Short summary

Inflammatory bowel disease (IBD) constitutes a specific diagnostic challenge in children and adolescents. Invasive endoscopic procedures are required to determine inflammation grade and localization. In the paediatric population, endoscopy requires generel anaesthesia. 

We aim to determine the accuracy of the PET/MRI in diagnosis and differentiation of  IBD as well as in inflammation monitoring in relation to biological therapy in patients with Crohn's disease. Furthermore we will investigate the role of PET/CT in a mouse model with chemically induced colitis and evaluate a potential treatment for IBD in this model. 

Rationale

Diagnosing and monitoring inflammation in pediatric IBD constitutes a specific challenge due to the particular clinical characteristics of the pediatric population. With a rising incidence of IBD, in the adult as well as in the pediatric setting, this challenge increases. 

The current diagnostic strategy involves visualisation of the intestinal mucosa through gastroduodenoscopy and ileocolonoscopy. In the pediatric population this requires general anesthesia and furthermore poses the risk of bowel perforation. In addition, a majority of patients with Crohn's disease have small bowel disease, which to a large extent is not visualised during endoscopy. 

Novel technologies have emerged, offering non-invasive ways to diagnose and non-invasively monitor inflammation. Position emission tomography (PET) has been applied and tested in the assessment of disease activity and the identification of inflammation in IBD. The PET scan utilises 18 Fluor labelled-fluro-2-deoxyglucose (FDG) and the increased uptake of this sugar molecule in inflammatory cells. When merging PET and CT excellent anatomical imaging is achieved. PET/CT has been shown to offer a sensitivity up to 100% in detecting deep ulcers and strictures.

The clinical use of PET/CT in IBD is limited due to significant radiation exposure. Recently, PET has been merged with Magnetic Resonance Imaging (MRI) scans leading to detailed anatomical imaging with minimal radiation exposure. 

To our knowledge no pediatric studies in IBD have been performed with PET/MRI.

Study aims

To evaluate whether PET/MRI is an accurate method to diagnose and differentiate Crohn's disease and Ulcerous colitis. 50 patients suspected of IBD will undergo the standard diagnostic evaluation program according to EPHGAN guidelines. A PET protocol will be added to the standard MR-enterography. Results from the PET/MRI scan will be compared to the combined findings of the standard evaluation, including disease activity index (PCDAI/PUCAI), faecal calprotectin, biochemistry as well as endoscopic and histological findings. 

A pilot study of 10-15 patients previously diagnosed with CD who will undergo PET/MRI scan as an investigational procedure before initiation of biological treatment with an anti-TNF-alpha antibody (infliximab, adalimumab) because of disease relapse or steroid dependent disease. Patients will be scheduled for a PET/MRI again after one month. This study will evaluate if PET/MRI can diagnose a flare in Crohn's disease and if PET/MRI is a reliable imaging tool to monitor intestinal inflammation. In this study the patient will act as his/her own control.

Additionally we aim to test if PET/CT scan can differentiate between normal and inflamed colon in mice with a chemically induced colitis and to evaluate the potential effect of chitin and agonistic anti-CD3 antibody in this animal model. 

Description of the cohort

Children and adolescents aged 8 - 25 years. For study 1 we include all patients diagnosed with Inflammatory bowel disease. For study 2 we include patients with Crohn's disase about to start anti-TNF-alpha therapy due to steroiddependent disease and/or relapse. 

Data and biological material

Clinical symptom scores (wPCDAI/PUCAI), blood, feces, endoscopy reports, histologic examination reports, PET/MRI reports. 

Collaborating researchers and departments

Department of Nuclear Medicine, Odense University Hospital

• Professor Poul Flemming Høilund-Carlsen, DMSc., 

Department of Nuclear Medicine, Odense University Hospital

• Consultant Henrik Petersen.

Department of Paediatrics, Lillebaelt Hospital

• Consultant Anne Mette Valsted.

Department of Gastroenterology, Odense University Hospital

• Professor Jens Kjeldsen, PhD.

Institute of Molecular Medicine, University of Southern Denmark

• Professor Uffe Holmskov, Ph.D., DMSc.