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BACKGROUND AND PURPOSE: Cerebral venous oxygen saturation can be used as an indirect measure of brain health, yet it often requires either an invasive procedure or a noninvasive technique with poor sensitivity. We aimed to test whether cerebral venous oxygen saturation could be measured using quantitative susceptibility mapping, an MR imaging technique, in 3 distinct groups: healthy term neonates, injured term neonates, and preterm neonates. MATERIALS AND METHODS: We acquired multiecho gradient-echo MR imaging data in 16 neonates with perinatal asphyxia and moderate or severe hypoxic-ischemic encephalopathy (8 term age: average, 40.0 [SD, 0.8] weeks’ gestational age; 8 preterm, 33.5 [SD, 2.0] weeks’ gestational age) and in 8 healthy term-age controls (39.3 [SD, 0.6] weeks, for a total of n = 24. Data were postprocessed as quantitative susceptibility mapping images, and magnetic susceptibility was measured in cerebral veins by thesholding out 99.95% of lower magnetic susceptibility values. RESULTS: The mean magnetic susceptibility value of the cerebral veins was found to be 0.36 (SD, 0.04) ppm in healthy term neonates, 0.36 (SD, 0.06) ppm in term injured neonates, and 0.29 (SD, 0.04) ppm in preterm injured neonates. Correspondingly, the derived cerebral venous oxygen saturation values were 73.6% (SD, 2.8%), 71.5% (SD, 7.4%), and 72.2% (SD, 5.9%). There was no statistically significant difference in cerebral venous oxygen saturation among the 3 groups (P = .751). CONCLUSIONS: Quantitative susceptibility mapping–derived oxygen saturation values in preterm and term neonates agreed well with values in past literature. Cerebral venous oxygen saturation in preterm and term neonates with hypoxic-ischemic encephalopathy, however, was not found to be significantly different between neonates or healthy controls.

Myelin water imaging (MWI) provides mild traumatic brain injury (mTBI) researchers with a specific myelin biomarker and helps to further elucidate microstructural and microarchitectural changes of white matter after mTBI. Improvement of scanner hardware and software with the implementation of MWI across scanner platforms will likely result in increased research regarding the role of myelin in traumatic brain injury (TBI). Future research should include detailed investigation of myelin between 2 weeks and 2 months after injury, the use of MWI in moderate and severe TBI, and investigation of the role of myelin in chronic TBI.

R2* relaxation provides a semiquantitative method of detecting myelin, iron and white matter fibre orientation angles. Compared with standard histogram-based analyses, angle-resolved analysis of R2* has previously been shown to substantially improve the detection of subtle differences in the brain between healthy siblings of subjects with multiple sclerosis and unrelated healthy controls. Neonates, who are born with very little myelin and iron, and an underdeveloped connectome, provide researchers with an opportunity to investigate whether R2* is intimately linked with fibre-angle or myelin content as it is in adults, which may in future studies be explored as a potential white matter developmental biomarker. Five healthy adult volunteers (mean age [±SD] = 31.2 [±8.3] years; three males) were recruited from Vancouver, Canada. Eight term neonates (mean age = 38.6 ± 1.2 weeks; five males) were recruited from the Children's Hospital of Chongqing Medical University neonatal ward. All subjects were scanned on identical 3 T Philips Achieva scanners equipped with an eight-channel SENSE head coil and underwent a multiecho gradient echo scan, a 32-direction DTI scan and a myelin water imaging scan. For both neonates and adults, bin-averaged R2* variation across the brain's white matter was found to be best explained by fibre orientation. For adults, this represented a difference in R2* values of 3.5 Hz from parallel to perpendicular fibres with respect to the main magnetic field. In neonates, the fibre orientation dependency displayed a cosine wave shape, with a small R2* range of 0.4 Hz. This minor relationship in neonates provides further evidence for the key role myelin probably plays in creating this fibre orientation dependence later in life, but suggests limited clinical application in newborn populations. Future studies should investigate fibre-orientation dependency in infants in the first 5 years, when substantial myelin development occurs.

BACKGROUND AND PURPOSE: It is difficult to distinguish punctate white matter lesions from focal hemorrhagic lesions in neonates on conventional MR imaging because both kinds of lesions show increased signal intensity on T1-weighted images and, frequently, decreased signal intensity on T2-weighted images. Our aim was to distinguish punctate white matter lesions and focal hemorrhagic lesions using quantitative measures. MATERIALS AND METHODS: In the current study, we acquired multiecho gradient recalled-echo MR imaging data from 24 neonates with hypoxic-ischemic encephalopathy and postprocessed them as R2* relaxation maps and quantitative susceptibility maps. Seven subjects who were found to have multifocal punctate white matter lesions and/or focal hemorrhagic lesions on R2* maps were included (mean gestational age at birth, 33 ± 4.28 weeks; mean gestational age at scanning, 38 ± 2 weeks). Manually drawing ROIs on R2* maps, we measured R2* and magnetic susceptibility values of the lesions, along with white matter regions within the corpus callosum as healthy comparison tissue. RESULTS: R2* and magnetic susceptibility values were both found to easily distinguish punctate white matter lesions, focal hemorrhagic lesions, and healthy white matter tissue from each other (P < .05), with a large Hedge g. R2* and magnetic susceptibility values were significantly increased in focal hemorrhagic lesions compared with punctate white matter lesions and healthy white matter tissue. Punctate white matter lesions were also found to have significantly increased values over healthy white matter tissue. CONCLUSIONS: R2* and quantitative susceptibility maps can be used to help clinicians distinguish and measure focal hemorrhages, punctate white matter lesions, and healthy white matter tissue.

