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Dellschaft N, Murray K, Ren Y, Marciani L, Gowland P, Spiller R, Hoad C. Assessing Water Content of the Human Colonic Chyme Using the MRI Parameter T1: A Key Biomarker of Colonic Function. Neurogastroenterol Motil 2025; 37:e14999. [PMID: 39789944 DOI: 10.1111/nmo.14999] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Revised: 12/10/2024] [Accepted: 12/23/2024] [Indexed: 01/12/2025]
Abstract
BACKGROUND The human colon receives 2 L of fluid daily. Small changes in the efficacy of absorption can lead to altered stool consistency with diarrhea or constipation. Drugs and formulations can also alter colonic water, which can be assessed using the magnetic resonance imaging (MRI) longitudinal relaxation time constant, T1. We explore the use of regional T1 assessment in evaluating disorders of colonic function. METHODS Individual participant data analysis of data from 12 studies from a single center of patients with constipation, irritable bowel syndrome with diarrhea (IBS-D), and healthy volunteers (HV). T1 was quantified by measuring the signal from the tissue at different times after a pulse which inverts the magnetization. KEY RESULTS When diarrhea was induced by a macrogol laxative T1 in the ascending colon, T1AC was negatively correlated with stool bacterial content, r2 = 0.78, p < 0.001. T1AC was increased by another laxative, rhubarb. Patients with IBS-D had elevated fasting T1AC (0.78 ± 0.28 s, N = 67) compared to HV (0.62 ± 0.21 s, N = 92) while those with constipation lay within the normal range (HV 10-90th centiles 0.33-0.91 s). Fasting T1AC in IBS-D was reduced by mesalazine treatment. T1 in the descending colon was consistently lower than T1AC, with a bigger reduction in patients with constipation than HV. Pre-feeding dietary fiber (bran, nopal, and psyllium) was associated with fasting T1AC at or above the normal 90th centile. CONCLUSIONS AND INFERENCES T1 is an MRI parameter which could be used to monitor effectiveness of novel agents designed to alter colonic water content and stool consistency.
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Affiliation(s)
- Neele Dellschaft
- Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, Nottingham, UK
- NIHR Nottingham Biomedical Research Centre (BRC), Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK
| | - Kathryn Murray
- NIHR Nottingham Biomedical Research Centre (BRC), Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK
- Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK
| | - Yi Ren
- School of Biosciences, University of Nottingham, Nottingham, UK
| | - Luca Marciani
- NIHR Nottingham Biomedical Research Centre (BRC), Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK
- Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK
| | - Penny Gowland
- Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, Nottingham, UK
- NIHR Nottingham Biomedical Research Centre (BRC), Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK
| | - Robin Spiller
- NIHR Nottingham Biomedical Research Centre (BRC), Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK
- Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK
| | - Caroline Hoad
- Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, Nottingham, UK
- NIHR Nottingham Biomedical Research Centre (BRC), Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK
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2
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Gunn D, Yeldho C, Hoad C, Menys A, Gowland P, Marciani L, Spiller R. Mechanisms underlying the laxative effect of lactulose: A randomized placebo-controlled trial showing increased small bowel water and motility unaltered by the 5-HT 3 receptor antagonist, ondansetron. Neurogastroenterol Motil 2024; 36:e14754. [PMID: 38316636 DOI: 10.1111/nmo.14754] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Revised: 01/16/2024] [Accepted: 01/18/2024] [Indexed: 02/07/2024]
Abstract
BACKGROUND Lactulose is a laxative which accelerates transit and softens stool. Our aim was to investigate its mechanism of action and use this model of diarrhea to investigate the anti-diarrheal actions of ondansetron. METHODS A double-blind, randomized, placebo-controlled crossover study of the effect of ondansetron 8 mg in 16 healthy volunteers. Serial MRI scans were performed fasted and 6 h after a meal. Participants then received lactulose 13.6 g twice daily and study drug for a further 36 h. On Day 3, they had further serial MRI scans for 4 h. Measurements included small bowel water content (SBWC), colonic volume, colonic gas, small bowel motility, whole gut transit, and ascending colon relaxation time (T1AC), a measure of colonic water content. KEY RESULTS Lactulose increased area under the curve (AUC) of SBWC from 0 to 240 min, mean difference 14.2 L · min (95% CI 4.1, 24.3), p = 0.009, and substantially increased small bowel motility after 4 h (mean (95% CI) 523 (457-646) a.u. to 852 (771-1178) a.u., p = 0.007). There were no changes in T1AC after 36 h treatment. Ondansetron did not significantly alter SBWC, small bowel motility, transit, colonic volumes, colonic gas nor T1AC, with or without lactulose. CONCLUSION & INFERENCES Lactulose increases SBWC and stimulates small bowel motility; however, unexpectedly it did not significantly alter colonic water content, suggesting its laxative effect is not osmotic but due to stimulation of motility. Ondansetron's lack of effect on intestinal water suggests its anti-diarrheal effect is not due to inhibition of secretion but more likely altered colonic motility.
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Affiliation(s)
- D Gunn
- NIHR Nottingham Biomedical Research Centre, Nottingham, UK
- Nottingham Digestive Diseases Centre, University of Nottingham, Nottingham, UK
| | - C Yeldho
- NIHR Nottingham Biomedical Research Centre, Nottingham, UK
- Nottingham Digestive Diseases Centre, University of Nottingham, Nottingham, UK
| | - C Hoad
- NIHR Nottingham Biomedical Research Centre, Nottingham, UK
- Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, UK
| | - A Menys
- Division of Medicine, Centre for Medical Imaging, University College London, London, UK
| | - P Gowland
- NIHR Nottingham Biomedical Research Centre, Nottingham, UK
- Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, UK
| | - L Marciani
- NIHR Nottingham Biomedical Research Centre, Nottingham, UK
- Nottingham Digestive Diseases Centre, University of Nottingham, Nottingham, UK
| | - R Spiller
- NIHR Nottingham Biomedical Research Centre, Nottingham, UK
- Nottingham Digestive Diseases Centre, University of Nottingham, Nottingham, UK
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3
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Kurpad AV, Pasanna RM, Hegde SG, Patil M, Mukhopadhyay A, Sachdev HS, Bhat KG, Sivadas A, Devi S. Bioavailability and daily requirement of vitamin B 12 in adult humans: an observational study of its colonic absorption and daily excretion as measured by [ 13C]-cyanocobalamin kinetics. Am J Clin Nutr 2023; 118:1214-1223. [PMID: 38044024 DOI: 10.1016/j.ajcnut.2023.08.020] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2023] [Revised: 08/28/2023] [Accepted: 08/30/2023] [Indexed: 12/05/2023] Open
Abstract
BACKGROUND Clinical and biochemical vitamin B12 (B12) deficiency is lower than anticipated in vegetarians. Extraileal absorption, such as from the colon, as well as reduced daily excretion, may be adaptive mechanisms to maintain B12 homeostasis with marginal intakes. OBJECTIVE To measure the absorption of B12 from the small and large intestine, and its daily rate of excretion from the body, using a [13C]-cyanocobalamin tracer. METHODS Oral B12 bioavailability was measured over 12 h after administration of [13C]-cyanocobalamin tracer (2.5 μg) in normal participants. The colonic B12 bioavailability was evaluated by direct instillation of [13C]-cyanocobalamin (5 μg) into the ascending colon. Bioavailability was calculated from 2-compartmental modeling of the tracer appearance in plasma. The excretion rate of B12 was measured from [13C]-cyanocobalamin elimination from the body over 4 wk after oral dosing (5 μg). RESULTS The oral B12 bioavailability (n = 11) was 63% ± 10% measured over 12 h. A late absorption peak, accounting for 12% of the absorption, was observed after an average lag time of 8.7 h from dosing. The colonic B12 bioavailability (n = 10) was 7% ± 5% over 4 h. The daily B12 excretion rate (n = 4) was 0.7 ± 0.2 μg/d. The minimum daily requirement of B12 in these participants was derived at 1 μg /d. CONCLUSIONS B12 is absorbed in the human colon. This observation confirms the potential contribution of the colon in daily B12 nutriture, and along with a possible lower requirement, could explain the absence of clinical deficiency in populations with marginal B12 intakes. TRIAL REGISTRATION NUMBER This study was registered in Clinical Trials Registry of India (CTRI) with the registration number CTRI/2018/04/012957, available from https://ctri.nic.in/Clinicaltrials/showallp.php?mid1=49319&EncHid=&userName=029108.
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Affiliation(s)
- Anura V Kurpad
- Department of Physiology, St. John's Medical College, Bengaluru, India.
| | - Roshni M Pasanna
- Division of Nutrition, St. John's Research Institute, Bengaluru, India
| | - Shalini G Hegde
- Department of Paediatric Surgery, St. John's Medical College, Bengaluru, India
| | - Mallikarjun Patil
- Department of Gastroenterology, St. John's Medical College, Bengaluru, India
| | | | - Harshpal S Sachdev
- Department of Paediatrics, Sitaram Bhartia Institute of Science and Research, New Delhi, India
| | - Kishor G Bhat
- Division of Nutrition, St. John's Research Institute, Bengaluru, India
| | - Ambily Sivadas
- Division of Nutrition, St. John's Research Institute, Bengaluru, India
| | - Sarita Devi
- Division of Nutrition, St. John's Research Institute, Bengaluru, India.
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4
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Jalanka J, Gunn D, Singh G, Krishnasamy S, Lingaya M, Crispie F, Finnegan L, Cotter P, James L, Nowak A, Major G, Spiller RC. Postinfective bowel dysfunction following Campylobacter enteritis is characterised by reduced microbiota diversity and impaired microbiota recovery. Gut 2023; 72:451-459. [PMID: 36171082 PMCID: PMC9933158 DOI: 10.1136/gutjnl-2021-326828] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Accepted: 07/14/2022] [Indexed: 12/08/2022]
Abstract
OBJECTIVES Persistent bowel dysfunction following gastroenteritis (postinfectious (PI)-BD) is well recognised, but the associated changes in microbiota remain unclear. Our aim was to define these changes after gastroenteritis caused by a single organism, Campylobacter jejuni, examining the dynamic changes in the microbiota and the impact of antibiotics. DESIGN A single-centre cohort study of 155 patients infected with Campylobacter jejuni. Features of the initial illness as well as current bowel symptoms and the intestinal microbiota composition were recorded soon after infection (visit 1, <40 days) as well as 40-60 days and >80 days later (visits 2 and 3). Microbiota were assessed using 16S rRNA sequencing. RESULTS PI-BD was found in 22 of the 99 patients who completed the trial. The cases reported significantly looser stools, with more somatic and gastrointestinal symptoms. Microbiota were assessed in 22 cases who had significantly lower diversity and altered microbiota composition compared with the 44 age-matched and sex-matched controls. Moreover 60 days after infection, cases showed a significantly lower abundance of 23 taxa including phylum Firmicutes, particularly in the order Clostridiales and the family Ruminoccocaceae, increased Proteobacteria abundance and increased levels of Fusobacteria and Gammaproteobacteria. The microbiota changes were linked with diet; higher fibre consumption being associated with lower levels of Gammaproteobacteria. CONCLUSION The microbiota of PI-BD patients appeared more disturbed by the initial infection compared with the microbiota of those who recovered. The prebiotic effect of high fibre diets may inhibit some of the disturbances seen in PI-BD. TRIAL REGISTRATION NUMBER NCT02040922.
