Performance characteristics of scintigraphic colon transit measurement in health and irritable bowel syndrome and relationship to bowel functions

Background The inter‐ and intra‐subject variations of scintigraphy, which are used to identify colonic transit disturbances in irritable bowel syndrome (IBS), are unclear. The relationship between colonic transit and bowel functions is incompletely understood. To assess inter‐ and intra‐subject variations of scintigraphic colonic transit measurements in 86 IBS patients and 17 healthy subjects and to quantify the relationship between colonic transit and bowel symptoms in 147 IBS patients and 46 healthy subjects. Methods Data from participants with multiple colonic transit measurements were analysed. Primary end points were colonic filling at 6 h (CF6h) and geometric center (GC) at 24 and 48 h for colonic transit. Bowel functions were assessed by daily stool diaries. Key Results Inter‐ and intra‐subject variations were greater for small intestinal than colonic transit. Overall, inter‐ and intra‐subject variations were relatively narrow for colonic transit (both GC24h and GC48h, with lower COV at 48 h); there was little intra‐subject variation in health and IBS‐constipation over a period of ≤3 weeks and over 2.0 years (median, range 0.1, 11.0 years). Significant intra‐individual differences in GC24h were observed only in IBS‐D patients. Colonic transit was significantly associated with stool form (accounting for 19–27% of the variance), frequency (19%), and ease of stool passage (12%). Conclusions & Inferences Despite inter‐subject variation in scintigraphic colonic transit results, the intra‐subject measurements are reproducible over time in healthy volunteers and patients with IBS; significant changes in colonic transit at 24 h were observed only in IBS‐D. Colonic transit is associated with stool form, frequency and ease of passage.     

Inter‐observer reproducibility and analysis of gastric volume measurements and gastric emptying assessed with magnetic resonance imaging

Background Magnetic resonance (MR) imaging provides direct, non‐invasive measurements of gastric function and emptying. The inter‐observer variability (IOV) of MR volume measurements and the most appropriate analysis of MR data have not been established. To assess IOV of total gastric volume (TGV) and gastric content volume (GCV) measurements from MR images and the ability of standard power exponential (PowExp), and a novel linear exponential (LinExp) model to describe MR data. Methods Ten healthy volunteers received three different volumes of a liquid nutrient test meal (200–800 mL) on 3 days in a randomized order. Magnetic resonance scans were acquired using a 1.5T system every 1–5 min for 60 min. Total gastric volume and GCV were measured independently by three observers. Volume data were fitted by PowExp and LinExp models to assess postprandial volume change and gastric emptying half time (T₅₀). Key Results An initial rise in GCV and TGV was often observed after meal ingestion, thereafter GCV and TGV decreased in an approximately linear fashion. Inter‐observer variability decreased with greater volumes from 12% at 200 mL to 6% at 600 and 800 mL. Inter‐observer variability for T₅₀ was <5%. PowExp and LinExp models provided comparable estimates of T₅₀; however, only LinExp described dynamic volume change in the early postprandial period. Conclusions & Inferences Gastric MR provides quantitative measurements of postprandial volume change with low IOV, unless the stomach is nearly empty. The novel LinExp model describes the dynamic volume changes in the early postprandial period more accurately than the PowExp model used in existing gastric emptying studies.     

Gastric emptying in normal subjects: reproducibility and relationship to characteristics of the migrating motor complex

This study was designed to clarify whether a part of the variability in gastric emptying could be ascribed to a relationship between meal ingestion and phase activity of the migrating motor complex and whether reproducibility is increased when meal ingestion takes place in relation to preselected characteristics of the migrating motor complex. We examined 12 healthy males, and the design included three examinations, twice with meal ingestion in a duodenal Phase I, and once in a Phase II. The meal consisted of an omelette labelled with ^99mTc followed by 150 ml water labelled with ¹¹¹In. The results showed that liquid lag phase (min) and was significantly shorter in Phase II than in Phase I (1 vs. 4, P = 0.007). The half emptying time of solid linear phase (min) was reproduced with nearly identical median and range values in the three series (I[1]: 67[51–87]; I[2]: 63[47–80]; 61[47–76]). With meal ingestion in Phase I a significant difference between inter- and intra-individual variance could not be demonstrated. With meal ingestion in Phase I a second examination in Phase I did not increase reproducibility of any of the variables compared to a second examination in Phase II. In conclusion, scientific investigations on gastric emptying have to be performed with phase related meal ingestion and a double-radionuclide technique.     

