Abstract
Cerebral aneurysms are abnormal focal dilatations of arterial vessel walls with pathological vessel structure alterations. Sudden rupture can lead to a subarachnoid hemorrhage, which is associated with a high mortality. Therefore, the origin of cerebral aneurysms as well as the progression to the point of rupture needs to be further investigated. Label-free multimodal multiphoton microscopy (MPM) was performed on resected human aneurysm domes and integrated three modalities: coherent anti-Stokes Raman scattering, endogenous two-photon fluorescence and second harmonic generation. We showed that MPM is a completely label-free and real-time powerful tool to detect pathognomonic histopathological changes in aneurysms, e.g. thickening and thinning of vessel walls, intimal hyperplasia, intra-wall haemorrhage, calcification as well as atherosclerotic changes. In particular, the loss or fragmentation of elastin as well as fibromatous wall remodelling appeared very distinct. Remarkably, cholesterol and lipid deposits were clearly visible in the multiphoton images. MPM provides morphological and biochemical information that are crucial for understanding the mechanisms of aneurysm formation and progression.
Highlights
Cerebral aneurysms are abnormal focal dilatations of arterial vessel walls with pathological vessel structure alterations
Additional imaging techniques on the microstructural level are needed to detect fine morphological and compositional changes that are crucial for understanding vessel wall remodelling, to uncover atherosclerotic changes and to provide the possibility to predict the risk of rupture
multiphoton microscopy (MPM) already assessed atherosclerotic plaque burden in different animal models such as p igs[13] and myocardial infarction-prone rabbits (WHHLMI)[25] as well as in human a ortas[26]. In accordance with these studies, we showed that MPM is able to detect lipid-laden foam cells and lipid droplets in human cerebral aneurysm domes
Summary
Cerebral aneurysms are abnormal focal dilatations of arterial vessel walls with pathological vessel structure alterations. Additional imaging techniques on the microstructural level are needed to detect fine morphological and compositional changes that are crucial for understanding vessel wall remodelling, to uncover atherosclerotic changes and to provide the possibility to predict the risk of rupture. Label-free multiphoton microscopy (MPM) including coherent anti-Stokes Raman scattering (CARS) microscopy in combination with endogenous two-photon fluorescence (TPEF) and second harmonic generation (SHG) could be helpful to fulfil this need. They visualize morphology and composition of different biological tissues and cells in a submicron resolution without photo-damage[9,10]. SHG visualizes highly ordered tissue structures, which are non-centrosymmetric like type I collagen fibers[18,19]
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