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Affiliation(s)
- Jonna Jalanka
- Nottingham Digestive Diseases Centre and NIHR Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust, the University of Nottingham, Nottingham, UK.,Human Microbiome Research Program, University of Helsinki Faculty of Medicine, Helsinki, Finland
| | - David Gunn
- Nottingham Digestive Diseases Centre and NIHR Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust, the University of Nottingham, Nottingham, UK
| | - Gulzar Singh
- Nottingham Digestive Diseases Centre and NIHR Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust, the University of Nottingham, Nottingham, UK
| | - Shanthi Krishnasamy
- Nottingham Digestive Diseases Centre and NIHR Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust, the University of Nottingham, Nottingham, UK.,Department of Dietetics, Faculty of Health Sciences, Universiti Kebangsaan Malaysia (UKM), Kuala Lumpur, Malaysia
| | - Melanie Lingaya
- Nottingham Digestive Diseases Centre and NIHR Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust, the University of Nottingham, Nottingham, UK
| | - Fiona Crispie
- Teagasc Food Research Centre, Moorepark, Fermoy, Cork, Ireland.,APC Microbiome Ireland, Cork, Ireland
| | - Laura Finnegan
- Teagasc Food Research Centre, Moorepark, Fermoy, Cork, Ireland.,APC Microbiome Ireland, Cork, Ireland
| | - Paul Cotter
- Teagasc Food Research Centre, Moorepark, Fermoy, Cork, Ireland.,APC Microbiome Ireland, Cork, Ireland
| | - Louise James
- Nottingham Digestive Diseases Centre and NIHR Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust, the University of Nottingham, Nottingham, UK
| | - Adam Nowak
- Nottingham Digestive Diseases Centre and NIHR Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust, the University of Nottingham, Nottingham, UK
| | - Giles Major
- Nottingham Digestive Diseases Centre and NIHR Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust, the University of Nottingham, Nottingham, UK
| | - Robin C Spiller
- Nottingham Digestive Diseases Centre and NIHR Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust, the University of Nottingham, Nottingham, UK
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5
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O’Farrell C, Simmons MJH, Batchelor HK, Stamatopoulos K. The Effect of Biorelevant Hydrodynamic Conditions on Drug Dissolution from Extended-Release Tablets in the Dynamic Colon Model. Pharmaceutics 2022; 14:2193. [PMID: 36297627 PMCID: PMC9609852 DOI: 10.3390/pharmaceutics14102193] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Revised: 10/06/2022] [Accepted: 10/11/2022] [Indexed: 11/06/2022] Open
Abstract
The in vitro release of theophylline from an extended-release dosage form was studied under different hydrodynamic conditions in a United States Pharmacopoeial (USP) dissolution system II and a bespoke in vitro tubular model of the human colon, the Dynamic Colon Model (DCM). Five biorelevant motility patterns extracted from in vivo data were applied to the DCM, mimicking the human proximal colon under baseline conditions and following stimulation using polyethylene glycol or maltose; these represent the lower and upper bounds of motility normally expected in vivo. In the USPII, tablet dissolution was affected by changing hydrodynamic conditions at different agitation speeds of 25, 50 and 100 rpm. Applying different motility patterns in the DCM affected the dissolution profiles produced, with theophylline release at 24 h ranging from 56.74 ± 2.00% (baseline) to 96.74 ± 9.63% (maltose-stimulated). The concentration profiles of theophylline were markedly localized when measured at different segments of the DCM tube, highlighting the importance of a segmented lumen in intestine models and in generating spatial information to support simple temporal dissolution profiles. The results suggested that the shear stresses invoked by the unstimulated, healthy adult human colon may be lower than those in the USPII at 25 rpm and thus insufficient to achieve total release of a therapeutic compound from a hydroxyethyl cellulose matrix. When operated under stimulated conditions, drug release in the DCM was between that achieved at 25 and 50 rpm in the USPII.
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Affiliation(s)
- Connor O’Farrell
- School of Chemical Engineering, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
| | - Mark J. H. Simmons
- School of Chemical Engineering, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
| | - Hannah K. Batchelor
- Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK
| | - Konstantinos Stamatopoulos
- School of Chemical Engineering, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
- Biopharmaceutics, DPD, MDS, GSK, David Jack Centre, Park Road, Ware, Hertfordshire SG12 0DP, UK
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6
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Dellschaft N, Hoad C, Marciani L, Gowland P, Spiller R. Small bowel water content assessed by MRI in health and disease: a collation of single-centre studies. Aliment Pharmacol Ther 2022; 55:327-338. [PMID: 34716925 DOI: 10.1111/apt.16673] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Revised: 07/12/2021] [Accepted: 10/13/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND New developments in MRI have allowed the non-invasive, accurate measurement of the small bowel water content (SBWC). AIMS To collate studies measuring SBWC following ingestion of a range of foods in both health and disease to provide data for adequately powering future studies in this area. METHODS This collation brings together 29 studies including 954 participants (530 healthy, 54 diverticulosis, 255 IBS, 53 functional constipation, 12 cystic fibrosis, 15 Crohn's disease, 20 coeliac disease, 15 scleroderma) which have been carried out in a single centre using comparable study designs. RESULTS Fasting SBWC (mean 82 [SD 65] mL) shows high variability with a small decline with advancing age (healthy volunteers only; individual patient data). Fasting values are increased in untreated coeliac disease (202 [290] mL, P = 0.004). Post-prandial SBWC shows less intra-individual variability than fasting values in healthy volunteers. SBWC is increased by eating, most markedly by high fat meals but also by fibre, both viscous and particulate. Indigestible residue accumulates in late post-prandial period but empties soon after ingestion of a high calorie meal which produces a significant drop (by 50 [52] mL) in healthy volunteers. The associated fall in SBWC is abnormal in people with cystic fibrosis (SBWC reduced by 10 [121] mL, P = 0.002) and in people with irritable bowel syndrome with diarrhoea (SBWC reduced by 17 [43] mL, P = 0.007). CONCLUSIONS SBWC as assessed by MRI is a valuable biomarker indicating the balance of secretion and absorption in health and disease and the impact of treatments.
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Affiliation(s)
- Neele Dellschaft
- Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, UK.,NIHR Nottingham Biomedical Research Centre (BRC), Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK
| | - Caroline Hoad
- Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, UK.,NIHR Nottingham Biomedical Research Centre (BRC), Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK
| | - Luca Marciani
- Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, UK.,NIHR Nottingham Biomedical Research Centre (BRC), Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK
| | - Penny Gowland
- Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, UK.,NIHR Nottingham Biomedical Research Centre (BRC), Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK
| | - Robin Spiller
- NIHR Nottingham Biomedical Research Centre (BRC), Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK.,Nottingham Digestive Diseases Centre, University of Nottingham, Nottingham, UK
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7
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Sulaiman S, Gershkovich P, Hoad CL, Calladine M, Spiller RC, Stolnik S, Marciani L. Application of In Vivo MRI Imaging to Track a Coated Capsule and Its Disintegration in the Gastrointestinal Tract in Human Volunteers. Pharmaceutics 2022; 14:pharmaceutics14020270. [PMID: 35214003 PMCID: PMC8879863 DOI: 10.3390/pharmaceutics14020270] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Revised: 12/30/2021] [Accepted: 01/19/2022] [Indexed: 02/04/2023] Open
Abstract
Oral specially coated formulations have the potential to improve treatment outcomes of a range of diseases in distal intestinal tract whilst limiting systemic drug absorption and adverse effects. Their development is challenging, partly because of limited knowledge of the physiological and pathological distal gastrointestinal factors, including colonic chyme fluid distribution and motor function. Recently, non-invasive techniques such as magnetic resonance imaging (MRI) have started to provide novel important insights. In this feasibility study, we formulated a coated capsule consisting of a hydroxypropyl methylcellulose (HPMC) shell, coated with a synthetic polymer based on polymethacrylate-based copolymer (Eudragit®) that can withstand the upper gastrointestinal tract conditions. The capsule was filled with olive oil as MRI-visible marker fluid. This allowed us to test the ability of MRI to track such a coated capsule in the gastrointestinal tract and to assess whether it is possible to image its loss of integrity by exploiting the ability of MRI to image fat and water separately and in combination. Ten healthy participants were administered capsules with varying amounts of coating and underwent MRI imaging of the gastrointestinal tract at 45 min intervals. The results indicate that it is feasible to track the capsules present in the gastrointestinal tract at different locations, as they were detected in all 10 participants. By the 360 min endpoint of the study, in nine participants the capsules were imaged in the small bowel, in eight participants in the terminal ileum, and in four in the colon. Loss of capsule integrity was observed in eight participants, occurring predominantly in distal intestinal regions. The data indicate that the described approach could be applied to assess performance of oral formulations in undisturbed distal gastrointestinal regions, without the need for ionizing radiation or contrast agents.
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Affiliation(s)
- Sarah Sulaiman
- Nottingham Digestive Diseases Centre, National Institute for Health Research (NIHR), Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust, University of Nottingham, Nottingham NG7 2UH, UK; (S.S.); (R.C.S.)
| | - Pavel Gershkovich
- School of Pharmacy, University of Nottingham, Nottingham NG7 2QL, UK; (P.G.); (M.C.); (S.S.)
| | - Caroline L. Hoad
- Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, Nottingham NG7 2QX, UK;
| | - Matthew Calladine
- School of Pharmacy, University of Nottingham, Nottingham NG7 2QL, UK; (P.G.); (M.C.); (S.S.)
| | - Robin C. Spiller
- Nottingham Digestive Diseases Centre, National Institute for Health Research (NIHR), Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust, University of Nottingham, Nottingham NG7 2UH, UK; (S.S.); (R.C.S.)
| | - Snow Stolnik
- School of Pharmacy, University of Nottingham, Nottingham NG7 2QL, UK; (P.G.); (M.C.); (S.S.)
| | - Luca Marciani
- Nottingham Digestive Diseases Centre, National Institute for Health Research (NIHR), Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust, University of Nottingham, Nottingham NG7 2UH, UK; (S.S.); (R.C.S.)
- Correspondence: ; Tel.: +44-11-5823-1248
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8
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O'Farrell C, Stamatopoulos K, Simmons M, Batchelor H. In vitro models to evaluate ingestible devices: Present status and current trends. Adv Drug Deliv Rev 2021; 178:113924. [PMID: 34390774 DOI: 10.1016/j.addr.2021.113924] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Revised: 08/03/2021] [Accepted: 08/09/2021] [Indexed: 12/14/2022]
Abstract
Orally ingestible medical devices offer significant opportunity in the diagnosis and treatment of gastrointestinal conditions. Their development necessitates the use of models that simulate the gastrointestinal environment on both a macro and micro scale. An evolution in scientific technology has enabled a wide range of in vitro, ex vivo and in vivo models to be developed that replicate the gastrointestinal tract. This review describes the landscape of the existing range of in vitro tools that are available to characterize ingestible devices. Models are presented with details on their benefits and limitations with regards to the evaluation of ingestible devices and examples of their use in the evaluation of such devices is presented where available. The multitude of models available provides a suite of tools that can be used in the evaluation of ingestible devices that should be selected on the functionality of the device and the mechanism of its function.
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Affiliation(s)
- Connor O'Farrell
- School of Chemical Engineering, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
| | - Konstantinos Stamatopoulos
- School of Chemical Engineering, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK; Biopharmaceutics, Pharmaceutical Development, PDS, MST, RD Platform Technology & Science, GSK, David Jack Centre, Park Road, Ware, Hertfordshire SG12 0DP, UK
| | - Mark Simmons
- School of Chemical Engineering, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
| | - Hannah Batchelor
- Strathclyde Institute of Pharmacy and Biomedical Sciences, 161 Cathedral Street, Glasgow G4 0RE, UK.
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9
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Schütt M, Stamatopoulos K, Batchelor HK, Simmons MJH, Alexiadis A. Modelling and Simulation of the Drug Release from a Solid Dosage Form in the Human Ascending Colon: The Influence of Different Motility Patterns and Fluid Viscosities. Pharmaceutics 2021; 13:pharmaceutics13060859. [PMID: 34200574 PMCID: PMC8226501 DOI: 10.3390/pharmaceutics13060859] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Revised: 05/26/2021] [Accepted: 06/02/2021] [Indexed: 12/18/2022] Open
Abstract
For colonic drug delivery, the ascending part of the colon is the most favourable site as it offers the most suitable environmental conditions for drug dissolution. Commonly, the performance of a drug formulation is assessed using standardised dissolution apparatus, which does not replicate the hydrodynamics and shear stress evoked by wall motion in the colon. In this work, computer simulations are used to analyse and understand the influence of different biorelevant motility patterns on the disintegration/drug release of a solid dosage form (tablet) under different fluid conditions (viscosities) to mimic the ascending colonic environment. Furthermore, the ability of the motility pattern to distribute the drug in the ascending colon luminal environment is analysed to provide data for a spatiotemporal concentration profile. The motility patterns used are derived from in vivo data representing different motility patterns in the human ascending colon. The applied motility patterns show considerable differences in the drug release rate from the tablet, as well as in the ability to distribute the drug along the colon. The drug dissolution/disintegration process from a solid dosage form is primarily influenced by the hydrodynamic and shear stress it experiences, i.e., a combination of motility pattern and fluid viscosity. Reduced fluid motion leads to a more pronounced influence of diffusion in the tablet dissolution process. The motility pattern that provoked frequent single shear stress peaks seemed to be more effective in achieving a higher drug release rate. The ability to simulate drug release profiles under biorelevant colonic environmental conditions provides valuable feedback to better understand the drug formulation and how this can be optimised to ensure that the drug is present in the desired concentration within the ascending colon.