Advances in the physiology of gastric emptying

There have been many recent advances in the understanding of various aspects of the physiology of gastric motility and gastric emptying. Earlier studies had discovered the remarkable ability of the stomach to regulate the timing and rate of emptying of ingested food constituents and the underlying motor activity. Recent studies have shown that two parallel neural circuits, the gastric inhibitory vagal motor circuit (GIVMC) and the gastric excitatory vagal motor circuit (GEVMC), mediate gastric inhibition and excitation and therefore the rate of gastric emptying. The GIVMC includes preganglionic cholinergic neurons in the DMV and the postganglionic inhibitory neurons in the myenteric plexus that act by releasing nitric oxide, ATP, and peptide VIP. The GEVMC includes distinct gastric excitatory preganglionic cholinergic neurons in the DMV and postganglionic excitatory cholinergic neurons in the myenteric plexus. Smooth muscle is the final target of these circuits. The role of the intramuscular interstitial cells of Cajal in neuromuscular transmission remains debatable. The two motor circuits are differentially regulated by different sets of neurons in the NTS and vagal afferents. In the digestive period, many hormones including cholecystokinin and GLP‐1 inhibit gastric emptying via the GIVMC, and in the inter‐digestive period, hormones ghrelin and motilin hasten gastric emptying by stimulating the GEVMC. The GIVMC and GEVMC are also connected to anorexigenic and orexigenic neural pathways, respectively. Identification of the control circuits of gastric emptying may provide better delineation of the pathophysiology of abnormal gastric emptying and its relationship to satiety signals and food intake.     

Tractostorm: The what,why, and how of tractography dissection reproducibility

Investigative studies of white matter (WM) brain structures using diffusion MRI (dMRI) tractography frequently require manual WM bundle segmentation, often called “virtual dissection.” Human errors and personal decisions make these manual segmentations hard to reproduce, which have not yet been quantified by the dMRI community. It is our opinion that if the field of dMRI tractography wants to be taken seriously as a widespread clinical tool, it is imperative to harmonize WM bundle segmentations and develop protocols aimed to be used in clinical settings. The EADC‐ADNI Harmonized Hippocampal Protocol achieved such standardization through a series of steps that must be reproduced for every WM bundle. This article is an observation of the problematic. A specific bundle segmentation protocol was used in order to provide a real‐life example, but the contribution of this article is to discuss the need for reproducibility and standardized protocol, as for any measurement tool. This study required the participation of 11 experts and 13 nonexperts in neuroanatomy and “virtual dissection” across various laboratories and hospitals. Intra‐rater agreement (Dice score) was approximately 0.77, while inter‐rater was approximately 0.65. The protocol provided to participants was not necessarily optimal, but its design mimics, in essence, what will be required in future protocols. Reporting tractometry results such as average fractional anisotropy, volume or streamline count of a particular bundle without a sufficient reproducibility score could make the analysis and interpretations more difficult. Coordinated efforts by the diffusion MRI tractography community are needed to quantify and account for reproducibility of WM bundle extraction protocols in this era of open and collaborative science.     