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.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.Significant changes in DMN connectivity were found following alcohol consumption (p0.01). 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 (p0.01).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.

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 mito chondrial 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 mitochon drial oxidative phosphorylation defects and resultant cell loss. Given the role of the caudate nucleus in cognitive and executive func tions, 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.

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)1Ca(V)2Ca(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)2.2Ca(V)1Ca(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.

Evidence suggests that obsessive-compulsive disorder (OCD) is associated with a dysfunction in the cortico-striatal-thalamic-cortical (CSTC) circuitry. Resting state functional connectivity magnetic resonance imaging (rs-fcMRI) allows measurements of resting state networks (RSNs), brain networks that are present at 'rest'. However, although OCD has a typical onset during childhood or adolescence, only two other studies have performed rs-fcMRI comparisons of RSNs in children and adolescents with OCD against healthy controls.In the present study, we performed resting state functional magnetic resonance imaging using a 3 Tesla MRI, in 11 medication-naïve children and adolescents with OCD and 9 healthy controls. In contrast to previous studies that relied on a priori determination of RSNs, we determined resting state functional connectivity with a data-driven independent component analysis (ICA).Consistent with previous reports in healthy adults, we identified 13 RSNs. Case-control un-adjusted statistical significance (p0.05) was found for two networks. Firstly, increased connectivity (OCDcontrol) in the right section of Brodmann area 43 of the auditory network; Secondly, decreased connectivity in the right section of Brodmann area 8 and Brodmann area 40 in the cingulate network.Our preliminary findings of case-control differences in RSNs lend further support to the CSTC hypothesis of OCD, as well as implicating other regions of the brain outside of the CSTC.

Obsessive–compulsive disorder (OCD) has a typical onset during childhood or adolescence. Although recent in-vivo proton magnetic resonance spectroscopy ( 1 H-MRS) studies report gray matter metabolite abnormalities in children and adolescents with OCD, there are no existing 1 H-MRS studies that measure white matter (WM) metabolite levels in this population. In the present study, we measured metabolite levels in the left and right prefrontal WM (LPFWM and RPFWM, respectively) of psychotropic-naive children and adolescents with OCD (LPFWM: N =15, mean age 13.3±2.4 years; right RPFWM: N =14, mean age 13.0±2.3 years) and healthy controls (LPFWM: N =17, mean age 11.8±2.7 years; RPFWM: N =18, mean age 12.2±2.8 years). Spectra were acquired using a 3T single voxel PRESS sequence (1.5×2.0×2.0cm 3 ). When age and sex effects were controlled, OCD patients had higher levels of RPFWM choline and N -acetyl-aspartate (NAA). In addition, RPFWM levels of NAA, creatine and myo-inositol were positively and significantly correlated with severity of OCD symptoms. In summary, this is the first published study of WM metabolite levels in children and adolescents with OCD. Our preliminary findings lend further support to the previous findings of WM abnormalities in OCD.

Ca2+ that enters through voltage-gated CaV2.2 channels and binds to a calcium sensor at the transmitter release site links membrane depolarization to activation of synaptic vesicle discharge. Recent evidence supports the hypothesis that the release site calcium sensor is within the single CaV2.2 channel domain. Thus, modeling presynaptic nanophysiology requires knowledge of the channel transport rate at physiological [Ca2+]ext. However, this value has only been determined previously for the non-presynaptic CaV1.x (L type) channel with a conductance of ∼2.4 pS at [Ca2+]ext=2 mM (Church and Stanley, JP 1996). Since at [Ba2+]ext=100 mM CaV1.x has a conductance of ∼24 pS while CaV2.2 has one of ∼14 pS we predicted that at [Ca2+]ext=2 mM the latter channel would have a conductance of ∼1.2 pS.Single calcium channels were recorded using low noise, quartz electrodes from freshly isolated chick dorsal root ganglion neurons which express virtually entirely CaV2.2 current. In the presence of [Ca2+]ext=2 mM and 2 μM nifedipine, to block CaV1.x, and 0.1 mM Ni+ to block CaV3.X, together with standard Na+ and K+ channel blockers and n-methyl-D glucamine+ as the primary cation, we noted two single inward channel conductances: ∼1.4 pS and ∼2.5 pS (N=4). The larger channel was identified as CaV2.2 since it was absent in 4 of 4 patches with ω-conotoxin GIVA (2.5 μM), a specific CaV2.2 blocker, but was present in 7 out of 8 patches with 2 mM [Ca2+ext] or [Ba2+ext] whereas the small channel remained (N=3). Thus, our data indicate that at physiological [Ca2+]ext, CaV2.2 has a much higher conductance, and hence larger single channel domain, than predicted.