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Ex Vivo Intestinal Sacs to Assess Mucosal Permeability in Models of Gastrointestinal Disease
Published on: February 9, 2016
MR Measures of Small Bowel Wall T2 Are Associated With Increased Permeability
Robert A Scott1,2, Hannah G Williams1,3, Caroline L Hoad1,3
1National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre at the Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK.
Background:
Increased small bowel permeability leads to bacterial translocation, associated with significant morbidity and mortality. Biomarkers are needed to evaluate these changes in vivo, stratify an individual's risk, and evaluate the efficacy of interventions. MRI is an established biomarker of small bowel inflammation.
Purpose:
To characterize changes in the small bowel with quantitative MRI measures associated with increased permeability induced by indomethacin.
Study Type:
Prospective single-center, double-blind, two-way crossover provocation study.
Subjects:
A provocation cohort (22 healthy volunteers) and intrasubject reproducibility cohort (8 healthy volunteers).
Field Strength/Sequence:
2D balanced turbo field echo sequences to measure small bowel wall thickness, T2 , and motility acquired at 3T.
Assessment:
Participants were randomized to receive indomethacin or placebo prior to assessment. After a minimum 2-week washout, measures were repeated with the alternative allocation. MR measures (wall thickness, T2 , motility) at each study visit were compared to the reference standard 2-hour lactulose/mannitol urinary excretion ratio (LMR) test performed by a lab technician. All analyses were performed blind.
Statistical Tests:
Normality was tested (Shapiro-Wilk's test). Paired testing (Student's t-test or Wilcoxon) determined the significance of paired differences with indomethacin provocation. Pearson's correlation coefficient compared significant measures with indomethacin provocation to LMR. Intrasubject (intraclass correlation) and interrater variability (Bland-Altman) were assessed.
Results:
Indomethacin provocation induced a significant increase in LMR compared to placebo (P < 0.05) and a significant increase in small bowel T2 (0.12 seconds compared to placebo 0.07 seconds, P < 0.05). Small bowel wall thickness (P = 0.17) and motility (P = 0.149) showed no significant change. T2 and LMR were positively correlated (r = 0.68, P < 0.05). T2 measurements were robust to interobserver (intraclass correlation 0.89) and intrasubject variability (Bland-Altman bias of 0.005 seconds, 95% confidence interval [CI] -0.04 to +0.05 seconds, and 0.0006 seconds, 95% CI -0.05 to +0.06 seconds).
Data Conclusion:
MR measures of small bowel wall T2 were significantly increased following indomethacin provocation and correlated with 2-hour LMR test results.
Level Of Evidence:
1 TECHNICAL EFFICACY STAGE: 2.
Insights
Magnetic resonance imaging (MRI) T2 measurements show increased small bowel permeability after indomethacin provocation. These MRI findings correlate with the lactulose/mannitol ratio test, offering a potential non-invasive biomarker.
Area of Science:
- Biomedical Imaging
- Gastroenterology
- Pharmacology
Background:
- Increased small bowel permeability is linked to serious health issues, necessitating reliable biomarkers for risk assessment and treatment evaluation.
- Current methods for assessing small bowel changes in vivo are limited.
- Magnetic resonance imaging (MRI) is an established tool for visualizing small bowel inflammation.
Purpose of the Study:
- To quantitatively assess small bowel changes using MRI measures following indomethacin-induced permeability.
- To establish MRI as a potential biomarker for evaluating small bowel permeability in vivo.
Main Methods:
- A prospective, double-blind, crossover study involving 22 healthy volunteers.
- Quantitative MRI sequences (2D balanced turbo field echo) at 3T measured small bowel wall thickness, T2 relaxation time, and motility.
- MRI findings were compared with the 2-hour lactulose/mannitol urinary excretion ratio (LMR) test.
Main Results:
- Indomethacin significantly increased LMR and small bowel T2 values compared to placebo (P < 0.05).
- Small bowel wall thickness and motility did not show significant changes.
- Small bowel T2 measurements demonstrated a strong positive correlation with LMR results (r = 0.68, P < 0.05) and were robust to interobserver and intrasubject variability.
Conclusions:
- Quantitative MRI T2 measurements can detect indomethacin-induced increases in small bowel permeability.
- Small bowel T2 shows promise as a non-invasive MRI biomarker correlating with the LMR test for assessing permeability.
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