NeuroImage
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The NTRK3 gene (also known as TRKC) encodes a high affinity receptor for the neurotrophin 3'-nucleotidase (NT3), which is implicated in oligodendrocyte and myelin development. We previously found that white matter integrity in young adults is related to common variants in genes encoding neurotrophins and their receptors. This underscores the importance of neurotrophins for white matter development. ⋯ FA was optimally predicted (based on the highest false discovery rate critical p), by five SNPs (rs1017412, rs2114252, rs16941261, rs3784406, and rs7176429; overall FDR critical p=0.028). Gene effects were widespread and included the corpus callosum genu and inferior longitudinal fasciculus - regions implicated in several neuropsychiatric disorders and previously associated with other neurotrophin-related genetic variants in an overlapping sample of subjects. NTRK3 genetic variants, and neurotrophins more generally, may influence white matter integrity in brain regions implicated in neuropsychiatric disorders.
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Intrinsic functional connectivity analysis using resting-state functional magnetic resonance imaging (rsfMRI) has become a powerful tool for examining brain functional organization. Global artifacts such as physiological noise pose a significant problem in estimation of intrinsic functional connectivity. Here we develop and test a novel random subspace method for functional connectivity (RSMFC) that effectively removes global artifacts in rsfMRI data. ⋯ Analysis of posterior cingulate cortex connectivity in experimental rsfMRI data from 22 healthy adults revealed strong functional connectivity in the default mode network, including more reliable identification of connectivity with left and right medial temporal lobe regions that were missed by GSReg. Notably, compared to GSReg, negative correlations with lateral fronto-parietal regions were significantly weaker in RSMFC. Our results suggest that RSMFC is an effective method for minimizing the effects of global artifacts and artificial negative correlations, while accurately recovering intrinsic functional brain networks.
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This study examined the sensitivity of ultra-high field (16.4 T) diffusion tensor imaging (DTI; 70 μm in-plane resolution, 1mm slice thickness) to evaluate the spatiotemporal development of severe mid-thoracic contusive spinal cord injury (SCI) in mice. In vivo imaging was performed prior to SCI, then again at 2h, 1 day, 3 days, 7 days, and 30 days post-SCI using a Bruker 16.4 T small animal nuclear magnetic resonance spectrometer. Cross-sectional spinal cord areas were measured in axial slices and various DTI parameters, i.e. fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (λ||) and radial diffusivity (λ⊥), were calculated for the total spared white matter (WM), ventral funiculi (VF), lateral funiculi (LF) and dorsal columns (DCs) and then correlated with histopathology. ⋯ In contrast, DTI parameters for the ventrolateral white matter changed more gradually with time, suggesting that these regions are undergoing more delayed degeneration in a manner that may be amenable to therapeutic intervention. Of all the DTI parameters, λ⊥ was most closely correlated to myelin content whereas changes in FA and λ|| appeared more indicative of axonal integrity, Wallerian degeneration and associated presence of macrophages. We conclude that longitudinal DTI at 16.4T provides a clinically relevant, objective measure for assessing white matter pathology following contusive SCI in mice that may aid the translation of putative neuroprotective strategies into the clinic.
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Comparative Study
Comparing neural response to painful electrical stimulation with functional MRI at 3 and 7 T.
Progressing from 3T to 7 T functional MRI enables marked improvements of human brain imaging in vivo. Although direct comparisons demonstrated advantages concerning blood oxygen level dependent (BOLD) signal response and spatial specificity, these mostly focused on single brain regions with rather simple tasks. Considering that physiological noise also increases with higher field strength, it is not entirely clear whether the advantages of 7T translate equally to the entire brain during tasks which elicit more complex neuronal processing. ⋯ To summarize, our findings support previously reported benefits obtained at ultra-high field strengths also for complex activation patterns elicited by painful electrical stimulation. However, this advantage depends on the region and even more on the contrast of interest. The greatest gain at 7 T was observed within the small brainstem region of the PAG, where the increased field strength offered marked improvement for the localization of activation foci with high spatial specificity.
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Restricted or hindered motion of water across axonal membranes as characterized with diffusion-weighted (DW) imaging may be a potential marker of axonal damage in white matter (WM) injury due to trauma, neurodegeneration, or other causes. This study sought to determine whether high b-value DW imaging with a stimulated echo (STEAM) sequence could improve the spatially resolved assessment of tissue architecture in the human spinal cord in vivo. Diffusion times from 76 ms to 1000 ms and b-values of up to 14,750 s/mm(2) were used to acquire axial DW images in six healthy volunteers, and four additional healthy volunteers were studied with a protocol focused on high b-value, higher-resolution imaging. ⋯ DW images at high b-value and fitting parameters using the large range of b-values available at the diffusion time of 1000 ms demonstrated signal and restriction differences between gray and white matter and even across white matter regions. These white matter differences may reflect variations in axonal density, diameter, or alignment. We conclude that high b-value DW imaging with a STEAM sequence on a conventional clinical scanner can provide accurate measures of diffusion hindrance and restriction in human spinal cord in vivo.