstances (e.g. privacy, safety, user acceptance) in which practitioners operate.  
A crucial aspect to ensure exploitation of the project results is the development of all techniques in 
the 3Dnet™ Suite environment (see above). As such the tools can be straightaway available in a 
clinically usable environment. In fact, the tool can be readily commercially delivered as an optional 
toolbox to clinical sites and to the 3DNet resellers internationally. 
It is recognised that at the end of the project, we may end up with some results that are not ready 
for clinical trials. To that end project partners will need to carry out further development work 
before they can commercially exploit the results in the marketplace. Also, we may need to have the 
results of the project certified before they can be commercialised. In any case, we will have already 
looked at the whole issue of certification during the actual project implementation stage.  
A market presenting a large opportunity for the output of the project is imaging for clinical trials for 
drugs and devices.  A market report from Decision Resources found that the market for agents to 
treat IBD totalled more than £0.6 billion in 2001 and is expected to increase to £1.2 billion by 2011. 
It is clear that new ICT tools will play a key role in the future of drug development and clinical trials 
by mitigating the cost and risk involved. We believe that there is a significant size market for systems 
like VIGOR++ in clinical trials, since it offers tools to quantitatively express the effect of therapy  
Another route for technology exploitation from the project is for researchers to set up new 
companies or enter into licensing agreement. Many researchers may be deterred by lack of 
knowledge of business processes. Where such advice is not provided by the participants’ own 
internal services, participant VOD will provide such advice (e.g. new business planning, from 
feasibility studies to obtaining finance) to those researchers interested in creating start-ups or in 
general seeking to commercialise their research results. 
Involvement in the exploitation of results 
The nature of the work in VIGOR++, which will result in ICT tools and proof-of-concept medical 
diagnosis systems for the healthcare and pharmaceutical industry, demands that the research team 
operate in a commercially responsible way from the outset, aware of the need to respond to the 
evolution of the external state-of-the-art. All partners have clear exploitation plans for their 
respective work and are therefore highly committed to the project goals. 
TUD (1) has a history of many successful applications developed in close cooperation with industry. 
Amongst these, it has developed methods for CT colonography with Philips Healthcare (Clinical 

76 
 
Science & Advanced Development) and AMC since 2001. These methods were clinically validated 
and integrated in Philips ViewForum workstation. TU Delft has an active IP policy, with dedicated 
patent officers and business developers working at the Valorisation Centre offering support to 
scientists that operate on the brink of research and industrial applications. Currently, the 
exploitation of results will include the use of the VIGOR++ code to enhance the service offered to 
collaborating partners and to make TUD more competitive within the VPH research arena. TUD also 
intends to use the ICT tools in future European Commission funded projects, both as a platform to 
deliver simulation results, and as starting point for future system concepts. 
UCLH (2) has widely studied the use of MRI in the assessment of Crohn’s disease activity, both in the 
small bowel and colon. Also, UCLH has extensive experience in computer aided detection software 
evaluation of the colon. Additionally, it has been active in creation of national and international 
guidelines in diagnosis and monitoring of the two main IBDs (Crohn's disease and ulcerative colitis). 
The principle investigators have had a special interest in the increased risks of cancer complicating 
long-term Crohn’s disease. Its prevention and early detection is currently highly dependent on 
expert colonoscopy, the acquisition of multiple biopsies and careful histological evaluation. The 
project has the clear potential to reduce if not to eliminate this expensive and invasive process, and 
thus to reduce the increased risk of death from colorectal cancer in IBD patients. Further, it would 
enable UCLH to pioneer the quantitative Crohn’s clinical disease severity index. 
ETHZ (3) has developed a platform for computational pathology together with the University 
Hospital Zurich. Machine learning is an integral part of the decision making in this processing 
pipeline which is primarily used for research purposes in the biomedical context of cancer research. 
The machine learning algorithms can also be employed in clinical diagnosis as shown in the micro-
metastases detection of skin cancer (melanoma) in lymph nodes. Over the last five years the 
machine learning laboratory has pursued research projects with Roche Diagnostics and with 
Hoffmann-La Roche AG i.e., on diabetes research. The mixture of industrial contract research and 
the support of spin-off companies in ETHZ’s exploitation strategy ensure that both established 
industries as well as SMEs and new companies will benefit from the developments of VIGOR++. 
ZIB (4) has developed Amira, an advanced framework for visual analysis of data, particularly 
biomedical data. Since Amira and a derived version Avizo were commercialized, ZIB has continued to 
develop the academic version ZIBamira. Concurrently, ZIB closely collaborates with Visage Imaging in 
Berlin, Germany (distributing the Amira software) and the VSG Visualisation Sciences Group in 
Bordeaux, France (distributing Avizo).  Industrial and institutional collaborators of ZIB will benefit 
from the results generated as a part of VIGOR++. The sophisticated visualisation techniques, 
including interactive manipulation, cutting, reformatting, and unfolding validated in this project will 
be especially of interest. Clearly, other projects in ZIB will also benefit from the research project. 
B3D (5) has developed 3Dnet™ Suite, an advanced analysis and visualisation technical framework for 
medical imaging. 3Dnet™ Suite is the outcome of many years research in the optimisation of novel 
algorithms for medical imaging and has evolved to a mature Software as a Service (SaaS) and cloud 
computing platform, upon which many medical imaging applications are based. A recent survey 
within our customer base suggests that 3Dnet™ Suite users realize an average of 12.3% in increased 
throughput and 17.1% in increased productivity. For example 3Dnet™ Suite has been applied in 

