A longitudinal study assessing the impact of elexacaftor/tezacaftor/ivacaftor on gut transit and function in people with cystic fibrosis using magnetic resonance imaging (MRI).

BACKGROUND: Gastrointestinal (GI) symptoms in cystic fibrosis (CF) are common and disruptive. The effect of cystic fibrosis transmembrane conductance regulator (CFTR) modulators on the GI tract is not fully understood. The aim was to use magnetic resonance imaging (MRI) to determine if elexacaftor/tezacaftor/ivacaftor (ETI) changed GI function and transit. METHODS: This was an 18 month prospective, longitudinal, observational study. We enrolled 24 people with CF aged 12 years or older to undergo MRI scans before starting ETI and 3, 6, and 18 months after starting ETI. The primary outcome measure was change in oro-caecal transit time (OCTT) at 6 and 18 months. Secondary outcome measures included change in small bowel water content (SBWC), change in the reduction in small bowel water content following a meal (DeltaSBWC) and change in total colonic volume (TCV). RESULTS: A total of 21 participants completed MRI scans at 6 months and 11 completed at 18 months. After 18 months of ETI, median OCTT significantly reduced, from >360 min [IQR 240->360] to 240 min [IQR 180-300] (p = 0.02, Wilcoxon signed-rank). Both SBWC and DeltaSBWC increased after starting ETI. TCV reduced significantly after 18 months (p = 0.005, Friedman). CONCLUSIONS: Our findings suggest an improvement in small bowel transit, small bowel response to food and a reduction in colonic volume after starting ETI. These effects may relate to CFTR activation in the small bowel. To our knowledge this is the first study to show a physiological change in GI transit and function in response to CFTR modulator use through imaging studies.

A robust brain network for sustained attention from adolescence to adulthood that predicts later substance use.

Substance use, including cigarettes and cannabis, is associated with poorer sustained attention in late adolescence and early adulthood. Previous studies were predominantly cross-sectional or under-powered and could not indicate if impairment in sustained attention was a predictor of substance use or a marker of the inclination to engage in such behavior. This study explored the relationship between sustained attention and substance use across a longitudinal span from ages 14 to 23 in over 1000 participants. Behaviors and brain connectivity associated with diminished sustained attention at age 14 predicted subsequent increases in cannabis and cigarette smoking, establishing sustained attention as a robust biomarker for vulnerability to substance use. Individual differences in network strength relevant to sustained attention were preserved across developmental stages and sustained attention networks generalized to participants in an external dataset. In summary, brain networks of sustained attention are robust, consistent, and able to predict aspects of later substance use.

Free-Breathing Functional Pulmonary Proton MRI: A Novel Approach Using Voxel-Wise Lung Ventilation (VOLVE) Assessment in Healthy Volunteers and Patients With Chronic Obstructive Pulmonary Disease.

BACKGROUND: In respiratory medicine, there is a need for sensitive measures of regional lung function that can be performed using standard imaging technology, without the need for inhaled or intravenous contrast agents. PURPOSE: To describe VOxel-wise Lung VEntilation (VOLVE), a new method for quantifying regional lung ventilation (V) and perfusion (Q) using free-breathing proton MRI, and to evaluate VOLVE in healthy never-smokers, healthy people with smoking history, and people with chronic obstructive pulmonary disease (COPD). STUDY TYPE: Prospective pilot. POPULATION: Twelve healthy never-smoker participants (age 30.3 ± 12.5 years, five male), four healthy participants with smoking history (>10 pack-years) (age 42.5 ± 18.3 years, one male), and 12 participants with COPD (age 62.8 ± 11.1 years, seven male). FIELD STRENGTH/SEQUENCE: Single-slice free-breathing two-dimensional fast field echo sequence at 3 T. ASSESSMENT: A novel postprocessing was developed to evaluate the MR signal changes in the lung parenchyma using a linear regression-based approach, which makes use of all the data in the time series for maximum sensitivity. V/Q-weighted maps were produced by computing the cross-correlation, lag and gradient between the respiratory/cardiac phase time course and lung parenchyma signal time courses. A comparison of histogram median and skewness values and spirometry was performed. STATISTICAL TESTS: Kruskal-Wallis tests with Dunn's multiple comparison tests to compare VOLVE metrics between groups; Spearman correlation to assess the correlation between MRI and spirometry-derived parameters; and Bland-Altman analysis and coefficient of variation to evaluate repeatability were used. A P-value <0.05 was considered significant. RESULTS: Significant differences between the groups were found for ventilation between healthy never-smoker and COPD groups (median XCCV, LagV, and GradV) and perfusion (median XCCQ, LagQ, and GradQ). Minimal bias and no significant differences between intravisit scans were found (P range = 0.12-0.97). DATA CONCLUSION: This preliminary study showed that VOLVE has potential to provide metrics of function quantification. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

