Abstract

Magnetic resonance imaging (MRI) allows non-invasive evaluation of inflammatory bowel disease (IBD) by assessing pathologically altered gut. Besides morphological changes, relaxation times and diffusion capacity of involved bowel segments can be obtained by MRI. The aim of this study was to assess the use of multiparametric MRI in the diagnosis of experimentally induced colitis in mice, and evaluate the diagnostic benefit of parameter combinations using machine learning. This study relied on colitis induction by Dextran Sodium Sulfate (DSS) and investigated the colon of mice in vivo as well as ex vivo. Receiver Operating Characteristics were used to calculate sensitivity, specificity, positive- and negative-predictive values (PPV and NPV) of these single values in detecting DSS-treatment as a reference condition. A Model Averaged Neural Network (avNNet) was trained on the multiparametric combination of the measured values, and its predictive capacity was compared to those of the single parameters using exact binomial tests. Within the in vivo subgroup (n = 19), the avNNet featured a sensitivity of 91.3% (95% CI: 86.6–96.0%), specificity of 92.3% (95% CI: 85.1–99.6%), PPV of 96.9% (94.0–99.9%) and NPV of 80.0% (95% CI: 69.9–90.1%), significantly outperforming all single parameters in at least 2 accuracy measures (p < 0.003) and performing significantly worse compared to none of the single values. Within the ex vivo subgroup (n = 30), the avNNet featured a sensitivity of 87.4% (95% CI: 82.6–92.2%), specificity of 82.9% (95% CI: 76.1–89.7%), PPV of 88.9% (84.3–93.5%) and NPV of 80.8% (95% CI: 73.8–87.9%), significantly outperforming all single parameters in at least 2 accuracy measures (p < 0.015), exceeded by none of the single parameters. In experimental mouse colitis, multiparametric MRI and the combination of several single measured values to an avNNet can significantly increase diagnostic accuracy compared to the single parameters alone. This pilot study will provide new avenues for the development of an MR-derived colitis score for optimized diagnosis and surveillance of inflammatory bowel disease.

Highlights

  • Inflammatory bowel diseases (IBD)–mainly consisting of Crohn’s disease (CD) and ulcerative colitis (UC)–are persistent or recurrent intestinal inflammations affecting the entire gastrointestinal system or the colonic mucosa, respectively [1]

  • The sensitive and quantitative analysis of structural changes of mouse colon tissues associated with experimentally induced IBD is urgently required for an objective evaluation of disease progression

  • Evaluation of IBD in mice remains a challenging task due to the small structures involved in inflamed bowels

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Summary

Introduction

Inflammatory bowel diseases (IBD)–mainly consisting of Crohn’s disease (CD) and ulcerative colitis (UC)–are persistent or recurrent intestinal inflammations affecting the entire gastrointestinal system or the colonic mucosa, respectively [1]. Genetically susceptible hosts feature deregulated mucosal T cell responses to enteric bacteria [2]. The details of these genetic-environmental-immunological interactions are still not resolved. DSS-induced colitis in mice closely resembles the morphological and symptomatic features of human UC [11], with a predominant affection of the mucosa and the distal left colon, but often extending throughout the entire colon. Colonoscopy allows direct visualization of the colonic mucosa, but is invasive and can cause complications [12]

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