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diagnostic screening of colonic cancer (Virtual colonoscopy) by examining and classifying 
morphological abnormalities of the lumen of the colon, indicating the presence of cancerous polyps. 
The company has now identified and analysed a market niche in creating virtual models of the GI 
tract and believes that the combination of 3Dnet™ Suite with the knowledge introduced by the 
other partners will result in a premium technically driven solution. 
AMC (6) is one of the leading research groups regarding imaging of Crohn’s disease, along with 
UCLH. It has developed MRI sequences for Crohn’s disease and performed several clinical studies on 
MRI in Crohn’s disease. Moreover, it routinely uses such techniques in patient care. AMC also has 
extensive experience in developing and evaluating other new methods for imaging the GI tract such 
as CT-colonography (virtual colonoscopy). In the field of MRI in Crohn’s disease crucial aspects not 
addressed until now and topic of the project are quantitative methods for determining all (potential) 
relevant imaging features of disease activity and extent. The colonoscopy and microscopy 
(histopathology) data to be acquired will influence the work of the research group and lead to 
enhanced understanding of the effects on Crohn’s disease genesis and treatment. 
VOD (7) is an innovation accelerator company with a project portfolio covering various emerging 
technical fields. Vodera assists high-tech start-ups, technology corporations and universities create 
competitive advantage by rapidly developing new systems and solutions, commercialising 
technology breakthroughs and transferring knowledge across projects and business units. The team 
is working with mature processes, such as technology roadmapping, that have been carefully 
developed and tested. The proposed project would enable the company to expand its knowledge 
base in the state of the art medical diagnostics, which is recognised to be one of the fastest growing 
areas in ICT. VIGOR++ would also allow Vodera to promote the expertise of the company to future 
clients and establish contacts with experts and suppliers of technologies throughout the EU. In 
parallel, Vodera’s participation in VIGOR++ will enable the consortium members to understand more 
about the innovation process and influence the research work by market developments. 
Management of intellectual property 
The Consortium Agreement will be governed by an IPR management cube, in which IPR issues are 
structured along three dimensions 
 
the type of the asset considered (content or technology) 
 
the point of creation of the asset (pre-existing assets vs. assets created during the project) 
 
the type of intended use (use by consortium partner during the project or after the project, 
commercial use outside the project, non-commercial use outside the project). 

78 
 
 
Figure 10 The IPR management cube.The Consortium Agreement will be signed by the consortium partners 
before the beginning of the project. It will identify potential issues concerning pre-existing IPR rights as well as 
those generated by the work of the consortium, settlement of internal disputes and commercial exploitation 
of results.  The Consortium Agreement, which will also govern and grant licenses to VIGOR++ consortium 
members and third party organisations wishing to benefit from VIGOR++ IPR.  
Protection of partners' background knowledge will be provided by use of confidentiality clauses in 
the Consortium Agreement. Pre-existing know-how will be brought in by each partner in order to 
contribute to the success of the VIGOR++ project. In principal, the IPRs for pre-existing technology 
stay with its original owners. Naturally, the use of these technologies is free of charge for the 
consortium partners during the project for purposes of the project. Partners will also be obliged to 
licence on fair and reasonable terms, any background necessary for exploitation of the foreground 
IPR developed in VIGOR++. 
Intellectual property rights issues will be on the agenda of each project management meeting. A 
decision will be made case by case after consultation with the Steering Committee if it is most 
suitable to proceed with a provisional patent application or, alternatively, to prepare a public 
presentation of the idea. The Project Manager will maintain an archive of all project -external and 
internal- technical documents and discussions. The archive may be later used as a base for resolving 
conflicts related to intellectual property rights filings. These procedures ensure that intellectual 
property will be secured in the interest of project partners.  
If it is not possible to determine exactly the ownership of that knowledge i.e. several partners 
participated in that specific development, ownership will be equally shared by each partner. The 
Consortium Agreement will state that intellectual property generated during the project can be 
licensed to the other partners under fair and reasonable terms. This agreement will be in line with 
the obligations of the EC model contract with regard to protection, use and access rights.  
A distinction between licenses for research purposes and licenses for exploitation will be made. It is 
the goal for most of the technology created as part of the VIGOR++ project to keep non-commercial 
use free of charge. 

