Objective: We hypothesized that structural details that have not been described previously would be revealed in cerebral cavernous malformations (CCM) through the use of high-field magnetic resonance and confocal microscopy. The structural details of CCMs excised from patients were sought by examination with high-field magnetic resonance imaging (MRI) and correlated with confocal microscopy of the same specimens. Novel features of CCM structure are outlined, including methodological limitations, venues for future research, and possible clinical implications.
Methods: CCM lesions excised from 4 patients were fixed in 2% paraformaldehyde and subjected to high-resolution MRI at 9.4 or 14.1-T by spin echo and gradient recalled echo methods. Histological validation of angioarchitecture was conducted on thick sections of CCM lesions using fluorescent probes to endothelium under confocal microscopy.
Results: Images of excised human CCM lesions were acquired with proton density-weighted, T1-weighted, T2-weighted spin echo, and T2*-weighted gradient recalled echo MRI. These images revealed large "bland" regions with thin-walled caverns and "honeycombed" regions with notable capillary proliferation and smaller caverns surrounding larger caverns. Proliferating capillaries and caverns of various sizes were also associated with the walls of apparent larger blood vessels in the lesions. Similar features were confirmed within thick sections of CCMs by confocal microscopy. MRI relaxation times in different regions of interest suggested the presence of different states of blood breakdown products in areas with apparent angiogenic proliferative activity.
Conclusion: High-field MRI techniques demonstrate novel features of CCM angioarchitecture, visible at near histological resolution, including regions with apparently different biological activity. These preliminary observations will motivate future research, correlating lesion biological and clinical activity with features of MRI at higher field strength.