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. (C) 2009 Elsevier B.V. All rights reserved.

Univ Wurzburg, Morphol Brain Res Unit, Psychiat Clin, D-97080 Wurzburg, Germany

Univ São Paulo, Sch Med, Dept Pathol, Aging Brain Project, BR-01246903 São Paulo, Brazil

Inst Israelita Ensino & Pesquisa Albert Einstein, BR-05651901 São Paulo, Brazil

Univ São Paulo, Sch Med, Dept Radiol, BR-05403001 São Paulo, Brazil

Universidade Federal de São Paulo, Dept Biosci, BR-11060001 Santos, Brazil

Fed Univ ABC, Ctr Math Computat & Cognit, Santo Andre, SP, Brazil

Univ São Paulo, Autopsy Serv São Paulo City, BR-05403000 São Paulo, Brazil

Univ São Paulo, Sch Med, Dept Pathol, BR-01246903 São Paulo, Brazil

Univ Rostock, Dept Psychiat & Psychotherapy, D-18147 Rostock, Germany

Univ Munich, D-81377 Munich, Germany

Universidade Federal de São Paulo, Dept Biosci, BR-11060001 Santos, Brazil

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