Advanced magnetic resonance imaging of cerebral cavernous malformations: part II. Imaging of lesions in murine models.
OBJECTIVE
We sought to assess the appearance of cerebral cavernous malformations (CCM) on magnetic resonance imaging (MRI) scans in murine Ccm1 and Ccm2 gene knockout models and to develop a technique of lesion localization for correlative pathobiological studies


METHODS
Brains from 18 CCM mutant mice (Ccm1 Trp53 and Ccm2 Trp53) and 28 control animals were imaged by gradient recalled echo (T2*)-weighted MRI scans at 4.7- and 14.1-T in vivo and/or ex vivo. After MRI scanning, the brains were removed and stained with hematoxylin and eosin, and cells were laser-microdissected for molecular biological studies.


RESULTS
T2*-weighted MRI scans of brains in vivo and ex vivo revealed lesions similar to human CCMs in mutant mice, but not in control animals. Stereotactic localization and hematoxylin and eosin staining of correlative tissue sections confirmed lesion histology and revealed other areas of dilated capillaries in the same brains. Some lesions were identified by MRI scans at 14.1-T, but not at 4.7-T. Polymerase chain reaction amplification from Ccm1 and beta-actin genes was demonstrated from nucleic acids extracted from laser microdissected lesional and perilesional cells.


CONCLUSIONS
The high-field MRI techniques offer new opportunities for further investigation of disease pathogenesis in vivo, and the localization, staging, and histobiological dissection of lesions, including the presumed earliest stages of CCM lesion development.
Shenkar
Robert
R
Division of Neurosurgery, Evanston Northwestern Healthcare, Evanston, Illinois 60201, USA. rshenkar@enh.org
Venkatasubramanian
Palamadai N
PN
Wyrwicz
Alice M
AM
Zhao
Jin-cheng
JC
Shi
Changbin
C
Akers
Amy
A
Marchuk
Douglas A
DA
Awad
Issam A
IA
D000818:Animals; D004195:Disease Models, Animal; D004587:Electrophoresis, Agar Gel; D005260:Female; D018390:Gene Targeting; D020786:Hemangioma, Cavernous, Central Nervous System / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D000075927:KRIT1 Protein; D007834:Lasers; D008279:Magnetic Resonance Imaging / Q000295:instrumentation / Q000379:methods*; D008297:Male; D008488:Medical Illustration; D051379:Mice; D008817:Mice, Mutant Strains; D042282:Microdissection; D008840:Microfilament Proteins / Q000235:genetics; D008869:Microtubule-Associated Proteins / Q000235:genetics; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012680:Sensitivity and Specificity; D013238:Stereotaxic Techniques; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D000075927:KRIT1 Protein; C491535:Krit1 protein, mouse; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C480498:osmosensing scaffold for MEKK3 protein, mouse