Orientation dependence of R2 relaxation in the newborn brain.

In MRI the transverse relaxation rate, R2 = 1/T2, shows dependence on the orientation of ordered tissue relative to the main magnetic field. In previous studies, orientation effects of R2 relaxation in the mature brain's white matter have been found to be described by a susceptibility-based model of diffusion through local magnetic field inhomogeneities created by the diamagnetic myelin sheaths. Orientation effects in human newborn white matter have not yet been investigated. The newborn brain is known to contain very little myelin and is therefore expected to exhibit a decrease in orientation dependence driven by susceptibility-based effects. We measured R2 orientation dependence in the white matter of human newborns. R2 data were acquired with a 3D Gradient and Spin Echo (GRASE) sequence and fiber orientation was mapped with diffusion tensor imaging (DTI). We found orientation dependence in newborn white matter that is not consistent with the susceptibility-based model and is best described by a model of residual dipolar coupling. In the near absence of myelin in the newborn brain, these findings suggest the presence of residual dipolar coupling between rotationally restricted water molecules. This has important implications for quantitative imaging methods such as myelin water imaging, and suggests orientation dependence of R2 as a potential marker in early brain development.

Pathological Insights From Quantitative Susceptibility Mapping and Diffusion Tensor Imaging in Ice Hockey Players Pre and Post-concussion.

Myelin sensitive MRI techniques, such as diffusion tensor imaging and myelin water imaging, have previously been used to reveal changes in myelin after sports-related concussions. What is not clear from these studies, however, is how myelin is affected: whether it becomes degraded and possibly removed, or whether the myelin sheath loosens and becomes "decompacted". Previously, our team revealed myelin specific changes in ice hockey players 2 weeks post-concussion using myelin water imaging. In that study, 45 subjects underwent a pre-season baseline scan, 11 of which sustained a concussion during play and received follow-up scans: eight were scanned within 3 days, 10 were scanned at 14 days, and nine were scanned at 60 days. In the current retrospective analysis, we used quantitative susceptibility mapping, along with the diffusion tensor imaging measures axial diffusivity and radial diffusivity, to investigate this myelin disruption. If sports-related concussive hits lead to myelin fragmentation in regions of lowered MWF, this should result in a measurable increase in magnetic susceptibility, due to the anisotropic myelin fragmenting into isotropic myelin debris, and the diamagnetic myelin tissue being removed, while no such changes should be expected if the myelin sheath simply loosens and becomes decompacted. An increase in radial diffusivity would likewise reveal myelin fragmentation, as myelin sheaths block water diffusion out of the axon, with little to no changes expected for myelin sheath loosening. Statistical analysis of the same voxels-of-interest that were found to have reduced myelin water fraction 2 weeks post-concussion, revealed no statistically significant changes in magnetic susceptibility, axial diffusivity, or radial diffusivity at any time-point post-concussion. This suggests that myelin water fraction changes are likely due to a loosening of the myelin sheath structure, as opposed to fragmentation and removal of myelin debris.

A preliminary study on the effects of acute ethanol ingestion on default mode network and temporal fractal properties of the brain.

OBJECT: To study the effect of acute alcohol intoxication on the functional connectivity of the default mode network (DMN) and temporal fractal properties of the healthy adult brain. MATERIALS AND METHODS: Eleven healthy male volunteers were asked to drink 0.59 g/kg of ethanol. Resting state blood oxygen level dependent (rsBOLD) MRI scans were obtained before consumption, 60 min post-consumption and 90 min post-consumption. Before each rsBOLD scan, pointed-resolved spectroscopy (PRESS) (1)H-MRS (magnetic resonance spectroscopy) scans were acquired to measure ethanol levels in the right basal ganglia. RESULTS: Significant changes in DMN connectivity were found following alcohol consumption (p < 0.01). Both increased and decreased regional connectivity were found after 60 min, whereas mostly decreased connectivity was found after 90 min. The fractal behaviour of the rsBOLD signal, which is believed to help reveal complexity of small-scale neuronal circuitry, became more ordered after both 60 and 90 min of alcohol consumption (p < 0.01). CONCLUSION: The DMN has been linked to personal identity and social behavior. As such, our preliminary findings may provide insight into the neuro-functional underpinnings of the cognitive and behavioral changes observed during acute alcohol intoxication. The reduced fractal dimension implies a change in function of small-scale neural networks towards less complex signaling.

Metabolite measurements in the caudate nucleus, anterior cingulate cortex and hippocampus among patients with mitochondrial disorders: a case-control study using proton magnetic resonance spectroscopy.

BACKGROUND: Mitochondrial disorders are clinical syndromes associated with mutations in the mitochondrial or nuclear genome that result in impaired oxidative phosphorylation and deficient energy production. Metabolic abnormalities in brain areas associated with cognitive functions could give rise to neuropsychiatric symptomatology. The aim of this study was to use single-voxel proton magnetic resonance spectroscopy to identify metabolic abnormalities in regions implicated in neuropsychiatric symptoms in patients with mitochondrial disorders. METHODS: N-acetyl-aspartate and creatine levels were measured in the caudate nucleus, anterior cingulate cortex and hippocampus in 15 patients with mitochondrial disorders compared with 15 healthy controls matched for age and sex. RESULTS: N-acetyl-aspartate levels were significantly lower in the caudate nucleus among patients with mitochondrial disorders (mean 7.04 ± 1.19 standard deviation [SD] institutional units) compared with healthy controls (mean 8.19 ± 1.18 SD institutional units; p = 0.02). Creatine levels were lower in the caudate nucleus among patients compared with controls (patients: mean 6.84 ± 1.42 SD institutional units; controls: mean 7.52 ± 0.76 SD institutional units; p = 0.03), but the results were no longer significant after correction for multiple comparisons. There were no significant differences in metabolite measurements between patients and controls in the anterior cingulate cortex and the hippocampus. INTERPRETATION: Metabolic abnormalities were identified exclusively in the caudate nucleus, with significantly lower N-acetyl-aspartate levels among patients compared with controls. These results suggest that the corpus striatum may be highly susceptible to mitochondrial oxidative phosphorylation defects and resultant cell loss. Given the role of the caudate nucleus in cognitive and executive functions, our findings raise the possibility that metabolic abnormalities in the caudate nucleus may contribute to cognitive impairment and neuropsychiatric symptoms in patients with mitochondrial disorders, which could be investigated in future studies.

N-type Ca2+ channels carry the largest current: implications for nanodomains and transmitter release.

Presynaptic terminals favor intermediate-conductance Ca(V)2.2 (N type) over high-conductance Ca(V)1 (L type) channels for single-channel, Ca(2+) nanodomain-triggered synaptic vesicle fusion. However, the standard Ca(V)1>Ca(V)2>Ca(V)3 conductance hierarchy is based on recordings using nonphysiological divalent ion concentrations. We found that, with physiological Ca(2+) gradients, the hierarchy was Ca(V)2.2>Ca(V)1>Ca(V)3. Mathematical modeling predicts that the Ca(V)2.2 Ca(2+) nanodomain, which is ∼25% more extensive than that generated by Ca(V)1, can activate a calcium-fusion sensor located on the proximal face of the synaptic vesicle.