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

Publication ,  Journal Article
Girard, R; Zeineddine, HA; Orsbon, C; Tan, H; Moore, T; Hobson, N; Shenkar, R; Lightle, R; Shi, C; Fam, MD; Cao, Y; Shen, L; Neander, AI ...
Published in: J Neurosci Methods
September 15, 2016

BACKGROUND: 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. NEW METHOD: 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. RESULTS: 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<0.0001) between the two techniques. Micro-CT revealed a 29% greater CCM lesion detection efficiency, and 80% improved time efficiency. COMPARISON WITH EXISTING METHOD: Serial integrated lesional area by histology showed a strong positive correlation with micro-CT estimated volume (r(2)=0.84, p<0.0001). CONCLUSIONS: Micro-CT allows high throughput assessment of lesion count and volume in pre-clinical murine models of CCM. This approach complements histology with improved accuracy and efficiency, and can be applied for lesion burden assessment in other brain diseases.

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Published In

J Neurosci Methods

DOI

EISSN

1872-678X

Publication Date

September 15, 2016

Volume

271

Start / End Page

14 / 24

Location

Netherlands

Related Subject Headings

  • rho-Associated Kinases
  • X-Ray Microtomography
  • Time Factors
  • Reproducibility of Results
  • Organ Size
  • Observer Variation
  • Neurology & Neurosurgery
  • Mice, Transgenic
  • Mice
  • Male
 

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Girard, R., Zeineddine, H. A., Orsbon, C., Tan, H., Moore, T., Hobson, N., … Awad, I. A. (2016). Micro-computed tomography in murine models of cerebral cavernous malformations as a paradigm for brain disease. J Neurosci Methods, 271, 14–24. https://doi.org/10.1016/j.jneumeth.2016.06.021
Girard, Romuald, Hussein A. Zeineddine, Courtney Orsbon, Huan Tan, Thomas Moore, Nick Hobson, Robert Shenkar, et al. “Micro-computed tomography in murine models of cerebral cavernous malformations as a paradigm for brain disease.J Neurosci Methods 271 (September 15, 2016): 14–24. https://doi.org/10.1016/j.jneumeth.2016.06.021.
Girard R, Zeineddine HA, Orsbon C, Tan H, Moore T, Hobson N, et al. Micro-computed tomography in murine models of cerebral cavernous malformations as a paradigm for brain disease. J Neurosci Methods. 2016 Sep 15;271:14–24.
Girard, Romuald, et al. “Micro-computed tomography in murine models of cerebral cavernous malformations as a paradigm for brain disease.J Neurosci Methods, vol. 271, Sept. 2016, pp. 14–24. Pubmed, doi:10.1016/j.jneumeth.2016.06.021.
Girard R, Zeineddine HA, Orsbon C, Tan H, Moore T, Hobson N, Shenkar R, Lightle R, Shi C, Fam MD, Cao Y, Shen L, Neander AI, Rorrer A, Gallione C, Tang AT, Kahn ML, Marchuk DA, Luo Z-X, Awad IA. Micro-computed tomography in murine models of cerebral cavernous malformations as a paradigm for brain disease. J Neurosci Methods. 2016 Sep 15;271:14–24.
Journal cover image

Published In

J Neurosci Methods

DOI

EISSN

1872-678X

Publication Date

September 15, 2016

Volume

271

Start / End Page

14 / 24

Location

Netherlands

Related Subject Headings

  • rho-Associated Kinases
  • X-Ray Microtomography
  • Time Factors
  • Reproducibility of Results
  • Organ Size
  • Observer Variation
  • Neurology & Neurosurgery
  • Mice, Transgenic
  • Mice
  • Male