MR- and optical-based multimodal and multiscale protocol for mice colorectal diseases diagnosis
Hugo Dorez1, Raphaël Sablong1, Hélène Ratiney1, Laurence Canaple2, Hervé Saint-Jalmes3, Sophie Gaillard1, Driffa Moussata1,4, and Olivier Beuf1

1Univ Lyon, INSA‐Lyon, Université Lyon 1, UJM-Saint Etienne, CNRS, Inserm, CREATIS UMR 5220, U1206, Lyon, France, 2Institut de Génomique Fonctionnelle de Lyon, Université de Lyon 1, UMR 5242 CNRS, Ecole Normale Supérieure de Lyon, Lyon, France, 3LTSI; INSERM U642; Université Rennes 1, Rennes, France, 4Hôpital Régional Universitaire de Tours - Service hépato-gastroentérologie, Tours, France


A multimodal and multiscale protocol was defined for the diagnosis of mice colorectal diseases. Based on endoluminal MRI, using dedicated endorectal coils, and optical modalities the protocol was assessed on a mouse model of colorectal cancer for a six-month period. Optical modalities were used for microscopic characterization of the surface of the colon wall where endoluminal MRI was used for in-depth macroscopic characterization and staging of lesions from inflammation to cancer. The protocol was then used to support in vivo MRS signal analysis that was used to assess the biochemical content of various anatomical structures (colon wall, visceral fat…).


Preclinical trials are often a prerequisite before the transfer to the clinic. To consider the benefit of a novel imaging technique or treatment, preclinical protocols must allow an evaluation at different scales with different sources of contrast. In this abstract, we propose a “generic” protocol combining endoluminal MRI with optical modalities that can be used to evaluate new diagnosis techniques or treatment for endocavitary applications. We have assessed the efficiency and reproducibility of the protocol on a mouse model of colorectal cancer (CRC) during which we have implemented in vivo MR spectroscopy.


The preclinical protocol combined endoluminal MRI, using dedicated endorectal coils (ERC)1, with optical modalities gathering: conventional endoscopy (CE), chromoendoscopy (ChE) and confocal laser endomicroscopy (CEM), using FITC as contrast agent2. The pathology model of CRC3 was chemically induced on 20 mice, and 12 healthy animals served as control. Each mouse was imaged with all modalities every six weeks for a six-month period. Images were classified by a radiologist regarding the characteristic stage of the development of CRC, as follows: healthy tissues, inflammation, infiltration, and tumors. The timeline of the protocol is represented in Figure 1. The endoluminal MRI acquisition protocol included high spatial resolution T1-weighted images and their associated T1-maps. Finally, we have assessed the potential of in vivo MRS, using ERC and the dedicated protocol, in the characterization of CRC on mice. After first order shim correction, PRESS mono-voxels (TE=16.2ms, TR=1500ms and various sizes from 0.125μL to 4μL acquired in less than 3 minutes), without water suppression, were precisely acquired at different locations (healthy colon walls, visceral fat, inflammatory lesions and tumors) confirmed by a radiologist.


Optical modalities were used to detect and microscopically characterize CRC lesions at the surface of the colon wall (CW) – see Figure 2. CE is used to depict suspicious areas where ChE and CEM are used to characterize the vascular network distribution surrounding the epithelial cells (see Figure 2). Endoluminal MRI (T1-weighted images) was performed for macroscopic in-depth characterization and staging (see Figure 2). At each stage of the pathology, in vivo MRS was evaluated. Characteristic spectra were acquired and exhibit various biochemical contents following the location (see Figure 3 and Table 1).


Based on this multiscale, multicontrast and multimodality protocol, the entire follow-up of the pathology can be performed. Colocalization between CE, ChE and CEM images improve the diagnosis of lesions by characterizing the macroscopic aspect to the microscopic development of abnormal cells in the epithelium. Some of flat lesions detected in CE were labeled at inflammation showing no aggressive behavior, but, when imaged with endoluminal MRI, these lesions appear to be more severe than expected drastically changing the short-term prognosis of the animal. This robust protocol to depict, characterize and stage colorectal abnormalities with different sources of contrast was then used to evaluate in vivo MRS. Based on images provided by both modalities, spectra were acquired in specific regions. Using ERC, acquisition times were kept as short as possible (less than 3 minutes) and prescribed volumes ranged from 0.12µL to 1µL to precisely fit with small anatomical structures. Achieved scan time and analysis volume made in vivo MRS suitable for clinical applications. Spectra acquired in the colon wall show similar line shape contributions to spectra acquired in visceral fat. A new longitudinal study will help to evaluate the benefit of this technique for the biochemical characterization of suspicious areas located. Nevertheless, for the first time reported in the literature, in vivo MRS was performed on mice colon and rectum thanks to ERC.


This multiscale and multicontrast protocol has demonstrated its efficiency and reliability to depict, to characterize and to stage the different patterns of a pathology through time. The protocol can also include MRS for CRC examination and could be used for other applications such as the study of the intestinal microbiota.


This work was supported by the LABEX PRIMES (ANR-11-LABX-0063) of Université de Lyon, within the program "Investissements d'Avenir" (ANR-11-IDEX-0007) operated by the French National Research Agency (ANR). This work was performed on the platform PILoT, member of France Life Imaging network (grant ANR-11-INBS-0006).


1. Dorez, H. et al. Endoluminal high-resolution MR imaging protocol for colon walls analysis in a mouse model of colitis. Magn. Reson. Mater. Phys. Biol. Med. 1–13 (2016). doi:10.1007/s10334-016-0539-2

2. Waldner, M. J., Wirtz, S., Neufert, C., Becker, C. & Neurath, M. F. Confocal laser endomicroscopy and narrow-band imaging-aided endoscopy for in vivo imaging of colitis and colon cancer in mice. Nat. Protoc. 6, 1471–1481 (2011).

3. Tanaka, T. et al. A novel inflammation-related mouse colon carcinogenesis model induced by azoxymethane and dextran sodium sulfate. Cancer Sci. 94, 965–973 (2003).


Figure 1 - Timeline of the multimodal protocol combining optical modalities (CE, Che and CEM) and endoluminal MRI, using dedicated ERC. The protocol is performed in two days for each animal: the first day, optical procedures are performed and, the next day, MRI acquisitions are performed. *AOM = azoxymethane, **DSS = dextran sulfate sodium

Figure 2 - Images of the different modalities used in this protocol. The first line shows the CE, combined with ChE, images of the surface of the colon wall. The different stage can hardly be differentiated from one to another. CEM images focused on the vascular network and the shape and distribution of epithelial cells. Endoluminal MRI is used for in-depth characterization and staging of lesions.

Figure 3 - In vivo MR spectra acquired with the ERC during the longitudinal study. (1) spectrum acquired in the colon wall closed to the ERC. (2) spectrum acquired in the colon lumen, essentially filled with mucus (water). (3) spectrum acquired in the visceral fat far from the ERC. Following the location, the different spectra show various biochemical contents. The red-dashed box probably identifies a phase correction problem.

Table 1 - Description of the biochemical contents observed in a 1 µL voxel located in the visceral fat (further from the ERC).

Proc. Intl. Soc. Mag. Reson. Med. 25 (2017)