MRI is a sensitive method for detecting subtle anatomic abnormalities in the neonatal brain. To optimize the usefulness for neonatal and pediatric care, systematic research, based on quantitative image analysis and functional correlation, is required. Normalization-based image analysis is one of the most effective methods for image quantification and statistical comparison. However, the application of this methodology to neonatal brain MRI scans is rare. Some of the difficulties are the rapid changes in T1 and T2 contrasts and the lack of contrast between brain structures, which prohibits accurate cross-subject image registration. Diffusion tensor imaging (DTI), which provides rich and quantitative anatomical contrast in neonate brains, is an ideal technology for normalization-based neonatal brain analysis. In this paper, we report the development of neonatal brain atlases with detailed anatomic information derived from DTI and co-registered anatomical MRI. Combined with a diffeomorphic transformation, we were able to normalize neonatal brain images to the atlas space and three-dimensionally parcellate images into 122 regions. The accuracy of the normalization was comparable to the reliability of human raters. This method was then applied to babies of 37 to 53 post-conceptional weeks to characterize developmental changes of the white matter, which indicated a posterior-to-anterior and a central-to-peripheral direction of maturation. We expect that future applications of this atlas will include investigations of the effect of prenatal events and the effects of preterm birth or low birth weights, as well as clinical applications, such as determining imaging biomarkers for various neurological disorders.

Objective To determine whether cognitive impairment and brain injury as measured by proton magnetic resonance spectroscopy (MRS) persist in the setting of highly active antiretroviral therapy (HAART). Design This study is an observational cohort study. Methods MRS was performed in 268 patients: HIV-negative controls (N=28), HIV-positive neuroasymptomatic (NA) subjects (N=124), and subjects with AIDS Dementia Complex (ADC; N=50) on stable ART with a mean duration of infection of 12 years and CD4 of 309 cells/mm3. Four metabolites were measured over creatine (Cr): N-acetyl aspartate (NAA), marker of neuronal integrity; Choline (Cho), myoinositol (MI), markers of inflammation, and glutamate and glutamine (Glx) in the basal ganglia (BG), frontal white matter (FWM) and mid-frontal Cortex (MFC). Analyses included ANOVA, ANCOVA, linear and nonparametric regression models. Results Cognitive impairment was found in 48% of HIV infected subjects. Both HIV positive groups showed significant increases in MI/Cr or Cho/Cr in all brain regions when compared to controls; a significant decrease in Glx/Cr in the FWM was observed in the NA group; only ADC subjects showed a significant reduction in NAA/ Cr although a significant trend for decreasing NAA/Cr in the BG was found across the groups. Effects related to aging and duration of infection but not central nervous system penetration effectiveness (CPE) were observed. Conclusions Brain inflammatory changes remain ubiquitous among HIV-infected subjects whereas neuronal injury occurs predominantly in those with cognitive impairment. Together these findings indicate that despite the widespread use of HAART, HIV-associated cognitive impairment and brain injury persist in the setting of chronic and stable disease.

IMPORTANCE The very early postnatal period witnesses extraordinary rates of growth, but structural brain development in this period has largely not been explored longitudinally. Such assessment may be key in detecting and treating the earliest signs of neurodevelopmental disorders.OBJECTIVE To assess structural growth trajectories and rates of change in the whole brain and regions of interest in infants during the first 3 months after birth. DESIGN, SETTING, AND PARTICIPANTS Serial structural T1-weighted and/or T2-weighted magnetic resonance images were obtained for 211 time points from 87 healthy term-born or term-equivalent preterm-born infants, aged 2 to 90 days, between October 5, 2007, and June 12, 2013. MAIN OUTCOMES AND MEASURESWe segmented whole-brain and multiple subcortical regions of interest using a novel application of Bayesian-based methods. We modeled growth and rate of growth trajectories nonparametrically and assessed left-right asymmetries and sexual dimorphisms.RESULTS Whole-brain volume at birth was approximately one-third of healthy elderly brain volume, and did not differ significantly between male and female infants (347 388 mm 3 and 335 509 mm 3 , respectively, P = .12). The growth rate was approximately 1%/d, slowing to 0.4%/d by the end of the first 3 months, when the brain reached just more than half of elderly adult brain volume. Overall growth in the first 90 days was 64%. There was a significant age-by-sex effect leading to widening separation in brain sizes with age between male and female infants (with male infants growing faster than females by 200.4 mm 3 /d, SE = 67.2, P = .003). Longer gestation was associated with larger brain size (2215 mm 3 /d, SE = 284, P = 4×10 −13 ). The expected brain size of an infant born one week earlier than average was 5% smaller than average; at 90 days it will not have caught up, being 2% smaller than average. The cerebellum grew at the highest rate, more than doubling in 90 days, and the hippocampus grew at the slowest rate, increasing by 47% in 90 days. There was left-right asymmetry in multiple regions of interest, particularly the lateral ventricles where the left was larger than the right by 462 mm 3 on average (approximately 5% of lateral ventricular volume at 2 months). We calculated volume-by-age percentile plots for assessing individual development. CONCLUSIONS AND RELEVANCENormative trajectories for early postnatal brain structural development can be determined from magnetic resonance imaging and could be used to improve the detection of deviant maturational patterns indicative of neurodevelopmental disorders.