Use of Magnetic Resonance Imaging for Visualization of Oral Dosage Forms in the Human Stomach: A Scoping Review.

Oral dosage forms are the most widely and frequently used formulations to deliver active pharmaceutical ingredients (APIs), due to their ease of administration and noninvasiveness. Knowledge of intragastric release rates and gastric mixing is crucial for predicting the API release profile, especially for immediate release formulations. However, knowledge of the intragastric fate of oral dosage forms in vivo to date is limited, particularly for dosage forms administered when the stomach is in the fed state. An improved understanding of gastric food processing, dosage form location, disintegration times, and food effects is essential for greater understanding for effective API formulation design. In vitro standard and controlled modeling has played a significant role in predicting the behavior of dosage forms in vivo. However, discrepancies are reported between in vitro and in vivo disintegration times, with these discrepancies being greatest in the fed state. Studying the fate of a dosage form in vivo is a challenging process, usually requiring the use of invasive methods, such as intubation. Noninvasive, whole body imaging techniques can however provide unique insights into this process. A scoping review was performed systematically to identify and critically appraise published studies using MRI to visualize oral solid dosage forms in vivo in healthy human subjects. The review identifies that so far, an all-purpose robust contrast agent or dosage form type has not been established for dosage form visualization and disintegration studies in the gastrointestinal system. Opportunities have been identified for future studies, with particular focus on characterizing dosage form disintegration for development after the consumption food, as exemplified by the standard Food and Drug Administration (FDA) high fat meal.

Differential effects of bilateral hippocampal CA3 damage on the implicit learning and recognition of complex event sequences.

Learning regularities in the environment is a fundament of human cognition, which is supported by a network of brain regions that include the hippocampus. In two experiments, we assessed the effects of selective bilateral damage to human hippocampal subregion CA3, which was associated with autobiographical episodic amnesia extending ~50 years prior to the damage, on the ability to recognize complex, deterministic event sequences presented either in a spatial or a non-spatial configuration. In contrast to findings from related paradigms, modalities, and homologue species, hippocampal damage did not preclude recognition memory for an event sequence studied and tested at four spatial locations, whereas recognition memory for an event sequence presented at a single location was at chance. In two additional experiments, recognition memory for novel single-items was intact, whereas the ability to recognize novel single-items in a different location from that presented at study was at chance. The results are at variance with a general role of the hippocampus in the learning and recognition of complex event sequences based on non-adjacent spatial and temporal dependencies. We discuss the impact of the results on established theoretical accounts of the hippocampal contributions to implicit sequence learning and episodic memory.

Colon length in pediatric health and constipation measured using magnetic resonance imaging and three dimensional skeletonization.

