title: Improved detection of incipient vascular changes by a biotechnological platform combining post mortem MRI in situ with neuropathology.
abstract: The histopathological counterpart of white matter hyperintensities is a matter of debate. Methodological and ethical limitations have prevented this question to be elucidated. We want to introduce a protocol applying state-of-the-art methods in order to solve fundamental questions regarding the neuroimaging-neuropathological uncertainties comprising the most common white matter hyperintensities [WMHs] seen in aging. By this protocol, the correlation between signal features in in situ, post mortem MRI-derived methods, including DTI and MTR and quantitative and qualitative histopathology can be investigated. We are mainly interested in determining the precise neuroanatomical substrate of incipient WMHs. A major issue in this protocol is the exact co-registration of small lesion in a tridimensional coordinate system that compensates tissue deformations after histological processing. The protocol is based on four principles: post mortem MRI in situ performed in a short post mortem interval, minimal brain deformation during processing, thick serial histological sections and computer-assisted 3D reconstruction of the histological sections. This protocol will greatly facilitate a systematic study of the location, pathogenesis, clinical impact, prognosis and prevention of WMHs.
authors.affiliation: Aging Brain Project, Department of Pathology, University of Sao Paulo Medical School, Av. Dr. Arnaldo 455, sala 1353-01246903, Sao Paulo, SP, Brazil. leagrinberg@usp.br
authors.forename: Lea Tenenholz
authors.initials: LT
authors.lastname: Grinberg
authors.forename: Edson
authors.initials: E
authors.lastname: Amaro Junior
authors.forename: Alexandre Valotta
authors.initials: AV
authors.lastname: da Silva
authors.forename: Rafael Emidio
authors.initials: RE
authors.lastname: da Silva
authors.forename: João Ricardo
authors.initials: JR
authors.lastname: Sato
authors.forename: Denis Dionizio
authors.initials: DD
authors.lastname: dos Santos
authors.forename: Silmara
authors.initials: S
authors.lastname: de Paula Pacheco
authors.forename: Renata Eloah
authors.initials: RE
authors.lastname: de Lucena Ferretti
authors.forename: Renata Elaine
authors.initials: RE
authors.lastname: Paraizo Leite
authors.forename: Carlos Augusto
authors.initials: CA
authors.lastname: Pasqualucci
authors.forename: Stefan J
authors.initials: SJ
authors.lastname: Teipel
authors.forename: Wilhelm H
authors.initials: WH
authors.lastname: Flatz
authors.forename: Helmut
authors.initials: H
authors.lastname: Heinsen
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000473:pathology; D016880:Anisotropy; D001921:Brain / Q000473:pathology*; D002561:Cerebrovascular Disorders / Q000473:pathology*; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D006801:Humans; D021621:Imaging, Three-Dimensional; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000473:pathology*