Konstantinos Arfanakis

White matter tractography using diffusion tensor deflection

Diffusion tensor MRI provides unique directional diffusion information that can be used to estimate the patterns of white matter connectivity in the human brain. In this study, the behavior of an algorithm for white matter tractography is examined. The algorithm, called TEND, uses the entire diffusion tensor to deflect the estimated fiber trajectory. Simulations and imaging experiments on in vivo human brains were performed to investigate the behavior of the tractography algorithm. The simulations show that the deflection term is less sensitive than the major eigenvector to image noise. In the human brain imaging experiments, estimated tracts were generated in corpus callosum, corticospinal tract, internal capsule, corona radiata, superior longitudinal fasciculus, inferior longitudinal fasciculus, fronto‐occipital fasciculus, and uncinate fasciculus. This approach is promising for mapping the organizational patterns of white matter in the human brain as well as mapping the relationship between major fiber trajectories and the location and extent of brain lesions. Hum. Brain Mapping 18:306–321, 2003.

Hierarchical clustering to measure connectivity in fMRI resting-state data

Low frequency oscillations, which are temporally correlated in functionally related brain regions, characterize the mammalian brain, even when no explicit cognitive tasks are performed. Functional connectivity MR imaging is used to map regions of the resting brain showing synchronous, regional and slow fluctuations in cerebral blood flow and oxygenation. In this study, we use a hierarchical clustering method to detect similarities of low-frequency fluctuations. We describe one measure of correlations in the low frequency range for classification of resting-state fMRI data. Furthermore, we investigate the contribution of motion and hardware instabilities to resting-state correlations and provide a method to reduce artifacts. For all cortical regions studied and clusters obtained, we quantify the degree of contamination of functional connectivity maps by the respiratory and cardiac cycle. Results indicate that patterns of functional connectivity can be obtained with hierarchical clustering that resemble known neuronal connections. The corresponding voxel time series do not show significant correlations in the respiratory or cardiac frequency band.

Diffusion tensor MRI in temporal lobe epilepsy

The purpose of this study was to investigate the diffusion characteristics of white matter in patients with focal temporal lobe epilepsy (TLE). Diffusion tensor imaging (DTI) was applied to patients and normal controls. Rotationally invariant mean diffusivity and diffusion anisotropy maps were calculated for all subjects. Comparisons between the two groups were performed for several white matter structures. Mean diffusivity and diffusion anisotropy of each selected structure were tested for correlations with age at onset and duration of epilepsy. Significantly lower diffusion anisotropy, and higher diffusivity in directions perpendicular to the axons, was detected in several white matter structures of the patients when compared to the controls. These structures were not located in the temporal lobes. No significant difference in mean diffusivity was detected between the selected structures from the two groups. Diffusion anisotropy was significantly correlated with age at onset of epilepsy in the posterior corpus callosum. Duration of epilepsy was not significantly correlated with the diffusion indices from any of the selected structures. The results of this study suggest that diffusion anisotropy may reveal abnormalities in patients with focal TLE. In addition, these abnormal changes are not necessarily restricted to the temporal lobes but might extend in other brain regions as well. Furthermore, the age at onset of epilepsy may be an important factor in determining the extent of the effect of epilepsy on white matter.

Common variants at 12q14 and 12q24 are associated with hippocampal volume

Aging is associated with reductions in hippocampal volume that are accelerated by Alzheimers disease and vascular risk factors. Our genome-wide association study (GWAS) of dementia-free persons (n = 9,232) identified 46 SNPs at four loci with P values of <4.0 × 10−7. In two additional samples (n = 2,318), associations were replicated at 12q14 within MSRB3-WIF1 (discovery and replication; rs17178006; P = 5.3 × 10−11) and at 12q24 near HRK-FBXW8 (rs7294919; P = 2.9 × 10−11). Remaining associations included one SNP at 2q24 within DPP4 (rs6741949; P = 2.9 × 10−7) and nine SNPs at 9p33 within ASTN2 (rs7852872; P = 1.0 × 10−7); along with the chromosome 12 associations, these loci were also associated with hippocampal volume (P < 0.05) in a third younger, more heterogeneous sample (n = 7,794). The SNP in ASTN2 also showed suggestive association with decline in cognition in a largely independent sample (n = 1,563). These associations implicate genes related to apoptosis (HRK), development (WIF1), oxidative stress (MSR3B), ubiquitination (FBXW8) and neuronal migration (ASTN2), as well as enzymes targeted by new diabetes medications (DPP4), indicating new genetic influences on hippocampal size and possibly the risk of cognitive decline and dementia.

