Gabriel A. Devenyi

BIDS apps: Improving ease of use, accessibility, and reproducibility of neuroimaging data analysis methods

The rate of progress in human neurosciences is limited by the inability to easily apply a wide range of analysis methods to the plethora of different datasets acquired in labs around the world. In this work, we introduce a framework for creating, testing, versioning and archiving portable applications for analyzing neuroimaging data organized and described in compliance with the Brain Imaging Data Structure (BIDS). The portability of these applications (BIDS Apps) is achieved by using container technologies that encapsulate all binary and other dependencies in one convenient package. BIDS Apps run on all three major operating systems with no need for complex setup and configuration and thanks to the comprehensiveness of the BIDS standard they require little manual user input. Previous containerized data processing solutions were limited to single user environments and not compatible with most multi-tenant High Performance Computing systems. BIDS Apps overcome this limitation by taking advantage of the Singularity container technology. As a proof of concept, this work is accompanied by 22 ready to use BIDS Apps, packaging a diverse set of commonly used neuroimaging algorithms.

Evaluating accuracy of striatal, pallidal, and thalamic segmentation methods: Comparing automated approaches to manual delineation

ABSTRACT Accurate automated quantification of subcortical structures is a greatly pursued endeavour in neuroimaging. In an effort to establish the validity and reliability of these methods in defining the striatum, globus pallidus, and thalamus, we investigated differences in volumetry between manual delineation and automated segmentations derived by widely used FreeSurfer and FSL packages, and a more recent segmentation method, the MAGeT‐Brain algorithm. In a first set of experiments, the basal ganglia and thalamus of thirty subjects (15 first episode psychosis [FEP], 15 controls) were manually defined and compared to the labels generated by the three automated methods. Our results suggest that all methods overestimate volumes compared to the manually derived “gold standard”, with the least pronounced differences produced using MAGeT. The least between‐method variability was noted for the striatum, whereas marked differences between manual segmentation and MAGeT compared to FreeSurfer and FSL emerged for the globus pallidus and thalamus. Correlations between manual segmentation and automated methods were strongest for MAGeT (range: 0.51 to 0.92; p<0.01, corrected), whereas FreeSurfer and FSL showed moderate to strong Pearson correlations (range 0.44–0.86; p<0.05, corrected), with the exception of FreeSurfer pallidal (r=0.31, p=0.10) and FSL thalamic segmentations (r=0.37, p=0.051). Bland‐Altman plots highlighted a tendency for greater volumetric differences between manual labels and automated methods at the lower end of the distribution (i.e. smaller structures), which was most prominent for bilateral thalamus across automated pipelines, and left globus pallidus for FSL. We then went on to examine volume and shape of the basal ganglia structures using automated techniques in 135 FEP patients and 88 controls. The striatum and globus pallidus were significantly larger in FEP patients compared to controls bilaterally, irrespective of the method used. MAGeT‐Brain was more sensitive to shape‐based group differences, and uncovered widespread surface expansions in the striatum and globus pallidus bilaterally in FEP patients compared to controls, and surface contractions in bilateral thalamus (FDR‐corrected). By contrast, after using a recommended cluster‐wise thresholding method, FSL only detected differences in the right ventral striatum (FEP>Control) and one cluster of the left thalamus (Control>FEP). These results suggest that different automated pipelines segment subcortical structures with varying degrees of variability compared to manual methods, with particularly pronounced differences found with FreeSurfer and FSL for the globus pallidus and thalamus. HIGHLIGHTSManual segmentation of subcortical structure is evaluated against 3 automated tools.Correspondence with manual labels was greatest with MAGeT‐Brain.Greatest between‐method variability was noted for FreeSurfer and FSL‐FIRST.Larger striatum and pallidum were found in first episode psychosis across methods.Subcortical shape profiles in patients vs. controls differed between MAGeT and FSL.

Manual segmentation of the fornix, fimbria, and alveus on high-resolution 3T MRI: Application via fully-automated mapping of the human memory circuit white and grey matter in healthy and pathological aging.

ABSTRACT Recently, much attention has been focused on the definition and structure of the hippocampus and its subfields, while the projections from the hippocampus have been relatively understudied. Here, we derive a reliable protocol for manual segmentation of hippocampal white matter regions (alveus, fimbria, and fornix) using high‐resolution magnetic resonance images that are complementary to our previous definitions of the hippocampal subfields, both of which are freely available at https://github.com/cobralab/atlases. Our segmentation methods demonstrated high inter‐ and intra‐rater reliability, were validated as inputs in automated segmentation, and were used to analyze the trajectory of these regions in both healthy aging (OASIS), and Alzheimers disease (AD) and mild cognitive impairment (MCI; using ADNI). We observed significant bilateral decreases in the fornix in healthy aging while the alveus and cornu ammonis (CA) 1 were well preserved (all ps<0.006). MCI and AD demonstrated significant decreases in fimbriae and fornices. Many hippocampal subfields exhibited decreased volume in both MCI and AD, yet no significant differences were found between MCI and AD cohorts themselves. Our results suggest a neuroprotective or compensatory role for the alveus and CA1 in healthy aging and suggest that an improved understanding of the volumetric trajectories of these structures is required. HIGHLIGHTSNovel high‐resolution manual segmentation of human alveus, fimbria, and fornix.Validation (precision and accuracy) of manual atlases for use in automatic segmentation.Application of automatic segmentation on AD/MCI and healthy aging datasets.Results suggest neuroprotective role for alveus and hippocampal CA1 region.

