BACKGROUND AND PURPOSE:Fast macromolecular proton fraction mapping is a recently emerged MRI method for quantitative myelin imaging. Our aim was to develop a clinically targeted technique for macromolecular proton fraction mapping of the fetal brain and test its capability to characterize normal prenatal myelination.
Background:
Apparent diffusion coefficient (ADC) is known as a quantitative biomarker of prenatal brain maturation. Fast macromolecular proton fraction (MPF) mapping is an emerging method for quantitative assessment of myelination that was recently adapted to fetal MRI.
Purpose:
To compare the capability of ADC and MPF to quantify the normal fetal brain development.
Study Type:
Prospective.
Population:
42 human fetuses in utero (gestational age (GA) = 27.7 ± 6.0, range 20–38 weeks).
Field Strength/Sequence:
1.5T; diffusion-weighted single-shot echo-planar spin-echo with five b-values for ADC mapping; spoiled multi-shot echo-planar gradient-echo with T1, proton density, and magnetization transfer contrast weightings for single-point MPF mapping.
Assessment:
Two operators measured ADC and MPF in the medulla, pons, cerebellum, thalamus, and frontal, occipital, and temporal cerebral white matter (WM).
Statistical Tests:
Mixed repeated-measures ANOVA with the factors of pregnancy trimester and brain structure; Pearson correlation coefficient (r); Hotelling-Williams test to compare strengths of correlations.
Results:
From 2nd to 3rd trimester, ADC significantly decreased in the thalamus and cerebellum (P<0.005). MPF significantly increased in the medulla, pons, thalamus, and cerebellum (P<0.005). Cerebral WM had significantly higher ADC and lower MPF compared to the medulla and pons in both trimesters. MPF (r range 0.83− 0.89, P<0.001) and ADC (r range −0.43 −0.75, P≤0.004) significantly correlated with GA and each other (r range −0.32 −0.60, P≤0.04) in the medulla, pons, thalamus, and cerebellum. No significant correlations and distinctions between regions and trimesters were observed for cerebral WM (P range 0.1–0.75). Correlations with GA were significantly stronger for MPF compared to ADC in the medulla, pons, and cerebellum (Hotelling-Williams test P<0.003) and similar in the thalamus. Structure-averaged MPF and ADC values strongly correlated (r=0.95, P<0.001).
Data Conclusion:
MPF and ADC demonstrated qualitatively similar but quantitatively different spatiotemporal patterns. MPF appeared more sensitive to changes in the brain structures with prenatal onset of myelination.
In vivo proton magnetic resonance spectroscopy ((1) H MRS) of outbred stock ICR male mice (originating from the Institute of Cancer Research) was used to study the brain (hippocampus) metabolic response to the pro-inflammatory stimulus and to the acute deficiency of the available energy, which was confirmed by measuring the maximum oxygen consumption. Inhibition of glycolysis by means of an injection with 2-deoxy-d-glucose (2DG) reduced the levels of gamma-aminobutyric acid (GABA, p < 0.05, in comparison with control, least significant difference (LSD) test), N-acetylaspartate (NAA, p < 0.05, LSD test) and choline compounds, and at the same time increased the levels of glutamate and glutamine. An opposite effect was found after injection with bacterial lipopolysaccharide (LPS) - a very common pro-inflammatory inducer. An increase in the amounts of GABA, NAA and choline compounds in the brain occurred in mice treated with LPS. Different metabolic responses to the energy deficiency and the pro-inflammatory stimuli can explain the contradictory results of the brain (1) H MRS studies under neurodegenerative pathology, which is accompanied by both mitochondrial dysfunction and inflammation. The prevalence of the excitatory metabolites such as glutamate and glutamine in 2DG treated mice is in good agreement with excitation observed during temporary reduction of the available energy under acute hypoxia or starvation. In turn, LPS, as an inducer of the sickness behavior, which was manifested as depression, sleepiness, loss of appetite etc., shifts the brain metabolic pattern toward the prevalence of the inhibitory neurotransmitter GABA.
Network mechanisms of depression development and especially of improvement from nonpharmacological treatment remain understudied. The current study is aimed at examining brain networks functional connectivity in depressed patients and its dynamics in nonpharmacological treatment. Resting state fMRI data of 21 healthy adults and 51 patients with mild or moderate depression were analyzed with spatial independent component analysis; then, correlations between time series of the components were calculated and compared between-group (study 1). Baseline and repeated-measure data of 14 treated (psychotherapy or fMRI neurofeedback) and 15 untreated depressed participants were similarly analyzed and correlated with changes in depression scores (study 2). Aside from diverse findings, studies 1 and 2 both revealed changes in within-default mode network (DMN) and DMN to executive control network (ECN) connections. Connectivity in one pair, initially lower in depression, decreased in no treatment group and was inversely correlated with Montgomery-Asberg depression score change in treatment group. Weak baseline connectivity in this pair also predicted improvement on Montgomery-Asberg scale in both treatment and no treatment groups. Coupling of another pair, initially stronger in depression, increased in therapy though was unrelated to improvement. The results demonstrate possible role of within-DMN and DMN-ECN functional connectivity in depression treatment and suggest that neural mechanisms of nonpharmacological treatment action may be unrelated to normalization of initially disrupted connectivity.
Patients with mild depression and apparently healthy individuals were presented images and asked to sort them into "pleasant" and "unpleasant" subsets. In both groups, the main differences between brain activation patterns during presentation of pleasant and unpleasant images were localized in the motor regions (precentral and postcentral gyrus) and in the cerebellum (p<0.05 with FWE correction). Most likely, these clusters are associated with motion (pressing a button in accordance with the instruction). According to the data of intergroup contrasts, patients with depression had less pronounced activation of frontal structures (middle frontal gyrus and other areas, including the white matter) in response to both positive and negative images (p<0.001). In healthy subjects, the response of the temporo-occipital areas (lingual and fusiform gyrus) to unpleasant stimuli was more intensive than in patients (p<0.001). This can be due to differences in the semantic image processing. Thus, in case of mild depression, the response of the amygdaloid complex, the key structure in the development in affective disorder, was not always observed. At the same time, the response of frontal and temporo-occipital regions has a certain potential as a biomarker of mild depression, although the reliability of the obtained data requires additional confirmation.
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