Histopathologische Korrelate von erweiterten perivaskulären Räumen in der zerebralen Amyloidangiopathie.
Zusammenfassung der Projektergebnisse
Dr. Valentina Perosa’s Walter Benjamin fellowship focused on the histopathological correlates of MRI-visible perivascular spaces (PVS) in cerebral amyloid angiopathy (CAA). This research aimed to investigate how PVS dilation correlates with vascular amyloid-β (Aβ) deposition in CAA. The project was conducted using cutting-edge neuroimaging techniques, including high and ultrahigh resolution 3T and 7T ex vivo MRI, combined with deep learning-based histopathological analyses and serial sectioning. Dr. Perosa applied artificial intelligence (AI) methods to analyze histopathological markers of neurodegenerative and vascular disease such as Aβ-plaques, CAA, iron deposition, and blood-brain barrier leakage, which allowed for a more objective and precise assessment of CAA- and AD-related pathology. Key findings of the project revealed a strong correlation between PVS dilation and vascular Aβ accumulation in the overlying cortex, supporting the hypothesis that enlarged PVS reflect impaired perivascular clearance. The results also established the correlation between burden of MRI- visible PVS and EPVS in histopathology. The project further demonstrated the utility of AI-assisted pathology in enhancing the reproducibility and scalability of neuropathological analyses, for example in analyzing reactive astrocytosis and cortical superficial siderosis (cSS), which were found to be linked to chronic inflammatory responses in CAA. The fellowship provided Dr. Perosa with an opportunity to master new methodologies and establish her expertise in ex vivo MRI and histopathological correlates. The integration of AI tools allowed for more efficient data analysis, contributing significantly to the understanding of CAA pathology. This work, published in high-impact journals, established Dr. Perosa as an independent investigator at Massachusetts General Hospital and Harvard Medical School, setting a foundation for her future research career.
Projektbezogene Publikationen (Auswahl)
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Deep learning assisted quantitative assessment of histopathological markers of Alzheimer’s disease and cerebral amyloid angiopathy. Acta Neuropathologica Communications, 9(1).
Perosa, Valentina; Scherlek, Ashley A.; Kozberg, Mariel G.; Smith, Lindsey; Westerling-Bui, Thomas; Auger, Corinne A.; Vasylechko, Serge; Greenberg, Steven M. & van Veluw, Susanne J.
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Perivascular space dilation is associated with vascular amyloid-β accumulation in the overlying cortex. Acta Neuropathologica, 143(3), 331-348.
Perosa, Valentina; Oltmer, Jan; Munting, Leon P.; Freeze, Whitney M.; Auger, Corinne A.; Scherlek, Ashley A.; van der Kouwe, Andre J.; Iglesias, Juan Eugenio; Atzeni, Alessia; Bacskai, Brian J.; Viswanathan, Anand; Frosch, Matthew P.; Greenberg, Steven M. & van, Veluw Susanne J.
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The Perivascular Space Race. Neurology, 98(3), 95-96.
van Veluw, Susanne J. & Perosa, Valentina
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Cortical superficial siderosis is associated with reactive astrogliosis in cerebral amyloid angiopathy. Journal of Neuroinflammation, 20(1).
Auger, Corinne A.; Perosa, Valentina; Greenberg, Steven M.; van Veluw, Susanne J. & Kozberg, Mariel G.
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Histopathological Correlates of Lobar Microbleeds in False‐Positive Cerebral Amyloid Angiopathy Cases. Annals of Neurology, 94(5), 856-870.
Perosa, Valentina; Auger, Corinne A.; Zanon, Zotin Maria Clara; Oltmer, Jan; Frosch, Matthew P.; Viswanathan, Anand; Greenberg, Steven M. & van Veluw, Susanne J.
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Enlarged perivascular spaces in the basal ganglia are associated with arteries not veins. Journal of Cerebral Blood Flow & Metabolism, 44(11), 1362-1377.
Oltmer, Jan; Mattern, Hendrik; Beck, Julia; Yakupov, Renat; Greenberg, Steven M.; Zwanenburg, Jaco JM; Arts, Tine; Düzel, Emrah; van Veluw, Susanne J.; Schreiber, Stefanie & Perosa, Valentina