Cerebellar anatomical alterations and attention to eyes in autism

The cerebellum is implicated in social cognition and is likely to be involved in the pathophysiology of autism spectrum disorder (ASD). The goal of our study was to explore cerebellar morphology in adults with ASD and its relationship to eye contact, as measured by fixation time allocated on the eye region using an eye-tracking device. Two-hundred ninety-four subjects with ASD and controls were included in our study and underwent a structural magnetic resonance imaging scan. Global segmentation and cortical parcellation of the cerebellum were performed. A sub-sample of 59 subjects underwent an eye tracking protocol in order to measure the fixation time allocated to the eye region. We did not observe any difference in global cerebellar volumes between ASD patients and controls; however, regional analyses found a decrease of the volume of the right anterior cerebellum in subjects with ASD compared to controls. There were significant correlations between fixation time on eyes and the volumes of the vermis and Crus I. Our results suggest that cerebellar morphology may be related to eye avoidance and reduced social attention. Eye tracking may be a promising neuro-anatomically based stratifying biomarker of ASD.

Regionally specific changes in the hippocampal circuitry accompany progression of cerebrospinal fluid biomarkers in preclinical Alzheimer's disease

Neuropathological and in vivo brain imaging studies agree that the cornu ammonis 1 and subiculum subfields of the hippocampus are most vulnerable to atrophy in the prodromal phases of Alzheimers disease (AD). However, there has been limited investigation of the structural integrity of the components of the hippocampal circuit, including subfields and extra‐hippocampal white matter structure, in relation to the progression of well‐accepted cerebrospinal fluid (CSF) biomarkers of AD, amyloid‐β 1‐42 (Aβ) and total‐tau (tau). We investigated these relationships in 88 aging asymptomatic individuals with a parental or multiple‐sibling familial history of AD. Apolipoprotein (APOE) ɛ4 risk allele carriers were identified, and all participants underwent cognitive testing, structural magnetic resonance imaging, and lumbar puncture for CSF assays of tau, phosphorylated‐tau (p‐tau) and Aβ. Individuals with a reduction in CSF Aβ levels (an indicator of amyloid accretion into neuritic plaques) as well as evident tau pathology (believed to be linked to neurodegeneration) exhibited lower subiculum volume, lower fornix microstructural integrity, and a trend towards lower cognitive score than individuals who showed only reduction in CSF Aβ. In contrast, persons with normal levels of tau showed an increase in structural MR markers in relation to declining levels of CSF Aβ. These results suggest that hippocampal subfield volume and extra‐hippocampal white matter microstructure demonstrate a complex pattern where an initial volume increase is followed by decline among asymptomatic individuals who, in some instances, may be a decade or more away from onset of cognitive or functional impairment.

Heritability of hippocampal subfield volumes using a twin and non-twin siblings design

The hippocampus is composed of distinct subfields linked to diverse functions and disorders. The subfields can be mapped using high‐resolution magnetic resonance images, and their volumes can potentially be used as quantitative phenotypes for genetic investigation of hippocampal function. We estimated the heritability of hippocampus subfield volumes of 465 subjects from the Human Connectome Project (twins and non‐twin siblings) using two methods. The first used a univariate model to estimate heritability with and without adjustment for total brain volume (TBV) and ipsilateral hippocampal volume to determine if heritability was uniquely attributable to subfield volume rather than confounds that attributed to global volumes. We observed the right: subiculum, cornu ammonis 2/3, and cornu ammonis 4/dentate gyrus subfields had the highest significant heritability estimates after adjusting for ipsilateral hippocampal volume. In the second analysis, we used a bivariate model to investigate the shared heritability and genetic correlation of the subfield volumes with TBV and ipsilateral hippocampal volume. Genetic correlation demonstrates shared genetic architecture between phenotypes and shared heritability is what proportion of the genetic architecture of one trait is shared by the other. Highest genetic correlations were between subfield volumes and ipsilateral hippocampal volume than with TBV. The pattern was opposite for shared heritability suggesting that subfields share greater proportion of the genetic architecture with TBV than with ipsilateral hippocampal volume. The relationship between the genetic architecture of TBV, hippocampal volume, and of individual subfields should be accounted for when using hippocampal subfield volumes as quantitative phenotypes for imaging genetics studies. Hum Brain Mapp 38:4337–4352, 2017.

