Magnetic resonance imaging biomarkers of gastrointestinal motor function and fluid distribution

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

Distinct abnormalities of small bowel and regional colonic volumes in subtypes of irritable bowel syndrome revealed by MRI

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

Differential effects of FODMAPs (Fermentable Oligo-, Di-, Mono-Saccharides and Polyols) on small and large intestinal contents in healthy subjects shown by MRI

OBJECTIVES: The objective of this study was to investigate whether ingestion of fructose and fructans (such as inulin) can exacerbate irritable bowel syndrome (IBS) symptoms. The aim was to better understand the origin of these symptoms by magnetic resonance imaging (MRI) of the gut. METHODS: A total of 16 healthy volunteers participated in a four-way, randomized, single-blind, crossover study in which they consumed 500 ml of water containing 40 g of either glucose, fructose, inulin, or a 1:1 mixture of 40 g glucose and 40 g fructose. MRI scans were performed hourly for 5 h, assessing the volume of gastric contents, small bowel water content (SBWC), and colonic gas. Breath hydrogen (H 2) was measured and symptoms recorded after each scan. RESULTS: Data are reported as mean (s.d.) (95 % CI) when normally distributed and median (range) when not. Fructose increased area under the curve (AUC) from 0 – 5 h of SBWC to 71 (23) l / min, significantly greater than for glucose at 36 (11 – 132) l / min ( P < 0.001), whereas AUC SBWC after inulin, 33 (17 – 106) l / min, was no different from that after glucose. Adding glucose to fructose decreased AUC SBWC to 55 (28) l / min ( P = 0.08) vs. fructose. Inulin substantially increased AUC colonic gas to 33 (20) l / min, signifi cantly greater than glucose and glucose + fructose (both P < 0.05). Breath H 2 rose more with inulin than with fructose. Glucose when combined with fructose signifi cantly reduced breath H 2 by 7,700 (3,121 – 12,300) p.p.m. / min relative to fructose alone ( P < 0.01, n = 13). CONCLUSIONS: Fructose but not inulin distends the small bowel with water. Adding glucose to fructose reduces the effect of fructose on SBWC and breath hydrogen. Inulin distends the colon with gas more than fructose, but causes few symptoms in healthy volunteers

Corticotrophin releasing factor increases ascending colon volume after a fructose test meal in healthy humans: a randomised control trial

Background: Poorly absorbed, fermentable carbohydrates can provoke irritable bowel syndrome (IBS) symptoms by escaping absorption in the small bowel and being rapidly fermented in the colon in some susceptible subjects. IBS patients are often anxious and stressed and stress accelerates small bowel transit which may exacerbate malabsorption. Objective: In this study we investigated the effect of intravenous injection of corticotrophin releasing factor (CRF) on fructose malabsorption and the resulting volume of water in the small bowel. Design: We performed a randomised, placebo controlled, cross-over study of CRF versus saline injection in 11 male and 10 female healthy subjects, examining the effect on the malabsorption of a 40 g fructose test meal and its transit through the gut which was assessed by serial Magnetic Resonance imaging (MRI) and breath hydrogen measurement. Orocaecal transit was assessed using the lactose-ureide C13 breath test and the adrenal response to CRF assessed by serial salivary cortisol measurements. Results: (Mean ± SD) CRF injection caused a significant rise in salivary cortisol which lasted 135 minutes. Small bowel water content (SBWC) rose from baseline, peaking at 45 minutes after fructose ingestion while breath hydrogen peaked later at 75 minutes. The area under the curve (AUC) for SBWC from -15 - 135 minutes was significantly lower after CRF versus saline (mean difference [95% CI] 7433 [275, 14591] mL.min, P = 0.04). Ascending colon volume rose after CRF, significantly more for male volunteers than female (P = 0.025). Conclusions: CRF constricts the small bowel and increases fructose malabsorption as shown by increased ascending colon volumes. This mechanism may help to explain the increased sensitivity of some stressed individuals to fructose malabsorption. This trial was registered at ClinicalTrials.gov as NCT0176328

Magnetic resonance imaging quantification of fasted state colonic liquid pockets in healthy humans

The rate and extent of drug dissolution and absorption from solid oral dosage forms is highly dependent on the volume of liquid in the gastrointestinal tract (GIT). However, little is known about the time course of GIT liquid volumes after drinking a glass of water (8 oz), particularly in the colon, which is a targeted site for both locally and systemically acting drug products. Previous magnetic resonance imaging (MRI) studies offered novel insights on GIT liquid distribution in fasted humans in the stomach and small intestine, and showed that freely mobile liquid in the intestine collects in fairly distinct regions or “pockets”. Based on this previous pilot data, we hypothesized that (1) it is possible to quantify the time course of the volume and number of liquid pockets in the undisturbed colon of fasted healthy humans following ingestion of 240 mL, using noninvasive MRI methods; (2) the amount of freely mobile water in the fasted human colon is of the order of only a few milliliters. Twelve healthy volunteers fasted overnight and underwent fasted abdominal MRI scans before drinking 240 mL (∼8 fluid ounces) of water. After ingesting the water they were scanned at frequent intervals for 2 h. The images were processed to quantify freely mobile water in the total and regional colon: ascending, transverse, and descending. The fasted colon contained (mean ± SEM) 11 ± 5 pockets of resting liquid with a total volume of 2 ± 1 mL (average). The colonic fluid peaked at 7 ± 4 mL 30 min after the water drink. This peak fluid was distributed in 17 ± 7 separate liquid pockets in the colon. The regional analysis showed that pockets of free fluid were found primarily in the ascending colon. The interindividual variability was very high; the subjects showed a range of number of colonic fluid pockets from 0 to 89 and total colonic freely mobile fluid volume from 0 to 49 mL. This is the first study measuring the time course of the number, regional location, and volume of pockets of freely mobile liquid in the undisturbed colon of fasted humans after ingestion of a glass of water. Novel insights into the colonic fluid environment will be particularly relevant to improve our understanding and design of the in vivo performance of controlled release formulations targeted to the colon. The in vivo quantitative information presented here can be input into physiologically based mechanistic models of dissolution and absorption, and can be used in the design and set up of novel in vitro performance tools predictive of the in vivo environment

