Defining and validating the role of intestinal ultrasound for assessment of inflammatory bowel disease

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dc.contributor.advisorAndrews, Jane
dc.contributor.advisorBryant, Robert
dc.contributor.authorGoodsall, Thomas Millington
dc.contributor.schoolAdelaide Medical School
dc.date.issued2024
dc.description.abstractIntroduction Inflammatory bowel disease (IBD) is a chronic condition necessitating regular assessment of disease activity via a composite of non-invasive and invasive tests including biomarkers, imaging and endoscopy. Treatment targets in Crohn’s disease and ulcerative colitis target have evolved toward endoscopic mucosal healing, with transmural healing considered a desirable deep treatment endpoint. Whilst endoscopy is invasive and associated with risk and cost, intestinal ultrasound (IUS) is a low cost and non-invasive method by which transmural intestinal inflammation can be assessed at the point-of-care by the treating specialist. Furthermore, IUS facilitates assessment of endoscopically inaccessible bowel such as in structuring Crohn’s disease and performs similarly to magnetic resonance enterography in terms of accuracy. IUS has been routinely used in select European IBD centres for more than 20 years, however, there has been no consensus on the optimal method to objectively assess disease activity and further validation data has been required to address gaps in the literature and support the use of intestinal ultrasound internationally in clinical trials and practice. Aims The aims of this these were to: 1. Explore and validate IUS in Crohn’s disease and describe the inter-rater and intra-rater reliability of IUS assessment at the point-of-care and in centralised reader models to inform future use of IUS in Crohn’s disease clinical trials. 2. Explore and validate the use of IUS to assess disease activity in ulcerative colitis. 3. Describe the use of IUS to assess Crohn’s disease during a global pandemic. Methods A systematic review of IUS activity indices in inflammatory bowel disease was performed to examine the available scoring methods and the gaps in the literature. To better define a unified approach to intestinal ultrasound assessment of Crohn’s disease activity and resolve areas of conflict and uncertainty identified in the systematic review, A Research and Development (RAND) appropriateness methodology was performed with an international panel of IUS experts. Following on from this, a validation study of IUS in Crohn’s disease was performed, with study parameters informed by the RAND appropriateness study. Inter- and intra-rater reliability were reported for both point-of-care and centralised readers with development of recommendations for the use of intestinal ultrasound in Crohn’s disease clinical trials. Thereafter, a validation study of the role of IUS combined with faecal calprotectin to determine ulcerative colitis activity was performed using histological activity as a gold standard. Finally, a cross-sectional study was performed to describe and understand the concerns and behaviours of patients with IBD during the Coronavirus -19 pandemic regarding disease activity monitoring during restricted healthcare access and perceptions of personal risk of infection or severe disease in the context of IBD medication use. Results Multiple indices of IUS activity assessment in IBD were identified in systematic review (n=21), most of which were at risk of bias and confounded by ambiguous parameter definitions and lack of validation. IUS was considered a highly useful assessment tool in Crohn’s disease in RAND analysis and the optimal machine calibration, performance, and documentation of intestinal ultrasound was defined. Bowel wall thickness was considered the most useful activity parameter using a cut-off of 3mm for all bowel segments and all age groups. It was not possible to achieve agreement on the optimal way to assess activity parameters of colour Doppler imaging, mesenteric inflammatory fat, or bowel wall stratification. It was also not possible to achieve agreement of which, if any, existing activity parameters were best suited to Crohn’s disease activity assessment. Crohn’s disease activity parameter inter- and intra-rater reliability was greatest for continuous BWT, categorical colour Doppler signal, binary inflammatory fat, and binary bowel wall stratification addressing the identified areas of uncertainty. In UC, a composite score of IUS activity and faecal calprotectin showed greater correlation with histological activity in ulcerative colitis than faecal calprotectin alone. Patient with inflammatory bowel disease reported heightened perceived susceptibility and severity risk with COVID-19 which resulted in unilateral medication cessation in 11% of respondents. Most respondents preferred telehealth and demonstrated a preference for non-invasive activity assessment as offered with intestinal ultrasound. Conclusions IUS is uniquely positioned as an assessment tool in IBD offering affordable, tolerable, and detailed assessment of transmural intestinal inflammation at the point-of-care. Disease activity assessment is accurate and reliable with substantial intra-rater and inter-rater correlation. This body of work has moved towards defining optimal IUS metrics for trials and clinical practice and advanced the field through provision of a structured approach to activity assessment and positioning IUS as an integral clinical tool.
dc.description.dissertationThesis (Ph.D.) -- University of Adelaide, Adelaide Medical School, 2024en
dc.identifier.urihttps://hdl.handle.net/2440/145894
dc.language.isoen
dc.provenanceThis electronic version is made publicly available by the University of Adelaide in accordance with its open access policy for student theses. Copyright in this thesis remains with the author. This thesis may incorporate third party material which has been used by the author pursuant to Fair Dealing exceptions. If you are the owner of any included third party copyright material you wish to be removed from this electronic version, please complete the take down form located at: http://www.adelaide.edu.au/legalsen
dc.subjectInflammatory bowel disease
dc.subjectCrohn’s disease
dc.subjectUlcerative colitis
dc.subjectintestinal ultrasound
dc.subjectclinical trial
dc.subjectvalidation study
dc.titleDefining and validating the role of intestinal ultrasound for assessment of inflammatory bowel disease
dc.typeThesisen

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