Intraluminal impact of food: New insights from MRI

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. 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

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

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

A Population-based PBPK Model for the Prediction of Time-Variant Bile Salt Disposition within GI Luminal Fluids

In vivo studies have shown cyclic bile salt (BS) outputs during fasting whereas higher amounts have been observed in fed states. This leads to fluctuations of intestinal BS concentrations ([BS]) that can affect the rate and extent of absorption of lipophilic drugs in particular. However, most PBPK models use fixed val-ues of [BS] in fasted and fed states albeit with different values in different regions of the GI tract. During fasting, there is a relationship between gallbladder volume (GBV) and the phase of the Interdigestive Mi-grating Motor Complex cycle (IMMCc), showing cyclic GBV changes with periodic filling and emptying. This relationship is also affected by the origin of the IMMCc (antral or duodenal). In fed states, meta-analysis indicated that GB residual volume (% of fasting maximum) was 46.4 ±27 %CV and 30.7 ±48 %CV for low- and high-fat meals respectively. The corresponding values for the duration of the emptying phase were for low fat meals 0.72h ±1%CV and for high fat meals 1.17h ±37%CV. The model, the Ad-vanced Dynamic Bile Salt Model (ADBSM), was built bottom-up and its parameters were not fitted against in vivo measurements of [BS]. It involved update of the dynamic luminal fluid volumes model based on meta-analysis of available imaging data. The ADBSM is incorporated into the Simcyp® (v18r2) PBPK simulator. The model predictivity was good (within 1.25 fold error for 11/20 of the clinical studies) and was assessed against clinical studies of luminal [BS] that provide only the type of meal (i.e., low- or high-fat), the timing of the meal and/or water intake events, and the number and age range of the study participants. The model is also an important component of models capturing enterohepatic recirculation of drug and metabolite. Further work is required to validate the current model and compare to simpler models with respect to drug absorption, especially of the lipophilic compounds

Imaging Measurement of Whole Gut Transit Time in Paediatric and Adult Functional Gastrointestinal Disorders: A Systematic Review and Narrative Synthesis

Background: functional gastrointestinal disorders (FGID) are common conditions in children and adults, often associated with abnormalities of whole gut transit. Currently, transit tests can be performed using several imaging methods including tracking of radiopaque markers, gamma scintigraphy with the use of radioisotopes, magnetic tracking methods, tracking of movement of Wireless Motility Capsules and emerging Magnetic Resonance Imaging (MRI) approaches. Objectives: to review recent literature on diagnostic imaging techniques used to investigate whole gut transit in FGIDs. Methods: a systematic review was carried out. The different techniques are described briefly, with particular emphasis on contemporary literature and new developments, particularly in the field of MRI. Conclusions: emerging MRI capsule marker methods are promising new tools to study whole gut transit in FGIDs

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

A simple and efficient method for polymer coating of iron oxide nanoparticles

Iron oxide nanoparticles (IONP) have many possible uses including as MRI contrast agents, for drug delivery and cell labelling, but need to be stabilised and to be rendered biocompatible through appropriate coatings. Many current coatings are suboptimal, so we have investigated methodology to produce thin coatings using biocompatible polymers. We have produced uncoated IONP by a co-precipitation method in a range of sizes and subsequently coated the nanoparticles using poly(glycerol adipate) using the interfacial deposition method. To produce the necessary thin coatings a relatively small addition of polymer (approx. 0.1-0.2mg polymer per 38mg IONP) was necessary. A number of different PGA polymer variants with different physicochemical properties were used and the results suggested that the polymer properties also affected the coating process. Optimum coatings only a few nm thick (1-3nm) were obtained with a linear poly(ethylene glycol)-PGA copolymer modified with 40% pendant oleic acid moieties. The resulting sterically stabilised IONP were stable against aggregation at and above physiological salt concentrations. Preliminary experiments demonstrated that the nanoparticles had relaxivity values comparable to commercially available IONP of a similar size and could be taken up readily by cells. This coating method therefore shows promise for a variety of medical applications

Colon hypersensitivity to distension, rather than excessive gas production, produces carbohydrate-related symptoms in individuals with irritable bowel syndrome

Background & Aims: Poorly digested, fermentable carbohydrates may induce symptoms of irritable bowel syndrome (IBS), via unclear mechanisms. We performed a randomized trial with magnetic resonance imaging (MRI) analysis to investigate correlations between symptoms and changes in small and large bowel contents following oral challenge. Methods: We performed a 3-period crossover study of 29 adult patients with IBS (based on Rome III criteria, with symptoms of abdominal pain or discomfort for at least 2 days/week) and reported bloating. In parallel we performed the same study of 29 healthy individuals (controls). Studies were performed in the United Kingdom from January 2013 through February 2015. On 3 separate occasions (at least 7 days apart), subjects were given a 500 ml drink containing 40 g of carbohydrate (glucose in the first period, fructose in the second, and inulin in the third, in a random order). Levels of breath hydrogen were measured and intestinal content was assessed by MRI before and at various time points after consumption of each drink. Symptoms were determined based on subjects’ responses to the Hospital Anxiety and Depression Scale questionnaire and the Patient Health Questionnaire-15. The primary endpoint was whether participants had a clinically important symptom response during the 300 minutes following consumption of the drink. Results: More patients with IBS reached the pre-defined symptom threshold after intake of inulin (13/29) or fructose (11/29) than glucose (6/29). Symptoms peaked sooner after intake of fructose than inulin. Fructose increased small bowel water content in both patients and controls whereas inulin increased colonic volume and gas in both. Fructose and inulin increased breath hydrogen levels in both groups, compared to glucose; fructose produced an earlier increase than inulin. Controls had lower symptom scores during the period after drink consumption than patients with IBS, despite similar MRI parameters and breath hydrogen responses. In patients who reached the symptom threshold after inulin intake, peak symptom intensity correlated with peak colonic gas (r = 0.57; P<0.05). Changes in MRI features and peak breath hydrogen levels were similar in patients who did and did not reach symptom threshold. Conclusions: Patients with IBS and healthy individuals without IBS (controls) have similar physiological responses following intake of fructose or inulin; patients more frequently report symptoms after inulin than controls. In patients with a response to inulin, symptoms relate to levels of intra-luminal gas, but peak gas levels do not differ significantly between responders, non-responders or controls. This indicates that colonic hypersensitivity to distension, rather than excessive gas production, produces carbohydrate-related symptoms in patients with IBS. Clinicaltrials.gov no: NCT0177685

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,