Volume Estimation of the Thalamus Using Freesurfer and Stereology: Consistency between Methods

Department of Neurology, University of Münster, Münster, Germany.
Neuroinformatics (Impact Factor: 2.83). 04/2012; 10(4):341-50. DOI: 10.1007/s12021-012-9147-0
Source: PubMed


Freely available automated MR image analysis techniques are being increasingly used to investigate neuroanatomical abnormalities in patients with neurological disorders. It is important to assess the specificity and validity of automated measurements of structure volumes with respect to reliable manual methods that rely on human anatomical expertise. The thalamus is widely investigated in many neurological and neuropsychiatric disorders using MRI, but thalamic volumes are notoriously difficult to quantify given the poor between-tissue contrast at the thalamic gray-white matter interface. In the present study we investigated the reliability of automatically determined thalamic volume measurements obtained using FreeSurfer software with respect to a manual stereological technique on 3D T1-weighted MR images obtained from a 3 T MR system. Further to demonstrating impressive consistency between stereological and FreeSurfer volume estimates of the thalamus in healthy subjects and neurological patients, we demonstrate that the extent of agreeability between stereology and FreeSurfer is equal to the agreeability between two human anatomists estimating thalamic volume using stereological methods. Using patients with juvenile myoclonic epilepsy as a model for thalamic atrophy, we also show that both automated and manual methods provide very similar ratios of thalamic volume loss in patients. This work promotes the use of FreeSurfer for reliable estimation of global volume in healthy and diseased thalami.

