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.
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.
Authors: Fritz-Georg Lehnhardt; Ulrich von Smekal; Benedikt Rückriem; Werner Stenzel; Michael Neveling; Wolf-Dieter Heiss; Andreas H Jacobs Journal: Arch Neurol Date: 2005-04
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Authors: H Tan; L Zhang; A G Mikati; R Girard; O Khanna; M D Fam; T Liu; Y Wang; R R Edelman; G Christoforidis; I A Awad Journal: AJNR Am J Neuroradiol Date: 2016-03-10 Impact factor: 3.825
Authors: Svetlana M Stamatovic; Nikola Sladojevic; Richard F Keep; Anuska V Andjelkovic Journal: Acta Neuropathol Date: 2015-09-18 Impact factor: 17.088
Authors: Giske Opheim; Anja van der Kolk; Karin Markenroth Bloch; Albert J Colon; Kathryn A Davis; Thomas R Henry; Jacobus F A Jansen; Stephen E Jones; Jullie W Pan; Karl Rössler; Joel M Stein; Maria C Strandberg; Siegfried Trattnig; Pierre-Francois Van de Moortele; Maria Isabel Vargas; Irene Wang; Fabrice Bartolomei; Neda Bernasconi; Andrea Bernasconi; Boris Bernhardt; Isabella Björkman-Burtscher; Mirco Cosottini; Sandhitsu R Das; Lucie Hertz-Pannier; Sara Inati; Michael T Jurkiewicz; Ali R Khan; Shuli Liang; Ruoyun Emily Ma; Srinivasan Mukundan; Heath Pardoe; Lars H Pinborg; Jonathan R Polimeni; Jean-Philippe Ranjeva; Esther Steijvers; Steven Stufflebeam; Tim J Veersema; Alexandre Vignaud; Natalie Voets; Serge Vulliemoz; Christopher J Wiggins; Rong Xue; Renzo Guerrini; Maxime Guye Journal: Neurology Date: 2020-12-22 Impact factor: 9.910