Magnetic resonance spectroscopy (MRS) provides unique information about the neurobiological substrates of brain function in health and disease. However, many of the physical principles underlying MRS are distinct from those underlying magnetic resonance imaging, and they may not be widely understood by neuroscientists new to this methodology. This review describes these physical principles and many of the technical methods in current use for MRS experiments. A better understanding these principles and methods may help investigators select pulse sequences and quantification methods best suited to the aims of their research program and avoid pitfalls that can hamper new investigators in this field.

Functional imaging studies consistently find that emotional stimuli activate the posterior cingulate cortex, a region that appears to have memory-related functions. However, prior imaging studies have not controlled for non-emotional stimulus features that might activate this region by engaging memory processes unrelated to emotion. This study examined whether emotional words activated the posterior cingulate cortex when these potentially confounding factors were controlled. Sixty-four pleasant and 64 unpleasant words were matched with neutral words on non-emotional features known to influence memory. Eight subjects underwent block-designed functional magnetic resonance imaging scans while evaluating the valence of these words. The posterior cingulate cortex was significantly activated bilaterally during both unpleasant and pleasant compared to neutral words. The strongest activation peak with both unpleasant and pleasant words was observed in the left subgenual cingulate cortex. Anteromedial orbital and left inferior and middle frontal cortices were also activated by both pleasant and unpleasant words. Right amygdala and auditory cortex were activated only by unpleasant words, while left frontal pole was activated only by pleasant words. The results show that activation of the posterior cingulate cortex by emotional stimuli cannot be attributed to the memory-enhancing effects of non-emotional stimulus features. The findings are consistent with the suggestion that this region may mediate interactions of emotional and memory-related processes. The results also extend prior findings that evaluating emotional words consistently activates the subgenual cingulate cortex, and suggest a means of probing this region in patients with mood disorders.

Methamphetamine is known to cause a cardiomyopathy which may be reversible with appropriate medical therapy and cessation of use. Late gadolinium enhancement cardiovascular magnetic resonance (CMR) has been shown to identify fibrosis in ischemic and non-ischemic cardiomyopathies. We present a case of severe methamphetamine-associated cardiomyopathy in which cardiac function recovered after 6 months. Evaluation by CMR using late gadolinium enhancement was notable for an absence of enhancement, suggesting an absence of irreversible myocyte injury and a good prognosis. CMR may be useful to predict recovery in toxin-associated non-ischemic cardiomyopathies.

We have longitudinally assessed normative brain growth patterns in naturalistically reared Macaca mulatta monkeys. Postnatal to early adulthood brain development in two cohorts of rhesus monkeys was analyzed using magnetic resonance imaging. Cohort A consisted of 24 rhesus monkeys (12 male, 12 female) and cohort B of 21 monkeys (11 male, 10 female). All subjects were scanned at 1, 4, 8, 13, 26, 39, and 52 weeks; cohort A had additional scans at 156 weeks (3 years) and 260 weeks (5 years). Age-specific segmentation templates were developed for automated volumetric analyses of the T1-weighted magnetic resonance imaging scans. Trajectories of total brain size as well as cerebral and subcortical subdivisions were evaluated over this period. Total brain volume was about 64 % of adult estimates in the 1-week-old monkey. Brain volume of the male subjects was always, on average, larger than the female subjects. While brain volume generally increased between any two imaging time points, there was a transient plateau of brain growth between 26 and 39 weeks in both cohorts of monkeys. The trajectory of enlargement differed across cortical regions with the occipital cortex demonstrating the most idiosyncratic pattern of maturation and the frontal and temporal lobes showing the greatest and most protracted growth. A variety of allometric measurements were also acquired and body weight gain was most closely associated with the rate of brain growth. These findings provide a valuable baseline for the effects of fetal and early postnatal manipulations on the pattern of abnormal brain growth related to neurodevelopmental disorders.

Background

Prior evidence suggests panic disorder (PD) is characterized by neurometabolic abnormalities, including increased brain lactate responses to neural activation. Increased lactate responses could reflect a general upregulation of metabolic responses to neural activation. However, prior studies in PD have not measured activity-dependent changes in brain metabolites other than lactate. Here we examine activity-dependent changes in both lactate and glutamate plus glutamine (glx) in PD.

Methods

Twenty-one PD patients (13 remitted, 8 symptomatic) and 12 healthy volunteers were studied. A single-voxel, J-difference, magnetic resonance spectroscopy editing sequence was used to measure lactate and glx changes in visual cortex induced by visual stimulation.

Results

The PD patients had significantly greater activity-dependent increases in brain lactate than healthy volunteers. The differences were significant for both remitted and symptomatic PD patients, who did not differ from each other. Activity-dependent changes in glx were significantly smaller in PD patients than in healthy volunteers. The temporal correlation between lactate and glx changes was significantly stronger in control subjects than in PD patients.

Conclusions

The novel demonstration that glx responses are diminished and temporally decoupled from lactate responses in PD contradicts the model of a general upregulation of activity-dependent brain metabolic responses in PD. The increase in activity-dependent brain lactate accumulation appears to be a trait feature of PD. Given the close relationship between lactate and pH in the brain, the findings are consistent with a model of brain metabolic and pH dysregulation associated with altered function of acid-sensitive fear circuits contributing to trait vulnerability in PD.

