Establishing Magnetic Resonance Imaging as an Accurate and Reliable Tool to Diagnose and Monitor Esophageal Cancer in a Rat Model

Abstract

ObjectiveTo assess the reliability of magnetic resonance imaging (MRI) for detection of esophageal cancer in the Levrat model of end-to-side esophagojejunostomy.BackgroundThe Levrat model has proven utility in terms of its ability to replicate Barrett’s carcinogenesis by inducing gastroduodenoesophageal reflux (GDER). Due to lack of data on the utility of non-invasive methods for detection of esophageal cancer, treatment efficacy studies have been limited, as adenocarcinoma histology has only been validated post-mortem. It would therefore be of great value if the validity and reliability of MRI could be established in this setting.MethodsChronic GDER reflux was induced in 19 male Sprague-Dawley rats using the modified Levrat model. At 40 weeks post-surgery, all animals underwent endoscopy, MRI scanning, and post-mortem histological analysis of the esophagus and anastomosis. With post-mortem histology serving as the gold standard, assessment of presence of esophageal cancer was made by five esophageal specialists and five radiologists on endoscopy and MRI, respectively.ResultsThe accuracy of MRI and endoscopic analysis to correctly identify cancer vs. no cancer was 85.3% and 50.5%, respectively. ROC curves demonstrated that MRI rating had an AUC of 0.966 (p<0.001) and endoscopy rating had an AUC of 0.534 (p = 0.804). The sensitivity and specificity of MRI for identifying cancer vs. no-cancer was 89.1% and 80% respectively, as compared to 45.5% and 57.5% for endoscopy. False positive rates of MRI and endoscopy were 20% and 42.5%, respectively.ConclusionsMRI is a more reliable diagnostic method than endoscopy in the Levrat model. The non-invasiveness of the tool and its potential to volumetrically quantify the size and number of tumors likely makes it even more useful in evaluating novel agents and their efficacy in treatment studies of esophageal cancer.

High yield reproducible rat model recapitulating human Barrett’s carcinogenesis

“…For the first time, we demonstrated macro-metastatic lesions originating from the primary tumors in the model[ 30 ]. Additionally, we further enhanced the utility of the model through combined magnetic resonance imaging (MRI) and small animal endoscopic biopsy to simultaneously track in vivo tumor volumes and molecular correlates longitudinally[ 31 ]. With these advancements, the animal model has been highly efficient, not only to develop preventative and treatment strategies, but also to provide a platform to better understand the molecular mechanisms that affect disease progression from inflammation to EAC.…”

Animal Models of Barrett's Esophagus and Esophageal Adenocarcinoma–Past, Present, and Future

“…With regards to follow-up, endoscopic assessment is erratic due to extraluminal development of majority of tumors and low yield from endocopic biopsies in rats. Recently, Kosovec et al 41 demonstrated the usefulness and advocated the use of MRI rather than endoscopy for tumor assessment during follow-up. In conclusion, there is a need for a better model to overcome these concerns.…”

“…Mice models are well-suited for molecular studies given that their genome is completely sequenced and transgenic mice are commercially available today. 42 There have been many attempts to utilize genetically modified [41][42][43][44][45][46] and xenograft mice models [47][48][49] in BE research. However, creation of reflux in mice models often leads to many dying in the early postoperative period due to difficulty in performing surgery at the scale of their sizes and their intolerance to surgical stress.…”

Regenerative Medicine Strategies for Esophageal Repair

“…Anastomosis reinforcement models focus on leaks and dehiscence and have been described at different anatomic locations in the esophagus in the dog. 138 The Levrat procedure is a well-established model involving an esophagojejunostomy, a procedure that produces retrograde flow of gastrointestinal contents into the distal part of the esophagus, resulting in Barrett's esophagus and eventually progressing to esophageal adenocarcinoma [139][140][141][142][143] (Fig. 7).…”