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Available from: Simon S Keller
    • "Morey et al. (2009) and Pardoe et al. (2009) found that FreeSurfer was better than FIRST in segmenting the hippocampus while results between the two methods were more equal in the amygdala . With regards to the basal ganglia and thalamus, there has been one validation study which found very high agreement between FreeSurfer and manual tracing in the thalamus of an adult cohort (ICCs >0.9, both hemispheres) (Keller et al. 2012). In our current pediatric study, the ICCs obtained for FreeSurfer in the thalamus were much lower than the adult study (left: 0.70, right: 0.74). "
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    ABSTRACT: Volumetric and morphometric neuroimaging studies of the basal ganglia and thalamus in pediatric populations have utilized existing automated segmentation tools including FIRST (Functional Magnetic Resonance Imaging of the Brain's Integrated Registration and Segmentation Tool) and FreeSurfer. These segmentation packages, however, are mostly based on adult training data. Given that there are marked differences between the pediatric and adult brain, it is likely an age-specific segmentation technique will produce more accurate segmentation results. In this study, we describe a new automated segmentation technique for analysis of 7-year-old basal ganglia and thalamus, called Pediatric Subcortical Segmentation Technique (PSST). PSST consists of a probabilistic 7-year-old subcortical gray matter atlas (accumbens, caudate, pallidum, putamen and thalamus) combined with a customized segmentation pipeline using existing tools: ANTs (Advanced Normalization Tools) and SPM (Statistical Parametric Mapping). The segmentation accuracy of PSST in 7-year-old data was compared against FIRST and FreeSurfer, relative to manual segmentation as the ground truth, utilizing spatial overlap (Dice's coefficient), volume correlation (intraclass correlation coefficient, ICC) and limits of agreement (Bland-Altman plots). PSST achieved spatial overlap scores ≥90 % and ICC scores ≥0.77 when compared with manual segmentation, for all structures except the accumbens. Compared with FIRST and FreeSurfer, PSST showed higher spatial overlap (p FDR < 0.05) and ICC scores, with less volumetric bias according to Bland-Altman plots. PSST is a customized segmentation pipeline with an age-specific atlas that accurately segments typical and atypical basal ganglia and thalami at age 7 years, and has the potential to be applied to other pediatric datasets.
    No preview · Article · Sep 2015 · Neuroinformatics
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    • "First, CA2 and CA3 were sampled together using the automated morphometric analysis, and therefore a direct comparison with CA2 alone is not permitted. We were aware of the lack of differentiation between CA2–3 at the onset of this study, and we chose to employ routines incorporated into FreeSurfer software to estimate hippocampal subfield volume given the software's free availability , fully automated image processing pipelines, and independently determined consistency between FreeSurfer automatically determined volumes and " gold standard " manually determined volumes of hippocampal (Dewey et al., 2010; Morey et al., 2009; Pardoe et al., 2009) and extrahippocampal (Dewey et al., 2010; Keller et al., 2012a) structures . More recent techniques have offered the possibility of automatically differentiating CA2 and CA3 (Bonnici et al., 2012). "
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    ABSTRACT: A particularly popular automated magnetic resonance imaging (MRI) hippocampal subfield mapping technique is the one described by Van Leemput et al. (2009: Hippocampus 19:549–557) that is currently distributed with FreeSurfer software. This method assesses the probabilistic locations of subfields based on a priori knowledge of subfield topology determined from high-field MRI. Many studies have applied this technique to conventionally acquired T1-weighted MRI data. In the present study, we investigated the relationship between this technique applied to conventional T1-weighted MRI data acquired at 3 T and postsurgical hippocampal histology in patients with medically intractable mesial temporal lobe epilepsy (mTLE) and hippocampal sclerosis (HS). Patients with mTLE (n = 82) exhibited significant volume loss of ipsilateral CA1, CA2-3, CA4-dentate gyrus (DG), subiculum, and fimbria relative to controls (n = 81). Histopathological analysis indicated that the most significant neuronal loss was observed in CA1, then CA4 and CA3, and more subtle neuronal loss in CA2, consistent with classical HS. Neuronal density of CA1 significantly correlated with MRI-determined volume of CA1, and increasingly so with CA2-3 and CA4–DG. Patients with increased HS based on histopathology had greater volume loss of the ipsilateral hippocampal regions on MRI. We conclude by suggesting that whilst time efficient and fully reproducible when applied to conventional single acquisition sequences, the use of the automated subfield technique described here may necessitate the application to multiacquisition high-resolution MR sequences for accurate delineation of hippocampal subfields. Hum Brain Mapp, 2014. © 2014 Wiley Periodicals, Inc.
    Full-text · Article · Sep 2014 · Human Brain Mapping
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    • "Volumes of bilateral thalami were generated according to the standard FreeSurfer segmentation and parcellation procedures, relying upon variations in voxel signal intensities, probabilistic atlas location, and local spatial relationships between the structures (Fischl et al., 2002). Previous research provided strong evidence for the reliability of thalamus volume estimation using FreeSurfer (Keller et al., 2012). See Supplemental Materials Fig. S1 for Freesurfer subcortical segmentation of the thalamus for two extreme examples from this study. "
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    ABSTRACT: The GABRB1 gene encodes the beta 1 subunit of gamma-aminobutyric acid A receptor (GABA A receptor), which is responsible for mediating inhibitory neurotransmission in the thalamus. Potential relationships between the GABRB1 gene, thalamus volume, and intelligence have been suggested by previous clinical studies, but have not been directly examined among nonclinical samples. The current study collected structural MRI, genetic, and behavioral data in 316 healthy Chinese adults (including 187 females and 129 males), and examined associations between GABRB1 variants, thalamus volume, and intelligence (measured by the Wechsler Adult Intelligence Scale Revised). After controlling for intracranial volume, sex, and age, GABRB1 genetic polymorphism at the SNP rs7435958 had the strongest association with thalamus volume (p=0.002 and 0.00008 for left and right thalamus volumes, respectively), with GG homozygotes having smaller bilateral thalamus volumes than the other genotypes. Furthermore, there were positive correlations between bilateral thalamus volumes and intelligence, especially for GABRB1 rs7435958 GG female homozygotes (r's=0.31 and 0.29, p<0.01, for the correlations of intelligence with left and right thalamus volumes, respectively). This study provides the first evidence for the involvement of the GABRB1 gene in thalamus structure and their interactive effects on intelligence. Future studies of the thalamus-intelligence associations should consider genetic factors as potential moderators.
    Full-text · Article · Sep 2014 · NeuroImage
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