Feasibility of MRI in Experimentally Induced Inflammatory Small Bowel Disease: A Pilot Study in a Porcine Model

Abstract

The purpose of this study was to compare the macroscopic and microscopic findings of experimentally induced inflammatory lesions in jejunum and ileum with magnetic resonance imaging (MRI) findings. Inflammatory small bowel lesions were experimentally induced in six pigs. Bowel segments in jejunum and ileum were isolated, and a solution with trinitrobenzenesulfonic acid and ethanol (TNBS-EtOH) was installed. MRI of the small bowel was performed 7 days after surgery. Before the MRI examination, a 6% mannitol solution was installed through a nasogastric tube. The MRI protocol consisted of single-shot turbo spin echo T2 sequences, steady state free precession (BFFE) sequences, and a 3D T1 gradient echo sequence with fat saturation and intravenous contrast. The following image findings were evaluated: increased bowel wall thickness (BWT), increased bowel wall enhancement (BWE), and bowel stenosis. After the MRI examination, the animals were sacrificed. The small bowel was removed and examined macroscopically and microscopically. Inflammatory lesions developed in jejunum and ileum in all animals. The lesions were visible macroscopically and microscopically. The microscopic findings consisted of variable degrees of inflammation, ulcer formation, and fibrosis. In jejunum the inflammatory lesions were not diagnosed with MRI, except in one pig with a bowel necrosis probably caused by an intramural injection or leakage of the TNBS-EtOH solution. In ileum the bowel wall thickness was increased and the inflammatory lesions were diagnosed with MRI. In conclusion, the inflammatory lesions were visible macroscopically and microscopically. Lesions in ileum had increased BWT and were possible to image with MRI. Lesions in jejunum had normal BWT and were not diagnosed with MRI, except in one pig with increased BWT probably caused by complications to the installation of TNBS-EtOH.

Quantitative Assessment of Inflammation in a Porcine Acute Terminal Ileitis Model: US with a Molecularly Targeted Contrast Agent

“…This results in a T-cell-dependent mucosal immune response and transmural infiltration of neutrophils (10,25). We observed that the volume of ethanol can be substantially reduced to 0.8 mL (compared with 40 mL, as published previously [22,23]), which caused moderate-to-severe TNBS-mediated inflammation with minimal discomfort to the animals. Another detail worth noting is the need to premedicate pigs with aspirin, indomethacin, or a specific thromboxane receptor blocker before injecting lipid-based particles such as MBs (16)(17)(18), because pigs have abundant intrapulmonary macrophages (26,27).…”

“…Pigs are increasingly being recognized as important large-animal models for IBD (21)(22)(23)(24). We modified published protocols of chemically induced ileitis using TNBS/ethanol installation (22,23) to create a reproducible and well-tolerated porcine terminal ileitis model.…”

“…We modified published protocols of chemically induced ileitis using TNBS/ethanol installation (22,23) to create a reproducible and well-tolerated porcine terminal ileitis model. In this model, ethanol breaks the physical barrier of the intestine, allowing TNBS to haptenize intestinal autologous or microbiota proteins.…”

Animal models of chemically induced intestinal inflammation: Predictivity and ethical issues

“…4). Several studies using porcine models of intestinal inflammation showed their predictive value for drug development and diagnostic tools applied in clinical practice (Kalima et al, 1976;Kim et al, 2010;Negaard et al, 2010;Pouillart et al, 2010). Nevertheless, the application of protocols including the management of large mammals implies the use of highly specialized facilities and personnel, thus restricting the feasibility of these studies only to specialized institutes.…”

Sacral nerve stimulation enhances early intestinal mucosal repair following mucosal injury in a pig model

“…The TNBS concentration and contact time were selected from previous rodent studies, namely 15 mg ml −1 , 50% ethanol, 15 min (Negaard et al . ; Brenna et al . ), while the volume (100 ml) was estimated in comparison with human rectal anatomy (Gandarillas & Bas, ).To limit the passage of stools and to delimit the contact area of TNBS, a latex plug (consisting of a glove filled with sterile compress) was inserted 15 cm from the anal margin and an anal strapping (anal encirclement with temporary suture) was used to prevent anal leakage of TNBS.…”