Brain development occurs rapidly during the first few years of life involving region-specific changes in both gray matter and white matter. Due to the inherent difficulties in acquiring magnetic resonance imaging data in young children, little is known about the properties of white matter in typically developing toddlers. In the context of an ongoing study of young children with autism spectrum disorder, we collected diffusion-weighted imaging data during natural nocturnal sleep in a sample of young (mean age=35months) typically developing male and female (n=41 and 25, respectively) children. Axial diffusivity, radial diffusivity, mean diffusivity and fractional anisotropy were measured at 99 points along the length of 18 major brain tracts. Influences of hemisphere, age, sex, and handedness were examined. We find that diffusion properties vary significantly along the length of the majority of tracks. We also identify hemispheric and sex differences in diffusion properties in several tracts. Finally, we find the relationship between age and diffusion parameters changes along the tract length illustrating variability in age-related white-matter development at the tract level.

Proton magnetic resonance spectroscopy ((1)H-MRS) studies showing increased lactate during neural activation support a broader role for lactate in brain energy metabolism than was traditionally recognized. Proton MRS measures of brain lactate responses have been used to study regional brain metabolism in clinical populations. This study examined whether variations in blood glucose influence the lactate response to visual stimulation in the visual cortex. Six subjects were scanned twice, receiving either saline or 21% glucose intravenously. Using (1)H-MRS at 1.5 Tesla with a long echo time (TE=288 ms), the lactate doublet was visible at 1.32 ppm in the visual cortex of all subjects. Lactate increased significantly from resting to visual stimulation. Hyperglycemia had no effect on this increase. The order of the slice-selective gradients for defining the spectroscopy voxel had a pronounced effect on the extent of contamination by signal originating outside the voxel. The results of this preliminary study demonstrate a method for observing a consistent activity-stimulated increase in brain lactate at 1.5 T and show that variations in blood glucose across the normal range have little effect on this response.

The fornix is the primary subcortical output fiber system of the hippocampal formation. In children with 22q11.2 deletion syndrome (22q11.2DS), hippocampal volume reduction has been commonly reported, but few studies as yet have evaluated the integrity of the fornix. Therefore, we investigated the fornix of 45 school-aged children with 22q11.2DS and 38 matched typically developing (TD) children. Probabilistic diffusion tensor imaging (DTI) tractography was used to reconstruct the body of the fornix in each child׳s brain native space. Compared with children, significantly lower fractional anisotropy (FA) and higher radial diffusivity (RD) was observed bilaterally in the body of the fornix in children with 22q11.2DS. Irregularities were especially prominent in the posterior aspect of the fornix where it emerges from the hippocampus. Smaller volumes of the hippocampal formations were also found in the 22q11.2DS group. The reduced hippocampal volumes were correlated with lower fornix FA and higher fornix RD in the right hemisphere. Our findings provide neuroanatomical evidence of disrupted hippocampal connectivity in children with 22q11.2DS, which may help to further understand the biological basis of spatial impairments, affective regulation, and other factors related to the ultra-high risk for schizophrenia in this population.

[This corrects the article DOI: 10.1186/s13229-015-0005-4.].

Background

Abnormalities in the corpus callosum have been reported in individuals with autism spectrum disorder (ASD), but few studies have evaluated young children. Sex differences in callosal organization and diffusion characteristics have also not been evaluated fully in ASD.

Methods

Structural and diffusion-weighted images were acquired in 139 preschool-aged children with ASD (112 males/27 females) and 82 typically developing (TD) controls (53 males/29 females). Longitudinal scanning at two additional annual time points was carried out in a subset of these participants. Callosal organization was evaluated using two approaches: 1) diffusion tensor imaging (DTI) tractography to define subregions based on cortical projection zones and 2) as a comparison to previous studies, midsagittal area analysis using Witelson subdivisions. Diffusion measures of callosal fibers were also evaluated.

Results

Analyses of cortical projection zone subregions revealed sex differences in the patterns of altered callosal organization. Relative to their sex-specific TD counterparts, both males and females with ASD had smaller regions dedicated to fibers projecting to superior frontal cortex, but patterns differed in callosal subregions projecting to other parts of frontal cortex. While males with ASD had a smaller callosal region dedicated to the orbitofrontal cortex, females with ASD had a smaller callosal region dedicated to the anterior frontal cortex. There were also sex differences in diffusion properties of callosal fibers. While no alterations were observed in males with ASD relative to TD males, mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were all increased in females with ASD relative to TD females. Analyses of Witelson subdivisions revealed a decrease in midsagittal area of the corpus callosum in both males and females with ASD but no regional differences in specific subdivisions. Longitudinal analyses revealed no diagnostic or sex differences in the growth rate or change in diffusion measures of the corpus callosum from 3 to 5 years of age.

Conclusions

There are sex differences in the pattern of altered corpus callosum neuroanatomy in preschool-aged children with ASD.