Cine MRI assessment of motility in the unprepared small bowel in the fasting and fed state: beyond the breath-hold

BackgroundThe 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.MethodsFifteen 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 ResultsExcellent agreement between observers was seen across the range of motility measurements acquired, with intraclass correlation coefficient (ICC) of 0.979 (P [less than] 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 [less than] 0.0001). Changes from the fasted to immediately postprandial state showed an average increase of 122.4% ± 98.7% (n = 15).Conclusions & InferencesThis 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

The effect of depth context in the segmentation of the colon in MRI volumes

Colonic volume content measurements can provide important information about the digestive tract physiology. Development of automated analyses will accelerate the translation of these measurements into clinical practice. In this paper, we test the effect of data dimension on the success of deep learning approaches to segment colons from MRI data. Deep learning network models were developed which used either 2D slices, complete 3D volumes and 2.5D partial volumes. These represent variations in the trade-off between the size and complexity of a network and its training regime, and the limitation of only being able to use a small section of the data at a time: full 3D networks, for example, have more image context available for decision making but require more powerful hardware to implement. For the datasets utilised here, 3D data was found to outperform 2.5D data, which in turn performed better than 2D datasets. The maximum Dice scores achieved by the networks were 0.898, 0.834 and 0.794 respectively. We also considered the effect of ablating varying amounts of data on the ability of the networks to label images correctly. We achieve dice scores of 0.829, 0.827 and 0.389 for 3D single slices ablation, 3D multi-slice ablation and 2.5D middle slice ablation.In addition, we examined another practical consideration of deep learning, that of how well a network performs on data from another acquisition device. Networks trained on images from a Philips Achieva MRI system yielded Dice scores of up to 0.77 in the 3D case when tested on images captured from a GE Medical Systems HDxt (both 1.5 Tesla) without any retraining. We also considered the effect of single versus multimodal MRI data showing that single modality dice scores can be boosted from 0.825 to 0.898 when adding an extra modality.https://www.medrxiv.org/content/10.1101/2020.03.06.20027722v

Application of In Vivo MRI Imaging to Track a Coated Capsule and Its Disintegration in the Gastrointestinal Tract in Human Volunteers

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

The MRI colonic function test: Reproducibility of the Macrogol stimulus challenge

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 intra-subject 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 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 12 participants completed the study: 9 female, mean age 26 years (SD 5) and body mass index 24.8kg/m2 (SD 3.2). All measures consistently increased above baseline following provocation with macrogol. The volume, water content and content mixing had good intra-subject reproducibility (ICC volume=0.84, water content=0.93, mixing=0.79,

Investigations of Anti‐Reflux Formulations Containing Alginates Using MRI: A Feasibility Study Using Conventional 3.0T and 0.5T Open Upright Scanning

Sodium alginates are widely used for their gelling, thickening, and stabilizing properties. Raft-producing formulations havebeen used widely for many years to treat the symptoms of anti-reflux disease and those suffering occasional symptoms. The aimof this study was to determine the feasibility of characterizing rafts formed from alginate-containing anti-reflux formulationsin vivo using either a supine high-field 3T scanner or an upright low-field 0.5T MRI scanner. Six healthy participants (one male,five female, age range 23–50 years) attended three study visits following an overnight fast and were scanned at one field strength(N = 3 at 0.5T, N = 3 at 3T) before and after ingestion of an acidic drink followed by one of three different alginate antirefluxformulations. These formulations had identical quantities (by mass) of sodium alginate, calcium carbonate, and sodium bicar-bonate. Raft position and volume were measured along with gastric contents and gas using T2-weighted MRI. Additionally, theimage textures of the raft and T2 properties were investigated at 3T. In vitro properties (raft strength, mass, and NMR chemicalanalysis) of the three different formulations were also determined. Alginate rafts were generated in all volunteers for all formula-tions. Gastric emptying of the acidic drink was consistent across all study days. Raft volumes measured showed some differencesbetween body positions, with upright maintaining a higher volume of raft for longer. In vitro analysis showed significant differ-ences in strength and mass between two of the formulations, which were likely caused by differences in the chemical structureof the alginates used in the formulations. In conclusion, characterization of anti-reflux alginate raft properties can be achievedusing both low-field upright and high-field supine MRI. Larger scale studies are needed to determine the differences betweenformulations in vivo