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      Predicting Fazekas scores from automatic segmentations of white matter signal abnormalities

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          Abstract

          Different measurements of white matter signal abnormalities (WMSA) are often used across studies, which hinders combination of WMSA data from different cohorts. We investigated associations between three commonly used measurements of WMSA, aiming to further understand the association between them and their potential interchangeability: the Fazekas scale, the lesion segmentation tool (LST), and FreeSurfer. We also aimed at proposing cut-off values for estimating low and high Fazekas scale WMSA burden from LST and FreeSurfer WMSA, to facilitate clinical use and interpretation of LST and FreeSurfer WMSA data. A population-based cohort of 709 individuals (all of them 70 years old, 52% female) was investigated. We found a strong association between LST and FreeSurfer WMSA, and an association of Fazekas scores with both LST and FreeSurfer WMSA. The proposed cut-off values were 0.00496 for LST and 0.00321 for FreeSurfer (Total Intracranial volumes (TIV)-corrected values). This study provides data on the association between Fazekas scores, hyperintense WMSA, and hypointense WMSA in a large population-based cohort. The proposed cut-off values for translating LST and FreeSurfer WMSA estimations to low and high Fazekas scale WMSA burden may facilitate the combination of WMSA measurements from different cohorts that used either a FLAIR or a T1-weigthed sequence.

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          Most cited references24

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          The effects of intracranial volume adjustment approaches on multiple regional MRI volumes in healthy aging and Alzheimer's disease

          In neurodegeneration research, normalization of regional volumes by intracranial volume (ICV) is important to estimate the extent of disease-driven atrophy. There is little agreement as to whether raw volumes, volume-to-ICV fractions or regional volumes from which the ICV factor has been regressed out should be used for volumetric brain imaging studies. Using multiple regional cortical and subcortical volumetric measures generated by Freesurfer (51 in total), the main aim of this study was to elucidate the implications of these adjustment approaches. Magnetic resonance imaging (MRI) data were analyzed from two large cohorts, the population-based PIVUS cohort (N = 406, all subjects age 75) and the Alzheimer disease Neuroimaging Initiative (ADNI) cohort (N = 724). Further, we studied whether the chosen ICV normalization approach influenced the relationship between hippocampus and cognition in the three diagnostic groups of the ADNI cohort (Alzheimer's disease, mild cognitive impairment, and healthy individuals). The ability of raw vs. adjusted hippocampal volumes to predict diagnostic status was also assessed. In both cohorts raw volumes correlate positively with ICV, but do not scale directly proportionally with it. The correlation direction is reversed for all volume-to-ICV fractions, except the lateral and third ventricles. Most gray matter fractions are larger in females, while lateral ventricle fractions are greater in males. Residual correction effectively eliminated the correlation between the regional volumes and ICV and removed gender differences. The association between hippocampal volumes and cognition was not altered by ICV normalization. Comparing prediction of diagnostic status using the different approaches, small but significant differences were found. The choice of normalization approach should be carefully considered when designing a volumetric brain imaging study.
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            Invited article: an MRI-based approach to the diagnosis of white matter disorders.

            There are many different white matter disorders, both inherited and acquired, and consequently the diagnostic process is difficult. Establishing a specific diagnosis is often delayed at great emotional and financial costs. The pattern of brain structures involved, as visualized by MRI, has proven to often have a high diagnostic specificity. We developed a comprehensive practical algorithm that relies mainly on the characteristics of brain MRI. The initial decision point defines a hypomyelination pattern, in which the cerebral white matter is hyperintense (normal), isointense, or slightly hypointense relative to the cortex on T1-weighted images, vs other pathologies with more prominent hypointensity of the cerebral white matter on T1-weighted images. In all types of pathology, the affected white matter is hyperintense on T2-weighted images, but, as a rule, the T2 hyperintensity is less marked in hypomyelination than in other pathologies. Some hypomyelinating disorders are typically associated with peripheral nerve involvement, while others are not. Lesions in patients with pathologies other than hypomyelination can be either confluent or isolated and multifocal. Among the diseases with confluent lesions, the distribution of the abnormalities is of high diagnostic value. Additional MRI features, such as white matter rarefaction, the presence of cysts, contrast enhancement, and the presence of calcifications, further narrow the diagnostic possibilities. Application of a systematic decision tree in MRI of white matter disorders facilitates the diagnosis of specific etiologic entities.
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              Neuropathologic correlates of white matter hyperintensities.

              White matter hyperintensities (WMH) are commonly seen on neuroimaging scans, but their underlying histopathologic substrate is unclear. The aim of this work was to establish the pathologic correlates of WMH in unselected elderly cases using two study designs. To avoid potential bias from comparisons of different anatomic regions, study 1 compared, region-by-region, the severity of WMH determined in vivo with measures of each of the major white matter (WM) components. Study 2 compared the histopathology of WMH with normal WM. Study 1: The periventricular and deep WM regions of three lobes in 23 brains with in vivo MRI scans were investigated using histologic and immunohistochemical stains. The severity of each pathologic measure was correlated with WMH severity determined using the Scheltens scale. Study 2: Lesioned and nonlesioned areas identified by postmortem MRI in the frontal WM of 20 brains were examined histologically and immunohistochemically. No single pathologic variable correlated with the severity of WMH; however, a multiple stepwise regression analysis revealed that vascular integrity predicted total Scheltens score (beta = -0.53, p = 0.01). Comparison of lesioned and nonlesioned areas demonstrated that vascular integrity was reduced in WMH [t(18) = 3.79, p = 0.001]. Blood-brain barrier integrity was also found to be reduced in WMH [t(5) = -5.31, p = 0.003]. White matter hyperintensities (WMH) involve a loss of vascular integrity, confirming the vascular origin of these lesions. This damage to the vasculature may in turn impair blood-brain barrier integrity and be one mechanism by which WMH evolve.
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                Author and article information

                Journal
                Aging (Albany NY)
                Aging (Albany NY)
                Aging
                Aging (Albany NY)
                Impact Journals
                1945-4589
                15 January 2020
                12 January 2020
                : 12
                : 1
                : 894-901
                Affiliations
                [1 ]Division of Clinical Geriatrics, Centre for Alzheimer Research, Department of Neurobiology, Care Sciences, and Society, Karolinska Institutet (KI), Stockholm, Sweden
                [2 ]Department of Clinical Neuroscience, KI, Stockholm, Sweden
                [3 ]Department of Radiology, Karolinska University Hospital, Stockholm, Sweden
                [4 ]Centre for Ageing and Health at The University of Gothenburg, Gothenburg, Sweden
                [5 ]Neuropsychiatric Epidemiology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at The University of Gothenburg, Gothenburg, Sweden
                [6 ]Department of Neuroimaging, Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK
                [7 ]Region Västra Götaland, Sahlgrenska University Hospital, Department of Neuropsychiatry, Gothenburg, Sweden
                [8 ]Region Västra Götaland, Sahlgrenska University Hospital, Psychosis Department, Gothenburg, Sweden
                Author notes
                [*]

                Co-senior authors

                Correspondence to: Nira Cedres; email: nira.cedres@ki.se
                Article
                102662 102662
                10.18632/aging.102662
                6977667
                31927535
                4fa6d704-d6a7-44ed-8aca-bf7bc15888d1
                Copyright © 2020 Cedres et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 16 September 2019
                : 24 December 2019
                Categories
                Research Paper

                Cell biology
                white matter,visual rating,hyperintensities,hypointensities,fazekas scale
                Cell biology
                white matter, visual rating, hyperintensities, hypointensities, fazekas scale

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