Spurious group differences due to head motion in a diffusion MRI study.

Diffusion-weighted MRI (DW-MRI) has become a popular imaging modality for probing the microstructural properties of white matter and comparing them between populations in vivo. However, the contrast in DW-MRI arises from the microscopic random motion of water molecules in brain tissues, which makes it particularly sensitive to macroscopic head motion. Although this has been known since the introduction of DW-MRI, most studies that use this modality for group comparisons do not report measures of head motion for each group and rely on registration-based correction methods that cannot eliminate the full effects of head motion on the DW-MRI contrast. In this work we use data from children with autism and typically developing children to investigate the effects of head motion on differences in anisotropy and diffusivity measures between groups. We show that group differences in head motion can induce group differences in DW-MRI measures, and that this is the case even when comparing groups that include control subjects only, where no anisotropy or diffusivity differences are expected. We also show that such effects can be more prominent in some white-matter pathways than others, and that they can be ameliorated by including motion as a nuisance regressor in the analyses. Our results demonstrate the importance of taking head motion into account in any population study where one group might exhibit more head motion than the other.

Entorhinal verrucae geometry is coincident and correlates with Alzheimer's lesions: a combined neuropathology and high-resolution ex vivo MRI analysis.

Entorhinal cortex displays a distinctive organization in layer II and forms small elevations on its surface called entorhinal verrucae. In Alzheimer's disease, the verrucae disappear due to neurofibrillary tangle formation and neuronal death. Isosurface models were reconstructed from high-resolution ex vivo MRI volumes scanned at 7.0 T and individual verruca were measured quantitatively for height, width, volume, and surface area on control and mild Alzheimer's cases. Mean verruca height was 0.13 ± 0.04 mm for our cognitively normal (controls) sample set whereas for mild AD samples mean height was 0.11 mm ± 0.05 mm (p < 0.001) in entorhinal cortex (n = 10 cases). These quantitative methods were validated by a significant correlation of verrucae height and volume with qualitative verrucae ratings (n = 36 cases). Entorhinal surfaces were significantly different from other cortical heights such as, cingulate, frontal, occipital, parietal and temporal cortices. Colocalization of verrucae with entorhinal islands was confirmed in ex vivo MRI and, moreover, verrucae ratings were negatively correlated to Braak and Braak pathological stage. This study characterizes novel methods to measure individual entorhinal verruca size, and shows that verrucae size correlates to Alzheimer's pathology. Taken together, these results suggest that verrucae may have the potential to serve as an early and specific morphological marker for mild cognitive impairment and Alzheimer's disease.

Improved tractography alignment using combined volumetric and surface registration.

Previously we introduced an automated high-dimensional non-linear registration framework, CVS, that combines volumetric and surface-based alignment to achieve robust and accurate correspondence in both cortical and sub-cortical regions (Postelnicu et al., 2009). In this paper we show that using CVS to compute cross-subject alignment from anatomical images, then applying the previously computed alignment to diffusion weighted MRI images, outperforms state-of-the-art techniques for computing cross-subject alignment directly from the DWI data itself. Specifically, we show that CVS outperforms the alignment component of TBSS in terms of degree-of-alignment of manually labeled tract models for the uncinate fasciculus, the inferior longitudinal fasciculus and the corticospinal tract. In addition, we compare linear alignment using FLIRT based on either fractional anisotropy or anatomical volumes across-subjects, and find a comparable effect. Together these results imply a clear advantage to aligning anatomy as opposed to lower resolution DWI data even when the final goal is diffusion analysis.

Evaluating the validity of volume-based and surface-based brain image registration for developmental cognitive neuroscience studies in children 4 to 11 years of age.

Understanding the neurophysiology of human cognitive development relies on methods that enable accurate comparison of structural and functional neuroimaging data across brains from people of different ages. A fundamental question is whether the substantial brain growth and related changes in brain morphology that occur in early childhood permit valid comparisons of brain structure and function across ages. Here we investigated whether valid comparisons can be made in children from ages 4 to 11, and whether there are differences in the use of volume-based versus surface-based registration approaches for aligning structural landmarks across these ages. Regions corresponding to the calcarine sulcus, central sulcus, and Sylvian fissure in both the hemispheres were manually labeled on T1-weighted structural magnetic resonance images from 31 children ranging in age from 4.2 to 11.2years old. Quantitative measures of shape similarity and volumetric-overlap of these manually labeled regions were calculated when brains were aligned using a 12-parameter affine transform, SPM's nonlinear normalization, a diffeomorphic registration (ANTS), and FreeSurfer's surface-based registration. Registration error for normalization into a common reference framework across participants in this age range was lower than commonly used functional imaging resolutions. Surface-based registration provided significantly better alignment of cortical landmarks than volume-based registration. In addition, registering children's brains to a common space does not result in an age-associated bias between older and younger children, making it feasible to accurately compare structural properties and patterns of brain activation in children from ages 4 to 11.

Predicting the location of entorhinal cortex from MRI.

Entorhinal cortex (EC) is a medial temporal lobe area critical to memory formation and spatial navigation that is among the earliest parts of the brain affected by Alzheimer's disease (AD). Accurate localization of EC would thus greatly facilitate early detection and diagnosis of AD. In this study, we used ultra-high resolution ex vivo MRI to directly visualize the architectonic features that define EC rostrocaudally and mediolaterally, then applied surface-based registration techniques to quantify the variability of EC with respect to cortical geometry, and made predictions of its location on in vivo scans. The results indicate that EC can be localized quite accurately based on cortical folding patterns, within 3 mm in vivo, a significant step forward in our ability to detect the earliest effects of AD when clinical intervention is most likely to be effective.

Direct visualization of the perforant pathway in the human brain with ex vivo diffusion tensor imaging.

Ex vivo magnetic resonance imaging yields high resolution images that reveal detailed cerebral anatomy and explicit cytoarchitecture in the cerebral cortex, subcortical structures, and white matter in the human brain. Our data illustrate neuroanatomical correlates of limbic circuitry with high resolution images at high field. In this report, we have studied ex vivo medial temporal lobe samples in high resolution structural MRI and high resolution diffusion MRI. Structural and diffusion MRIs were registered to each other and to histological sections stained for myelin for validation of the perforant pathway. We demonstrate probability maps and fiber tracking from diffusion tensor data that allows the direct visualization of the perforant pathway. Although it is not possible to validate the DTI data with invasive measures, results described here provide an additional line of evidence of the perforant pathway trajectory in the human brain and that the perforant pathway may cross the hippocampal sulcus.