Devkumar Mustafi PhD, Presenter: Nothing to Disclose

Urszula Dougherty MS, Abstract Co-Author: Nothing to Disclose

Erica Markiewicz BA, Abstract Co-Author: Nothing to Disclose

Xiaobing Fan PhD, Abstract Co-Author: Nothing to Disclose

Marc Bissonnette MD, Abstract Co-Author: Nothing to Disclose

Gregory Stanislaus Karczmar PhD, Abstract Co-Author: Research Consultant, Perceptive Informatics, Inc Research Consultant, BioClinica, Inc

Colon cancer is a leading cause of cancer-deaths in the US. Ulcerative colitis is causally linked to colitis-associated neoplastic progression but is difficult to detect and monitor non-invasively. Goals of this study were to determine MRI characteristics of early colitis-associated colon cancer and to assess vitamin D chemopreventive efficacy.

This study included CF1 female control mice (n=12), and mice treated with azoxymethane i.p. and dextran sulfate sodium in the drinking water (n=25) to induce colitis and colon cancer. Mice were fed a Western diet or Western diet supplemented with vitamin D (500 µg/kg chow). Western diets are relatively deficient in vitamin D and calcium. Mice were studied serially using anatomic and dynamic contrast enhanced MRI (DCEMRI) with a Gd-based contrast agent. In vivo MR and ex vivo histological images were co-registered using an agar based color-coded phantom in a flexible tube (2 mm o. d.) that was inserted via the rectum to the cecum. The phantom provided visual and MRI-detectable reference markers to co-register in vivo and ex vivo images.

We demonstrated that: 1) a visible reference marker could be used to successfully co-register MRI abnormalities with histological features identified in H&E stained sections; 2) T2 values distinguished normal colon from colitis, and from focal neoplastic lesions (p<0.005); 3) Ktrans values assessed by DCEMRI (a measure of perfusion/capillary permeability) reliably distinguished normal colon from tumor (0.12±0.01 min-1 vs. 0.61±0.05 min-1, respectively, p<0.001); 4) blood vessel diameters were >3-fold larger adjacent to early colonic tumors compared to vessels in control mice, suggesting that MRI might be used to detect dilated blood vessels as biomarkers of early colorectal cancer; 5) Vitamin D reduced the number of colonic tumors and degree of inflammation detected by MRI (p<0.001).

A novel technique was successfully developed to co-register MR and histological images. Several reliable image-based markers for colitis and colon cancer were identified. These MRI methods could monitor the chemopreventive efficacy of vitamin D in this model in real time and without sacrifice.

Non-invasive MRI/DCEMRI studies of colitis and colon cancer in mice will improve understanding of these diseases, produce new MRI markers to improve diagnosis, and guide development of new therapies.

Mustafi, D, Dougherty, U, Markiewicz, E, Fan, X, Bissonnette, M, Karczmar, G, Magnetic Resonance Imaging of Tumor Initiation and Progression, and Response to Vitamin D in a Mouse Model of Colitis and Colitis-associated Colon Cancer.  Radiological Society of North America 2013 Scientific Assembly and Annual Meeting, December 1 - December 6, 2013 ,Chicago IL. http://archive.rsna.org/2013/13018831.html