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Importantly, the Consortium Agreement will take into account the “Guide to Intellectual Property 
Rights for FP7 projects” Version 28/06/2007, issued by Research DG. The IPR management of the 
project will also take into account the following published regulations and directives: 
 
Commission regulation (EC) No 772/2004 of 27 April 2004 on the application of Article 81(3) of the 
Treaty to categories of technology transfer agreements. 
 
Communication from Commission Notice Guidelines on the application of Article 81(3) of the Treaty. 
 
Directive 2004/48/EC of the European Parliament and of the council of 29 April 2004 on enforcement 
of Intellectual Property Rights. 
Ethical issues 
The project will comply with national data protection legislation, European Union legislation, respect 
international conventions and declarations and take into account the Opinions of the European 
Group on Ethics. A specific task has been included in the work plan to explicitly address ethical 
issues.  
The researchers who handle the medical data will ensure that the data from volunteers will remain 
anonymous. The anonymisation will take place at the collection points (AMC,UCLH), i.e. prior to 
provision for analysis to the ICT project partners. Informed consent will be required whenever ICT 
research involves volunteers in experimentation, and accessing personal medical data records. 
Before consent is sought, information will be given specifying the risks, and benefits for those 
involved in a way they understand. 
The consortium will follow the Helsinki Declaration, the Charter of Fundamental Rights of the EU, 
the EU directives related to good clinical practice and other international regulations related to 
conducting clinical studies involving humans. Local Ethical Committees will be in place to ensure the 
adequate attention to ethical issues. The partners have broad experience regarding such aspects 
through previous clinical projects similar to VIGOR++. 
Table 12 Ethical Issues Table. 
 
YES  
PAGE 
Informed Consent 
• 
Does the project involve children? 
• 
Does the project involve patients or persons not able to give 
consent? 
• 
Does the project involve adult healthy volunteers? 
x 
21 WP2 (T2.1 - T2.4) 
• 
Does the project involve Human Genetic Material? 
• 
Does the project involve Human biological samples? 
X 
21  WP2 (T2.1 - T2.4) 
• 
Does the project involve Human data collection 
x 
21  WP2 (T2.1 - T2.4) 

80 
 
 
YES  
PAGE 
Informed Consent 
• 
Does the project involve children? 
• 
Does the project involve patients or persons not able to give 
consent? 
• 
Does the project involve adult healthy volunteers? 
x 
21 WP2 (T2.1 - T2.4) 
Research on Human embryo/foetus 
• 
Does the project involve Human Embryos? 
• 
Does the project involve Human Foetal Tissue / Cells? 
• 
Does the project involve Human Embryonic Stem Cells? 
Privacy 
• 
Does the project involve processing of genetic information or 
personal data (e.g. health, sexual lifestyle, ethnicity, political 
opinion, religious or philosophical conviction)? 
x 
21  W2 (T2.1 - T2.4) 
• 
Does the project involve tracking the location or observation of 
people? 
Research on Animals  
• 
Does the project involve research on animals? 
• 
Are those animals transgenic small laboratory animals? 
• 
Are those animals transgenic farm animals? 
• 
Are those animals cloned farm animals? 
• 
Are those animals nonhuman primates? 
Research Involving Developing Countries 
• 
Use of local resources (genetic, animal, plant etc) 
• 
Benefit to local community (capacity building i.e. access to 
healthcare, education etc) 
Dual Use 
• 
Research having direct military application 
• 
Research having the potential for terrorist abuse 
 
 

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