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HIV exposed-uninfected (HEU) infants and children are at risk of developmental delays as compared to HIV uninfected unexposed (HUU) populations. The effects of exposure to in utero HIV and ART regimens on the HEU the developing brain are not well understood. In a cohort of 2-week-old newborns, we used diffusion tensor imaging (DTI) tractography and graph theory to examine the influence of HIV and ART exposure in utero on neonate white matter integrity and organisation. The cohort included HEU infants born to mothers who started ART before conception (HEUpre) and after conception (HEUpost), as well as HUU infants from the same community. We investigated HIV exposure and ART duration group differences in DTI metrics (fractional anisotropy (FA) and mean diffusivity (MD)) and graph measures across white matter. We found increased MD in white matter connections involving the thalamus and limbic system in the HEUpre group compared to HUU. We further identified reduced nodal efficiency in the basal ganglia. Within the HEUpost group, we observed reduced FA in cortical-subcortical and cerebellar connections as well as decreased transitivity in the hindbrain area compared to HUU. Overall, our analysis demonstrated distinct alterations in white matter integrity related to the timing of maternal ART initiation that influence regional brain network properties. [ABSTRACT FROM AUTHOR]

Perivascular spaces (PVS) are compartments surrounding cerebral blood vessels that become visible on MRI when enlarged. Enlarged PVS (EPVS) are commonly seen in patients with cerebral small vessel disease (CSVD) and have been suggested to reflect dysfunctional perivascular clearance of soluble waste products from the brain. In this study, we investigated histopathological correlates of EPVS and how they relate to vascular amyloid-β (Aβ) in cerebral amyloid angiopathy (CAA), a form of CSVD that commonly co-exists with Alzheimer's disease (AD) pathology. We used ex vivo MRI, semi-automatic segmentation and validated deep-learning-based models to quantify EPVS and associated histopathological abnormalities. Severity of MRI-visible PVS during life was significantly associated with severity of MRI-visible PVS on ex vivo MRI in formalin fixed intact hemispheres and corresponded with PVS enlargement on histopathology in the same areas. EPVS were located mainly around the white matter portion of perforating cortical arterioles and their burden was associated with CAA severity in the overlying cortex. Furthermore, we observed markedly reduced smooth muscle cells and increased vascular Aβ accumulation, extending into the WM, in individually affected vessels with an EPVS. Overall, these findings are consistent with the notion that EPVS reflect impaired outward flow along arterioles and have implications for our understanding of perivascular clearance mechanisms, which play an important role in the pathophysiology of CAA and AD. [ABSTRACT FROM AUTHOR]

Chemical exchange saturation transfer (CEST) enables detection of molecules such as glycogen, whose concentrations are too low to impact the signal intensity of standard MR imaging. Detection of these molecules is achieved by selectively saturating a molecule of interest and by measuring the reduction in water signal due to saturation transfer. CEST effects are dependent on parameters such as CEST agent concentration, pH, temperature, relaxation rate, magnetic field strength as well as on experimental parameters such as repetition time, RF irradiation amplitude, and the imaging readout scheme. Measurement of molecules with exchangeable protons that resonate very close to water, e.g., hydroxyl groups in glycogen, is challenging especially at lower magnetic field strengths, mainly due to the effect of direct water saturation. Therefore, optimal RF irradiation parameters that maximize the CEST signal and reduce the competing factors are important for better quantification of glycogen-weighted CEST effects. In this study, analytical solution of the Bloch-McConnell equations was used to find optimal continuous wave RF irradiation parameters for detection of glycogen. In vivo tests were performed on a human calf muscle at different saturation powers to validate the optimal saturation parameters determined via simulation. The selected parameters were applied in vitro to CEST measurements in a phantom with varying glycogen concentrations and also in vivo in a human calf muscle. Our results show the possibility of detecting glycogen using CEST MRI at 3 T. It is further shown that the glycoCEST signal can be maximized by optimizing the RF pulse irradiation parameters (duration and power) and that different glycogen concentrations can be identified when applying the optimized saturation pulse. [ABSTRACT FROM AUTHOR]