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Affiliation(s)
- Michael Schütt
- School of Chemical Engineering, University of Birmingham, Birmingham B15 2TT, UK;
- Correspondence: (M.S.); (K.S.); (A.A.)
| | - Konstantinos Stamatopoulos
- School of Chemical Engineering, University of Birmingham, Birmingham B15 2TT, UK;
- Biopharmaceutics, Pharmaceutical Development, PDS, MST, RD Platform Technology & Science, GSK, David Jack Centre, Park Road, Ware SG12 0DP, UK
- Correspondence: (M.S.); (K.S.); (A.A.)
| | - Hannah K. Batchelor
- Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK;
| | - Mark J. H. Simmons
- School of Chemical Engineering, University of Birmingham, Birmingham B15 2TT, UK;
| | - Alessio Alexiadis
- School of Chemical Engineering, University of Birmingham, Birmingham B15 2TT, UK;
- Correspondence: (M.S.); (K.S.); (A.A.)
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10
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Sharif H, Hoad CL, Abrehart N, Gowland PA, Spiller RC, Kirkham S, Loganathan S, Papadopoulos M, Benninga MA, Devadason D, Marciani L. Colonic Volume Changes in Paediatric Constipation Compared to Normal Values Measured Using MRI. Diagnostics (Basel) 2021; 11:974. [PMID: 34071217 PMCID: PMC8226615 DOI: 10.3390/diagnostics11060974] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Revised: 05/19/2021] [Accepted: 05/26/2021] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Functional constipation in children is common. Management of this condition can be challenging and is often based on symptom reports. Increased, objective knowledge of colonic volume changes in constipation compared to health could provide additional information. However, very little data on paediatric colonic volume is available except from methods that are invasive or require unphysiological colonic preparations. OBJECTIVES (1) To measure volumes of the undisturbed colon in children with functional constipation (FC) using magnetic resonance imaging (MRI) and provide initial normal range values for healthy controls, and (2) to investigate possible correlation of colonic volume with whole gut transit time (WGTT). METHODS Total and regional (ascending, transverse, descending, sigmoid, and rectum) colon volumes were measured from MRI images of 35 participants aged 7-18 years (16 with FC and 19 healthy controls), and corrected for body surface area. Linear regression was used to explore the relationship between total colon volume and WGTT. RESULTS Total colonic volume was significantly higher, with a median (interquartile range) of 309 mL (243-384 mL) for the FC group than for the healthy controls of 227 mL (180-263 mL). The largest increase between patients and controls was in the sigmoid colon-rectum region. In a linear regression model, there was a positive significant correlation between total colonic volume and WGTT (R = 0.56, p = 0.0005). CONCLUSIONS This initial study shows increased volumes of the colon in children with FC, in a physiological state, without use of any bowel preparation. Increased knowledge of colonic morphology may improve understanding of FC in this age group and help to direct treatment.
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Affiliation(s)
- Hayfa Sharif
- Translational Medical Sciences, NIHR Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust, University of Nottingham, Nottingham NG7 2UH, UK; (H.S.); (N.A.); (R.C.S.)
- Ministry of Health, Civil Service Commission, Amiri Hospital, Kuwait City 15300, Kuwait
| | - Caroline L. Hoad
- Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, Nottingham NG7 2RD, UK; (C.L.H.); (P.A.G.)
| | - Nichola Abrehart
- Translational Medical Sciences, NIHR Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust, University of Nottingham, Nottingham NG7 2UH, UK; (H.S.); (N.A.); (R.C.S.)
| | - Penny A. Gowland
- Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, Nottingham NG7 2RD, UK; (C.L.H.); (P.A.G.)
| | - Robin C. Spiller
- Translational Medical Sciences, NIHR Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust, University of Nottingham, Nottingham NG7 2UH, UK; (H.S.); (N.A.); (R.C.S.)
| | - Sian Kirkham
- Nottingham Children’s Hospital, Nottingham University Hospitals NHS Trust, Nottingham NG7 2UH, UK; (S.K.); (S.L.); (M.P.); (D.D.)
| | - Sabarinathan Loganathan
- Nottingham Children’s Hospital, Nottingham University Hospitals NHS Trust, Nottingham NG7 2UH, UK; (S.K.); (S.L.); (M.P.); (D.D.)
| | - Michalis Papadopoulos
- Nottingham Children’s Hospital, Nottingham University Hospitals NHS Trust, Nottingham NG7 2UH, UK; (S.K.); (S.L.); (M.P.); (D.D.)
| | - Marc A. Benninga
- Department of Pediatric Gastroenterology, Emma Children’s Hospital, Amsterdam UMC, 9, 1105 AZ Amsterdam, The Netherlands;
| | - David Devadason
- Nottingham Children’s Hospital, Nottingham University Hospitals NHS Trust, Nottingham NG7 2UH, UK; (S.K.); (S.L.); (M.P.); (D.D.)
| | - Luca Marciani
- Translational Medical Sciences, NIHR Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust, University of Nottingham, Nottingham NG7 2UH, UK; (H.S.); (N.A.); (R.C.S.)
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11
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Hung J, Liu T, Yi C, Wong M, Lei W, Chen C. Influence of probiotics on gastrointestinal symptoms in patients undergoing colonoscopy. ADVANCES IN DIGESTIVE MEDICINE 2021. [DOI: 10.1002/aid2.13186] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Affiliation(s)
- Jui‐Sheng Hung
- Department of Medicine, Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation and Tzu Chi University Hualien Taiwan
| | - Tso‐Tsai Liu
- Department of Medicine, Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation and Tzu Chi University Hualien Taiwan
| | - Chih‐Hsun Yi
- Department of Medicine, Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation and Tzu Chi University Hualien Taiwan
| | - Ming‐Wun Wong
- Department of Medicine, Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation and Tzu Chi University Hualien Taiwan
| | - Wei‐Yi Lei
- Department of Medicine, Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation and Tzu Chi University Hualien Taiwan
| | - Chien‐Lin Chen
- Department of Medicine, Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation and Tzu Chi University Hualien Taiwan
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12
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Krishnasamy S, Lomer MCE, Marciani L, Hoad CL, Pritchard SE, Paul J, Gowland PA, Spiller RC. Processing Apples to Puree or Juice Speeds Gastric Emptying and Reduces Postprandial Intestinal Volumes and Satiety in Healthy Adults. J Nutr 2020; 150:2890-2899. [PMID: 32805050 DOI: 10.1093/jn/nxaa191] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2019] [Revised: 01/16/2020] [Accepted: 06/12/2020] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Whole apples produce greater satiety than processed apples, but the underlying mechanisms remain unclear. OBJECTIVE Our aim was to assess the intragastric processing of apple preparations and the associated small and large bowel contents using MRI. METHODS An open label, 3-way crossover, randomized, controlled trial. Eighteen healthy adults (mean ± SD age, 25 ± 4 y; BMI, 22.7 ± 3.5 kg/m2) underwent serial MRI scans on 3 occasions separated by 7 d, after consumption of isocaloric (178 kcal) portions of either whole apples, apple puree, or apple juice. Gastric emptying, small bowel water content (SBWC; primary endpoint), were measured at baseline and at 45 min intervals (0-270 min) postmeal ingestion. Fullness and satiety were also assessed at each time point. Treatment effects between groups were analyzed using ANOVA. RESULTS Gastric emptying half-time (GE t50) was greater (P < 0.0001) after participants consumed whole apple (mean ± SEM), 65 (3.3) min compared with when they consumed apple puree (41 [2.8] min) or apple juice (38 [2.9] min), times that did not differ. Postprandial area under the curve (AUC) (135-270 min) SBWC was also greater for whole apples than puree (P = 0.025) and juice (P = 0.0004) but juice and puree did not differ. AUC for fullness and satiety (0-270 min) postingestion was also greater (P = 0.002 and 0.004, respectively) for whole apple compared with juice but juice and puree did not differ. CONCLUSIONS Gastric emptying is slower after whole apple consumption causing a greater sensation of fullness and satiety than puree or juice in healthy adults. Whole apples increased small bowel and colonic contents during the later phase of the study which may be relevant for subsequent food consumption.This study was registered at clinicaltrials.gov as NCT03714464.
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Affiliation(s)
- Shanthi Krishnasamy
- Faculty of Health Sciences, Universiti Kebangsaan Malaysia (UKM), Kuala Lumpur, Malaysia.,National Institute of Health Research, Nottingham Biomedical Research Centre (BRC) at Nottingham University Hospitals National Health Service Trust and University of Nottingham, Nottingham, United Kingdom.,Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, United Kingdom
| | | | - Luca Marciani
- National Institute of Health Research, Nottingham Biomedical Research Centre (BRC) at Nottingham University Hospitals National Health Service Trust and University of Nottingham, Nottingham, United Kingdom.,Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, United Kingdom
| | - Caroline Louise Hoad
- National Institute of Health Research, Nottingham Biomedical Research Centre (BRC) at Nottingham University Hospitals National Health Service Trust and University of Nottingham, Nottingham, United Kingdom.,Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, Nottingham, United Kingdom
| | - Susan Elizabeth Pritchard
- Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, Nottingham, United Kingdom
| | - Joe Paul
- Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, Nottingham, United Kingdom
| | - Penny Ann Gowland
- Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, Nottingham, United Kingdom
| | - Robin Charles Spiller
- National Institute of Health Research, Nottingham Biomedical Research Centre (BRC) at Nottingham University Hospitals National Health Service Trust and University of Nottingham, Nottingham, United Kingdom.,Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, United Kingdom
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13
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Wilkinson-Smith V, Menys A, Bradley C, Corsetti M, Marciani L, Atkinson D, Coupland C, Taylor SA, Gowland P, Spiller R, Hoad C. The MRI colonic function test: Reproducibility of the Macrogol stimulus challenge. Neurogastroenterol Motil 2020; 32:e13942. [PMID: 32677154 DOI: 10.1111/nmo.13942] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Revised: 06/01/2020] [Accepted: 06/18/2020] [Indexed: 12/29/2022]
Abstract
BACKGROUND Magnetic resonance imaging (MRI) of the colonic response to a macrogol challenge drink can be used to assess the mechanisms underlying severe constipation. We measured the intrasubject reproducibility of MRI measures of colonic function to aid their implementation as a possible clinical test. METHODS Healthy participants attended for MRI on two occasions (identical protocols, minimum 1 week apart). They underwent a fasted scan and then consumed the macrogol drink. Subjects were scanned at 60 and 120 minutes, with maximum value reached used for comparison. The colonic volume, water content, mixing of colonic content and the movement of the colon walls were measured. Coefficients of variation and intraclass correlation coefficients (ICC) were calculated. RESULTS Twelve participants completed the study: nine female, mean age 26 years (SD 5) and body mass index 24.8 kg/m2 (SD 3.2). All measures consistently increased above baseline following provocation with macrogol. The volume, water content and content mixing had good intrasubject reproducibility (ICC volume = 0.84, water content = 0.93, mixing = 0.79, P < .001). With the wall movement, the response to the challenge was generally large, but more variable between visits resulting in a lower ICC overall (ascending colon = 0.65, descending colon = 0.76, P < .001). CONCLUSIONS The colonic response to the macrogol stimulus as assessed by MRI is heterogeneous but large compared to baseline, with moderate to good reproducibility, making the test suitable to study potential pathologies underlying GI disorders such as constipation. More data are needed to better define the normal range for comparison with patient groups who may have both hypo- and hypermotile responses.
