Altered White Matter Tracts in the Somatosensory, Salience, Motor, and Default Mode Networks in 7-Year-Old Children Living with Human Immunodeficiency Virus: A Tractographic Analysis.

Introduction: Even with the increased access and early initiation of combination antiretroviral therapy, children with perinatally acquired human immunodeficiency virus (CPHIV) continue to demonstrate white matter alterations. Children perinatally HIV-exposed, but uninfected (CHEU) alike show differences in white matter integrity compared with children who are HIV-unexposed and uninfected (CHUU). Objectives: Mapping white matter connections that link gray matter regions that form resting-state (RS) functional networks may demonstrate whether structural and functional connectivity alterations in HIV infection and exposure may be related. We hypothesized reduced structural connectivity in CPHIV within the default mode network (DMN), visual, ventral DMN (vDMN), somatosensory, salience, auditory, motor, executive, basal ganglia, and posterior DMN (pDMN). We also hypothesized that CHEU will have increased structural connectivity compared with CHUU in the vDMN, somatosensory, pDMN, dorsal attention, salience, auditory, motor and basal ganglia. Methods: Study participants were 61 seven-year-old CPHIV and 46 age-matched children who are HIV uninfected (CHU) (19 CHEU). We used diffusion tensor imaging-based tractography to investigate white matter connections that link gray matter regions within RS functional networks. Results: We found altered white matter integrity in the somatosensory, salience, default mode, and motor networks of CPHIV compared with CHU. The superior temporal cortex, superior frontal cortex, and putamen were affected in all four networks and have also been reported to demonstrate morphological alterations in the same cohort. In CHEU, white matter integrity was higher in the visual network, pDMN, and motor network compared with CHUU. Conclusion: Our results suggest that altered white matter integrity may influence gray matter morphology and functional network alterations. Impact statement The long-term effects of human immunodeficiency virus (HIV) and exposure on the developing brain in the combination antiretroviral therapy era are still not well known. We use diffusion tensor imaging-based tractography to explore these effects on white matter connections that link gray matter regions within functional networks. Our findings provide a context for HIV-associated white matter and connectivity abnormalities.

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.

White Matter Abnormalities in Children with HIV Infection and Exposure.

Background: Due to changes in guidelines and access to treatment, more children start combination antiretroviral therapy (ART) in infancy. With few studies examining the long-term effects of perinatal HIV infection and early ART on neurodevelopment, much is still unknown about brain maturation in the presence of HIV and ART. Follow-up studies of HIV infected (HIV+) children are important for monitoring brain development in the presence of HIV infection and ART. Methods: We use diffusion tensor imaging (DTI) to examine white matter (WM) in 65 HIV+ and 46 control (HIV exposed uninfected (HEU) and HIV unexposed uninfected (HU)) 7-year-old children. This is a follow up of a cohort studied at 5 years, where we previously reported lower fractional anisotropy (FA) in corticospinal tract (CST) and mean diffusivity (MD) increases in inferior/superior longitudinal fasciculi (ILF/SLF), inferior fronto-occipital fasciculus (IFOF) and uncinate fasciculus (UF) in HIV+ children compared to uninfected controls. In addition, we also found a difference in FA related to age at which ART was initiated. Results: At 7 years, we found two regions in the left IFOF and left ILF with lower FA in HIV+ children compared to controls. Higher MD was observed in a similar region in the IFOF, albeit bilaterally, as well as multiple clusters bilaterally in the superior corona radiata (SCR), the anterior thalamic radiation (ATR) and the right forceps minor. Unlike at 5 years, we found no impact on WM of ART initiation. In HEU children, we found a cluster in the right posterior corona radiata with higher FA compared to HU children, while bilateral regions in the CST demonstrated reduced MD. Conclusions: At age 7, despite early ART and viral load (VL) suppression, we continue to observe differences in WM integrity. WM damage observed at age 5 years persists, and new damage is evident. The continued observation of regions with lower FA and higher MD in HIV+ children point to disruptions in ongoing white matter development regardless of early ART. Lastly, in HEU children we find higher FA and lower MD in clusters in the CST tract suggesting that perinatal HIV/ART exposure has a long-term impact on WM development.

Heavy Prenatal Alcohol Exposure is Related to Smaller Corpus Callosum in Newborn MRI Scans.

