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Introduction: Many children living with HIV (CLWH) display impaired cognition. Although early combination antiretrovira therapy (ART) produces improved cognitive outcomes, more long-term outcome data are needed. After concluding the Children with HIV Early antiRetroviral (CHER) trial in 2011, we investigated cognitive performance, at seven and nine years of age. Participants had been randomized to deferred ART (ART-Def; n = 22); immediate time-limited ART for 40 weeks (ART40W; n = 30) and immediate time-limited ART for 96 weeks (ART-96W; n = 18). We also recruited HIV-exposed uninfected (CHEU; n = 28) and HIV-unexposed (CHU; n = 35) children. Methods: Data were collected between May 2012 and December 2017. Mixed-model repeated-measures ANOVAs assessed differences over time between CLWH (ART-40W, ART-96W and ART-Def) and CHIV- CHEU and CHU between ART-Early (ART-40W and ART-96W), ART-Def, CHEU and CHU; and between ART-40W, ART-96W, ART-Def, CHEU and CHU. Results: All comparisons found significant effects of Time for most outcome variables (better scores at nine than at seven years; ps < 0.05). The first ANOVAs found that for (a) motor dexterity, CLWH performed worse than CHIV- at seven years (p < 0.001) but improved to equivalence at nine years, (b) visual-spatial processing and problem solving, only CLWH (p < 0.04) showed significant performance improvement over time and (c) working memory and executive function, CLWH performed worse than CHIV- at both seven and nine years (p = 0.03 and 0.04). The second ANOVAs found that for (a) working memory, CHU performed better than ART-Early and CHEU (p < 0.01 and 0.17). Similarly, for motor dexterity, ART-Def performed worse than ART-96W, CHEU and CHU at seven years (p < 0.04, 0.20). Conclusions: Although neurocognitive developmental trajectories for treatment groups and controls were largely similar (i.e. performance improvements from 7 to 9), all ART-treated children, regardless of treatment arm, remain at risk for cognitive deficits over early school ages. Although the nature of these deficits may change as cognitive development proceeds, there are potential negative consequences for these children's future learning, reasoning and adaptive functioning. Keywords: antiretroviral therapy; The Children with HIV Early Antiretrovira Therapy (CHER) trial; HIV/AIDS; HIV-associated neurocognitive impairment; paediatric HIV; working memory, 1 | INTRODUCTION Despite treatment advances, many children living with HIV (CLWH) have impaired cognitive performance [1-3]. Early and severe HIV-related neurological manifestations such as encephalopathy, increase the risk of [...]

Background: Prenatal alcohol exposure (PAE) is associated with smaller regional and global brain volumes. In rats, gestational choline supplementation mitigates adverse developmental effects of ethanol exposure. Our recent randomized, double‐blind, placebo‐controlled maternal choline supplementation trial showed improved somatic and functional outcomes in infants at 6.5 and 12 months postpartum. Here, we examined whether maternal choline supplementation protected the newborn brain from PAE‐related volume reductions and, if so, whether these volume changes were associated with improved infant recognition memory. Methods: Fifty‐two infants born to heavy‐drinking women who had participated in a choline supplementation trial during pregnancy underwent structural magnetic resonance imaging with a multi‐echo FLASH protocol on a 3T Siemens Allegra MRI (median age = 2.8 weeks postpartum). Subcortical regions were manually segmented. Recognition memory was assessed at 12 months on the Fagan Test of Infant Intelligence (FTII). We examined the effects of choline on regional brain volumes, whether choline‐related volume increases were associated with higher FTII scores, and the degree to which the regional volume increases mediated the effects of choline on the FTII. Results: Usable MRI data were acquired in 50 infants (choline: n = 27; placebo: n = 23). Normalized volumes were larger in six of 12 regions in the choline than placebo arm (t ≥ 2.05, p ≤ 0.05) and were correlated with the degree of maternal choline adherence (β ≥ 0.28, p ≤ 0.04). Larger right putamen and corpus callosum were related to higher FTII scores (r = 0.36, p = 0.02) with a trend toward partial mediation of the choline effect on recognition memory. Conclusions: High‐dose choline supplementation during pregnancy mitigated PAE‐related regional volume reductions, with larger volumes associated with improved 12‐month recognition memory. These results provide the first evidence that choline may be neuroprotective against PAE‐related brain structural deficits in humans. [ABSTRACT FROM AUTHOR]