Small subclinical hyperintense lesions are frequently encountered on brain diffusion-weighted imaging (DWI) scans of patients with cerebral amyloid angiopathy (CAA). Interpretation of these DWI+ lesions, however, has been limited by absence of histopathological examination. We aimed to determine whether DWI+ lesions represent acute microinfarcts on histopathology in brains with advanced CAA, using a combined in vivo MRI—ex vivo MRI—histopathology approach. We first investigated the histopathology of a punctate cortical DWI+ lesion observed on clinical in vivo MRI 7 days prior to death in a CAA case. Subsequently, we assessed the use of ex vivo DWI to identify similar punctate cortical lesions post-mortem. Intact formalin-fixed hemispheres of 12 consecutive cases with CAA and three non-CAA controls were subjected to high-resolution 3 T ex vivo DWI and T2 imaging. Small cortical lesions were classified as either DWI+/T2+ or DWI−/T2+. A representative subset of lesions from three CAA cases was selected for detailed histopathological examination. The DWI+ lesion observed on in vivo MRI could be matched to an area with evidence of recent ischemia on histopathology. Ex vivo MRI of the intact hemispheres revealed a total of 130 DWI+/T2+ lesions in 10/12 CAA cases, but none in controls (p = 0.022). DWI+/T2+ lesions examined histopathologically proved to be acute microinfarcts (classification accuracy 100%), characterized by presence of eosinophilic neurons on hematoxylin and eosin and absence of reactive astrocytes on glial fibrillary acidic protein-stained sections. In conclusion, we suggest that small DWI+ lesions in CAA represent acute microinfarcts. Furthermore, our findings support the use of ex vivo DWI as a method to detect acute microinfarcts post-mortem, which may benefit future histopathological investigations on the etiology of microinfarcts. [ABSTRACT FROM AUTHOR]

Background: Traumatic axonal injury (TAI) may be reversible, yet there are currently no clinical imaging tools to detect axonal recovery in patients with traumatic brain injury (TBI). We used diffusion tensor imaging (DTI) to characterize serial changes in fractional anisotropy (FA) within TAI lesions of the corpus callosum (CC). We hypothesized that recovery of FA within a TAI lesion correlates with better functional outcome.Methods: Patients who underwent both an acute DTI scan (≤day 7) and a subacute DTI scan (day 14 to inpatient rehabilitation discharge) at a single institution were retrospectively analyzed. TAI lesions were manually traced on the acute diffusion-weighted images. Fractional anisotropy (FA), apparent diffusion coefficient (ADC), axial diffusivity (AD), and radial diffusivity (RD) were measured within the TAI lesions at each time point. FA recovery was defined by a longitudinal increase in CC FA that exceeded the coefficient of variation for FA based on values from healthy controls. Acute FA, ADC, AD, and RD were compared in lesions with and without FA recovery, and correlations were tested between lesional FA recovery and functional recovery, as determined by disability rating scale score at discharge from inpatient rehabilitation.Results: Eleven TAI lesions were identified in 7 patients. DTI detected FA recovery within 2 of 11 TAI lesions. Acute FA, ADC, AD, and RD did not differ between lesions with and without FA recovery. Lesional FA recovery did not correlate with disability rating scale scores.Conclusions: In this retrospective longitudinal study, we provide initial evidence that FA can recover within TAI lesions. However, FA recovery did not correlate with improved functional outcomes. Prospective histopathological and clinical studies are needed to further elucidate whether lesional FA recovery indicates axonal healing and has prognostic significance. [ABSTRACT FROM AUTHOR]

Even with the increased roll out of combination antiretroviral therapy (cART), paediatric HIV infection is associated with neurodevelopmental delays and neurocognitive deficits that may be accompanied by alterations in brain structure. Few neuroimaging studies have been done in children initiating ART before 2 years of age, and even fewer in children within the critical stage of brain development between 5 and 11 years. We hypothesized that early ART would limit HIV-related brain morphometric deficits at age 7. Study participants were 7-year old HIV-infected (HIV+) children from the Children with HIV Early Antiretroviral Therapy (CHER) trial whose viral loads were supressed at a young age, and age-matched uninfected controls. We used structural magnetic resonance imaging (MRI) and FreeSurfer (http://www.freesurfer.net/) software to investigate effects of HIV and age at ART initiation on cortical thickness, gyrification and regional brain volumes. HIV+ children showed reduced gyrification compared to controls in bilateral medial parietal regions, as well as reduced volumes of the right putamen, left hippocampus, and global white and gray matter and thicker cortex in small lateral occipital region. Earlier ART initiation was associated with lower gyrification and thicker cortex in medial frontal regions. Although early ART appears to preserve cortical thickness and volumes of certain brain structures, HIV infection is nevertheless associated with reduced gyrification in the parietal cortex, and lower putamen and hippocampus volumes. Our results indicate that in early childhood gyrification is more sensitive than cortical thickness to timing of ART initiation. Future work will clarify the implications of these morphometric effects for neuropsychological function. [ABSTRACT FROM AUTHOR]