Performance characteristics of the measurement of gastric volume using single photon emission computed tomography

Background A non‐invasive single photon emission computed tomography (SPECT) method was developed and validated to measure gastric volumes (GV). The natural variation in gastric volume responses and performance characteristics of SPECT imaging are unclear. Methods The primary aim of this study was to assess the performance characteristics of SPECT imaging by estimating the inter‐individual coefficients of variation (COV) in fasting and postprandial GV in 433 participants in prior research studies over the last decade, and the intra‐individual COV in all volunteers who had undergone at least two studies. The secondary aim was to assess the relationship of gender, BMI and age on GV. Key Results The COV_INTER for all subjects in the study (n = 433) was 32.6% fasting, 16.0% fed, and 19.0%Δ fed – fasting. The COV_INTRA for 47 subjects with repeat estimates of gastric volume was 37.0% fasting, 17.6% fed, and 22.0%Δ fed – fasting. COV_INTRA was stable over time interval from 2 to 60 months. There were no significant differences by gender or subgroups. Mean fed and gastric accommodation volumes were associated with age and BMI but the magnitude of variation attributable was <5%. Conclusions & Inferences COV_INTRA and COV_INTER of GV by SPECT are very similar, and there is a small effect of age and BMI. These data are important for planning future studies of GV and further validate SPECT for studies of gastric motility disorders and obesity.     

Helicobacter pylori infection and gastric emptying of solids in humans

Helicobacter pylori has been implicated in a number of upper gastrointestinal illnesses. In a controlled study, we have investigated the relationship between H. pylori infection and gastric emptying of solids in two groups of patients with chronic symptoms of dyspepsia. In the first group, 19 patients with non-ulcer dyspepsia and H. pylori infection underwent a standard test of gastric emptying after ingestion of 500 μCi of Tc-labelled chicken liver. The results were compared to a control group of 16 uninfected volunteers. We also studied a second group of 20 patients with previously diagnosed idiopathic gastroparesis for the prevalence of H. pylori infection and its relationship to symptom severity and rates of gastric emptying. In the first group of patients, the half-time of gastric emptying was significantly less among the infected patients compared to the uninfected volunteers (108 ± 9 vs. 142 ± 14 min, P < 0.05). In the second group of patients with gastroparesis, the prevalence of H. pylori was not significantly different among these patients than among 21 age and sex matched controls (20% vs. 38%, P = 0.32). Gastric emptying was markedly slow in all 20 patients in the second group but less so among the four with H. pylori infection. Symptom scores were no different between infected and uninfected patients. We conclude that H. pylori infection is not associated with abnormally slow gastric emptying. On the contrary, gastric H. pylori infection appears to be associated with mildly accelerated emptying of solids compared to normal controls. Idiopathic gastroparesis and dyspepsia related H. pylori infection are separate but sometimes overlapping disorders.     

Day‐to‐day reproducibility of prolonged ambulatory colonic manometry in healthy subjects

Background Although colonic manometry provides useful information regarding colonic physiology, considerable variability has been reported both for regional motility and manometric patterns. Whether colonic manometry is reproducible is not known. Methods Seven healthy volunteers (three men, four women, mean age = 34 years) underwent two studies of 24‐h ambulatory colonic manometry, each 2 weeks apart. Manometry was performed by placing a six‐sensor solid‐state probe, up to the hepatic flexure and anchored to colonic mucosa. Colonic motility was assessed by the number and area‐under‐curve (AUC) of pressure waves and motility patterns such as high‐amplitude propagating contractions (HAPC). Waking and meal‐induced gastrocolonic responses were also assessed. Paired t‐test was used to examine the reproducibility and intra and interindividual variability. Key Results The number of pressure waves and propagating pressure waves and HAPC, and AUC were similar between the two studies. Diurnal variation, waking and meal‐induced gastrocolonic responses were also reproducible. There was some variability in the incidence of individual colonic motor patterns. Conclusions & Inferences Colonic manometry findings were generally reproducible, particularly for the assessment of key physiologic changes, such as meal‐induced gastrocolonic, HAPC, and waking responses.     

