Similar cortical morphometry trajectories from 5 to 9 years in children with perinatal HIV who started treatment before age 2 years and uninfected controls.

BACKGROUND: Life-long early ART (started before age 2 years), often with periods of treatment interruption, is now the standard of care in pediatric HIV infection. Although cross-sectional studies have investigated HIV-related differences in cortical morphology in the setting of early ART and ART interruption, the long-term impact on cortical developmental trajectories is unclear. This study compares the longitudinal trajectories of cortical thickness and folding (gyrification) from age 5 to 9 years in a subset of children perinatally infected with HIV (CPHIV) from the Children with HIV Early antiRetroviral therapy (CHER) trial to age-matched children without HIV infection. METHODS: 75 CHER participants in follow-up care at FAMCRU (Family Centre for Research with Ubuntu), as well as 66 age-matched controls, received magnetic resonance imaging (MRI) on a 3 T Siemens Allegra at ages 5, 7 and/or 9 years. MR images were processed, and cortical surfaces reconstructed using the FreeSurfer longitudinal processing stream. Vertex-wise linear mixed effects (LME) analyses were performed across the whole brain to compare the means and linear rates of change of cortical thickness and gyrification from 5 to 9 years between CPHIV and controls, as well as to examine effects of ART interruption. RESULTS: Children without HIV demonstrated generalized cortical thinning from 5 to 9 years, with the rate of thinning varying by region, as well as regional age-related gyrification increases. Overall, the means and developmental trajectories of cortical thickness and gyrification were similar in CPHIV. However, at an uncorrected p < 0.005, 6 regions were identified where the cortex of CPHIV was thicker than in uninfected children, namely bilateral insula, left supramarginal, lateral orbitofrontal and superior temporal, and right medial superior frontal regions. Planned ART interruption did not affect development of cortical morphometry. CONCLUSIONS: Although our results suggest that normal development of cortical morphometry between the ages of 5 and 9 years is preserved in CPHIV who started ART early, these findings require further confirmation with longitudinal follow-up through the vulnerable adolescent period.

Repeatability and reproducibility of prospective motion- and shim corrected 2D glycoCEST MRI.

BACKGROUND: Repeated glycoCEST MRI measurements on the same subject should produce similar results under the same environmental and experimental conditions. However, fluctuations in the static B0 field, which may occur between and within measurements due to heating of the shim iron or subject motion, may alter results and affect reproducibility. Here we investigate the repeatability and reproducibility of glycoCEST measurements and examine the effectiveness of a real-time shim- and motion navigated chemical exchange saturation transfer (CEST) sequence to improve reproducibility. METHODS: In nine subjects, double volumetric navigated (DvNav)-CEST acquisitions in the calf muscle were repeated five times in each of two sessions-the first without correction, and the second with real-time shim- and motion correction applied. In both sessions a dynamically changing field was introduced by running a 5-minute gradient intensive diffusion sequence. We evaluated the effect of the introduced B0 inhomogeneity on the reproducibility of glycoCEST, where the small chemical shift difference between the hydroxyl and bulk water protons at 3 T makes CEST quantification extremely sensitive to magnetic field inhomogeneities. RESULTS: With real-time shim- and motion correction, glycoCEST results were relatively consistent with mean coefficient of variation (CoV) 2.7%±1.4% across all subjects, whereas without correction the results were less consistent with CoV 84%±71%. CONCLUSIONS: Our results demonstrate that real-time shim- and motion correction can mitigate effects of B0 field fluctuations and improve reproducibility of glycoCEST data. This is important when conducting longitudinal studies or when using glycoCEST MRI to assess treatment or physiological responses over time.