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Affiliation(s)
- Victoria Wilkinson-Smith
- Nottingham Digestive Diseases Centre, University of Nottingham, Nottingham, UK.,National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
| | | | - Christopher Bradley
- National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK.,Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, UK
| | - Maura Corsetti
- Nottingham Digestive Diseases Centre, University of Nottingham, Nottingham, UK.,National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
| | - Luca Marciani
- Nottingham Digestive Diseases Centre, University of Nottingham, Nottingham, UK.,National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
| | - David Atkinson
- Centre for Medical Imaging, University College London, London, UK
| | - Carol Coupland
- Division of Primary Care, University of Nottingham, Nottingham, UK
| | - Stuart A Taylor
- Centre for Medical Imaging, University College London, London, UK
| | - Penny Gowland
- National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK.,Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, UK
| | - Robin Spiller
- Nottingham Digestive Diseases Centre, University of Nottingham, Nottingham, UK.,National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
| | - Caroline Hoad
- National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK.,Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, UK
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14
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Dynamic Colon Model (DCM): A Cine-MRI Informed Biorelevant In Vitro Model of the Human Proximal Large Intestine Characterized by Positron Imaging Techniques. Pharmaceutics 2020; 12:pharmaceutics12070659. [PMID: 32668624 PMCID: PMC7407282 DOI: 10.3390/pharmaceutics12070659] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2020] [Revised: 07/09/2020] [Accepted: 07/10/2020] [Indexed: 12/17/2022] Open
Abstract
This work used in vivo MRI images of human colon wall motion to inform a biorelevant Dynamic Colon Model (DCM) to understand the interplay of wall motion, volume, viscosity, fluid, and particle motion within the colon lumen. Hydrodynamics and particle motion within the DCM were characterized using Positron Emission Tomography (PET) and Positron Emission Particle Tracking (PEPT), respectively. In vitro PET images showed that fluid of higher viscosity follows the wall motion with poor mixing, whereas good mixing was observed for a low viscosity fluid. PEPT data showed particle displacements comparable to the in vivo data. Increasing fluid viscosity favors the net forward propulsion of the tracked particles. The use of a floating particle demonstrated shorter residence times and greater velocities on the liquid surface, suggesting a surface wave that was moving faster than the bulk liquid. The DCM can provide an understanding of flow motion and behavior of particles with different buoyancy, which in turn may improve the design of drug formulations, whereby fragments of the dosage form and/or drug particles are suspended in the proximal colon.
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15
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Spiller R, Hoad C. Enhancing our understanding of small bowel function using modern imaging techniques. Neurogastroenterol Motil 2020; 32:e13616. [PMID: 31136064 DOI: 10.1111/nmo.13616] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2019] [Revised: 04/10/2019] [Accepted: 04/17/2019] [Indexed: 02/08/2023]
Abstract
Small intestinal function is critical to digestive health and patients believe an abnormal reaction to food is responsible for many of their symptoms. Despite this, our ability to assess disturbed function in clinical practice has been limited, particularly after ingestion of the complex nutrients which make up normal food. Recent advances in both wireless capsules and magnetic resonance imaging have provided new insights. This review will briefly describe the limitations of past techniques and focus on how these newer techniques are changing our understanding, particularly of how patients' gastrointestinal tracts respond to food.
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Affiliation(s)
- Robin Spiller
- NIHR Nottingham Biomedical Research Centre, University of Nottingham, Nottingham, UK
| | - Caroline Hoad
- NIHR Nottingham Biomedical Research Centre, University of Nottingham, Nottingham, UK.,Sir Peter Mansfield Imaging Centre, Department of Physics, University of Nottingham, Nottingham, UK
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16
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Intraluminal Impact of Food: New Insights from MRI. Nutrients 2019; 11:nu11051147. [PMID: 31126027 PMCID: PMC6567872 DOI: 10.3390/nu11051147] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2019] [Revised: 05/13/2019] [Accepted: 05/20/2019] [Indexed: 02/07/2023] Open
Abstract
Understanding how the gut responds to food has always been limited by the available investigatory techniques. Previous methods involving intubation and aspiration are largely limited to liquid-only meals. The aim of this review is to describe how MRI has allowed analysis of the processing of complex multiphase meals. This has demonstrated the role of physical factors such as viscosity, fat and fibre content in controlling gastric secretion and motility. It has also allowed the description of changes induced in small bowel water content and the role of osmotic effects of poorly absorbed carbohydrates such as fructose, sorbitol and mannitol. Intestinal secretions can be shown to be stimulated by a range of fruit and vegetables and the effect of this on colonic water content can also be measured. This has been used to demonstrate the mode of action of commonly used laxatives including bran and psyllium. The wealth of data which can be obtained together with its non-invasive nature and safety makes the technique ideal for the serial evaluation of the impact of different nutrients and drugs in both health and disease.
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17
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Menys A, Hoad C, Spiller R, Scott SM, Atkinson D, Marciani L, Taylor SA. Spatio-temporal motility MRI analysis of the stomach and colon. Neurogastroenterol Motil 2019; 31:e13557. [PMID: 30821098 DOI: 10.1111/nmo.13557] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2018] [Revised: 11/26/2018] [Accepted: 01/01/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND MRI is increasingly used to objectively assess gastrointestinal motility. However, motility metrics often do not offer insights into the nature of contractile action. This study introduces a systematic method of making spatio-temporal measurements of contractions, based on changes in bowel lumen diameter. METHODS Two heterogeneous cohorts of subjects were selected displaying gastric (n = 15) and colonic motility (n = 20) on which to test the spatio-temporal motility MRI (STMM) technique. STMM involved delineating the bowel lumen along with inner and outer bowel wall along a section of the gastrointestinal tract. A series of diameter measurements were made automatically across the central axis of the lumen. Measurements were automatically propagated through the time series using a previously validated algorithm. Contractions were quantitatively summarized with two methods measuring (a) normalized contraction plot (NCP) and (b) combined velocity distance (CVD) both of which can be visualized as spatio-temporal motility maps. Both metrics were correlated against subjective visual scoring systems. KEY RESULTS Good correlation was seen between reader scores and both motility metrics (NCP, R = 0.85, P < 0.001, CVD, R = 0.93, R < 0.001) in the gastric data. Good correlation was also seen between the reader scores and the two metrics in the colonic data (NCP, R = 0.82, P < 0.001, CVD, R = 0.78, R < 0.001). CONCLUSIONS AND INFERENCES Spatio-temporal motility MRI analysis of the stomach and colon correlates well with reader scores in a range of datasets and provides both a quantitative and qualitative means of assessing contractile activity in the gastrointestinal tract.
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Affiliation(s)
- Alex Menys
- Centre for Medical Imaging, UCL, London, UK
| | - Caroline Hoad
- Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, Nottingham, UK.,Nottingham Digestive Diseases Centre and National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK
| | - Robin Spiller
- Nottingham Digestive Diseases Centre and National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK
| | - S Mark Scott
- Wingate Centre for Neurogastroenterology, Blizard Institute, QMUL, London, UK
| | | | - Luca Marciani
- Nottingham Digestive Diseases Centre and National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK
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18
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Sulaiman S, Marciani L. MRI of the Colon in the Pharmaceutical Field: The Future before us. Pharmaceutics 2019; 11:pharmaceutics11040146. [PMID: 30934716 PMCID: PMC6523257 DOI: 10.3390/pharmaceutics11040146] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2019] [Revised: 03/22/2019] [Accepted: 03/22/2019] [Indexed: 12/14/2022] Open
Abstract
Oral solid drug formulation is the most common route for administration and it is vital to increase knowledge of the gastrointestinal physiological environment to understand dissolution and absorption processes and to develop reliable biorelevant in vitro tools. In particular, colon targeted drug formulations have raised the attention of pharmaceutical scientists because of the great potential of colonic drug delivery. However, the distal bowel is still a relatively understudied part of the gastrointestinal tract. Recently, magnetic resonance imaging (MRI) has been gaining an emerging role in studying the colon. This article provides a comprehensive; contemporary review of the literature on luminal MRI of the colonic environment of the last 15 years with specific focus on colon physiological dimensions; motility; chyme and fluids; transit and luminal flow. The work reviewed provides novel physiological insight that will have a profound impact on our understanding of the colonic environment for drug delivery and absorption and will ultimately help to raise the in vitro/in vivo relevance of computer simulations and bench models.
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Affiliation(s)
- Sarah Sulaiman
- Nottingham Digestive Diseases Centre and National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham NG7 2UH, UK.
| | - Luca Marciani
- Nottingham Digestive Diseases Centre and National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham NG7 2UH, UK.
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19
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Abstract
Symptoms of abdominal pain, nausea, vomiting, bloating, abdominal distention, diarrhea, and constipation are common and may relate to abnormalities in gastrointestinal motility. There are a number of different options to study gastrointestinal motility. This article reviews novel and standard motility tests available in the stomach, small bowel, and colon. The indications for testing, technical details, advantages, and disadvantages of each test will be summarized.
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20
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Mark EB, Bødker MB, Grønlund D, Østergaard LR, Frøkjaer JB, Drewes AM. MRI analysis of fecal volume and dryness: Validation study using an experimental oxycodone-induced constipation model. J Magn Reson Imaging 2019; 50:733-745. [PMID: 30609164 DOI: 10.1002/jmri.26628] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2018] [Revised: 12/12/2018] [Accepted: 12/12/2018] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Opioids are known to affect gastrointestinal motility, but their effect on fluid absorption and secretion is poorly understood in humans. PURPOSE To investigate the effect of oxycodone on colonic fecal volume and stool dryness by using a novel MRI-based technique. STUDY TYPE Prospective, randomized, double-blinded, crossover study. SUBJECTS Twenty-five healthy male volunteers (median age: 24 years [range: 21-56]; mean body mass index [BMI]: 23.9 kg/m2 [range: 22.9-25.0]) without known gastrointestinal disease. FIELD STRENGTH/SEQUENCE T2 -weighted and two-point Dixon MRI scans of the abdomen at 1.5 T. ASSESSMENT Subjects were treated for 5 days with prolonged-release oxycodone or a placebo. Imaging was performed on the first and last study day in each period. Images of the colon were analyzed with semiautomatic k-means-based segmentation software. Regional colonic fecal volumes were quantified excluding gas volume and colon wall. Two-point Dixon and T2 -weighted MRI signal intensity were assessed as a proxy of colonic stool dryness. Data were obtained in a previously reported study. STATISTICAL TESTS Intraclass correlation coefficients were used to test the reliability of measurements between days, while repeated measures mixed models were applied to test treatment effects. RESULTS After oxycodone treatment, total colonic fecal volume was significantly increased compared with placebo (mean change 100 mL vs. -13 mL; P = 0.001), with the largest increase (24%) observed in the ascending colon/cecum (P = 0.001). Dixon signal increased (less water in colon content) after oxycodone treatment compared with placebo (mean 0.09 vs. -0.02; P < 0.001). T2 -weighted signal decreased (less water in colon content) after oxycodone treatment compared with placebo (mean -0.03 vs. 0.03; P = 0.002). DATA CONCLUSION The 5-day oxycodone treatment increased colonic fecal volume and increased stool dryness compared with placebo. This imaging-based method for noninvasive analysis of colon content has the potential to characterize gastrointestinal symptoms in general, such as in constipation. LEVEL OF EVIDENCE 2 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2019;50:733-745.
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Affiliation(s)
- Esben B Mark
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark.,Mech-Sense, Department of Radiology, Aalborg University Hospital, Aalborg, Denmark.,Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Mark B Bødker
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
| | - Debbie Grønlund
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark.,Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Lasse R Østergaard
- Department of Health Science and Technology, Aalborg University, Aalborg Øst, Denmark
| | - Jens B Frøkjaer
- Mech-Sense, Department of Radiology, Aalborg University Hospital, Aalborg, Denmark.,Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Asbjørn M Drewes
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark.,Mech-Sense, Department of Radiology, Aalborg University Hospital, Aalborg, Denmark.,Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
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21
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Hoad C, Clarke C, Marciani L, Graves MJ, Corsetti M. Will MRI of gastrointestinal function parallel the clinical success of cine cardiac MRI? Br J Radiol 2019; 92:20180433. [PMID: 30299989 PMCID: PMC6435057 DOI: 10.1259/bjr.20180433] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2018] [Revised: 09/21/2018] [Accepted: 10/03/2018] [Indexed: 12/11/2022] Open
Abstract
Cine cardiac MRI is generally accepted as the "gold-standard" for functional myocardial assessment. It only took a few years after the development of commercial MRI systems for functional cardiac imaging to be developed, with electrocardiogram (ECG)-gated cine imaging first reported in 1988. The function of the gastrointestinal (GI) tract is more complex to study compared to the heart. However, the idea of having a non-invasive tool to study the GI function that also allows the concurrent assessment of different aspects of this function has become more and more attractive in the gastroenterological field. This review summarises key literature of the last 5 years to describe the current status of MRI in respect to the evaluation of GI function, highlighting the gaps and challenges and the future prospects. As the clinical application of a new technique requires that its clinical utility is confirmed by demonstration of its ability to enable clinicians to make a diagnosis and/or predict the treatment response, this review also considers whether or not this has been achieved, and how MRI has been validated against techniques currently recognised as the gold standard in clinical practice.