Optimizing analysis of stable isotope breath tests to estimate gastric emptying of solids

Abstract  Breath tests (BT) using ¹³C–substrates have been proposed for the measurement of gastric emptying (GE). The mathematical analysis of the breath ¹³CO₂ excretion that most accurately predicts GE t _1/2 from simultaneous scintigraphy is unresolved. To compare five mathematical methods to estimate GE t _1/2 by BT with t _1/2 from simultaneous scintigraphy. Data acquired from a dual-labelled solid–liquid meal containing ^99mTc sulphur colloid and ¹³C- Spirulina platensis from 57 healthy volunteers were used to compare four mathematical methods reported in the literature [Ghoos method; generalized linear regression (Viramontes); linear regression (Szarka); Wagner–Nelson method] and the total cumulative breath ¹³CO₂ excretion with ≥12 breath samples collected over at least 4 h. The concordance correlation coefficient (CCC) for the t _1/2 results obtained with each method using BT data was compared with the results obtained with scintigraphy. The linear regression and generalized linear regression methods used five samples at 45, 90, 120, 150 and 180 min. All methods, except for the Wagner–Nelson method, resulted in mean GE t _1/2 that approximated t _1/2 obtained with scintigraphy. The highest CCC was observed with the linear regression method. Simple cumulative excretion of breath ¹³CO₂ provides a better CCC than the Ghoos method. The linear regression and generalized linear regression methods (which also require relatively few breath samples) provide the most accurate analyses of breath ¹³CO₂ excretion in stable isotope GEBT.     

Colestyramine slows gastric emptying of liquids and reduces appetite in healthy subjects

Background There is evidence to suggest that the particulate resin colestyramine, a bile acid sequestrant formerly used as a cholesterol‐lowering agent, enhances secretion of the gut hormone cholecystokinin (CCK). Established physiological actions of CCK include inhibition of gastric emptying and induction of satiation. This study evaluated the hypothesis that colestyramine, which is luminally retained, would slow gastric emptying of liquids and suppress appetite in humans. Methods Nine healthy volunteers consumed 500 mL liquid test meals containing 4 g colestyramine, 12 g colestyramine, or control (water alone), on three occasions, in a randomized order. The effect of colestyramine on gastric emptying was determined non‐invasively using the ¹³C‐acetate breath test, and appetite and other gut‐centered sensations were rated using visual analog scale questionnaires. Key Results Colestyramine dose dependently slowed liquid gastric emptying compared with control (water) (4 g vs control, ～20% reduction, P < 0.05; 12 g vs control, ～35% reduction, P < 0.01). Colestyramine also significantly reduced hunger (4 g vs control, ～20% reduction, P < 0.01), and the amount of food participants felt able to eat (12 g vs control, ～32% reduction, P < 0.001), but increased bloating (both doses, P < 0.05), with no effect on ratings of nausea. Conclusions & Inferences This study provides the first evidence that colestyramine significantly slows liquid gastric emptying and reduces appetite in healthy humans. Colestyramine therefore presents an attractive gut‐brain signaling research tool in that it is not absorbed and thus lacks potentially confounding postabsorptive effects. Furthermore, with clear effects on gastric emptying and appetite, colestyramine now merits consideration as a trial therapeutic strategy for appetite suppression and weight loss.     

Comparison of calculations to estimate gastric emptying half‐time of solids in humans

Background Measuring solid gastric emptying (GE) at 4 h is used to identify gastroparesis. GE half‐time (GE T_1/2) is useful to assess overall and early GE. Aim To examine the validity of hourly imaging as a measurement of GE T_1/2 compared with estimates from more detailed imaging. Methods 155 human subjects (99 female, 56 male) underwent scintigraphic GE of a solid–liquid meal. We calculated the GE T_1/2 using linear interpolation based on a full set of abdominal images obtained over 4 h, and the GE T_1/2 based on images at 1, 2, 3, and 4 h after the meal with interpolation of data. Key Results Differences in GE T_1/2 values (entire set of scan times compared with just the hourly scans) were small [overall median (5th, 95th percentiles) = ?0.2[?7.5, 4.6] min] with slightly greater differences in males compared with females. The agreement between the two methods was very high [concordance correlation coefficient (CCC) (95% CI) = 0.993 (0.990, 0.995)] and a Bland–Altman plot indicated the variation in the results between the two methods did not change appreciably across the range of GE studied (within ±10 min for all but four subjects). Calculated GE T_1/2 values, omitting the 3‐h data from the hourly measurements, were associated with similar high accuracy overall and for fast GE, but were less accurate with slow GE. Conclusions & Inferences Results of GE T_1/2 solids, using hourly imaging over 4 h, are accurate in the range 75–235 min which reflects the typical range of GE of solids in health and disease.     