Preliminary evidence of white matter abnormality in the uncinate fasciculus in generalized social anxiety disorder.

BACKGROUND Individuals with generalized social anxiety disorder (GSAD) exhibit exaggerated amygdala reactivity to aversive social stimuli. These findings could be explained by microstructural abnormalities in white matter (WM) tracts that connect the amygdala and prefrontal cortex, which is known to modulate the amygdalas response to threat. The goal of this study was to investigate brain frontal WM abnormalities using diffusion tensor imaging (DTI) in patients with social anxiety disorder. METHODS A Turboprop DTI sequence was used to acquire diffusion tensor images in 30 patients with GSAD and 30 matched healthy control subjects. Fractional anisotropy, an index of axonal organization, within WM was quantified in individual subjects, and an automated voxel-based, whole-brain method was used to analyze group differences. RESULTS Compared with healthy control subjects, patients had significantly lower fractional anisotropy localized to the right uncinate fasciculus WM near the orbitofrontal cortex. There were no areas of higher fractional anisotropy in patients than controls. CONCLUSIONS These findings point to an abnormality in the uncinate fasciculus, the major WM tract connecting the frontal cortex to the amygdala and other limbic temporal regions, in GSAD, which could underlie the aberrant amygdala-prefrontal interactions resulting in dysfunctional social threat processing in this illness.

Postmortem MRI of Human Brain Hemispheres: T2 Relaxation Times during Formaldehyde Fixation

Unlike in vivo imaging, postmortem MRI allows for invasive examination of the tissue specimen immediately after the MR scan. However, natural tissue decomposition and chemical fixation cause the postmortem tissues MRI properties to be different from those found in vivo. Moreover, these properties change as postmortem fixation time elapses. The goal of this study was to characterize the T2 relaxation changes that occur over time in cadaveric human brain hemispheres during fixation. Five hemispheres immersed in formaldehyde solution were scanned on a weekly basis for 3 months postmortem, and once again at 6 months postmortem. The T2 relaxation times were measured throughout the hemispheres. Over time, T2 values near the edges of the hemispheres decreased rapidly after death, while T2 values of deep tissue decreased more slowly. This difference is likely due to the relatively large distance from the hemisphere surface, and other barriers limiting diffusion of formaldehyde molecules to deep tissues. In addition, T2 values in deep tissue did not continuously decay to a plateau, but instead reached a minimum and then increased to a plateau. This final increase may be due to the effects of prolonged tissue decomposition, a hypothesis that is supported by numerical simulations of the fixation process. Magn Reson Med, 2009.

Selective Changes in White Matter Integrity in MCI and Older Adults with Cognitive Complaints

BACKGROUND White matter changes measured using diffusion tensor imaging have been reported in Alzheimers disease and amnestic mild cognitive impairment, but changes in earlier pre-mild cognitive impairment stages have not been fully investigated. METHODS In a cross-sectional analysis, older adults with mild cognitive impairment (n=28), older adults with cognitive complaints but without psychometric impairment (n=29) and healthy controls (n=35) were compared. Measures included whole-brain diffusion tensor imaging, T1-weighted structural magnetic resonance imaging, and neuropsychological assessment. Diffusion images were analyzed using Tract-Based Spatial Statistics. Voxel-wise fractional anisotropy and mean, axial, and radial diffusivities were assessed and compared between groups. Significant tract clusters were extracted in order to perform further region of interest comparisons. Brain volume was estimated using FreeSurfer based on T1 structural images. RESULTS The mild cognitive impairment group showed lower fractional anisotropy and higher radial diffusivity than controls in bilateral parahippocampal white matter. When comparing extracted diffusivity measurements from bilateral parahippocampal white matter clusters, the cognitive complaint group had values that were intermediate to the mild cognitive impairment and healthy control groups. Group difference in diffusion tensor imaging measures remained significant after controlling for hippocampal atrophy. Across the entire sample, diffusion tensor imaging indices in parahippocampal white matter were correlated with memory function. CONCLUSIONS These findings are consistent with previous results showing changes in parahippocampal white matter in Alzheimers disease and mild cognitive impairment compared to controls. The intermediate pattern found in the cognitive complaint group suggests the potential of diffusion tensor imaging to contribute to earlier detection of neurodegenerative changes during prodromal stages. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.