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Affiliation(s)
| | - Christopher Clarke
- Department of Radiology, Nottingham University Hospitals NHS Trust, Nottingham, UK
| | | | - Martin John Graves
- Department of Radiology, Cambridge University Hospitals NHS Trust, Cambridge, UK
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22
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Khalaf A, Nowak A, Menys A, Marciani L, Taylor SA, Spiller RC, Gowland PA, Moran GW, Hoad CL. Cine MRI assessment of motility in the unprepared small bowel in the fasting and fed state: Beyond the breath-hold. Neurogastroenterol Motil 2019; 31:e13466. [PMID: 30230099 DOI: 10.1111/nmo.13466] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2018] [Revised: 08/06/2018] [Accepted: 08/14/2018] [Indexed: 02/08/2023]
Abstract
BACKGROUND The symptoms of functional bowel disorders are common in postprandial but investigations are generally undertaken in the fasted state using invasive procedures. MRI provides a noninvasive tool to study the gastrointestinal tract in an unperturbed, fed state. The aim of this study was to develop a technique to assess small bowel motility from cine MRI data in the unprepared bowel in fasting and fed states. METHODS Fifteen healthy volunteers underwent a baseline MRI scan after which they consumed a 400 g soup. Subjects then underwent a postprandial scan followed by further scans at regular intervals. Small bowel motility was assessed using single-slice bTFE cine MRI. An optimized processing technique was used to generate motility data based on power spectrum analysis of voxel-signal changes with time. Interobserver variability (n = 15) and intra-observer (n = 6) variability were assessed. Changes in the motility index were compared between fasted and immediate postprandial state. KEY RESULTS Excellent agreement between observers was seen across the range of motility measurements acquired, with intraclass correlation coefficient (ICC) of 0.979 (P < 0.0001) and Bland-Altman limits of agreement 95% CI: -28.9 to 45.9 au. Intra-observer variability was low with ICC of 0.992 and 0.960 (2 observers, P < 0.0001). Changes from the fasted to immediately postprandial state showed an average increase of 122.4% ± 98.7% (n = 15). CONCLUSIONS & INFERENCES This optimized technique showed excellent inter and intra observer agreement. It was sensitive to changes in motility induced feeding. This technique will be useful to study contractile activity and regional patterns along the gastrointestinal tract under physiological conditions.
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Affiliation(s)
- Asseel Khalaf
- Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK.,NIHR Nottingham Biomedical Research Centre (BRC), Nottingham University Hospitals NHS Trust, University of Nottingham, Nottingham, UK
| | - Adam Nowak
- NIHR Nottingham Biomedical Research Centre (BRC), Nottingham University Hospitals NHS Trust, University of Nottingham, Nottingham, UK
| | - Alex Menys
- Division of Medicine, Centre for Medical Imaging, UCL, London, UK
| | - Luca Marciani
- Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK.,NIHR Nottingham Biomedical Research Centre (BRC), Nottingham University Hospitals NHS Trust, University of Nottingham, Nottingham, UK
| | - Stuart A Taylor
- Division of Medicine, Centre for Medical Imaging, UCL, London, UK
| | - Robin C Spiller
- Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK.,NIHR Nottingham Biomedical Research Centre (BRC), Nottingham University Hospitals NHS Trust, University of Nottingham, Nottingham, UK
| | - Penny A Gowland
- Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, Nottingham, UK
| | - Gordon W Moran
- Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK.,NIHR Nottingham Biomedical Research Centre (BRC), Nottingham University Hospitals NHS Trust, University of Nottingham, Nottingham, UK
| | - Caroline L Hoad
- NIHR Nottingham Biomedical Research Centre (BRC), Nottingham University Hospitals NHS Trust, University of Nottingham, Nottingham, UK.,Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, Nottingham, UK
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23
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Wilkinson-Smith VC, Major G, Ashleigh L, Murray K, Hoad CL, Marciani L, Gowland PA, Spiller RC. Insights Into the Different Effects of Food on Intestinal Secretion Using Magnetic Resonance Imaging. JPEN J Parenter Enteral Nutr 2018; 42:1342-1348. [PMID: 29603286 DOI: 10.1002/jpen.1157] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2017] [Accepted: 02/08/2018] [Indexed: 12/17/2023]
Abstract
BACKGROUND Plant foods may stimulate intestinal secretion through chemicals designed to deter herbivores, including lactucins in lettuce and rhein in rhubarb. This may increase ileostomy output and induce diarrhoea in people with intact bowels. OBJECTIVE We aimed to determine the effect of food on intestinal water content using Magnetic Resonance Imaging (MRI). DESIGN A three period crossover trial of isocaloric meals in adults without bowel disorders. Meals: 2 slices white bread with 10 g butter; 300 g rhubarb with 60 mL lactose free cream; 300 g lettuce with 30 mL mayonnaise. PRIMARY OUTCOME Area under curve (AUC) small bowel water content (SBWC) using MRI. SECONDARY OUTCOMES ascending colon water content; T1 relaxation time of ascending colon (T1AC); gastric volume; visual analogue scales of bloating and satiety (0-100). MRI analysts were blinded. Scanned fasting and hourly to 180 min postprandial. Symptoms scored half-hourly. RESULTS 9 female and 6 male subjects completed the study. AUC SBWC fell after bread but rose after lettuce and even more after rhubarb, difference from baseline being (Bread AUC -5662 (1209) ml.min vs Lettuce 3194 (1574) ml.min and Rhubarb 10586 (1629) ml.min (P < 0.01). Rhubarb induced a rise in T1AC but differences at 3 hours were not significant (P = 0.06). Gastric volume at T = 0 significantly was higher for both lettuce and rhubarb (571 ± 92 and 558 ± 89 mls) respectively compared to bread (314 ± 108 mls) (p < 0.0001). Symptom scores were higher for lettuce > rhubarb > bread. CONCLUSION Lettuce and rhubarb meals increased intestinal water content, demonstrating how different foods can alter ileal flow and stool consistency.
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Affiliation(s)
- Victoria C Wilkinson-Smith
- National Institute for Health Research, Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, United Kingdom
- Nottingham Digestive Diseases Centre, University of Nottingham, Nottingham, United Kingdom
| | - Giles Major
- National Institute for Health Research, Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, United Kingdom
- Nottingham Digestive Diseases Centre, University of Nottingham, Nottingham, United Kingdom
| | - Lucy Ashleigh
- Nottingham Digestive Diseases Centre, University of Nottingham, Nottingham, United Kingdom
| | - Kathryn Murray
- National Institute for Health Research, Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, United Kingdom
- Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, United Kingdom
| | - Caroline L Hoad
- National Institute for Health Research, Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, United Kingdom
- Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, United Kingdom
| | - Luca Marciani
- National Institute for Health Research, Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, United Kingdom
- Nottingham Digestive Diseases Centre, University of Nottingham, Nottingham, United Kingdom
- Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, United Kingdom
| | - Penny A Gowland
- National Institute for Health Research, Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, United Kingdom
- Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, United Kingdom
| | - Robin C Spiller
- National Institute for Health Research, Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, United Kingdom
- Nottingham Digestive Diseases Centre, University of Nottingham, Nottingham, United Kingdom
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24
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Major G, Murray K, Singh G, Nowak A, Hoad CL, Marciani L, Silos-Santiago A, Kurtz CB, Johnston JM, Gowland P, Spiller R. Demonstration of differences in colonic volumes, transit, chyme consistency, and response to psyllium between healthy and constipated subjects using magnetic resonance imaging. Neurogastroenterol Motil 2018; 30:e13400. [PMID: 30062794 DOI: 10.1111/nmo.13400] [Citation(s) in RCA: 44] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2017] [Accepted: 05/28/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND In functional gastrointestinal disorders a lack of objective biomarkers limits evaluation of underlying mechanisms. We aimed to demonstrate the utility of magnetic resonance imaging for this task using psyllium, an effective constipation treatment, in patients and controls. METHODS Two crossover studies: (i) adults without constipation (controls, n = 9) took three treatments in randomized order for 6 days - maltodextrin (placebo), psyllium 3.5 g t.d.s and 7 g t.d.s., (ii) adults with chronic constipation (patients, n = 20) took placebo and psyllium 7 g t.d.s. for 6 days. MRI was performed fasting and postprandially on day 6. Measurements included small bowel and ascending colon water content, colonic volume, transit time, and MR relaxometry (T1, T2) to assess colonic chyme. Stool water percentage was measured. RESULTS 7 g psyllium t.d.s. increased fasting colonic volumes in controls from median 372 mL (IQR 284-601) to 578 mL (IQR 510-882), and in patients from median 831 mL (IQR 745-934) to 1104 mL (847-1316), P < .05. Mean postprandial small bowel water was higher in controls and patients after 7 g psyllium t.d.s. vs placebo. Whole gut transit was slower in patients than controls (P < .05). T1 of the descending colon chyme (fasting) was lower in patients (213 ms, 176-420) than controls (440 ms, 352-884, P < .05) on placebo, but increased by 7 g psyllium t.d.s. (590 ms, 446-1338), P < .001. Descending colon T1 correlated with baseline stool water content and stool frequency on treatment. CONCLUSIONS AND INFERENCES MRI measurements can objectively demonstrate the mode of action of therapy targeting intestinal fluid content in constipation.
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Affiliation(s)
- G Major
- Nottingham Digestive Diseases Centre and National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, UK
| | - K Murray
- Nottingham Digestive Diseases Centre and National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, UK.,Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, UK
| | - G Singh
- Nottingham Digestive Diseases Centre and National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, UK
| | - A Nowak
- Nottingham Digestive Diseases Centre and National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, UK
| | - C L Hoad
- Nottingham Digestive Diseases Centre and National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, UK.,Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, UK
| | - L Marciani
- Nottingham Digestive Diseases Centre and National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, UK
| | | | - C B Kurtz
- Ironwood Pharmaceuticals Inc., Cambridge, MA, USA
| | - J M Johnston
- Ironwood Pharmaceuticals Inc., Cambridge, MA, USA
| | - P Gowland
- Nottingham Digestive Diseases Centre and National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, UK.,Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, UK
| | - R Spiller
- Nottingham Digestive Diseases Centre and National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, UK
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25
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de Jonge CS, Smout AJPM, Nederveen AJ, Stoker J. Evaluation of gastrointestinal motility with MRI: Advances, challenges and opportunities. Neurogastroenterol Motil 2018; 30. [PMID: 29265641 DOI: 10.1111/nmo.13257] [Citation(s) in RCA: 44] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2017] [Accepted: 10/30/2017] [Indexed: 12/19/2022]
Abstract
Dynamic magnetic resonance imaging (MRI) of gastrointestinal motility has developed rapidly over the past few years. The non-invasive and non-ionizing character of MRI is an important advantage together with the fact that it is fast and can visualize the entire gastrointestinal tract. Advances in imaging and quantification techniques have facilitated assessment of gastric, small intestinal, and colonic motility in a clinical setting. Automated quantitative motility assessment using dynamic MRI meets the need for non-invasive techniques. Recently, studies have begun to examine this technique in patients, including those with IBD, pseudo-obstruction and functional bowel disorders. Remaining challenges for clinical implementation are processing the large amount of data, standardization and validation of the numerous MRI metrics and subsequently assessment of the potential role of dynamic MRI. This review examines the methods, advances, and remaining challenges of evaluation of gastrointestinal motility with MRI. It accompanies an article by Khalaf et al. in this journal that describes a new protocol for assessment of pan-intestinal motility in fasted and fed state in a single MRI session.
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Affiliation(s)
- C S de Jonge
- Department of Radiology and Nuclear Medicine, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, the Netherlands
| | - A J P M Smout
- Department of Gastroenterology & Hepatology, Academic Medical Center (AMC), Amsterdam, the Netherlands
| | - A J Nederveen
- Department of Radiology and Nuclear Medicine, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, the Netherlands
| | - J Stoker
- Department of Radiology and Nuclear Medicine, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, the Netherlands
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26
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Müller-Lissner S, Bassotti G, Coffin B, Drewes AM, Breivik H, Eisenberg E, Emmanuel A, Laroche F, Meissner W, Morlion B. Opioid-Induced Constipation and Bowel Dysfunction: A Clinical Guideline. PAIN MEDICINE (MALDEN, MASS.) 2017; 18:1837-1863. [PMID: 28034973 PMCID: PMC5914368 DOI: 10.1093/pm/pnw255] [Citation(s) in RCA: 77] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
OBJECTIVE To formulate timely evidence-based guidelines for the management of opioid-induced bowel dysfunction. SETTING Constipation is a major untoward effect of opioids. Increasing prescription of opioids has correlated to increased incidence of opioid-induced constipation. However, the inhibitory effects of opioids are not confined to the colon, but also affect higher segments of the gastrointestinal tract, leading to the coining of the term "opioid-induced bowel dysfunction." METHODS A literature search was conducted using Medline, EMBASE, and EMBASE Classic, and the Cochrane Central Register of Controlled Trials. Predefined search terms and inclusion/exclusion criteria were used to identify and categorize relevant papers. A series of statements were formulated and justified by a comment, then labeled with the degree of agreement and their level of evidence as judged by the Strength of Recommendation Taxonomy (SORT) system. RESULTS From a list of 10,832 potentially relevant studies, 33 citations were identified for review. Screening the reference lists of the pertinent papers identified additional publications. Current definitions, prevalence, and mechanism of opioid-induced bowel dysfunction were reviewed, and a treatment algorithm and statements regarding patient management were developed to provide guidance on clinical best practice in the management of patients with opioid-induced constipation and opioid-induced bowel dysfunction. CONCLUSIONS In recent years, more insight has been gained in the pathophysiology of this "entity"; new treatment approaches have been developed, but guidelines on clinical best practice are still lacking. Current knowledge is insufficient regarding management of the opioid side effects on the upper gastrointestinal tract, but recommendations can be derived from what we know at present.