Recent magnetic resonance imaging (MRI) studies showed that colonic volumes in children are different between health and functional constipation. The length of the colon has however been rarely measured and principally using unphysiological colon preparations or cadaver studies. The main objective of this study was to measure the length of the undisturbed colon in children with functional constipation (FC) and healthy controls. Here, the colon of 19 healthy controls (10-18 years old) and 16 children with FC (7-18 years old) was imaged using MRI. Different regions of the colon (ascending, transverse, descending, and sigmoid-rectum) were first segmented manually on the MRI images. Three-dimensional skeletonization image analysis methods were then used to reduce the regions of interest to a central, measurable line. Total colon length (corrected for body surface area) in healthy controls was 56±2 cm/m2 (mean±SEM). Total colon length was significantly longer in children with FC 69±3 cm/m2 compared to controls (p = 0.0037). The colon regions showing the largest differences between groups were the ascending colon (p = 0.0479) and the sigmoid-rectum (p = 0.0003). In a linear regression model, there was a positive significant correlation between total colon length and age (R = 0.45, p = 0.0064), height (R = 0.49, p = 0.0031), weight (R = 0.46, p = 0.0059) and colon volume (R = 0.4543, p = 0.0061). Our findings showed significant differences in colon lengths between healthy controls and children with constipation. A new objective diagnostic imaging endpoint such as colon length may help to improve knowledge of colon morphology and function and, in turn, understanding of colon functional pathology.

Population clustering of structural brain aging and its association with brain development.

Structural brain aging has demonstrated strong inter-individual heterogeneity and mirroring patterns with brain development. However, due to the lack of large-scale longitudinal neuroimaging studies, most of the existing research focused on the cross-sectional changes of brain aging. In this investigation, we present a data-driven approach that incorporate both cross-sectional changes and longitudinal trajectories of structural brain aging and identified two brain aging patterns among 37,013 healthy participants from UK Biobank. Participants with accelerated brain aging also demonstrated accelerated biological aging, cognitive decline and increased genetic susceptibilities to major neuropsychiatric disorders. Further, by integrating longitudinal neuroimaging studies from a multi-center adolescent cohort, we validated the "last in, first out" mirroring hypothesis and identified brain regions with manifested mirroring patterns between brain aging and brain development. Genomic analyses revealed risk loci and genes contributing to accelerated brain aging and delayed brain development, providing molecular basis for elucidating the biological mechanisms underlying brain aging and related disorders.

The impact of variations in subject geometry, respiration and coil repositioning on the specific absorption rate in parallel transmit abdominal imaging at 7 T.

Parallel transmit MRI at 7 T has increasingly been adopted in research projects and provides increased signal-to-noise ratios and novel contrasts. However, the interactions of fields in the body need to be carefully considered to ensure safe scanning. Recent advances in physically flexible body coils have allowed for high-field abdominal imaging, but the effects of increased variability on energy deposition need further exploration. The aim of this study was to assess the impact of subject geometry, respiration phase and coil positioning on the specific absorption rate (SAR). Ten healthy subjects (body mass index [BMI] = 25 ± 5 kg m-2 ) were scanned (at 3 T) during exhale breath-hold and images used to generate body models. Seven of these subjects were also scanned during inhale. Simplifications of the coil and body models were first explored, and then finite-difference time-domain simulations were run with a typical eight-channel parallel transmit coil positioned over the abdomen. Simulations were used to generate 10 g averaged SAR (SAR10g ) maps across 100,000 phase settings, and the worst-case scenario 10 g averaged SAR (wocSAR10g ) was identified using trigonometric maximisation. The average maximum SAR10g across the 10 subjects with 1 W input power per channel was 1.77 W kg-1 . Hotspots were always close to the body surface near the muscle wall boundary. The wocSAR10g across the 10 subjects ranged from 2.3 to 3.2 W kg-1 and was inversely correlated to fat volume percentage (R = 8) and BMI (R = 0.6). The coefficient of variation values in SAR10g due to variations in subject geometry, respiration phase and realistic coil repositioning were 12%, 4% and 12%, respectively. This study found that the variability due to realistic coil repositioning was similar to the variability due to differing healthy subject geometries for abdominal imaging. This is important as it suggests that population-based modelling is likely to be more useful than individual modelling in setting safe thresholds for abdominal imaging.

Association between vmPFC gray matter volume and smoking initiation in adolescents.

