About the Project
The DOME study: Development Of MR Elastography of the bowel
Crohn’s disease (CD) is a life-long pan-enteric Inflammatory Bowel Disease (IBD). The UK IBD prevalence is 620,000 (1).
CD has a relapsing and remitting disease pattern with a progressive disease behaviour from an inflammatory disease phenotype to a more fibrostenotic disease behaviour. 15% of CD patients experience such complications at diagnosis with half developing more progressive disease in the first decade (2-4). Predominantly fibrotic stricturing CD is unresponsive to medical therapy and is best treated by surgery (5) so exact characterisation is paramount.
Contrast-based Magnetic resonance (MR) enterography has a diagnostic accuracy of 90%(6) for inflammatory disease in CD. The sensitivity and specificity of MRI for fibrotic disease is 0.94 and 0.89 respectively, though this relies on contrast enhancement (7).
Contrast agents (8, 9) add cost, carry risk of nephrogenic systemic fibrosis and allergic reaction (10). Brain deposits following repeated use of gadolinium-based contrast agents (11) have been described. A contrast-free MRI modality is urgently needed.
MR elastography is an emerging technique which uses an external driver to generate pressure waves. These pressure waves behave differently within tissues of different physical properties. The MR imaging is coupled to the external driver to generate images which can be used to define tissue stiffness. Present research has investigated liver stiffness in chronic liver disease(12, 13), but the field is now expanding(14). Our hypothesis is that the normal bowel wall and the inflamed and fibrotic bowel walls will have different
tissue stiffness. This technology and may allow a contrast-free method to measure disease activity and to more accurately characterise the disease behaviour.
This work will be undertaken on a 3T MR scanner at SPMIC. The studentship will involve:
Year 1: 5 optimisation scans to be followed by validation in a larger cohort (15 volunteers)
Year 1/2: Finish Validation and repeatability study in the healthy cohort to analyse intra-class correlation
Year 3: CD study (20 subjects): Correlation of elastography outcomes to standard of care (MaRIA score) and exploratory MR (T2 relaxometry, Diffusion weighted imaging and small bowel Motility, in collaboration with SME MOTILENT) and biochemical read-outs (C-reactive protein and faecal calprotectin).
The student will enrol in the n-Trans PhD programme, supplemented by modules in MRI methods, acquisition and data analysis. Student will undertake training in research methods, Good Clinical Practice, Ethics and enrol in the Graduate School Researcher Development Programme. Work will be presented at international conferences and submitted for publication.
References
1. Ghosh N, Premchand P. A UK cost of care model for inflammatory bowel disease. Frontline Gastroenterology. 2015:flgastro-2014-100514.
2. Louis E, Collard A, Oger A, Degroote E, El Yafi FAN, Belaiche J. Behaviour of Crohn9s disease according to the Vienna classification: changing pattern over the course of the disease. Gut. 2001;49(6):777-82.
3. Cosnes J, Cattan S, Blain A, Beaugerie L, Carbonnel F, Parc R, et al. Long‐term evolution of disease behavior of Crohn's disease. Inflammatory bowel diseases. 2002;8(4):244-50.
4. Thia KT, Sandborn WJ, Harmsen WS, Zinsmeister AR, Loftus EV, Jr. Risk factors associated with progression to intestinal complications of Crohn's disease in a population-based cohort. Gastroenterology. 2010;139(4):1147-55.
5. Moran GW, Dubeau MF, Kaplan GG, Yang H, Seow CH, Fedorak RN, et al. Phenotypic features of Crohn's disease associated with failure of medical treatment. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2014;12(3):434-42.e1.
6. Ordas I, Rimola J, Rodriguez S, Paredes JM, Martinez-Perez MJ, Blanc E, et al. Accuracy of magnetic resonance enterography in assessing response to therapy and mucosal healing in patients with Crohn's disease. Gastroenterology. 2014;146(2):374-82 e1.
7. Rimola J, Planell N, Rodríguez S, Delgado S, Ordás I, Ramírez-Morros A, et al. Characterization of inflammation and fibrosis in Crohn’s disease lesions by magnetic resonance imaging. The American journal of gastroenterology. 2015;110(3):432-40.
8. Rieder F, de Bruyn JR, Bao Tung P, Katsanos K, Annese V, Higgins PDR, et al. Results of the 4th Scientific Workshop of the ECCO (Group II): Markers of intestinal fibrosis in inflammatory bowel disease. Journal of Crohns & Colitis. 2014;8(10):1166-78.
9. Ordas I, Rimola J, Rodriguez S, Paredes JM, Martinez-Perez MJ, Blanc E, et al. Accuracy of Magnetic Resonance Enterography in Assessing Response to Therapy and Mucosal Healing in Patients With Crohn's Disease. Gastroenterology. 2014;146(2):374-+.
10. http://www.acr.org/quality-safety/resources/contrast-manual (2014) Manual on Contrast Media v9.; 2014.
11. Administration USFaD. FDA Drug Safety Communication: FDA evaluating the risk of brain deposits with repeated use of gadolinium-based contrast agents for magnetic resonance imaging (MRI); Accessed on the 8th August 2016. 2016.
12. Dulai PS, Sirlin CB, Loomba R. MRI and MRE for non-invasive quantitative assessment of hepatic steatosis and fibrosis in NAFLD and NASH: Clinical trials to clinical practice. Journal of hepatology. 2016;65(5):1006-16.
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