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Title: The application of novel imaging modalities in the monitoring of inflammatory activity in Crohn's disease
Author: Russo, Evangelos Alessios
ISNI:       0000 0004 5366 0782
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2015
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Clinical scores, serum and faecal markers, and endoscopy all have limitations in their use as instruments to monitor disease activity in Crohn's disease (CD). Recently, 18F-FDG-PET and novel MRI techniques have been proposed as sensitive and specific methods to quantify the inflammatory load. The aim of this work was to assess the reliability, responsiveness and, to an extent, the validity of outcome measures in these modalities, in monitoring inflammatory activity over a 12-week interval. In addition, two receptors, TSPO and IL-2R were assessed on tissue specimens ex-vivo for their potential to act as alternative targets for molecular imaging in CD. Three distinct groups of patients were recruited, 2 of which participated in the clinical imaging study, and one to donate tissue for the laboratory work. Dual timepoint FDG-PET and MRI scanning was performed within 1 week (Group 1) to assess the test-retest reliability of the imaging outcome measures, and before, and twelve weeks into anti-TNFα therapy (Group 2) to assess their responsiveness indices. The third group contributed tissue during scheduled intestinal resection for assessment of TSPO and IL-2R interactions with their corresponding radioligands. To support the latter study, stored tissue sections were also obtained for immunohistochemical assessment of target receptor expression. Results on 22 patients show that PET endpoints such as SUVMAX and SUVMEAN have high responsiveness and reliability indices and demonstrated significant differences in anti-TNF responders compared to non-responders. The finding of luminal FDG signal may affect the face validity of the scan. MRI modalities appeared less responsive at three months. Analysis on ex-vivo specimens showed increased abundance of TSPO in normal bowel, but a relative over-expression in inflamed specimens which was not statistically significant. IL-2R appeared more abundant in transmural sections containing severe CD, but autoradiographic corroboration was not achieved for technical reasons.
Supervisor: Orchard, Timothy; Matthews, Paul Sponsor: Wellcome Trust ; GlaxoSmithKline
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available