Investigation of the mouse colon wall using endoscopic MRI and confocal endomicroscopy
Hugo Dorez1, Raphaël Sablong1, Laurence Canaple2, Sophie Gaillard1, Hervé Saint-Jalmes3,4, Driffa Moussata5, and Olivier Beuf1

1CREATIS, Université de Lyon ; CNRS UMR5220 ; Inserm U1044 ; INSA-Lyon ; Université Claude Bernard Lyon 1, Villeurbanne, France, 2IGFL, ENS Lyon, Lyon, France, 3LTSI - Inserm U642, Rennes, France, 4CRLCC, Rennes, France, 5Hôpital Régional Universitaire de Tours, Tours, France

Synopsis

The purpose of this project is to provide new tools and protocols to evaluate digestive pathologies. To this end, endoscopic MRI, using endoluminal coils, was combined with confocal endomicroscopy (CEM). Both modalities provide complementary information. CEM is well suited to investigate the surface of the colon wall whereas endoscopic MRI can assess deeper structures. It allows characterizing and staging the first steps of cancer development. The study was performed on a mouse model of colitis following 24 animals. This opens perspectives to better understand digestive pathologies such as colorectal cancer and inflammatory bowel disease.

Background and purpose

Imaging the colon wall requires high spatial resolution to assess deep wall structures in details(1). Confocal endomicroscopy (CEM) provides detailed images at the surface of the mucosa whereas local endoscopic MR coils (EC) provide valuable in depth information. The overall purpose of this project is to combine MRI with optical imaging(2) to provide new tools and protocols for lesion characterization and staging (inflammatory bowel disease and colorectal cancer).

Materials and methods

EC at a working frequency of 200MHz (proton frequency at 4.7T) with active decoupling circuit were built(3) and used with a CEM CellVizio® system (MaunaKea Tech). A dedicated protocol using FLASH and RARE sequences but also a spectroscopy sequence was developed to obtain anatomical images, parametric T1- and T2-maps and to quantify the biochemical contents of suspicious areas. The total acquisition time is about 45 minutes. Tools and protocols were assessed in vivo on a mouse model of colitis(4) during 6 months period (24 animals). First, a conventional endoscopy, using a conventional mini multi-purpose rigid endoscope (Karl Storz), is performed to clean the colon of feces and to locate regions of interest. Then, CEM examination is done on suspicious areas after a 25µL retro-orbital injection of FITC-Dextran (5%). The optical probe of the CEM system is inserted into the operating sheath of the endoscope. The CEM examination is performed in order to assess the mucosa of the colon wall (60µm exploration depth). After the insertion of the endoscopic coil into the mouse rectum, the MR examination is carried out using the dedicated protocol.

Results

CEM and MRI are complementary modalities which allow a complete and precise investigation of colon wall lesions. Information provided by CEM at the surface of the colon wall (about 60µm deep) can be further investigated using endoscopic MRI. This is useful for assessing the infiltration of malignant lesions inside the different layers of the colon wall. CEM was able to assess changes in the vascular network architecture with the evolution of the pathology. Based on conventional endoscopy and CEM, suspicious lesions can be further assessed using endoscopic MRI. EC shows a huge improvement in SNR (compared with dedicated quadrature volume coil) that can be used to increase the in-plane spatial resolution up to 40x40µm² in a still limited acquisition time (approximately 10 minutes). The corresponding high resolution T1- and T2-maps are free of the SNR profile decay. Maps are both enhancing the structure contrast and give access to quantitative relaxation times values. It becomes also easier to depict colon walls and assess changes or colon wall thickness (Fig 2). During the 6 months follow-up, the different states of the pathology were observed, inflammation evolving into cancer. An increase in the T2 relaxation times with the pathology was also noticed for the mucosa (Fig 3) of several mice. Changes in the vascular network architecture were also observed for those mice. CEM images can be correlated with the evolution of T2 relaxation times of the same tissue. The combination of those two modalities allows having an early detection of inflammation which is the first step of cancer development.

Discussion

The combination of CEM and endoscopic MRI provide complementary information about the colon wall which are very helpful in the diagnosis of colorectal pathologies. Further improvements will be done to automatically classify CEM images. A graph theory approach will be set up to automatically threshold and classified these images. A larger analysis of the T1 and T2 relaxation times will be performed to confirm the trend presented in this abstract. New endoluminal coils will be designed to improve the quality factor and so the image quality. It should allow investigating deeper still with a high SNR. The results will then be compared with histopathologic slices. A 2nd longitudinal study involving 30 animals is currently carried out in the laboratory with these improvements.

Acknowledgements

ANR-11-LABX-006 3/ANR-11-IDEX-0007

References

1. Beaumont C, Pandey T, Gaines Fricke R, Laryea J, Jambhekar K. MR Evaluation of Rectal Cancer: Current Concepts. Curr Probl Diagn Radiol. 2013 May;42(3):99–112.

2. Waldner M, et al., “Confocal Laser Endomicroscopy and Narrow-Band Imaging-Aided Endoscopy for in Vivo Imaging of Colitis and Colon Cancer in Mice.” Nature Protocols. 2011 September;6(9):1471-1481.

3. Dorez H, et al., "Endoluminal MRI coils for mice rectal wall assessment", ISMRM 2014; #1345.

4. Tanaka T, Kohno H, Suzuki R, Yamada Y, Sugie S, Mori H. A novel inflammation-related mouse colon carcinogenesis model induced by azoxymethane and dextran sodium sulfate. Cancer Sci. 2003 Nov 1;94(11):965–73.

Figures

CEM and endoscopic MRI can be used for assessing the entire colon wall. Exploration depths for CEM is approximately 60µm whereas endoscopic MRI is approximately 3mm.

Anatomical T1w (a) MR image and the corresponding high resolution (80x80µm²) T1 map (b). On (c), anatomical T2w MR image and the corresponding high resolution T2 map (on (d), in plane spatial resolution78x78µm²). The contrast is enhanced when using parametric maps.

On (a), T2 map of the mouse colon wall. White arrow locates the first layer of the colon wall (mucosa). On (b), evolution of the T2 relaxation time from week of treatment 8 to 27. An increase of the T2 relaxation time is noticed since week of treatment 14.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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