Smoking of cigarettes among young adolescents is a pressing public health issue. However, the neural mechanisms underlying smoking initiation and sustenance during adolescence, especially the potential causal interactions between altered brain development and smoking behaviour, remain elusive. Here, using large longitudinal adolescence imaging genetic cohorts, we identify associations between left ventromedial prefrontal cortex (vmPFC) gray matter volume (GMV) and subsequent self-reported smoking initiation, and between right vmPFC GMV and the maintenance of smoking behaviour. Rule-breaking behaviour mediates the association between smaller left vmPFC GMV and smoking behaviour based on longitudinal cross-lagged analysis and Mendelian randomisation. In contrast, smoking behaviour associated longitudinal covariation of right vmPFC GMV and sensation seeking (especially hedonic experience) highlights a potential reward-based mechanism for sustaining addictive behaviour. Taken together, our findings reveal vmPFC GMV as a possible biomarker for the early stages of nicotine addiction, with implications for its prevention and treatment.

Measuring chemical exchange saturation transfer exchange rates in the human brain using a particle swarm optimisation algorithm.

The z-spectrum contains many pools with different exchange rates and T2 values, which can make it difficult to interpret in vivo data and complicates the design of experiments aimed at providing sensitivity to one pool. This work aims to characterise the main pools observable with MRI at 7T in the human brain. To achieve this, we acquired z-spectra at multiple saturation powers in the human brain at 7T. We used simulations to optimise the use of particle swarm optimisation (PSO) to fit these data, validating this approach using further simulations and creatine phantoms. We then used the PSO to fit data from grey and white matter for the pool size, exchange rate, and T2 of five proton pools (magnetisation transfer, amides, amines, nuclear Overhauser enhancement NOE-3.5ppm and NOE-1.7ppm in addition to water). We then devised an approach for using PSO to fit z-spectra while limiting the computational burden, and we investigated the sensitivity of the fit to T2 and k for three overlapping pools. We used this to measure the exchange rate of creatine and to show that it varied with temperature, as expected. In the brain we measured a significantly larger pool size in white matter than in grey matter for the magnetisation transfer pool and the NOE-3.5ppm pool. For all other parameters we found no significant difference between grey and white matter. We showed that PSO can be used to fit z-spectra acquired at a range of B1 to provide information about peak position, amplitude, exchange rate, and T2 in vivo in the human brain. These data could provide more sensitivity to change in some clinical conditions and will also provide key information for further experimental design.

Chronotype, Longitudinal Volumetric Brain Variations Throughout Adolescence, and Depressive Symptom Development.

OBJECTIVE: Adolescence is a critical period for circadian rhythm, with a strong shift toward eveningness around age 14. Also, eveningness in adolescence has been found to predict later onset of depressive symptoms. However, no previous study has investigated structural variations associated with chronotype in early adolescence and how this adds to the development of depressive symptoms. METHOD: Assessment of 128 community-based adolescents (51% girls) at age 14 and 19 years was performed. Using whole-brain voxel-based morphometry, baseline (at age 14) regional gray matter volumes (GMVs), follow-up (at age 19) regional GMVs, and longitudinal changes (between 14 and 19) associated with Morningness/Eveningness Scale in Children score and sleep habits at baseline were measured. The association of GMV with depressive symptoms at 19 years was studied, and the role of potential clinical and genetic factors as mediators and moderators was assessed. RESULTS: Higher eveningness was associated with larger GMV in the right medial prefrontal cortex at ages 14 and 19 in the whole sample. GMV in this region related to depressive symptoms at age 19 in catechol-O-methyltransferase (COMT) Val/Val, but not in Met COMT, carriers. Larger GMV also was observed in the right fusiform gyrus at age 14, which was explained by later wake-up time during weekends. CONCLUSION: In adolescence, eveningness and its related sleep habits correlated with distinct developmental patterns. Eveningness was specifically associated with GMV changes in the medial prefrontal cortex; this could serve as a brain vulnerability factor for later self-reported depressive symptoms in COMT Val/Val carriers.

A randomised crossover trial of tezacaftor-ivacaftor for gut dysfunction in cystic fibrosis with magnetic resonance imaging (MRI) outcomes: a pilot study.