Diffusion tensor imaging (DTI) studies have shown that prenatal exposure to methamphetamine is associated with alterations in white matter microstructure, but to date no tractography studies have been performed in neonates. The striato-thalamo-orbitofrontal circuit and its associated limbic-striatal areas, the primary circuit responsible for reinforcement, has been postulated to be dysfunctional in drug addiction. This study investigated potential white matter changes in the striatal-orbitofrontal circuit in neonates with prenatal methamphetamine exposure. Mothers were recruited antenatally and interviewed regarding methamphetamine use during pregnancy, and DTI sequences were acquired in the first postnatal month. Target regions of interest were manually delineated, white matter bundles connecting pairs of targets were determined using probabilistic tractography in AFNI-FATCAT, and fractional anisotropy (FA) and diffusion measures were determined in white matter connections. Regression analysis showed that increasing methamphetamine exposure was associated with reduced FA in several connections between the striatum and midbrain, orbitofrontal cortex, and associated limbic structures, following adjustment for potential confounding variables. Our results are consistent with previous findings in older children and extend them to show that these changes are already evident in neonates. The observed alterations are likely to play a role in the deficits in attention and inhibitory control frequently seen in children with prenatal methamphetamine exposure. [ABSTRACT FROM AUTHOR]

Though social influence is a critical factor in the initiation and maintenance of marijuana use, the neural correlates of influence in those who use marijuana are unknown. In this study, marijuana-using young adults (MJ; n = 20) and controls (CON; n = 23) performed a decision-making task in which they made a perceptual choice after viewing the choices of unknown peers via photographs, while they underwent functional magnetic resonance imaging scans. The MJ and CON groups did not show differences in the overall number of choices that agreed with versus opposed group influence, but only the MJ group showed reaction time slowing when deciding against group choices. Longer reaction times were associated with greater activation of frontal regions. The MJ goup, compared to CON, showed significantly greater activation in the caudate when presented with peer information. Across groups, caudate activation was associated with self-reported susceptibility to influence. These findings indicate that young adults who use MJ may exhibit increased effort when confronted with opposing peer influence, as well as exhibit greater responsivity of the caudate to social information. These results not only better define the neural basis of social decisions, but also suggest that marijuana use is associated with exaggerated neural activity during decision making that involves social information. [ABSTRACT FROM AUTHOR]

Metabolic imaging of the human brain by in-vivo magnetic resonance spectroscopic imaging (MRSI) can non-invasively probe neurochemistry in healthy and disease conditions. MRSI at ultra-high field (≥ 7 T) provides increased sensitivity for fast high-resolution metabolic imaging, but comes with technical challenges due to non-uniform B0 field. Here, we show that an integrated RF-receive/B0-shim (AC/DC) array coil can be used to mitigate 7 T B0 inhomogeneity, which improves spectral quality and metabolite quantification over a whole-brain slab. Our results from simulations, phantoms, healthy and brain tumor human subjects indicate improvements of global B0 homogeneity by 55%, narrower spectral linewidth by 29%, higher signal-to-noise ratio by 31%, more precise metabolite quantification by 22%, and an increase by 21% of the brain volume that can be reliably analyzed. AC/DC shimming provide the highest correlation (R2 = 0.98, P = 0.001) with ground-truth values for metabolite concentration. Clinical translation of AC/DC and MRSI is demonstrated in a patient with mutant-IDH1 glioma where it enables imaging of D-2-hydroxyglutarate oncometabolite with a 2.8-fold increase in contrast-to-noise ratio at higher resolution and more brain coverage compared to previous 7 T studies. Hence, AC/DC technology may help ultra-high field MRSI become more feasible to take advantage of higher signal/contrast-to-noise in clinical applications. [ABSTRACT FROM AUTHOR]

We present an ultra-high resolution MRI dataset of an ex vivo human brain specimen. The brain specimen was donated by a 58-year-old woman who had no history of neurological disease and died of non-neurological causes. After fixation in 10% formalin, the specimen was imaged on a 7 Tesla MRI scanner at 100 µm isotropic resolution using a custom-built 31-channel receive array coil. Single-echo multi-flip Fast Low-Angle SHot (FLASH) data were acquired over 100 hours of scan time (25 hours per flip angle), allowing derivation of synthesized FLASH volumes. This dataset provides an unprecedented view of the three-dimensional neuroanatomy of the human brain. To optimize the utility of this resource, we warped the dataset into standard stereotactic space. We now distribute the dataset in both native space and stereotactic space to the academic community via multiple platforms. We envision that this dataset will have a broad range of investigational, educational, and clinical applications that will advance understanding of human brain anatomy in health and disease. Measurement(s) nuclear magnetic resonance assay Technology Type(s) MRI Scanner Factor Type(s) flip angle Sample Characteristic - Organism Homo sapiens Machine-accessible metadata file describing the reported data: 10.6084/m9.figshare.9958688 [ABSTRACT FROM AUTHOR]