Purpose. To evaluate whether 3T clinical MRI with a small-animal coil and gradient-echo (GE) sequence could be used to characterize long-term left ventricular remodelling (LVR) following nonreperfused myocardial infarction (MI) using semi-automatic segmentation software (SASS) in a rat model. Materials and Methods. 5 healthy rats were used to validate left ventricular mass (LVM) measured by MRI with postmortem values. 5 sham and 7 infarcted rats were scanned at 2 and 4 weeks after surgery to allow for functional and structural analysis of the heart. Measurements included ejection fraction (EF), end-diastolic volume (EDV), end-systolic volume (ESV), and LVM. Changes in different regions of the heart were quantified using wall thickness analyses. Results. LVM validation in healthy rats demonstrated high correlation between MR and postmortem values. Functional assessment at 4 weeks after MI revealed considerable reduction in EF, increases in ESV, EDV, and LVM, and contractile dysfunction in infarcted and noninfarcted regions. Conclusion. Clinical 3T MRI with a small animal coil and GE sequence generated images in a rat heart with adequate signal-to-noise ratio (SNR) for successful semiautomatic segmentation to accurately and rapidly evaluate long- term LVR after MI., 1. Introduction Assessment of ventricular function and mass is an important guide for predicting survival in patients suffering from different cardiovascular diseases, such as ischemic heart disease [1]. In addition, [...]

Purpose: CEST MRI allows for indirect detection of molecules with exchangeable protons, measured as a reduction in water signal because of continuous transfer of saturated protons. CEST requires saturation pulses on the order of a second, as well as repeated acquisitions at different offset frequencies. The resulting extended scan time makes CEST susceptible to subject motion, which introduces field inhomogeneity, shifting offset frequencies and causing distortions in CEST spectra that resemble true CEST effects. This is a particular problem for molecules that resonate close to water, such as hydroxyl group in glycogen. To address this, a technique for real‐time measurement and correction of motion and field inhomogeneity is proposed. Methods: A CEST sequence was modified to include double volumetric navigators (DvNavs) for real‐time simultaneous motion and shim correction. Phantom tests were conducted to investigate the effects of motion and shim changes on CEST quantification and to validate the accuracy of DvNav motion and shim estimates. To evaluate DvNav shim and motion correction in vivo, acquisitions including 5 experimental conditions were performed in the calf muscle of 2 volunteers. Results: Phantom data show that DvNav‐CEST accurately estimates frequency and linear gradient changes because of motion and corrects resulting image distortions. In addition, DvNav‐CEST improves CEST quantification in vivo in the presence of motion. Conclusion: The proposed technique allows for real‐time simultaneous motion and shim correction with no additional scanning time, enabling accurate CEST quantification even in the presence of motion and field inhomogeneity. [ABSTRACT FROM AUTHOR]

Background: Schizophrenia is characterized by small reductions in cortical gray matter volume, particularly in the temporal and prefrontal cortices. The question of whether cortical thickness is reduced in schizophrenia has not been addressed using magnetic resonance imaging (MRI) techniques. Our objectives were to test the hypothesis that cortical thinning in patients with schizophrenia (relative to control subjects) is greater in temporal and prefrontal regions of interest (ROIs) than in control ROIs (superior parietal, calcarine, postcentral, central, and precentral cortices), and to obtain an unbiased estimate of the distribution of cortical thinning in patients (relative to controls) by constructing mean and statistical cortical thickness difference maps. Methods: Participants included 33 right-handed outpatients receiving medication and meeting DSM-IV criteria for schizophrenia and 32 healthy volunteers, matched on age and parental socioeconomic status. After high-resolution MRI scans, models of the gray-white and pial surfaces were generated for each individual's cortex, and the distance between these 2 surfaces was used to compute cortical thickness. A surface-based averaging technique that aligned the main cortical folds across individuals allowed between-group comparisons of thickness within ROIs, and at multiple, uniformly sampled loci across the cortical ribbon. Results: Relative to controls, patients showed greater cortical thinning in temporal-prefrontal ROIs than in control ROIs, as revealed by a significant (P<.009) interaction between group and region type. Cortical thickness difference maps revealed significant (at P<.05, corrected) thinning within the orbitofrontal cortices bilaterally; the inferior frontal, inferior temporal, and occipitotemporal cortices on the left; and within the medial temporal and medial frontal cortices on the right. Superior parietal and primary somatosensory and motor cortices were relatively spared, even at subthreshold significance levels. Conclusions: Patients with chronic schizophrenia showed widespread cortical thinning that particularly affected the prefrontal and temporal cortices. This thinning might reflect underlying neuropathological abnormalities in cortical structure. [ABSTRACT FROM AUTHOR]