Human postprandial gastric emptying of indigestible solids can occur unrelated to antral phase III

According to animal experiments, postprandial gastric emptying of indigestible solids is mainly related to the antral phase III activity of the migrating motor complex. Gastric emptying of indigestible solids in humans has not been directly correlated to pressure recordings. The aim of the present study was to investigate the postprandial emptying pattern of indigestible solids in humans and its relation to fed and fasted antral motility. Ten healthy volunteers participated. After an overnight fast they had a standard breakfast. Two sizes of radiopaque markers (ROMs) were given with the test meal; ten cubes each of side measurement 1.5 mm and 3 mm, respectively. Emptying of the ROMs from the stomach was followed by fluoroscopy with simultaneous antral manometry. In six of the subjects, fasting antral manometry was performed on one day and on another day, the emptying of 7 mm cylindrical particles together with 3 mm cubes, in the absence of a gastric tube was recorded. All ROMs were emptied within 5 h (range 1.5-4.5 h). In all subjects, the smaller particles (1.5 mm) showed a slight, insignificant tendency to move from the stomach more rapidly than the larger (3 mm) particles. None of the subjects had an antral phase III before all ROMs were emptied from the stomach. Instead, the typical irregular postprandial pressure activity was present in all subjects until the emptying was completed. Furthermore, the highest postprandial motility index during the emptying study was far below the motility index during phase III, but comparable to the motility index during late phase II. Emptying of the 7 mm particles occurred significantly more slowly at 1.5-2.5 h, but otherwise was similar to the emptying of the smaller particles. There was no difference between emptying of the 3 mm cubes with or without the presence of the tube. Contrary to common opinion, gastric emptying of indigestible solids after a meal can occur unrelated to the antral phase III, at least up to a particle size of 3 mm and perhaps even 7 mm. These findings are of great importance for the evaluation of gastric emptying of indigestible solids, including the pharmacodynamics of orally administered drugs.     

Cyclooxygenase-2 inhibition increases gastric tone and delays gastric emptying in rats.

We evaluated the effects of cyclooxygenase-2 (COX-2) selective inhibitors, COX-1 selective inhibitor, or COX non-selective inhibitor on gastric emptying and intestinal transit of liquids, and evaluated the effect of a COX-2 selective inhibitor on gastric tonus (GT). Male Wistar rats were treated per os with saline (control), rofecoxib, celecoxib, ketorolac, rofecoxib + ketorolac, celecoxib + ketorolac, or indomethacin. After 1 h, rats were gavage-fed (1.5 mL) with the test meal (5% glucose solution with 0.05 g mL(-1) phenol red) and killed 10, 20 or 30 min later. Gastric, proximal, medial or distal small intestine dye recovery (GDR and IDR, respectively) were measured by spectrophotometry. The animals of the other group were treated with i.v. valdecoxib or saline, and GT was continuously observed for 120 min using a pletismomether system. Compared with the control group, treatment with COX-2 inhibitors, alone or with ketocolac, as well as with indomethacin increased GDR (P < 0.05) at 10-, 20- or 30-min postprandial intervals. Ketorolac alone did not change the GDR, but increased the proximal IDR (P < 0.05) at 10 min, and decreased medial IDR (P < 0.05) at 10 and 20 min. Valdecoxib increased (P < 0.01) GT 60, 80 and 100 min after administration. In conclusion, COX-2 inhibition delayed the gastric emptying of liquids and increased GT in rats.     

A novel MRI-based three-dimensional model of stomach volume,surface area,and geometry in response to gastric filling and emptying

Background

Gastric motility and accommodation have a critical role in maintaining normal gastrointestinal homeostasis. Different modalities can be adopted to quantify those processes, that is, scintigraphy to measure emptying time and intragastric Barostat for accommodation assessment. However, magnetic resonance imaging (MRI) can assess the same parameters noninvasively without ionizing radiation. Our study aimed to develop a detailed three-dimensional (3D) MRI model of the stomach to describe gastric volumes, surface areas, wall tension distribution, and interobserver agreement.