Development of a high angular resolution diffusion imaging human brain template.

Brain diffusion templates contain rich information about the microstructure of the brain, and are used as references in spatial normalization or in the development of brain atlases. The accuracy of diffusion templates constructed based on the diffusion tensor (DT) model is limited in regions with complex neuronal micro-architecture. High angular resolution diffusion imaging (HARDI) overcomes limitations of the DT model and is capable of resolving intravoxel heterogeneity. However, when HARDI is combined with multiple-shot sequences to minimize image artifacts, the scan time becomes inappropriate for human brain imaging. In this work, an artifact-free HARDI template of the human brain was developed from low angular resolution multiple-shot diffusion data. The resulting HARDI template was produced in ICBM-152 space based on Turboprop diffusion data, was shown to resolve complex neuronal micro-architecture in regions with intravoxel heterogeneity, and contained fiber orientation information consistent with known human brain anatomy.

k-space undersampling in PROPELLER imaging

PROPELLER MRI (periodically rotated overlapping parallel lines with enhanced reconstruction) provides images with significantly fewer B0‐related artifacts than echo‐planar imaging (EPI), as well as reduced sensitivity to motion compared to conventional multiple‐shot fast spin‐echo (FSE). However, the minimum imaging time in PROPELLER is markedly longer than in EPI and 50% longer than in conventional multiple‐shot FSE. Often in MRI, imaging time is reduced by undersampling k‐space. In the present study, the effects of undersampling on PROPELLER images were evaluated using simulated and in vivo data sets. Undersampling using PROPELLER patterns with reduced number of samples per line, number of lines per blade, or number of blades per acquisition, while maintaining the same k‐space field of view (FOVk) and uniform sampling at the edges of FOVk, reduced imaging time but led to severe image artifacts. In contrast, undersampling by means of removing whole blades from a PROPELLER sampling pattern that sufficiently samples k‐space produced only minimal image artifacts, mainly manifested as blurring in directions parallel to the blades removed, even when reducing imaging time by as much as 50%. Finally, undersampling using asymmetric blades and taking advantage of Hermitian symmetries to fill‐in the missing data significantly reduced imaging time without causing image artifacts. Magn Reson Med 53:675–683, 2005.

Independent component analysis applied to diffusion tensor MRI.

The accuracy of the outcome in a diffusion tensor imaging (DTI) experiment depends on the acquisition scheme as well as the postprocessing methods used. In the present study, the DTI results acquired after applying different combinations of diffusion‐weighted (DW) gradient orientations were initially compared. Then, spatially independent component analysis (ICA) was applied to the T2 and DW images. In all cases a single component was detected that was similar to the map of the trace of the diffusion tensor, but contained a reduced amount of noise. Furthermore, when no correction for eddy current artifacts was used in the image acquisition scheme, the effects of eddy currents were separated by ICA into independent components. After these components were removed, conventional estimation of the diffusion tensor was performed on the modified data. No artifact was contained in the final rotationally invariant scalar quantities that describe the intrinsic diffusion properties. Additionally, independent components that mapped major white matter fiber tracts in the human brain were identified. Finally, the noise included in the original T2 and DW images was also separated by ICA into independent components. These components were subsequently removed and a reduction of noise in the final DTI results was achieved. Magn Reson Med 47:354–363, 2002.