Neuroanatomical and Symptomatic Sex Differences in Individuals at Clinical High Risk for Psychosis

Sex differences have been widely observed in clinical presentation, functional outcome and neuroanatomy in individuals with a first-episode of psychosis, and chronic patients suffering from schizophrenia. However, little is known about sex differences in the high-risk stages for psychosis. The present study investigated sex differences in cortical and subcortical neuroanatomy in individuals at clinical high risk (CHR) for psychosis and healthy controls (CTL), and the relationship between anatomy and clinical symptoms in males at CHR. Magnetic resonance images were collected in 26 individuals at CHR (13 men) and 29 CTLs (15 men) to determine total and regional brain volumes and morphology, cortical thickness, and surface area (SA). Clinical symptoms were assessed with the brief psychiatric rating scale. Significant sex-by-diagnosis interactions were observed with opposite directions of effect in male and female CHR subjects relative to their same-sex controls in multiple cortical and subcortical areas. The right postcentral, left superior parietal, inferior parietal supramarginal, and angular gyri [<5% false discovery rate (FDR)] were thicker in male and thinner in female CHR subjects compared with their same-sex CTLs. The same pattern was observed in the right superior parietal gyrus SA at the regional and vertex level. Using a recently developed surface-based morphology pipeline, we observed sex-specific shape differences in the left hippocampus (<5% FDR) and amygdala (<10% FDR). Negative symptom burden was significantly higher in male compared with female CHR subjects (p = 0.04) and was positively associated with areal expansion of the left amygdala in males (<5% FDR). Some limitations of the study include the sample size, and data acquisition at 1.5 T. This study demonstrates neuroanatomical sex differences in CHR subjects, which may be associated with variations in symptomatology in men and women with psychotic symptoms.

Patterns of reduced cortical thickness and striatum pathological morphology in cocaine addiction.

Substance addiction is regarded as an important public health problem, perpetuated by fronto-striatal circuit pathology. A usual finding in neuroimaging human and murine studies is cortical thinning and lower volume when compared to healthy controls. In this study we wished to replicate cortical thinning findings and find if striatum morphology may explain the cortical pathology. For this we analyzed T1w neuroimaging data from an ongoing addiction Mexican dataset. This dataset includes cocaine addicts diagnosed by expert psychiatrists and healthy controls. For the analysis we used voxel-based morphometry, cortical thickness and volumetric analysis of the basal ganglia, and we correlated striatum volume with cortical thickness to find pathological patterns. Our group contrast showed cortical thinning and striatum volume differences in cocaine addicts correlated to their years of substance use, craving and age. Our correlation between striatum-cortex morphology showed higher significant correlations in healthy controls, not observed in cocaine addicts. The correlation between striatum volume and cortical thickness in healthy controls involved similar areas as those shown with less cortical thickness in cocaine addicts. We suggest that striatum morphological changes in addiction may explain the pattern of cortical thinning observed across several substances addiction studies.

A 3D MRI-based atlas of a lizard brain

Magnetic resonance imaging (MRI) is an established technique for neuroanatomical analysis, being particularly useful in the medical sciences. However, the application of MRI to evolutionary neuroscience is still in its infancy. Few magnetic resonance brain atlases exist outside the standard model organisms in neuroscience and no magnetic resonance atlas has been produced for any reptile brain. A detailed understanding of reptilian brain anatomy is necessary to elucidate the evolutionary origin of enigmatic brain structures such as the cerebral cortex. Here, we present a magnetic resonance atlas for the brain of a representative squamate reptile, the Australian tawny dragon (Agamidae: Ctenophorus decresii), which has been the subject of numerous ecological and behavioral studies. We used a high‐field 11.74T magnet, a paramagnetic contrasting‐enhancing agent and minimum‐deformation modeling of the brains of thirteen adult male individuals. From this, we created a high‐resolution three‐dimensional model of a lizard brain. The 3D‐MRI model can be freely downloaded and allows a better comprehension of brain areas, nuclei, and fiber tracts, facilitating comparison with other species and setting the basis for future comparative evolution imaging studies. The MRI model and atlas of a tawny dragon brain (Ctenophorus decresii) can be viewed online and downloaded using the Wiley Biolucida Server at wiley.biolucida.net.

Warping an atlas derived from serial histology to 5 high-resolution MRIs

Previous work from our group demonstrated the use of multiple input atlases to a modified multi-atlas framework (MAGeT-Brain) to improve subject-based segmentation accuracy. Currently, segmentation of the striatum, globus pallidus and thalamus are generated from a single high-resolution and -contrast MRI atlas derived from annotated serial histological sections. Here, we warp this atlas to five high-resolution MRI templates to create five de novo atlases. The overall goal of this work is to use these newly warped atlases as input to MAGeT-Brain in an effort to consolidate and improve the workflow presented in previous manuscripts from our group, allowing for simultaneous multi-structure segmentation. The work presented details the methodology used for the creation of the atlases using a technique previously proposed, where atlas labels are modified to mimic the intensity and contrast profile of MRI to facilitate atlas-to-template nonlinear transformation estimation. Dice’s Kappa metric was used to demonstrate high quality registration and segmentation accuracy of the atlases. The final atlases are available at https://github.com/CobraLab/atlases/tree/master/5-atlas-subcortical.