Methods

Twelve healthy volunteers underwent an MRI protocol of six axial T2-weighted acquisitions. Each dataset was used to construct a 3D model of the stomach: First, the volumes of the whole stomach, gastric liquid, and air were segmented. After landmark placing, a raw 3D model was generated from segmentation data. Subsequently, irregularities were removed, and the model was divided into compartments. Finally, surface area and 3D geometry parameters (inverse curvatures) were extracted. The inverse curvatures were used as a proxy for wall tension distribution without measuring the intragastric pressure.

Key Results

The model was able to describe changes in volume and surface geometry for each compartment with a distinct pattern in response to filling and emptying. The surface tension was distributed nonhomogeneously between compartments and showed dynamical changes at various time points.

Conclusion & Inferences

The presented model offers a detailed tool for evaluating gastric volumes, surface geometry, and wall tension in response to filling and emptying and will provide insights into gastric emptying and accommodation in diseases such as diabetic gastroparesis.     

Functional brain segmentation using inter‐subject correlation in fMRI

The human brain continuously processes massive amounts of rich sensory information. To better understand such highly complex brain processes, modern neuroimaging studies are increasingly utilizing experimental setups that better mimic daily‐life situations. A new exploratory data‐analysis approach, functional segmentation inter‐subject correlation analysis (FuSeISC), was proposed to facilitate the analysis of functional magnetic resonance (fMRI) data sets collected in these experiments. The method provides a new type of functional segmentation of brain areas, not only characterizing areas that display similar processing across subjects but also areas in which processing across subjects is highly variable. FuSeISC was tested using fMRI data sets collected during traditional block‐design stimuli (37 subjects) as well as naturalistic auditory narratives (19 subjects). The method identified spatially local and/or bilaterally symmetric clusters in several cortical areas, many of which are known to be processing the types of stimuli used in the experiments. The method is not only useful for spatial exploration of large fMRI data sets obtained using naturalistic stimuli, but also has other potential applications, such as generation of a functional brain atlases including both lower‐ and higher‐order processing areas. Finally, as a part of FuSeISC, a criterion‐based sparsification of the shared nearest‐neighbor graph was proposed for detecting clusters in noisy data. In the tests with synthetic data, this technique was superior to well‐known clustering methods, such as Ward's method, affinity propagation, and K‐means . Hum Brain Mapp 38:2643–2665, 2017. © 2017 Wiley Periodicals, Inc.     

Inter‐rater reliability of the Abnormal Involuntary Movements Scale (AIMS) in a multi‐centre trial: results from Department of Veterans Affairs Cooperative Study #394

The US Department of Veterans' Affairs (VA) conducted Cooperative Study #394 at nine sites to determine whether vitamin E was a safe and effective treatment for tardive dyskinesia (TD). The study used the Abnormal Involuntary Movement Scale (AIMS) to measure TD. To monitor inter‐rater reliability (IRR) on the AIMS, personnel at each site did initial AIMS assessments, on seven occasions, on a set of five unique subjects from videotapes. On four of these occasions raters re‐assessed sets of five subjects from seven to 13 months after their initial ratings. We analysed the initial ratings of 34 videotaped subjects and the second ratings of 19. To measure IRR, we used the intra‐class correlation coefficient (ICC) for each initial or second rating of the sets of interviews. The ICCs ranged from 0.50 to 0.86, and the ICC for the initial ratings over all 34 subjects was good (0.75; 95% confidence interval 0.64 to 0.83). To determine whether there was significant ‘rater drift’ during the study, we performed linear mixed effects regression on the data with fixed effects for rating (initial or second), rater type, and site and a random effect for rating. The results indicated that scores varied little between ratings (about 0.05 points). Copyright © 2000 Whurr Publishers Ltd.