BACKGROUND: Magnetic resonance imaging (MRI) studies have consistently demonstrated disproportionately smaller corpus callosa in individuals with a history of prenatal alcohol exposure (PAE) but have not previously examined the feasibility of detecting this effect in infants. Tissue segmentation of the newborn brain is challenging because analysis techniques developed for the adult brain are not directly transferable, and segmentation for cerebral morphometry is difficult in neonates, due to the latter's incomplete myelination. This study is the first to use volumetric structural MRI to investigate PAE effects in newborns using manual tracing and to examine the cross-sectional area of the corpus callosum (CC). METHODS: Forty-three nonsedated infants born to 32 Cape Coloured heavy drinkers and 11 controls recruited prospectively during pregnancy were scanned using a custom-designed birdcage coil for infants, which increases signal-to-noise ratio almost 2-fold compared to the standard head coil. Alcohol use was ascertained prospectively during pregnancy, and fetal alcohol spectrum disorders diagnosis was conducted by expert dysmorphologists. Data were acquired using a multi-echo FLASH protocol adapted for newborns, and a knowledge-based procedure was used to hand-segment the neonatal brains. RESULTS: CC was disproportionately smaller in alcohol-exposed neonates than controls after controlling for intracranial volume. By contrast, CC area was unrelated to infant sex, gestational age, age at scan, or maternal smoking, marijuana, or methamphetamine use during pregnancy. CONCLUSIONS: Given that midline craniofacial anomalies have been recognized as a hallmark of fetal alcohol syndrome in humans and animal models since this syndrome was first identified, the CC deficit identified here in newborns may support early identification of a range of midline structural impairments. Smaller CC during the newborn period may provide an early indicator of fetal alcohol-related cognitive deficits that have been linked to this critically important brain structure in childhood and adolescence.

3D GABA imaging with real-time motion correction, shim update and reacquisition of adiabatic spiral MRSI.

Gamma-aminobutyric acid (GABA) and glutamate (Glu) are the major neurotransmitters in the brain. They are crucial for the functioning of healthy brain and their alteration is a major mechanism in the pathophysiology of many neuro-psychiatric disorders. Magnetic resonance spectroscopy (MRS) is the only way to measure GABA and Glu non-invasively in vivo. GABA detection is particularly challenging and requires special MRS techniques. The most popular is MEscher-GArwood (MEGA) difference editing with single-voxel Point RESolved Spectroscopy (PRESS) localization. This technique has three major limitations: a) MEGA editing is a subtraction technique, hence is very sensitive to scanner instabilities and motion artifacts. b) PRESS is prone to localization errors at high fields (≥3T) that compromise accurate quantification. c) Single-voxel spectroscopy can (similar to a biopsy) only probe steady GABA and Glu levels in a single location at a time. To mitigate these problems, we implemented a 3D MEGA-editing MRS imaging sequence with the following three features: a) Real-time motion correction, dynamic shim updates, and selective reacquisition to eliminate subtraction artifacts due to scanner instabilities and subject motion. b) Localization by Adiabatic SElective Refocusing (LASER) to improve the localization accuracy and signal-to-noise ratio. c) K-space encoding via a weighted stack of spirals provides 3D metabolic mapping with flexible scan times. Simulations, phantom and in vivo experiments prove that our MEGA-LASER sequence enables 3D mapping of GABA+ and Glx (Glutamate+Gluatmine), by providing 1.66 times larger signal for the 3.02ppm multiplet of GABA+ compared to MEGA-PRESS, leading to clinically feasible scan times for 3D brain imaging. Hence, our sequence allows accurate and robust 3D-mapping of brain GABA+ and Glx levels to be performed at clinical 3T MR scanners for use in neuroscience and clinical applications.

Long-term left ventricular remodelling in rat model of nonreperfused myocardial infarction: sequential MR imaging using a 3T clinical scanner.

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.

Cine magnetic resonance imaging with simultaneous audio to evaluate pediatric velopharyngeal insufficiency.

OBJECTIVE: To develop a protocol linking cine magnetic resonance (MR) imaging to simultaneously acquired audio recordings of specific phonatory tasks to evaluate velopharyngeal insufficiency (VPI) in children. DESIGN: Institutional review board-approved development and application of a novel dynamic cine MR imaging protocol linked to simultaneously recorded audio. SETTING: A tertiary care multidisciplinary pediatric airway center. PARTICIPANTS: Three healthy adult volunteers and 5 pediatric volunteers (age range, 9.3-18.9 years; mean age, 12.4 years) from the multidisciplinary pediatric airway center with VPI who previously had undergone nasopharyngoscopy, videofluoroscopy, or both. INTERVENTIONS: Cine MR imaging with simultaneously acquired audio files was performed in 3 adult volunteers to optimize the protocol and then in 5 pediatric volunteers meeting the inclusion criteria. MAIN OUTCOME MEASURES: High-resolution cine MR images with clear intelligible audio recordings of specific phonatory tasks. RESULTS: Using 3 healthy adult volunteers, a cine MR imaging VPI protocol was developed that links simultaneously acquired cine MR images to audio recordings of specific validated phonatory tasks. Five school-aged children with VPI from our multidisciplinary pediatric airway center were then enrolled and underwent cine MR imaging using this protocol. The cine MR images and audio recordings acquired were of sufficient diagnostic quality to evaluate VPI closure patterns in school-aged children with VPI. CONCLUSION: Cine MR imaging linked to audio is a quick, safe, and well-tolerated dynamic diagnostic imaging tool that may eventually have the potential to guide more precisely the selection and application of surgical techniques for VPI.