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Sharif, Hayfa (2023) Novel magnetic resonance imaging approaches to study diseases of gastrointestinal function in children. PhD thesis, University of Nottingham.

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Abstract

Background: Gastrointestinal (GI) function in paediatric health and GI disease is a largely unexplored area due to limitations and invasiveness of current techniques. Magnetic resonance imaging (MRI) has been increasingly used to study GI function in adults, but very little has been translated to the paediatric arena to date.

Aims: This work aimed therefore to develop and deploy new MRI methods and endpoints to study gastrointestinal function in paediatric health and disease.

Methods: The work carried out comprised four main work packages.

1. The translation of existing adult MRI measurement protocols of gastric emptying and small bowel motility to paediatric health and patients with Crohn’s disease (CD). The MRI scanning protocol was implemented on a 1.5T MRI scanner and 15 children (13 healthy volunteers and 2 patients with CD) were imaged before and serially after a feeding intervention. Gastric emptying, gallbladder volumes, small bowel water content and small bowel motility were measured. The motility measurements were carried out on a new commercial platform.

2. The evaluation of the safety and feasibility of new MRI methods to measure whole gut transit time (WGTT) in paediatric constipation. This was a first-in-child clinical trial of a new mini-capsule medical device that our team had recently developed was used. Thirty-five children between 7 and 18 years old (19 healthy volunteers and 16 patients with constipation) were studied. They ingested 24 mini-capsules per day for three days and were then imaged following a common radiopaque markers protocol. Whole gut transit time was determined from the count of the mini-capsules remaining in the gut at days 4 and 7.

3. The development of quantitative measurements of colon volume and colon length in paediatric health and constipation. The images from the 35 participants of the above study were used retrospectively to measure regional and total colon volumes by drawing regions of interest manually. Regional and total colon lengths were subsequently measured using a 3D skeletonization method.

4. The development and validation of a protocol for quantitative MRI measurements of gastric emptying on a 0.5T open-design scanner where the participants could sit upright. An initial development and protocol design phase was carried out first. After this, 6 healthy participants were studied before and serially after ingesting an oral glucose challenge drink whilst concomitant 13C stable isotope breath samples were collected for validation.

Key results: MRI measurements of GI function were successfully carried out in children from the age of 6 to 18 years old, without the need for bowel preparations or general anaesthetic.

The data showed rapid increase in small bowel motility after a meal stimulus.

It was safe and feasible to use the new mini-capsule device to measure WGTT in health and paediatric constipation using MRI. The young patients with constipation had WGTT twice as long as the healthy controls (P < 0.0001). Their colon, corrected for body surface area, had 40% larger volume (P =0.0081) and was 17% longer (P =0.0037) than for the controls, with the sigmoid-rectum area being most affected.

Lastly, a new protocol to measure gastric emptying in the upright position was developed and demonstrated.

Conclusions: This work achieved its aims successfully. New methods and endpoints to study gastrointestinal function in paediatric health and disease were developed and deployed. Original data quantifying aspects of paediatric GI function was collected, advancing the field. Such data and methods can help to provide a better understanding of paediatric GI function and dysfunction ultimately helping, in turn, diagnosis and treatment.

Item Type:	Thesis (University of Nottingham only) (PhD)
Supervisors:	Marciani, Luca Smyth, Alan Gowland, Penny Devadason, David
Keywords:	Magnetic resonance imaging; Paediatrics; Gastrointestinal function
Subjects:	W Medicine and related subjects (NLM Classification) > WI Digestive system W Medicine and related subjects (NLM Classification) > WS Pediatrics
Faculties/Schools:	UK Campuses > Faculty of Medicine and Health Sciences > School of Medicine
Item ID:	73597
Depositing User:	Sharif, Hayfa
Date Deposited:	31 Jul 2023 04:41
Last Modified:	31 Jul 2023 04:41
URI:	https://eprints.nottingham.ac.uk/id/eprint/73597

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