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A first-in-child feasibility study of a new mini-capsule medical device to measure whole gut transit in pediatric constipation using MRI (MAGIC)1Nottingham Digestive Diseases Centre and NIHR Nottingham Biomedical Research Centre, University of Nottingham, Nottingham, United Kingdom, 2Clinical Radiology, Amiri Hospital, Ministry Of Health, Civil Service Commission, Kuwait, 3Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, Nottingham, United Kingdom, 4Medical Physics and Clinical Engineering, Nottingham University Hospitals, Queen’s Medical Centre, Nottingham, United Kingdom, 5Nottingham Children’s Hospital, Nottingham University Hospitals NHS Trust, Queen’s Medical Centre, Nottingham, United Kingdom, 6NUH YPAG, Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom
Synopsis
We developed a new MRI mini-capsule marker device to measure whole gut transit (WGTT) in pediatric constipation to overcome image quality and ionizing radiation limitations of current X-ray methods. Thirty five healthy children and 16 patients with constipation were asked to swallow a number of mini-capsules and imaged, following a common X-ray radiopaque marker protocol. The capsules were imaged successfully in the colon. WGTT was calculated from the capsules count and was significantly longer in the patients compared to the controls. The study also showed excellent feasibility and safety of using the new device and methods in children with constipation.
Background
Fourteen percent of children suffer from constipation at some point in their life 1. In England alone, 27,500 constipated children per year are referred to hospital 2. Management of these children can be difficult and is based largely on symptom reports. An objective measure of gastrointestinal transit time could help a more informed, early therapy selection. However, the gut transit time is very often not tested since current X-ray radiopaque marker (ROM) methods are unable to define the colon anatomy well and also provide a radiation dose, not suitable for young patients. We developed a magnetic resonance imaging (MRI) mini-capsule device alternative to the old x-ray ROM methods to measure whole gut transit.Aims
The primary objective of this study was to collect initial data on gastrointestinal transit in pediatric constipation using the new mini-capsules. We also aimed to collect initial reference ranges for healthy controls and initial information on the safety and feasibility of using the new mini-capsules device.Methods
Thirty five young persons aged 7 to 18 years old with and without constipation were studied. These were 19 healthy young participants (8 male; 11 female; age 16±2 years old; BMI 25±5 kg/m2) and 16 patients (7 male; 9 female; age 11±3 years old; BMI 25±9 kg/m2).The mini-capsules (Figure 1) were small (8mm×4mm), inert, made of plastic and filled with a MRI-visible oil-in-water emulsion. They were co-designed with our Young Persons Advisory Panel (YPAG) and manufactured by JEB Technologies (Suffolk, UK). The participants were asked to swallow 24 mini-capsules each day for 3 consecutive days and were imaged on the 4th day and 7thday (a common X-ray ROM protocol) using a wide-bore, 3T Philips Ingenia scanner sited at the Sir Peter Mansfield Imaging Centre at the University of Nottingham, using a 16 channel RF abdominal receiver coil. A short breath-hold Multiple-echo (mDIXON) sequence (TE1/TE2 = 1.32/2.2 ms, TR = 10 ms, FA = 20°, FOV = 250x350 mm3, ACQ res = 1.8 × 1.8 × 4.4 mm3) was used to acquire both axial and coronal images for measurement of whole gut transit time (WGTT).An additional scan (not part of the actual clinical protocol) was carried out at day 28 if any mini-capsules were detected at day 7, in order to confirm exit of the device from the body for regulatory purposes. EQ-5D-Y Quality of Life (QoL) visual analogue scores (VAS) and safety data were also collected.Whole gut transit time was calculated from the count of the mini-capsules on a derived in-phase minus out-of-phase image set. A common X-ray ROM calculation 3 was then applied, whereby each marker detected in the colon contributes to one hour to the whole gut transit time.Results
The mini-capsules were imaged successfully in the colon of the participants (Figure 2). The whole gut transit time was 78±35 hours (mean±SD) for the young patients with constipation, significantly longer than that for the healthy controls 36±16 hours, p<0.0001(figure 3). There were no significant differences in QoL VAS scores before and after the mini-capsules test for patients (p=0.5547) and also for healthy controls (p<0.5469). The young patients’ EQ-5D-Y was 10% lower than for healthy controls with no significant differences between groups (p=0.7797).Discussion
MAGIC, a first-in-child feasibility study of a new medical device to measure whole gut transit in paediatric constipation using MRI, was successful. The data show that the device had the intended purpose and performance: whole gut transit time was the primary endpoint of the study and it was measured successfully in 35 young participants. Significant differences in whole gut transit time between young patients with constipation and young healthy controls were also detected. The study also showed excellent feasibility and safety of using the new device and methods. All 35 participants who received the device completed the mini-capsule and MRI study successfully. The young participants’ Quality of Life scores showed that the young participants were not affected negatively by undergoing the mini-capsules and MRI study. Feedback from the young participant and parents/carers was excellent. This method is also suitable for use in other complex cases of constipation.Acknowledgements
This work was funded by the Ministry Of
Health, Civil Service Commission, Kuwait.and the National Institute for Health Research (NIHR)
Invention for Innovation (i4i) award programme. The views expressed are those
of the authors and not necessarily those of the National Health Service (NHS),
the NIHR, or the Department of Health & Social Care.
References
1. Robin SG, Keller C, Zwiener R, et al. Prevalence of Pediatric Functional Gastrointestinal Disorders Utilizing the Rome IV Criteria. Journal of Pediatrics 2018;195:134-139.
2. NICE. Costing report. Constipation in children and young people. . Clinical guideline 99 2010.
3. Metcalf AM, Phillips SF, Zinsmeister AR, et al. Simplified assessment of segmental colonic transit. Gastroenterology 1987;92:40-7.
4. Keller J, Bassotti G, Clarke J, et al. Advances in the diagnosis and classification of gastric and intestinal motility disorders. Nature Reviews Gastroenterology &Amp; Hepatology 2018;15:291.
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