Researchers from Amsterdam UMC – location VUmc and Leiden University, have recently written an invited review on post-mortem MRI and histology studies in multiple sclerosis (MS), Alzheimer’s disease (AD), Parkinson’s disease (PD) and traumatic brain injury (TBI), and their relevance as radiological (bio)markers for the clinical (research) setting. The manuscript is published in Neuroscience Bulletin.
Post-mortem MRI and histology studies in neurologic disease: a translational approach
In this review, combined post-mortem brain magnetic resonance imaging (MRI) and histology studies are highlighted, illustrating the relevance of translational approaches to define novel MRI signatures of neuropathological lesions in neuroinflammatory and neurodegenerative disorders. Initial studies combining post-mortem MRI and histology have validated various MRI sequences, assessing their sensitivity and specificity as diagnostic biomarkers in neurologic disease. More recent studies have focused on defining new radiological (bio)markers and implementing them in the clinical (research) setting. By combining neurological and neuroanatomical expertise with radiological development and pathological validation, a cycle emerges that allows for the discovery of novel MRI biomarkers to be implemented in vivo. Examples of this cycle are presented for multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, and traumatic brain injury. Some applications have been shown to be successful, while others require further validation. In conclusion, there is much to explore with post-mortem MRI and histology studies, which can eventually be of high relevance for clinical practice.
We are proud to present the publication of our manuscript “Normal Aging Brain Collection Amsterdam (NABCA): A comprehensive collection of postmortem high-field imaging, neuropathological and morphometric datasets of non-neurological controls.” In open access journal Neuroimage: Clinical. We would like to thank everyone who has contributed to this publication.
Click on this link to go to the manuscript.
Well-characterized, high-quality brain tissue of non-neurological control subjects is a prerequisite to study the healthy aging brain, and can serve as a control for the study of neurological disorders. The Normal Aging Brain Collection Amsterdam (NABCA) provides a comprehensive collection of post-mortem (ultra-)high-field MRI (3Tesla and 7 Tesla) and neuropathological datasets of non-neurological controls. By providing MRI within the pipeline, NABCA uniquely stimulates translational neurosciences; from molecular and morphometric tissue studies to the clinical setting. We describe our pipeline, including a description of our on-call autopsy team, donor selection, in situ and ex vivo post-mortem MRI protocols, brain dissection and neuropathological diagnosis. A demographic, radiological and pathological overview of five selected cases on all these aspects is provided. Additionally, information is given on data management, data and tissue application procedures, including review by a scientific advisory board, and setting up a material transfer agreement before distribution of tissue. Finally, we focus on future prospects, which includes laying the foundation for a unique platform for neuroanatomical, histopathological and neuro-radiological education, of professionals, students and the general (lay) audience.
A collaborative effort from researchers at Leiden University and Amsterdam UMC, have led to the publication of a post-mortem MRI and histology manuscript, published in Neuroimage: Clinical.
“7T MRI allows detection of disturbed cortical lamination of the medial temporal lobe in patients with Alzheimer’s disease” (open access)
Using 7T T2*-weighted imaging, we scanned post-mortem hemispheres of Alzheimer patients and age-matched controls to describe the patterns of appearance of cortical lamination on T2*-weighted MRI in the medial temporal lobe and to assess the changes in Alzheimer patients versus controls. While controls showed a hypointense line of Baillarger in the majority of the cases, appearance of cortical lamination varied to a greater extent in the Alzheimer patients. Severely distorted cortical lamination was also observed in advanced stage Alzheimer patients and presented itself as a broad hypointense inhomogeneous band, covering a large part of the cortical width. Histology indicated that the changes in the appearance of visible cortical lamination were not only associated with myelin changes, but also with diffuse cortical iron alterations and depositions. Therefore, imaging cortical lamination alterations in Alzheimer patients using T2*-weighted MRI might provide new information on involved neuroanatomical structures in an advanced neurodegenerative stage.
Researchers from the department of Anatomy and Neurosciences, Amsterdam UMC – location VUmc have combined MRI and histology to determine the the micro-scale correlates of macro-scale network measures of segregation and integration in multiple sclerosis.
Abnormalities in segregative and integrative properties of brain networks have been observed in multiple sclerosis (MS) and are related to clinical functioning. This study aims to investigate the micro-scale correlates of macro-scale network measures of segregation and integration in MS.
Eight MS patients underwent post-mortem in situ whole-brain diffusion tensor (DT) imaging and subsequent brain dissection. Macro-scale structural network topology was derived from DT data using graph theory. Clustering coefficient and mean white matter (WM) fiber length were measures of nodal segregation and integration. Thirty-three tissue blocks were collected from five cortical brain regions. Using immunohistochemistry micro-scale tissue properties were evaluated, including, neuronal size, neuronal density, axonal density and total cell density. Nodal network properties and tissue properties were correlated.
A negative correlation between clustering coefficient and WM fiber length was found. Higher clustering coefficient was associated with smaller neuronal size and lower axonal density, and vice versa for fiber length. Higher whole-brain WM lesion load was associated with higher whole-brain clustering, shorter whole-brain fiber length, lower neuronal size and axonal density.
Structural network properties on MRI associate with neuronal size and axonal density, suggesting that macro-scale network measures may grasp cortical neuroaxonal degeneration in MS.
Colleagues from the department of Anatomy and Neurosciences, Amsterdam UMC – location VUmc, have recently published on post-translational modifications of alpha-synuclein (aSyn), in particular phosphorylation at Serine 129 (Ser129-p) and truncation of its C-terminus (CTT) in Parkinson’s disease (PD). Read the manuscript, with exceptional pictures, here: https://www.biorxiv.org/content/early/2018/11/14/470476
An international team led by Prof. Vincenzo Bonifati from the Erasmus MC Rotterdam, Department of Clinical Genetics, has discovered for the first time variants in a gene (termed LRP10) in patients with familial forms of Parkinson’s disease, Parkinson’s disease and dementia, and Dementia with Lewy bodies. The paper reporting this discovery will be published in The Lancet Neurology this week. ‘This discovery opens a novel window on the molecular mechanisms of these common neurodegenerative diseases, and might pave the way to the identification of novel biomarkers and novel disease-modifying therapies’, says Prof. Bonifati.