Background: People with cystic fibrosis (CF) can experience recurrent chest infections, pancreatic exocrine insufficiency and gastrointestinal symptoms. New cystic fibrosis transmembrane conductance regulator (CFTR) modulator drugs improve lung function but gastrointestinal effects are unclear. We aimed to see if a CFTR modulator (tezacaftor-ivacaftor,TEZ/IVA) improves gastrointestinal outcomes in CF. Methods: We conducted a randomised, double-blind, placebo-controlled, two-period crossover trial (2019-2020) at Nottingham University Hospitals. The effects of TEZ/IVA on gut physiology were measured using MRI. Participants were randomly assigned to treatment sequences AB or BA (A:TEZ/IVA, B:placebo, each 28 days), with a 28-day washout period. Participants had serial MRI scans at baseline and after 19-23 days of each treatment. Due to the COVID-19 pandemic, a protocol amendment allowed for observer-blind comparisons prior to and during TEZ/IVA. In such cases, participants were not blind to the treatment but researchers remained blind. The primary outcome was oro-caecal transit time (OCTT). Secondary outcomes included MRI metrics, symptoms and stool biomarkers. Results: We randomised 13 participants. Before the COVID-19 pandemic 8 participants completed the full protocol and 1 dropped out. The remaining 4 participants followed the amended protocol. There were no significant differences between placebo and TEZ/IVA for OCTT (TEZ/IVA >360minutes [225,>360] vs. placebo 330minutes [285,>360], p=0.8) or secondary outcomes. There were no adverse events. Conclusions: Our data contribute to a research gap in the extra-pulmonary effects of CFTR modulators. We found no effect after TEZ/IVA on MRI metrics of gut function, GI symptoms or stool calprotectin. Effects might be detectable with larger studies, longer treatment or more effective CFTR modulators. ClinicalTrialsgov registration: NCT04006873 (02/07/2019).

Structural differences in adolescent brains can predict alcohol misuse.

Alcohol misuse during adolescence (AAM) has been associated with disruptive development of adolescent brains. In this longitudinal machine learning (ML) study, we could predict AAM significantly from brain structure (T1-weighted imaging and DTI) with accuracies of 73 -78% in the IMAGEN dataset (n∼1182). Our results not only show that structural differences in brain can predict AAM, but also suggests that such differences might precede AAM behavior in the data. We predicted 10 phenotypes of AAM at age 22 using brain MRI features at ages 14, 19, and 22. Binge drinking was found to be the most predictable phenotype. The most informative brain features were located in the ventricular CSF, and in white matter tracts of the corpus callosum, internal capsule, and brain stem. In the cortex, they were spread across the occipital, frontal, and temporal lobes and in the cingulate cortex. We also experimented with four different ML models and several confound control techniques. Support Vector Machine (SVM) with rbf kernel and Gradient Boosting consistently performed better than the linear models, linear SVM and Logistic Regression. Our study also demonstrates how the choice of the predicted phenotype, ML model, and confound correction technique are all crucial decisions in an explorative ML study analyzing psychiatric disorders with small effect sizes such as AAM.

Magnetic resonance imaging of the gastrointestinal tract shows reduced small bowel motility and altered chyme in cystic fibrosis compared to controls.

People with cystic fibrosis (CF) experience digestive symptoms but the mechanisms are incompletely understood. Here we explore causes and consequences of slower gastrointestinal transit using magnetic resonance imaging (MRI). Twelve people with CF and 12 healthy controls, matched for age and gender, underwent MRI scans, both fasted and after standardised meals, over 6.5 h. Fasted small bowel motility scores were lower in CF than in controls. No difference in ascending colon chyme T1 was detected. The difference in texture between small bowel and colon contents, seen in health, was diminished in CF. The ascending colon in CF participants had an abnormal appearance compared to controls. MRI offers unique potential to evaluate gut luminal content, colonic mucosa and intestinal motor activity. These new data support the theoretical cycle of desiccation, dysmotility and delayed transit as a cause of gastrointestinal symptoms in CF.

Brain Signatures During Reward Anticipation Predict Persistent Attention-Deficit/Hyperactivity Disorder Symptoms.

