Within-Subject Template Estimation for Unbiased Longitudinal Image Analysis

Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.
NeuroImage (Impact Factor: 6.36). 03/2012; 61(4):1402-18. DOI: 10.1016/j.neuroimage.2012.02.084
Source: PubMed


Longitudinal image analysis has become increasingly important in clinical studies of normal aging and neurodegenerative disorders. Furthermore, there is a growing appreciation of the potential utility of longitudinally acquired structural images and reliable image processing to evaluate disease modifying therapies. Challenges have been related to the variability that is inherent in the available cross-sectional processing tools, to the introduction of bias in longitudinal processing and to potential over-regularization. In this paper we introduce a novel longitudinal image processing framework, based on unbiased, robust, within-subject template creation, for automatic surface reconstruction and segmentation of brain MRI of arbitrarily many time points. We demonstrate that it is essential to treat all input images exactly the same as removing only interpolation asymmetries is not sufficient to remove processing bias. We successfully reduce variability and avoid over-regularization by initializing the processing in each time point with common information from the subject template. The presented results show a significant increase in precision and discrimination power while preserving the ability to detect large anatomical deviations; as such they hold great potential in clinical applications, e.g. allowing for smaller sample sizes or shorter trials to establish disease specific biomarkers or to quantify drug effects.

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Available from: Nick Schmansky, Jan 06, 2014
    • "Anatomic segmentation and cortical thickness measurements were performed using FreeSurfer's longitudinal processing stream (v5.3; Desikan-Killiany atlas for surface parcellation and probabilistic atlas for subcortical segmentation) (Reuter et al., 2012). In order to ensure accuracy, FreeSurfer's output was reviewed, manually corrected and rerun as needed by an experienced MRI postprocessor. "
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    ABSTRACT: Background Fatigue is a common and disabling symptom of multiple sclerosis (MS) patients. Structural changes in several brain areas have been reported to correlate with fatigue in MS patients but none consistently. Objective To study the association between global and regional measures of brain atrophy and fatigue in patients with early relapsing MS. Methods Clinically isolated syndrome and relapsing MS patients within 12 months of clinical onset were enrolled in a neuroprotection trial of riluzole versus placebo with up to 36 months of follow-up. MRI metrics included brain volumes measured by SIENAX normalized measurements [normalized brain parenchymal volume (nBPV), normalized normal-appearing white and gray matter volume (nNAWMV and nGMV)] and T2 lesion volume (T2LV). Cortical thickness, thalamic volume and cerebellar cortical volume were measured using Freesurfer's longitudinal pipeline (v5.3) and a lesion inpainting approach. Fatigue was evaluated using the Modified Fatigue Impact Scale (MFIS). Mixed model regression measured time trends and associations between imaging and fatigue severity, adjusting for age and sex. Results Forty-three patients (mean age 36 years; 31 females) were enrolled within 7.5±4.9 months of symptom onset. Baseline and change over baseline in lesion volumes, grey matter, white matter, basal ganglia and total parenchymal volumes were not associated with change in MFIS score over time. Lower thalamic volume at baseline predicted increasing physical subscale of MFIS score during the study (p=0.017). There was a trend toward baseline thalamic volume and cerebellar cortical volume predicting subsequent change in total MFIS score (p=0.055 and 0.082 respectively). On-study change in thalamic or cerebellar cortical volume was not associated with on-study change in MFIS score. Conclusion Global measures of tissue loss are not strongly associated with fatigue in patients with early MS. However, thalamic and cerebellar cortical atrophy may be predictive of subsequent changes in fatigue in these patients.
    No preview · Article · Jan 2016 · Multiple Sclerosis and Related Disorders
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    • "Image processing. Cortical reconstruction was performed using the longitudinal stream of FreeSurfer version 5.3 [36], which creates a within-unbiased subject template space and average image from both time points using robust, inverse consistent registration [37]. Cortical thickness values were automatically quantified within FreeSurfer on a vertex-by-vertex basis by computing the average shortest distance between the white matter boundary and the pial sur- face [38]. "
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    ABSTRACT: Limited attention has been directed toward the influence of non-abusive parenting behaviour on brain structure in adolescents. It has been suggested that environmental influences during this period are likely to impact the way that the brain develops over time. The aim of this study was to investigate the association between aggressive and positive parenting behaviors on brain development from early to late adolescence, and in turn, psychological and academic functioning during late adolescence, using a multi-wave longitudinal design. Three hundred and sixty seven magnetic resonance imaging (MRI) scans were obtained over three time points from 166 adolescents (11-20 years). At the first time point, observed measures of maternal aggressive and positive behaviors were obtained. At the final time point, measures of psychological and academic functioning were obtained. Results indicated that a higher frequency of maternal aggressive behavior was associated with alterations in the development of right superior frontal and lateral parietal cortical thickness, and of nucleus accumbens volume, in males. Development of the superior frontal cortex in males mediated the relationship between maternal aggressive behaviour and measures of late adolescent functioning. We suggest that our results support an association between negative parenting and adolescent functioning, which may be mediated by immature or delayed brain maturation.
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    • "For the longitudinal processing , an unbiased within-subject template (Reuter and Fischl, 2011) was created using robust, inverse consistent registration between the available time points for each individual (Reuter et al., 2010). Several preprocessing steps, such as skull stripping, Talairach transformations, atlas registration, as well as spherical surface maps and parcellations were initialized with common information from the within-subject template, significantly increasing reliability and statistical power (Reuter et al., 2012). Cortical thickness was smoothed with a 20 mm full-width at half-height Gaussian kernel. "
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