Confocal Raman microspectroscopy imaging reveals structural protein reorganization in human intracranial aneurysm tissue

Intracranial aneurysms are pathological dilatations of cerebral arteries that may rupture and cause subarachnoid hemorrhage. Extracellular matrix remodeling, particularly of Collagen and Elastin, is central to aneurysm progression, but detailed molecular insights remain limited. In this proof-of-concept study, we applied confocal Raman microspectroscopy to matched aneurysmal and healthy basilar artery tissue from the same patient, complemented by an additional control from a second patient. Raman imaging was performed on cryo-sectioned samples using a 532 nm excitation laser. Data were processed using a non-negative matrix factorization-based component analysis with reference spectra of Collagen Types I, III, IV and Elastin. Spectral differences were analyzed by Amide I peak deconvolution and Principal Component Analysis. Aneurysmal tissue showed reduced Collagen and Elastin signals and altered spatial organization. Amide I deconvolution indicated a shift from β-sheet-dominated to α-helical and disordered protein structures. Principal Component Analysis revealed consistent spectral markers separating healthy from diseased tissue. These results demonstrate the potential of confocal Raman microspectroscopy to detect extracellular matrix remodeling and protein conformational changes in intracranial aneurysms, supporting the development of spectroscopic markers for aneurysm wall integrity and rupture risk.