MRI and histopathologic study of a novel cholesterol-fed rabbit model of xanthogranuloma

Yuanxin Chen; Amanda M Hamilton; Katie M Parkins; Jian-Xiong Wang; Kem A Rogers; Michael M Zeineh; Brian K Rutt; John A Ronald

doi:10.1002/jmri.25213

MRI and histopathologic study of a novel cholesterol-fed rabbit model of xanthogranuloma

J Magn Reson Imaging. 2016 Sep;44(3):673-82. doi: 10.1002/jmri.25213. Epub 2016 Feb 26.

Authors

Yuanxin Chen¹, Amanda M Hamilton¹, Katie M Parkins¹, Jian-Xiong Wang², Kem A Rogers³, Michael M Zeineh⁴, Brian K Rutt⁴, John A Ronald^{1

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Affiliations

¹ Imaging Research Laboratories, Robarts Research Institute, Western University, London, Ontario, Canada.
² Advanced Imaging Research Center and Radiology Department, UT Southwestern Medical Center, Dallas, Texas, USA.
³ Department of Anatomy and Cell Biology, Western University, London, Ontario, Canada.
⁴ Department of Radiology, Stanford University, Stanford, California, USA.
⁵ Department of Medical Biophysics, Western University, London, Ontario, Canada.
⁶ Lawson Health Research Institute, London, Ontario, Canada.

Abstract

Purpose: To develop a rabbit model of xanthogranuloma based on supplementation of dietary cholesterol. The aim of this study was to analyze the xanthogranulomatous lesions using magnetic resonance imaging (MRI) and histological examination.

Materials and methods: Rabbits were fed a low-level cholesterol (CH) diet (n = 10) or normal chow (n = 5) for 24 months. In vivo brain imaging was performed on a 3T MR system using fast imaging employing steady state acquisition, susceptibility-weighted imaging, spoiled gradient recalled, T1 -weighted inversion recovery imaging and T1 relaxometry, PD-weighted and T2 -weighted spin-echo imaging and T2 relaxometry, iterative decomposition of water and fat with echo asymmetry and least-squares estimation, ultrashort TE MRI (UTE-MRI), and T2* relaxometry. MR images were evaluated using a Likert scale for lesion presence and quantitative analysis of lesion size, ventricular volume, and T1 , T2 , and T2* values of lesions was performed. After imaging, brain specimens were examined using histological methods.

Results: In vivo MRI revealed that 6 of 10 CH-fed rabbits developed lesions in the choroid plexus. Region-of-interest analysis showed that for CH-fed rabbits the mean lesion volume was 8.5 ± 2.6 mm(3) and the volume of the lateral ventricle was significantly increased compared to controls (P < 0.01). The lesions showed significantly shorter mean T2 values (35 ± 12 msec, P < 0.001), longer mean T1 values (1581 ± 146 msec, P < 0.05), and shorter T2* values (22 ± 13 msec, P < 0.001) compared to adjacent brain structures. The ultrashort T2* components were visible using UTE-MRI. Histopathologic evaluation of lesions demonstrated features of human xanthogranuloma.

Conclusion: Rabbits fed a low-level CH diet develop sizable intraventricular masses that have similar histopathological features as human xanthogranuloma. Multiparametric MRI techniques were able to provide information about the complex composition of these lesions. J. Magn. Reson. Imaging 2016;44:673-682.

Keywords: cholesterol; hypercholesterolemia; magnetic resonance imaging; rabbit model; xanthogranuloma.

Publication types

Comparative Study
Evaluation Study

MeSH terms

Animals
Brain Diseases / diagnostic imaging*
Brain Diseases / pathology*
Cholesterol, Dietary*
Disease Models, Animal*
Magnetic Resonance Imaging / methods*
Male
Rabbits
Reproducibility of Results
Sensitivity and Specificity
Xanthogranuloma, Juvenile / diagnostic imaging*
Xanthogranuloma, Juvenile / pathology*

Substances

Cholesterol, Dietary

Abstract

Publication types

MeSH terms

Substances

Grants and funding