OBJECTIVE: Children experiencing attention-deficit/hyperactivity disorder (ADHD) symptoms may retain symptoms into adulthood, but little is known about the underlying mechanism. METHOD: To identify biomarkers of persistent ADHD symptom development, we carried out whole-brain analyses of neuroimaging data during the anticipation phase of the Monetary-Incentive-Delay (MID) task in 1,368 adolescents recruited by the IMAGEN Consortium at age 14 years, whose behavioral measurements were followed up longitudinally at age 16. In particular, we focused on comparing individuals with persistent high ADHD symptoms at both ages 14 and 16 years to unaffected control individuals, but also exploring which individuals demonstrating symptom remission (with high ADHD symptoms at age 14 but much reduced at age 16). RESULTS: We identified reduced activations in the medial frontal cortex and the thalamus during reward anticipation as neuro-biomarkers for persistent ADHD symptoms across time. The genetic relevance of the above findings was further supported by the associations of the polygenic risk scores of ADHD with both the persistent and control status and the activations of both brain regions. Furthermore, in an exploratory analysis, the thalamic activation might also help to distinguish persons with persistent ADHD from those remitted in both an exploratory sample (odds ratio = 9.43, p < .001) and an independent generalization sample (odds ratio = 4.64, p = .003). CONCLUSION: Using a well-established and widely applied functional magnetic resonance imaging task, we have identified neural biomarkers that could discriminate ADHD symptoms that persist throughout adolescence from controls and potentially those likely to remit during adolescent development as well.

Quantitative Magnetic Resonance Imaging in Perianal Crohn's Disease at 1.5 and 3.0 T: A Feasibility Study.

Perianal Crohn's Disease (pCD) is a common manifestation of Crohn's Disease. Absence of reliable disease measures makes disease monitoring unreliable. Qualitative MRI has been increasingly used for diagnosing and monitoring pCD and has shown potential for assessing response to treatment. Quantitative MRI sequences, such as diffusion-weighted imaging (DWI), dynamic contrast enhancement (DCE) and magnetisation transfer (MT), along with T2 relaxometry, offer opportunities to improve diagnostic capability. Quantitative MRI sequences (DWI, DCE, MT and T2) were used in a cohort of 25 pCD patients before and 12 weeks after biological therapy at two different field strengths (1.5 and 3 T). Disease activity was measured with the Perianal Crohn's Disease Activity index (PDAI) and serum C-reactive protein (CRP). Diseased tissue areas on MRI were defined by a radiologist. A baseline model to predict outcome at 12 weeks was developed. No differences were seen in the quantitative MR measured in the diseased tissue regions from baseline to 12 weeks; however, PDAI and CRP decreased. Baseline PDAI, CRP, T2 relaxometry and surgical history were found to have a moderate ability to predict response after 12 weeks of biological treatment. Validation in larger cohorts with MRI and clinical measures are needed in order to further develop the model.

Assessing Lymphatic Uptake of Lipids Using Magnetic Resonance Imaging: A Feasibility Study in Healthy Human Volunteers with Potential Application for Tracking Lymph Node Delivery of Drugs and Formulation Excipients.

Dietary lipids and some pharmaceutical lipid excipients can facilitate the targeted delivery of drugs to the intestinal lymphatics. Here, the feasibility of magnetic resonance imaging (MRI) for imaging lipid uptake into the intestinal lymphatics was assessed, shedding light on which lymph nodes can be targeted using this approach. Three healthy male volunteers were scanned at 3.0 T at baseline, 120, 180, 240, and 300 min post high-fat meal. A sagittal multi-slice image was acquired using a diffusion-weighted whole-body imaging sequence with background suppression (DWIBS) (pre inversion TI = 260 ms). Changes in area, major, and minor axis length were compared at each time point. Apparent diffusion coefficient (ADC) was calculated (b = 0 and 600 s/mm2) across eight slices. An average of 22 nodes could be visualised across all time points. ADC increased at 120 and 180 min compared to the baseline in all three participants by an average of 9.2% and 6.8%, respectively. In two participants, mean node area and major axis lengths increased at 120 and 180 min relative to the baseline. In conclusion, the method described shows potential for repeated lymph node measurements and the tracking of lipid uptake into the lymphatics. Further studies should focus on methodology optimisation in a larger cohort.

Colonic Volume Changes in Paediatric Constipation Compared to Normal Values Measured Using MRI.

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.