Micro-computed tomography in murine models of cerebral cavernous malformations as a paradigm for brain disease

• Published in: Journal of neuroscience methods 2016-09, Vol.271, p.14-24
• Main Authors: Girard, Romuald, Zeineddine, Hussein A., Orsbon, Courtney, Tan, Huan, Moore, Thomas, Hobson, Nick, Shenkar, Robert, Lightle, Rhonda, Shi, Changbin, Fam, Maged D., Cao, Ying, Shen, Le, Neander, April I., Rorrer, Autumn, Gallione, Carol, Tang, Alan T., Kahn, Mark L., Marchuk, Douglas A., Luo, Zhe-Xi, Awad, Issam A.
• Format: Article
• Language: English
• Subjects: Animals; Brain - diagnostic imaging; Cerebral cavernous malformation; Contrast Media; Disease Models, Animal; Female; Hemangioma, Cavernous, Central Nervous System - diagnostic imaging; Histological Techniques; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; Iodine; Iodine contrast; Male; Mice; Mice, Transgenic; Micro-CT; Morphometry; Observer Variation; Organ Size; Reproducibility of Results; rho-Associated Kinases - genetics; rho-Associated Kinases - metabolism; Time Factors; X-Ray Microtomography - methods
• ISSN: 0165-0270; 1872-678X
• DOI: 10.1016/j.jneumeth.2016.06.021

[Display omitted] •DiceCT was utilized to image lesions while preserving histologic validation.•Novel soaking technique in CCM murine model using micro-CT imaging.•CCM lesion burden identified on micro-CT images was verified with histology.•Micro-CT volumetric analysis of lesion burden correlated with histologic area.•Micro-CT can complement histology to optimize workflow and maximize information. Cerebral cavernous malformations (CCMs) are hemorrhagic brain lesions, where murine models allow major mechanistic discoveries, ushering genetic manipulations and preclinical assessment of therapies. Histology for lesion counting and morphometry is essential yet tedious and time consuming. We herein describe the application and validations of X-ray micro-computed tomography (micro-CT), a non-destructive technique allowing three-dimensional CCM lesion count and volumetric measurements, in transgenic murine brains. We hereby describe a new contrast soaking technique not previously applied to murine models of CCM disease. Volumetric segmentation and image processing paradigm allowed for histologic correlations and quantitative validations not previously reported with the micro-CT technique in brain vascular disease. Twenty-two hyper-dense areas on micro-CT images, identified as CCM lesions, were matched by histology. The inter-rater reliability analysis showed strong consistency in the CCM lesion identification and staging (K=0.89, p