Lesion Explorer: A comprehensive segmentation and parcellation package to obtain regional volumetrics for subcortical hyperintensities and intracranial tissue

LC Campbell Cognitive Neurology Research Unit, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
NeuroImage (Impact Factor: 6.36). 01/2011; 54(2):963-73. DOI: 10.1016/j.neuroimage.2010.09.013
Source: PubMed


Subcortical hyperintensities (SH) are a commonly observed phenomenon on MRI of the aging brain (Kertesz et al., 1988). Conflicting behavioral, cognitive and pathological associations reported in the literature underline the need to develop an intracranial volumetric analysis technique to elucidate pathophysiological origins of SH in Alzheimer's disease (AD), vascular cognitive impairment (VCI) and normal aging (De Leeuw et al., 2001; Mayer and Kier, 1991; Pantoni and Garcia, 1997; Sachdev et al., 2008). The challenge is to develop processing tools that effectively and reliably quantify subcortical small vessel disease in the context of brain tissue compartments. Segmentation and brain region parcellation should account for SH subtypes which are often classified as: periventricular (pvSH) and deep white (dwSH), incidental white matter disease or lacunar infarcts and Virchow-Robin spaces. Lesion Explorer (LE) was developed as the final component of a comprehensive volumetric segmentation and parcellation image processing stream built upon previously published methods (Dade et al., 2004; Kovacevic et al., 2002). Inter-rater and inter-method reliability was accomplished both globally and regionally. Volumetric analysis showed high inter-rater reliability both globally (ICC=.99) and regionally (ICC=.98). Pixel-wise spatial congruence was also high (SI=.97). Whole brain pvSH volumes yielded high inter-rater reliability (ICC=.99). Volumetric analysis against an alternative kNN segmentation revealed high inter-method reliability (ICC=.97). Comparison with visual rating scales showed high significant correlations (ARWMC: r=.86; CHIPS: r=.87). The pipeline yields a comprehensive and reliable individualized volumetric profile for subcortical vasculopathy that includes regionalized (26 brain regions) measures for: GM, WM, sCSF, vCSF, lacunar and non-lacunar pvSH and dwSH.

