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

ABSTRACT 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.

Download full-text


Available from: Nick Schmansky, Jan 06, 2014
  • Source
    • "Analyses were performed to determine the association between regional cortical thickness and cognitive function. For the longitudinal analyses of cortical thinning, vertex-wise comparisons of per cent change of cortical thickness among the diagnostic groups were analysed using the longitudinal two-stage GLM in Freesurfer (Reuter et al., 2012). In the longitudinal analysis, the per cent change of cortical thickness was the dependent factor and the diagnostic group was the independent factor. "
    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND Mild cognitive impairment in Parkinson’s disease (PD-MCI) is associated with progression to dementia (PDD) in a majority of patients. Determining structural imaging biomarkers associated with prodromal PDD may allow for the earlier identification of those at risk, and allow for targeted disease modifying therapies METHODS 105 non-demented subjects with newly diagnosed idiopathic Parkinson’s disease (PD) and 37 healthy matched controls had serial 3T structural MRI scans with clinical and neuropsychological assessments at baseline which were repeated after18 months. The MDS Task Force criteria were used to classify the PD subjects into PD-MCI (n=39) and PD with no cognitive impairment (PD-NC) (n=66). Freesurfer image processing software was used to measure cortical thickness and subcortical volumes at baseline and follow-up. We compared regional percentage change of cortical thinning and subcortical atrophy over 18 months. RESULTS At baseline, PD-MCI cases demonstrated widespread cortical thinning relative to controls and atrophy of the nucleus accumbens compared to both controls and PD-NC. Regional cortical thickness at baseline was correlated with global cognition in the combined PD cohort. Over 18 months, PD-MCI demonstrated more severe cortical thinning in frontal and temporo-parietal cortices, including hippocampal atrophy, relative to PD-NC and healthy controls, while PD-NC showed more severe frontal cortical thinning compared to healthy controls. At baseline, PD-NC converters showed bilateral temporal cortex thinning relative to the PD-NC stable subjects. CONCLUSION Although loss of both cortical and subcortical volume occurs in non-demented PD, our longitudinal analyses revealed that PD-MCI shows more extensive atrophy and greater percentage of cortical thinning comparing to PD-NC. In particular, an extension of cortical thinning in the temporo-parietal regions in addition to frontal atrophy could be a biomarker in therapeutic studies of PD-MCI for progression towards dementia.
    Brain 06/2015; DOI:10.1093/brain/awv211 · 10.23 Impact Factor
  • Source
    • "This approach extracts reliable volume and thickness estimates by creating an unbiased within-subject template space and image from the three cross-sectionally processed time points (baseline and follow-ups) using a consistent robust inverse registration method (Reuter, Rosas, & Fischl, 2010). Processing steps such as Talairach transforms, atlas registration, and spherical surface maps and parcellations are initialized with common information from the within-subject template, increasing reliability and statistical power (Reuter et al., 2012). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Studies suggest marijuana impacts gray and white matter neural tissue development, however few prospective studies have determined the relationship between cortical thickness and cannabis use spanning adolescence to young adulthood. This study aimed to understand how heavy marijuana use influences cortical thickness trajectories across adolescence. Subjects were adolescents with heavy marijuana use and concomitant alcohol use (MJ+ALC, n=30) and controls (CON, n=38) with limited substance use histories. Participants underwent magnetic resonance imaging and comprehensive substance use assessment at three independent time points. Repeated measures analysis of covariance was used to look at main effects of group, time, and Group×Time interactions on cortical thickness. MJ+ALC showed thicker cortical estimates across the brain (23 regions), particularly in frontal and parietal lobes (ps<.05). More cumulative marijuana use was associated with increased thickness estimates by 3-year follow-up (ps<.05). Heavy marijuana use during adolescence and into young adulthood may be associated with altered neural tissue development and interference with neuromaturation that can have neurobehavioral consequences. Continued follow-up of adolescent marijuana users will help understand ongoing neural changes that are associated with development of problematic use into adulthood, as well as potential for neural recovery with cessation of use. Copyright © 2015. Published by Elsevier Ltd.
    Developmental Cognitive Neuroscience 04/2015; 28. DOI:10.1016/j.dcn.2015.04.006 · 3.71 Impact Factor
  • Source
    • "The left and right hippocampal volumes were measured from T1- weighted SPGR images using longitudinal Freesurfer v.5.1 (Reuter et al., 2012) applied to all three scan sessions. No significant differences were observed between the left and right hippocampal volumes, so they were summed to create a single bilateral volume, which was normalized by dividing by the total intracranial volume. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Healthy aging is associated with cognitive declines typically accompanied by increased task-related brain activity in comparison to younger counterparts. The Scaffolding Theory of Aging and Cognition (STAC) (Park and Reuter-Lorenz, 2009; Reuter-Lorenz and Park, 2014) posits that compensatory brain processes are responsible for maintaining normal cognitive performance in older adults, despite accumulation of aging-related neural damage. Cross-sectional studies indicate that cognitively intact elders at genetic risk for Alzheimer's disease (AD) demonstrate patterns of increased brain activity compared to low risk elders, suggesting that compensation represents an early response to AD-associated pathology. Whether this compensatory response persists or declines with the onset of cognitive impairment can only be addressed using a longitudinal design. The current prospective, 5-year longitudinal study examined brain activation in APOE ε4 carriers (N=24) and non-carriers (N=21). All participants, ages 65-85 and cognitively intact at study entry, underwent task-activated fMRI, structural MRI, and neuropsychological assessments at baseline, 18, and 57months. fMRI activation was measured in response to a semantic memory task requiring participants to discriminate famous from non-famous names. Results indicated that the trajectory of change in brain activation while performing this semantic memory task differed between APOE ε4 carriers and non-carriers. The APOE ε4 group exhibited greater activation than the Low Risk group at baseline, but they subsequently showed a progressive decline in activation during the follow-up periods with corresponding emergence of episodic memory loss and hippocampal atrophy. In contrast, the non-carriers demonstrated a gradual increase in activation over the 5-year period. Our results are consistent with the STAC model by demonstrating that compensation varies with the severity of underlying neural damage and can be exhausted with the onset of cognitive symptoms and increased structural brain pathology. Our fMRI results could not be attributed to changes in task performance, group differences in cerebral perfusion, or regional cortical atrophy. Copyright © 2015 Elsevier Inc. All rights reserved.
    NeuroImage 02/2015; 111. DOI:10.1016/j.neuroimage.2015.02.011 · 6.36 Impact Factor
Show more