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Affiliation(s)
| | - Gabrio Bassotti
- Gastroenterology and Hepatology Section, Department of Medicine, University of Perugia School of Medicine, Piazza Università, 1, Perugia, Italy
| | - Benoit Coffin
- AP-HP Hôpital Louis Mourier, University Denis Diderot-Paris 7, INSERM U987, Paris, France
| | - Asbjørn Mohr Drewes
- Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
| | - Harald Breivik
- Department of Pain Management and Research, University of Oslo, Rikshospitalet, Oslo, Norway
| | - Elon Eisenberg
- Institute of Pain Medicine, Rambam Health Care Campus, The Technion, Israel Institute of Technology, Haifa, Israel
| | - Anton Emmanuel
- GI Physiology Unit, University College Hospital, Queen Square, London, UK
| | | | | | - Bart Morlion
- The Leuven Center for Algology and Pain Management, University of Leuven, KU Leuven, Leuven, Belgium
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27
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Pritchard SE, Paul J, Major G, Marciani L, Gowland PA, Spiller RC, Hoad CL. Assessment of motion of colonic contents in the human colon using MRI tagging. Neurogastroenterol Motil 2017; 29. [PMID: 28439942 DOI: 10.1111/nmo.13091] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2016] [Accepted: 03/20/2017] [Indexed: 02/08/2023]
Abstract
BACKGROUND We have previously reported a non-invasive, semi-automated technique to assess motility of the wall of the ascending colon (AC) using Magnetic Resonance Imaging. This study investigated the feasibility of using a tagged MRI technique to visualize and assess the degree of flow within the human ascending colon in healthy subjects and those suffering from constipation. METHODS An open-labeled study of 11 subjects with constipation and 11 subjects without bowel disorders was performed. MRI scans were acquired fasted, then 60 and 120 minutes after ingestion of a 500 mL macrogol preparation. The amount of free fluid in the small and large bowel was assessed using a heavily T2-weighted MRI sequence. The internal movement of the contents of the AC was visualized using a cine tagged MRI sequence and assessed by a novel analysis technique. Comparisons were made between fasting and postprandial scans within individuals, and between the constipation and control groups. KEY RESULTS Macrogol significantly increased the mobile, MR visible water content of the ascending colon at 60 minutes postingestion compared to fasted data (controls P=.001, constipated group P=.0039). The contents of the AC showed increased motion in healthy subjects but not in the constipated group with significant differences between groups at 60 minutes (P<.002) and 120 minutes (P<.003). CONCLUSIONS AND INFERENCES This study successfully demonstrated the use of a novel MRI tagging technique to visualize and assess the motion of ascending colon contents following a 500 mL macrogol challenge. Significant differences were demonstrated between healthy and constipated subjects.
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Affiliation(s)
- S E Pritchard
- Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, Nottingham, UK
| | - J Paul
- Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, Nottingham, UK
| | - G Major
- Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK.,NIHR Biomedical Research Unit in Gastrointestinal and Liver Diseases at Nottingham University Hospitals NHS Trust and The University of Nottingham, Nottingham, UK
| | - L Marciani
- Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK.,NIHR Biomedical Research Unit in Gastrointestinal and Liver Diseases at Nottingham University Hospitals NHS Trust and The University of Nottingham, Nottingham, UK
| | - P A Gowland
- Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, Nottingham, UK
| | - R C Spiller
- Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK.,NIHR Biomedical Research Unit in Gastrointestinal and Liver Diseases at Nottingham University Hospitals NHS Trust and The University of Nottingham, Nottingham, UK
| | - C L Hoad
- Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, Nottingham, UK.,NIHR Biomedical Research Unit in Gastrointestinal and Liver Diseases at Nottingham University Hospitals NHS Trust and The University of Nottingham, Nottingham, UK
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28
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Murray K, Hoad CL, Mudie DM, Wright J, Heissam K, Abrehart N, Pritchard SE, Al Atwah S, Gowland PA, Garnett MC, Amidon GE, Spiller RC, Amidon GL, Marciani L. Magnetic Resonance Imaging Quantification of Fasted State Colonic Liquid Pockets in Healthy Humans. Mol Pharm 2017. [DOI: 10.1021/acs.molpharmaceut.7b00095] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Affiliation(s)
- Kathryn Murray
- Nottingham Digestive Diseases Centre and NIHR Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham NG7 2UH, United Kingdom
| | - Caroline L. Hoad
- Nottingham Digestive Diseases Centre and NIHR Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham NG7 2UH, United Kingdom
- Sir
Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, Nottingham NG7 2RD, United Kingdom
| | | | - Jeff Wright
- Nottingham Digestive Diseases Centre and NIHR Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham NG7 2UH, United Kingdom
| | - Khaled Heissam
- Nottingham Digestive Diseases Centre and NIHR Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham NG7 2UH, United Kingdom
| | - Nichola Abrehart
- Nottingham Digestive Diseases Centre and NIHR Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham NG7 2UH, United Kingdom
| | - Susan E. Pritchard
- Sir
Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, Nottingham NG7 2RD, United Kingdom
| | - Salem Al Atwah
- Nottingham Digestive Diseases Centre and NIHR Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham NG7 2UH, United Kingdom
| | - Penny A. Gowland
- Sir
Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, Nottingham NG7 2RD, United Kingdom
| | - Martin C. Garnett
- School
of Pharmacy, University of Nottingham, Nottingham NG7 2RD, United Kingdom
| | - Gregory E. Amidon
- College
of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109-1065, United States
| | - Robin C. Spiller
- Nottingham Digestive Diseases Centre and NIHR Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham NG7 2UH, United Kingdom
| | - Gordon L. Amidon
- College
of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109-1065, United States
| | - Luca Marciani
- Nottingham Digestive Diseases Centre and NIHR Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham NG7 2UH, United Kingdom
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29
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Grønlund D, Poulsen JL, Sandberg TH, Olesen AE, Madzak A, Krogh K, Frøkjaer JB, Drewes AM. Established and emerging methods for assessment of small and large intestinal motility. Neurogastroenterol Motil 2017; 29. [PMID: 28086261 DOI: 10.1111/nmo.13008] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2016] [Accepted: 11/11/2016] [Indexed: 12/13/2022]
Abstract
BACKGROUND Gastrointestinal symptoms are common in the general population and may originate from disturbances in gut motility. However, fundamental mechanistic understanding of motility remains inadequate, especially of the less accessible regions of the small bowel and colon. Hence, refinement and validation of objective methods to evaluate motility of the whole gut is important. Such techniques may be applied in clinical settings as diagnostic tools, in research to elucidate underlying mechanisms of diseases, and to evaluate how the gut responds to various drugs. A wide array of such methods exists; however, a limited number are used universally due to drawbacks like radiation exposure, lack of standardization, and difficulties interpreting data. In recent years, several new methods such as the 3D-Transit system and magnetic resonance imaging assessments on small bowel and colonic motility have emerged, with the advantages that they are less invasive, use no radiation, and provide much more detailed information. PURPOSE This review outlines well-established and emerging methods to evaluate small bowel and colonic motility in clinical settings and in research. The latter include the 3D-Transit system, magnetic resonance imaging assessments, and high-resolution manometry. Procedures, indications, and the relative strengths and weaknesses of each method are summarized.
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Affiliation(s)
- D Grønlund
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark.,Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - J L Poulsen
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark.,Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - T H Sandberg
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
| | - A E Olesen
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark.,Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.,Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark
| | - A Madzak
- Mech-Sense, Department of Radiology, Aalborg University Hospital, Aalborg, Denmark
| | - K Krogh
- Neurogastroenterology Unit, Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - J B Frøkjaer
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.,Mech-Sense, Department of Radiology, Aalborg University Hospital, Aalborg, Denmark
| | - A M Drewes
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark.,Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
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30
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Hens B, Corsetti M, Spiller R, Marciani L, Vanuytsel T, Tack J, Talattof A, Amidon GL, Koziolek M, Weitschies W, Wilson CG, Bennink RJ, Brouwers J, Augustijns P. Exploring gastrointestinal variables affecting drug and formulation behavior: Methodologies, challenges and opportunities. Int J Pharm 2017; 519:79-97. [DOI: 10.1016/j.ijpharm.2016.11.063] [Citation(s) in RCA: 67] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2016] [Revised: 11/28/2016] [Accepted: 11/29/2016] [Indexed: 12/16/2022]
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31
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Lam C, Chaddock G, Marciani Laurea L, Costigan C, Cox E, Hoad C, Pritchard S, Gowland P, Spiller R. Distinct Abnormalities of Small Bowel and Regional Colonic Volumes in Subtypes of Irritable Bowel Syndrome Revealed by MRI. Am J Gastroenterol 2017; 112:346-355. [PMID: 27958282 PMCID: PMC5318666 DOI: 10.1038/ajg.2016.538] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2016] [Accepted: 08/02/2016] [Indexed: 02/07/2023]
Abstract
OBJECTIVES Non-invasive biomarkers which identify different mechanisms of disease in subgroups of irritable bowel syndrome (IBS) could be valuable. Our aim was to seek useful magnetic resonance imaging (MRI) parameters that could distinguish each IBS subtypes. METHODS 34 healthy volunteers (HV), 30 IBS with diarrhea (IBS-D), 16 IBS with constipation (IBS-C), and 11 IBS with mixed bowel habit (IBS-M) underwent whole-gut transit and small and large bowel volumes assessment with MRI scans from t=0 to t=360 min. Since the bowel frequency for IBS-M were similar to IBS-D, IBS-M and IBS-D were grouped together and labeled as IBS non-constipation group (IBS-nonC). RESULTS Median (interquartile range): fasting small bowel water content in IBS-nonC was 21 (10-42), significantly less than HV at 44 ml (15-70), P<0.01 as was the postprandial area under the curve (AUC) P<0.01. The fasting transverse colon volumes in IBS-C were significantly larger at 253 (200-329) compared with HV, IBS-nonC whose values were 165 (117-255) and 198 (106-270) ml, respectively, P=0.02. Whole-gut transit time for IBS-C was prolonged at 69 (51-111), compared with HV at 34 (4-63) and IBS-D at 34 (17-78) h, P=0.03. Bloating score (VAS 0-10 cm) correlated with transverse colon volume at t=405 min, Spearman r=0.21, P=0.04. CONCLUSIONS The constricted small bowel in IBS-nonC and the dilated transverse colon in IBS-C point to significant differences in underlying mechanisms of disease.