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Available from: Joel Ramirez, Oct 09, 2015
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    • "is study demonstrates that WMH in periventricular and deep white matter are associated with decreased gray matter CBF and structural profiles in regions that are remote from the WMH lesions . The etiology of WMH remains a topic of intense research ( Thompson and Hakim , 2009 ; Debette and Markus , 2010 ; Gibson et al . , 2010 ; Uh et al . , 2010 ; Ramirez et al . , 2011 ; Makedonov et al . , 2013a ; van der Holst et al . , 2013 ; Wardlaw et al . , 2013 ) with one prevailing view that the lesions are caused by underlying vascular insufficiency ( Brickman et al . , 2009 ; Makedonov et al . , 2013b ; Wardlaw et al . , 2013 ) . A number of studies show that hypertension , diabetes , obesity and smoking are"
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    ABSTRACT: Cerebral White Matter Hyperintensities (WMH) are associated with vascular risk factors and age-related cognitive decline. WMH have primarily been associated with global white matter and gray matter (GM) changes and less is known about regional effects in GM. The purpose of this study was to test for an association between WMH and two GM imaging measures: cerebral blood flow (CBF) and voxel-based morphometry (VBM). Twenty-six elderly adults with mild to severe WMH participated in this cross-sectional 3 Tesla magnetic resonance imaging (MRI) study. MRI measures of GM CBF and VBM were derived from arterial spin labeling (ASL) and T1-weighted images, respectively. Fluid-attenuated inversion recovery (FLAIR) images were used to quantify the WMH lesion burden (mL). GM CBF and VBM data were used as dependent variables. WMH lesion burden, age and sex were used in a regression model. Visual rating of WMH with the Fazekas method was used to compare the WMH lesion volume regression approach. WMH volume was normally distributed for this group (mean volume of 22.7 mL, range: 2.2-70.6 mL). CBF analysis revealed negative associations between WMH volume and CBF in the left anterior putamen, subcallosal, accumbens, anterior caudate, orbital frontal, anterior insula, and frontal pole (corrected p < 0.05). VBM analysis revealed negative associations between WMH and GM volume in lingual gyrus, intracalcarine, and bilateral hippocampus (corrected p < 0.05). The visual rating scale corroborated the regression findings (corrected p < 0.05). WMH lesion volume was associated with intra-group GM CBF and structural differences in this cohort of WMH adults with mild to severe lesion burden.
    Frontiers in Aging Neuroscience 07/2015; 7:131. DOI:10.3389/fnagi.2015.00131 · 4.00 Impact Factor
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    • "MRI processing MRI processing was performed at the brain imaging laboratory of the L.C. Campbell Cognitive Neurology Research Unit at the Sunnybrook Research Institute, University of Toronto, Canada. Segmentation of SH and lacunes was accomplished using a modified version of Lesion Explorer (LE) [6] "
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    ABSTRACT: Background: Subcortical hyperintensities within the cholinergic fiber projections (chSH) on MRI are believed to reflect cerebral small vessel disease (SVD) which may adversely impact cognition. Additionally, hippocampal atrophy represents a commonly used biomarker to support the diagnosis of Alzheimer's disease (AD). Objective: To examine potential differences in neuropsychological test performance between AD patients (n = 234) with high and low chSH volumes and whether these differences corresponded to hippocampal atrophy. Methods: A modified version of Lesion Explorer was used to volumetrically quantify chSH severity. The Sunnybrook Hippocampal Volumetry Tool was applied to obtain hippocampal volumes. Composite z-scores to assess executive, memory, and visuospatial functioning were generated from standardized neuropsychological test performance scores. Results: Inter-method technique validation demonstrated a high degree of correspondence with the Cholinergic Pathways Hyperintensities Scale (n = 40, ρ = 0.84, p < 0.001). After adjusting for brain atrophy, disease severity, global SH volumes, and demographic variables, multivariate analyses revealed a significant group difference, with the high chSH group demonstrating poorer memory function compared to the low chSH group (p = 0.03). A significant difference was found between low and high chSH groups in total (p < 0.05) and left (p < 0.01) hippocampal volume. Conclusion: These results suggest degradation of the cholinergic projections due to strategic SVD may independently contribute to memory dysfunction and hippocampal atrophy. Future studies examining subcortical vasculopathy in the cholinergic pathways may have implications on the development of therapeutic strategies for dementia and SVD.
    Journal of Alzheimer's disease: JAD 08/2014; 43(3). DOI:10.3233/JAD-140588 · 4.15 Impact Factor
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    • "using Analyze ver.10.0 b1 for Linux (Mayo Clinic Biomedical Imaging Resource, Rochester, MN) for visual rating and in-house software for segmentation analyses. Segmentation of lacunes and WMH was accomplished using Lesion Explorer [21], a highly reliable, previously published in-house software package, which employs a tri-feature (T1, T2, and PD) segmentation approach and an individualized semi-automatic regional parcellation procedure. As this software package was designed to reject VRS due to their relative cerebrospinal fluid (CSF) intensity on PD sequences, the modification to obtain VRS required a simple decrease in PD localized threshold weighting to 0 (while leaving the T2 and T1 thresholds the same). "
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    ABSTRACT: Background: Visible Virchow-Robin spaces (VRS) are commonly used markers for small vessel disease in aging and dementia. Objective: However, as previous reports were based on subjective visual ratings, the goal of this project was to validate and apply an MRI-based quantitative measure of VRS as a potential neuroimaging biomarker. Methods: A modified version of Lesion Explorer was applied to MRIs from Alzheimer's disease patients (AD: n = 203) and normal elderly controls (NC: n = 94). Inter-rater reliability, technique validity, group/gender differences, and correlations with other small vessel disease markers were examined (lacunes and white matter hyperintensities, WMH). Results: Inter-rater reliability and spatial congruence was excellent (ICC = 0.99, SI = 0.96), and VRS volumes were highly correlated with established rating scales (CS: ρ = 0.84, p < 0.001; BG: ρ = 0.75, p < 0.001). Compared to NC, AD had significantly greater volumes of WMH (p < 0.01), lacunes (p < 0.001), and VRS in the white matter (p < 0.01), but not in the basal ganglia (n.s.). Compared to women, demented and non-demented men had greater VRS in the white matter (p < 0.001), but not in the basal ganglia (n.s.). Additionally, VRS were correlated with lacunes and WMH, but only in AD (r = 0.3, p < 0.01). Conclusion: Compared to women, men may be more susceptible to greater volumes of VRS, particularly in the white matter. Results support the hypothesis that VRS in the white matter may be more related to AD-related vascular pathology compared to VRS found in the basal ganglia. Future work using this novel VRS segmentation tool will examine its potential utility as an imaging biomarker of vascular rather than parenchymal amyloid.
    Journal of Alzheimer's disease: JAD 08/2014; 43(2). DOI:10.3233/JAD-132528 · 4.15 Impact Factor
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