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Affiliation(s)
- Ching Lam
- NIHR Biomedical Research Unit in Gastrointestinal and Liver Diseases, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
| | - Gemma Chaddock
- Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, UK
| | - Luca Marciani Laurea
- NIHR Biomedical Research Unit in Gastrointestinal and Liver Diseases, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
| | - Carolyn Costigan
- NIHR Biomedical Research Unit in Gastrointestinal and Liver Diseases, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
| | - Eleanor Cox
- Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, UK
| | - Caroline Hoad
- Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, UK
| | - Susan Pritchard
- Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, UK
| | - Penny Gowland
- Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, UK
| | - Robin Spiller
- NIHR Biomedical Research Unit in Gastrointestinal and Liver Diseases, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK,NIHR Biomedical Research Unit in Gastrointestinal and Liver Diseases, Nottingham University Hospitals NHS Trust and the University of Nottingham, Derby Road, NG7 2UH, Nottingham, UK. E-mail:
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Bendezú RA, Mego M, Monclus E, Merino X, Accarino A, Malagelada JR, Navazo I, Azpiroz F. Colonic content: effect of diet, meals, and defecation. Neurogastroenterol Motil 2017; 29. [PMID: 27545449 DOI: 10.1111/nmo.12930] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2016] [Accepted: 07/27/2016] [Indexed: 02/08/2023]
Abstract
BACKGROUND The metabolic activity of colonic microbiota is influenced by diet; however, the relationship between metabolism and colonic content is not known. Our aim was to determine the effect of meals, defecation, and diet on colonic content. METHODS In 10 healthy subjects, two abdominal MRI scans were acquired during fasting, 1 week apart, and after 3 days on low- and high-residue diets, respectively. With each diet, daily fecal output and the number of daytime anal gas evacuations were measured. On the first study day, a second scan was acquired 4 hours after a test meal (n=6) or after 4 hours with nil ingestion (n=4). On the second study day, a scan was also acquired after a spontaneous bowel movement. RESULTS On the low-residue diet, daily fecal volume averaged 145 ± 15 mL; subjects passed 10.6 ± 1.6 daytime anal gas evacuations and, by the third day, non-gaseous colonic content was 479 ± 36 mL. The high-residue diet increased the three parameters to 16.5 ± 2.9 anal gas evacuations, 223 ± 19 mL fecal output, and 616 ± 55 mL non-gaseous colonic content (P<.05 vs low-residue diet for all). On the low-residue diet, non-gaseous content in the right colon had increased by 41 ± 11 mL, 4 hours after the test meal, whereas no significant change was observed after 4-hour fast (-15 ± 8 mL; P=.006 vs fed). Defecation significantly reduced the non-gaseous content in distal colonic segments. CONCLUSION & INFERENCES Colonic content exhibits physiologic variations with an approximate 1/3 daily turnover produced by meals and defecation, superimposed over diet-related day-to-day variations.
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Affiliation(s)
- R A Bendezú
- Digestive System Research Unit, University Hospital Vall d'Hebron, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Spain
| | - M Mego
- Digestive System Research Unit, University Hospital Vall d'Hebron, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Spain
| | - E Monclus
- Department of Computer Languages and System, Universidad Politécnica de Cataluña, Barcelona, Spain
| | - X Merino
- Radiology Department, University Hospital Vall d'Hebron, Barcelona, Spain
| | - A Accarino
- Digestive System Research Unit, University Hospital Vall d'Hebron, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Spain
| | - J R Malagelada
- Digestive System Research Unit, University Hospital Vall d'Hebron, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Spain
| | - I Navazo
- Department of Computer Languages and System, Universidad Politécnica de Cataluña, Barcelona, Spain
| | - F Azpiroz
- Digestive System Research Unit, University Hospital Vall d'Hebron, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Spain
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Yamano HO, Matsushita HO, Yoshikawa K, Takagi R, Harada E, Tanaka Y, Nakaoka M, Himori R, Yoshida Y, Satou K, Imai Y. Randomised clinical study comparing the effectiveness and physiological effects of hypertonic and isotonic polyethylene glycol solutions for bowel cleansing. BMJ Open Gastroenterol 2016; 3:e000101. [PMID: 27547443 PMCID: PMC4985908 DOI: 10.1136/bmjgast-2016-000101] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2016] [Revised: 06/25/2016] [Accepted: 07/03/2016] [Indexed: 12/23/2022] Open
Abstract
Objectives Bowel cleansing is necessary before colonoscopy, but is a burden to patients because of the long cleansing time and large dose volume. A low-volume (2 L) hypertonic polyethylene glycol-ascorbic acid solution (PEG-Asc) has been introduced, but its possible dehydration effects have not been quantitatively studied. We compared the efficacy and safety including the dehydration risk between hypertonic PEG-Asc and isotonic PEG regimens. Design This was an observer-blinded randomised study. Participants (n=310) were allocated to receive 1 of 3 regimens on the day of colonoscopy: PEG-Asc (1.5 L) and water (0.75 L) dosed with 1 split (PEG-Asc-S) or 4 splits (PEG-Asc-M), or PEG-electrolyte solution (PEG-ES; 2.25 L) dosed with no split. Dehydration was analysed by measuring haematocrit (Ht). Results The cleansing time using the hypertonic PEG-Asc-S (3.33±0.48 hours) was significantly longer than that with isotonic PEG-ES (3.05±0.56 hours; p<0.001). PEG-Asc-M (3.00±0.53 hours) did not have this same disadvantage. Successful cleansing was achieved in more than 94% of participants using each of the 3 regimens. The percentage changes in Ht from baseline (before dosing) to the end of dosing with PEG-Asc-S (3.53±3.32%) and PEG-Asc-M (4.11±3.07%) were significantly greater than that with PEG-ES (1.31±3.01%). Conclusions These 3 lower volume regimens were efficacious and had no serious adverse effects. Even patients cleansed with isotonic PEG-ES showed significant physiological dehydration at the end of dosing. The four-split PEG-Asc-M regimen is recommended because of its shorter cleansing time without causing serious nausea. Trial registration number UMIN000013103; Results.
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Affiliation(s)
- Hiro-O Yamano
- Digestive Disease Center, Akita Red Cross Hospital , Akita , Japan
| | | | | | - Ryo Takagi
- Digestive Disease Center, Akita Red Cross Hospital , Akita , Japan
| | - Eiji Harada
- Digestive Disease Center, Akita Red Cross Hospital , Akita , Japan
| | - Yoshihito Tanaka
- Digestive Disease Center, Akita Red Cross Hospital , Akita , Japan
| | - Michiko Nakaoka
- Digestive Disease Center, Akita Red Cross Hospital , Akita , Japan
| | - Ryogo Himori
- Digestive Disease Center, Akita Red Cross Hospital , Akita , Japan
| | - Yuko Yoshida
- Digestive Disease Center, Akita Red Cross Hospital , Akita , Japan
| | - Kentarou Satou
- Digestive Disease Center, Akita Red Cross Hospital , Akita , Japan
| | - Yasushi Imai
- Digestive Disease Center, Akita Red Cross Hospital , Akita , Japan
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Abstract
Ingestion and digestion of food as well as expulsion of residual material from our gastrointestinal tract requires normal propulsive, i.e. motor, function. Hypomotility refers to inherited or acquired changes that come with decreased contractile forces or slower transit. It not only often causes symptoms but also may compromise nutritional status or lead to other complications. While severe forms, such as pseudo-obstruction or ileus, may have a tremendous functional impact, the less severe forms of hypomotility may well be more relevant, as they contribute to common disorders, such as functional dyspepsia, gastroparesis, chronic constipation, and irritable bowel syndrome (IBS). Clinical testing can identify changes in contractile activity, defined by lower amplitudes or abnormal patterns, and the related effects on transit. However, such biomarkers show a limited correlation with overall symptom severity as experienced by patients. Similarly, targeting hypomotility with pharmacological interventions often alters gut motor function but does not consistently improve symptoms. Novel diagnostic approaches may change this apparent paradox and enable us to obtain more comprehensive information by integrating data on electrical activity, mechanical forces, patterns, wall stiffness, and motions with information of the flow of luminal contents. New drugs with more selective effects or more specific delivery may improve benefits and limit adverse effects. Lastly, the complex regulation of gastrointestinal motility involves the brain-gut axis as a reciprocal pathway for afferent and efferent signaling. Considering the role of visceral input in emotion and the effects of emotion on visceral activity, understanding and managing hypomotility disorders requires an integrative approach based on the mind-body continuum or biopsychosocial model of diseases.
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Affiliation(s)
- Klaus Bielefeldt
- Department of Internal Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Ashok Tuteja
- Department of Medicine, University of Utah, Salt Lake City, UT, USA
| | - Salman Nusrat
- Department of Medicine, Oklahoma University Medical Center, Oklahoma City, OK, USA
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Lam C, Chaddock G, Marciani L, Costigan C, Paul J, Cox E, Hoad C, Menys A, Pritchard S, Garsed K, Taylor S, Atkinson D, Gowland P, Spiller R. Colonic response to laxative ingestion as assessed by MRI differs in constipated irritable bowel syndrome compared to functional constipation. Neurogastroenterol Motil 2016; 28:861-70. [PMID: 26871949 PMCID: PMC4949702 DOI: 10.1111/nmo.12784] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2015] [Accepted: 12/31/2015] [Indexed: 12/20/2022]
Abstract
BACKGROUND Functional constipation (FC) and irritable bowel syndrome with constipation (IBS-C) share many symptoms but underlying mechanisms may be different. We have developed a magnetic resonance imaging (MRI) technique to measure intestinal volumes, transit, and motility in response to a laxative, Moviprep(®) . We aim to use these biomarkers to study the pathophysiology in IBS-C and FC. METHODS Twenty-four FC and 24 IBS-C were studied. Transit was assessed using the weighted average position score (WAPS) of five MRI marker pills, taken 24 h before MRI scanning. Following baseline scan, participants ingested 1 L of Moviprep(®) followed by hourly scans. Magnetic resonance imaging parameters and bowel symptoms were scored from 0 to 4 h. KEY RESULTS Weighted average position score for FC was 3.6 (2.5-4.2), significantly greater than IBS-C at 2.0 (1.5-3.2), p = 0.01, indicating slower transit for FC. Functional constipation showed greater fasting small bowel water content, 83 (63-142) mL vs 39 (15-70) mL in IBS-C, p < 0.01 and greater ascending colon volume (AC), 314 (101) mL vs 226 (71) mL in IBS-C, p < 0.01. FC motility index was lower at 0.055 (0.044) compared to IBS-C, 0.107 (0.070), p < 0.01. Time to first bowel movement following ingestion of Moviprep(®) was greater for FC, being 295 (116-526) min, compared to IBS-C at 84 (49-111) min, p < 0.01, and correlated with AC volume 2 h after Moviprep(®) , r = 0.44, p < 0.01. Using a cut-off >230 min distinguishes FC from IBS-C with low sensitivity of 55% but high specificity of 95%. CONCLUSION & INFERENCES Our objective MRI biomarkers allow a distinction between FC and IBS-C.
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Affiliation(s)
- C. Lam
- NIHR Nottingham Digestive Diseases Biomedical Research Unit and Nottingham Digestive Diseases CentreSchool of MedicineUniversity of NottinghamNottinghamUK
| | - G. Chaddock
- Sir Peter Mansfield Imaging CentreUniversity of NottinghamNottinghamUK
| | - L. Marciani
- NIHR Nottingham Digestive Diseases Biomedical Research Unit and Nottingham Digestive Diseases CentreSchool of MedicineUniversity of NottinghamNottinghamUK
| | - C. Costigan
- NIHR Nottingham Digestive Diseases Biomedical Research Unit and Nottingham Digestive Diseases CentreSchool of MedicineUniversity of NottinghamNottinghamUK
| | - J. Paul
- Sir Peter Mansfield Imaging CentreUniversity of NottinghamNottinghamUK
| | - E. Cox
- Sir Peter Mansfield Imaging CentreUniversity of NottinghamNottinghamUK
| | - C. Hoad
- NIHR Nottingham Digestive Diseases Biomedical Research Unit and Nottingham Digestive Diseases CentreSchool of MedicineUniversity of NottinghamNottinghamUK,Sir Peter Mansfield Imaging CentreUniversity of NottinghamNottinghamUK
| | - A. Menys
- Centre for Medical ImagingDivision of MedicineUniversity College LondonLondonUK
| | - S. Pritchard
- Sir Peter Mansfield Imaging CentreUniversity of NottinghamNottinghamUK
| | - K. Garsed
- Royal Derby Hospitals Foundation TrustDerbyUK
| | - S. Taylor
- Centre for Medical ImagingDivision of MedicineUniversity College LondonLondonUK
| | - D. Atkinson
- Centre for Medical ImagingDivision of MedicineUniversity College LondonLondonUK
| | - P. Gowland
- Sir Peter Mansfield Imaging CentreUniversity of NottinghamNottinghamUK
| | - R. Spiller
- NIHR Nottingham Digestive Diseases Biomedical Research Unit and Nottingham Digestive Diseases CentreSchool of MedicineUniversity of NottinghamNottinghamUK
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Whitehead WE, Palsson OS, Simrén M. Biomarkers to distinguish functional constipation from irritable bowel syndrome with constipation. Neurogastroenterol Motil 2016; 28:783-92. [PMID: 27214096 DOI: 10.1111/nmo.12852] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2016] [Accepted: 04/13/2016] [Indexed: 12/15/2022]
Abstract
Treatments for functional constipation (FC) and irritable bowel syndrome with constipation (IBS-C) differ, but symptom criteria do not reliably distinguish between them; some regard FC and IBS-C as parts of a single constipation spectrum. Our goal was to review studies comparing FC and IBS-C to identify possible biomarkers that separate them. A systematic review identified 15 studies that compared physiologic tests in FC vs IBS-C. Pain thresholds were lower in IBS-C than FC for 3/5 studies and not different in 2/5. Colonic motility was decreased more in FC than IBS-C for 3/3 studies, and whole gut transit was delayed more in FC than IBS-C in 3/8 studies and not different in 5/8. Pelvic floor dyssynergia was unrelated to diagnosis. Sympathetic arousal, measured in only one study, was greater in IBS-C than FC. The most reliable separation of FC from IBS-C was shown by a novel new magnetic resonance imaging technique described in this issue of the journal. These authors showed that drinking one liter of polyethylene glycol laxative significantly increased water content in the small intestine, volume of contents in the ascending colon, and time to first evacuation in FC vs IBS-C; and resulted in less colon motility and delayed whole gut transit in FC compared to IBS-C. Although replication is needed, this well-tolerated, non-invasive test promises to become a new standard for differential diagnosis of FC vs IBS-C. These data suggest that FC and IBS-C are different disorders rather than points on a constipation spectrum.
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Affiliation(s)
- W E Whitehead
- Center for Functional Gastrointestinal and Motility Disorders, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - O S Palsson
- Center for Functional Gastrointestinal and Motility Disorders, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - M Simrén
- Center for Functional Gastrointestinal and Motility Disorders, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.,Department of Internal Medicine & Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
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Opioid-induced bowel dysfunction in healthy volunteers assessed with questionnaires and MRI. Eur J Gastroenterol Hepatol 2016; 28:514-24. [PMID: 26795566 DOI: 10.1097/meg.0000000000000574] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
OBJECTIVE Opioid treatment is associated with numerous gastrointestinal adverse effects collectively known as opioid-induced bowel dysfunction (OIBD). Most current knowledge of the pathophysiology derives from animal studies limited by species differences and clinical studies, which have substantial confounders that make evaluation difficult. An experimental model of OIBD in healthy volunteers in a controlled setting is therefore highly warranted. The aim of this study was to assess bowel function in healthy volunteers during opioid treatment using subjective and objective methods. METHODS Twenty-five healthy men were assigned randomly to oxycodone or placebo for 5 days in a cross-over design. The analgesic effect was assessed with muscle pressure algometry and adverse effects were measured using questionnaires including the bowel function index, gastrointestinal symptom rating scale, patient assessment of constipation symptoms and the Bristol stool form scale. Colorectal volumes were determined using a newly developed MRI method. RESULTS Compared with baseline, oxycodone increased pain detection thresholds by 8% (P=0.02). Subjective OIBD was observed as increased bowel function index (464% increase; P<0.001), gastrointestinal symptom rating scale (37% increase; P<0.001) and patient assessment of constipation symptoms (198% increase; P<0.001). Objectively, stools were harder and drier during oxycodone treatment (P<0.001) and segmental colorectal volumes increased in the caecum/ascending colon by 41% (P=0.005) and in the transverse colon by 20% (P=0.005). No associations were detected between questionnaire scores and colorectal volumes. CONCLUSION Experimental OIBD in healthy volunteers was induced during oxycodone treatment. This model has potential for future interventional studies to discriminate the efficacies of different laxatives, peripheral morphine antagonists and opioid treatments.
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Enck P, Aziz Q, Barbara G, Farmer AD, Fukudo S, Mayer EA, Niesler B, Quigley EMM, Rajilić-Stojanović M, Schemann M, Schwille-Kiuntke J, Simren M, Zipfel S, Spiller RC. Irritable bowel syndrome. Nat Rev Dis Primers 2016; 2:16014. [PMID: 27159638 PMCID: PMC5001845 DOI: 10.1038/nrdp.2016.14] [Citation(s) in RCA: 633] [Impact Index Per Article: 70.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Irritable bowel syndrome (IBS) is a functional gastrointestinal disease with a high population prevalence. The disorder can be debilitating in some patients, whereas others may have mild or moderate symptoms. The most important single risk factors are female sex, younger age and preceding gastrointestinal infections. Clinical symptoms of IBS include abdominal pain or discomfort, stool irregularities and bloating, as well as other somatic, visceral and psychiatric comorbidities. Currently, the diagnosis of IBS is based on symptoms and the exclusion of other organic diseases, and therapy includes drug treatment of the predominant symptoms, nutrition and psychotherapy. Although the underlying pathogenesis is far from understood, aetiological factors include increased epithelial hyperpermeability, dysbiosis, inflammation, visceral hypersensitivity, epigenetics and genetics, and altered brain-gut interactions. IBS considerably affects quality of life and imposes a profound burden on patients, physicians and the health-care system. The past decade has seen remarkable progress in our understanding of functional bowel disorders such as IBS that will be summarized in this Primer.
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Affiliation(s)
- Paul Enck
- Department of Internal Medicine VI (Psychosomatic Medicine and Psychotherapy), University Hospital Tübingen, Tübingen, Germany
| | - Qasim Aziz
- Wingate Institute of Neurogastroenterology, Barts and London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Giovanni Barbara
- Department of Medical and Surgical Sciences, St. Orsola-Malpighi Hospital, Bologna, Italy
| | - Adam D Farmer
- Wingate Institute of Neurogastroenterology, Barts and London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Shin Fukudo
- Department of Behavioural Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Emeran A Mayer
- Oppenheimer Center for Neurobiology of Stress, Division of Digestive Diseases, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
| | - Beate Niesler
- Department of Human Molecular Genetics, University of Heidelberg, Heidelberg, Germany
| | - Eamonn M M Quigley
- Lynda K and David M Underwood Center for Digestive Disorders, Division of Gastroenterology and Hepatology, Houston Methodist Hospital, Weill Cornell Medical College, Houston, Texas, USA
| | - Mirjana Rajilić-Stojanović
- Department of Biochemical Engineering and Biotechnology, Faculty of Technology and Metallurgy, University of Belgrade, Belgrade, Serbia
| | - Michael Schemann
- Department of Human Biology, Technical University Munich, Freising-Weihenstephan, Germany
| | - Juliane Schwille-Kiuntke
- Department of Internal Medicine VI (Psychosomatic Medicine and Psychotherapy), University Hospital Tübingen, Tübingen, Germany
| | - Magnus Simren
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Stephan Zipfel
- Department of Internal Medicine VI (Psychosomatic Medicine and Psychotherapy), University Hospital Tübingen, Tübingen, Germany
| | - Robin C Spiller
- NIHR Nottingham Digestive Diseases Biomedical Research Unit, University of Nottingham, Nottingham, UK
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Hoad CL, Menys A, Garsed K, Marciani L, Hamy V, Murray K, Costigan C, Atkinson D, Major G, Spiller RC, Taylor SA, Gowland PA. Colon wall motility: comparison of novel quantitative semi-automatic measurements using cine MRI. Neurogastroenterol Motil 2016; 28:327-35. [PMID: 26612075 DOI: 10.1111/nmo.12727] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2015] [Accepted: 10/15/2015] [Indexed: 02/08/2023]
Abstract
BACKGROUND Recently, cine magnetic resonance imaging (MRI) has shown promise for visualizing movement of the colonic wall, although assessment of data has been subjective and observer dependent. This study aimed to develop an objective and semi-automatic imaging metric of ascending colonic wall movement, using image registration techniques. METHODS Cine balanced turbo field echo MRI images of ascending colonic motility were acquired over 2 min from 23 healthy volunteers (HVs) at baseline and following two different macrogol stimulus drinks (11 HVs drank 1 L and 12 HVs drank 2 L). Motility metrics derived from large scale geometric and small scale pixel movement parameters following image registration were developed using the post ingestion data and compared to observer grading of wall motion. Inter and intra-observer variability in the highest correlating metric was assessed using Bland-Altman analysis calculated from two separate observations on a subset of data. KEY RESULTS All the metrics tested showed significant correlation with the observer rating scores. Line analysis (LA) produced the highest correlation coefficient of 0.74 (95% CI: 0.55-0.86), p < 0.001 (Spearman Rho). Bland-Altman analysis of the inter- and intra-observer variability for the LA metric, showed almost zero bias and small limits of agreement between observations (-0.039 to 0.052 intra-observer and -0.051 to 0.054 inter-observer, range of measurement 0-0.353). CONCLUSIONS & INFERENCES The LA index of colonic motility derived from cine MRI registered data provides a quick, accurate and non-invasive method to detect wall motion within the ascending colon following a colonic stimulus in the form of a macrogol drink.
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Affiliation(s)
- C L Hoad
- Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, Nottingham, UK.,NIHR Biomedical Research Unit in Gastrointestinal and Liver Diseases, Nottingham University Hospitals Trust and the University of Nottingham, Nottingham, UK
| | - A Menys
- Centre for Medical Imaging, Division of Medicine, University College London, London, UK
| | - K Garsed
- NIHR Biomedical Research Unit in Gastrointestinal and Liver Diseases, Nottingham University Hospitals Trust and the University of Nottingham, Nottingham, UK
| | - L Marciani
- NIHR Biomedical Research Unit in Gastrointestinal and Liver Diseases, Nottingham University Hospitals Trust and the University of Nottingham, Nottingham, UK.,Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK
| | - V Hamy
- Centre for Medical Imaging, Division of Medicine, University College London, London, UK
| | - K Murray
- Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, Nottingham, UK
| | - C Costigan
- Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, Nottingham, UK
| | - D Atkinson
- Centre for Medical Imaging, Division of Medicine, University College London, London, UK
| | - G Major
- NIHR Biomedical Research Unit in Gastrointestinal and Liver Diseases, Nottingham University Hospitals Trust and the University of Nottingham, Nottingham, UK
| | - R C Spiller
- NIHR Biomedical Research Unit in Gastrointestinal and Liver Diseases, Nottingham University Hospitals Trust and the University of Nottingham, Nottingham, UK.,Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK
| | - S A Taylor
- Centre for Medical Imaging, Division of Medicine, University College London, London, UK
| | - P A Gowland
- Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, Nottingham, UK
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40
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Alyami J, Spiller RC, Marciani L. Magnetic resonance imaging to evaluate gastrointestinal function. Neurogastroenterol Motil 2015; 27:1687-92. [PMID: 26598049 DOI: 10.1111/nmo.12726] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2015] [Accepted: 10/14/2015] [Indexed: 02/08/2023]
Abstract
Magnetic resonance imaging of gastrointestinal (GI) function has advanced substantially in the last few years. The ability to obtain high resolution images of the undisturbed bowel with tunable tissue contrast and using no ionizing radiation are clear advantages, particularly for children and women of reproductive age. Barriers to diffusion in clinical practice so far include the need to demonstrate clinical value and the burden of data processing. Both difficulties are being addressed and the technique is providing novel insights into both upper and lower GI disorders of function at an ever increasing rate.
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Affiliation(s)
- J Alyami
- Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK.,NIHR Nottingham Digestive Disease Biomedical Research Unit, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK
| | - R C Spiller
- Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK.,NIHR Nottingham Digestive Disease Biomedical Research Unit, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK
| | - L Marciani
- Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK.,NIHR Nottingham Digestive Disease Biomedical Research Unit, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK
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Khalaf A, Hoad CL, Spiller RC, Gowland PA, Moran GW, Marciani L. Magnetic resonance imaging biomarkers of gastrointestinal motor function and fluid distribution. World J Gastrointest Pathophysiol 2015; 6:140-149. [PMID: 26600972 PMCID: PMC4644878 DOI: 10.4291/wjgp.v6.i4.140] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2015] [Revised: 09/28/2015] [Accepted: 10/27/2015] [Indexed: 02/07/2023] Open
Abstract
Magnetic resonance imaging (MRI) is a well established technique that has revolutionized diagnostic radiology. Until recently, the impact that MRI has had in the assessment of gastrointestinal motor function and bowel fluid distribution in health and in disease has been more limited, despite the novel insights that MRI can provide along the entire gastrointestinal tract. MRI biomarkers include intestinal motility indices, small bowel water content and whole gut transit time. The present review discusses new developments and applications of MRI in the upper gastrointestinal tract, the small bowel and the colon reported in the literature in the last 5 years.
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A novel semi-automatic segmentation method for volumetric assessment of the colon based on magnetic resonance imaging. ACTA ACUST UNITED AC 2015; 40:2232-41. [DOI: 10.1007/s00261-015-0475-z] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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