An Integrative Approach to the Current Treatment of HIV-Associated Neurocognitive Disorders and the Implementation of Leukemia Inhibitor Factor as a Mediator of Neurocognitive Preservation.

HIV-associated neurocognitive disorders (HANDs) continue to impact patients despite antiretroviral therapy. A combination of antiretroviral therapies can diminish the HIV viral load to near undetectable levels, but fails to preserve neurocognitive integrity. The cytokine leukemia inhibitory factor (LIF) has shown neuroprotective properties that could mitigate neurodegeneration in HANDs. The LIF promotes neurogenesis, neural cell differentiation, and survival. Combination antiretroviral therapy reduces severe forms of HANDs, but neurocognitive impairment persists; additionally, some antiretrovirals have additional adverse neurotoxic effects. The LIF counteracts neurotoxic viral proteins and limits neural cell damage in models of neuroinflammation. Adding the LIF as an adjuvant therapy to enhance neuroprotection merits further research for managing HANDs. The successful implementation of the LIF to current therapies would contribute to achieving a better quality of life for the affected population.

In vivo detection of penetrating arteriole alterations in cerebral white matter in patients with diabetes with 7 T MRI.

Cerebral small vessel disease (SVD) is responsible for primary intracerebral hemorrhages, lacunar infarcts and white matter hyperintensity in T2 weighted images. While the brain lesions attributed to small vessel disease can be characterized by conventional MRI, it remains challenging to noninvasively measure the early pathological changes of the small underlying vessels. We evaluated the feasibility of detecting alterations in white matter penetrating arterioles (PA) in patients with diabetes with ultra-high field 7 T MRI. 19 participants with diabetes mellitus (DM) and 19 age- and sex-matched healthy controls were scanned with whole brain T2 and susceptibility weighted MRI and a single slice phase contrast MRI 15 mm above the corpus callosum. The PC-MRI scans were repeated three times. PA masks were manually drawn on the first images after anonymization or automatically segmented on all three images. For each PA, lumen diameter, flow velocity and volume flow rate were derived by model-based analyses of complex difference images. Quasi-Poisson regression was performed for PA count using disease condition, age, and sex as independent variables. Linear mixed effect model analyses were performed for the other measurements using disease condition and age as fixed effect and participant pair specific disease condition as random effect. No severe radiological features of SVD were observed in T2 and susceptibility weighted images in any of the participants except for white matter hyperintensities with Fazekas score of 1 or 2 in 68% and 26% of patients and controls, respectively. The minimum diameter of visible PA was 78 µm and the majority had diameters <250 µm. Among the manually segmented PA with tilt angle less than 30o from the slice normal direction, flow velocities were lower in the DM group (1.9 ± 0.6 vs. 2.2 ± 0.6; p = 0.022), while no significant difference was observed in count, diameter, or volume flow rate. Similar results were observed in the automatically segmented PA. We also observed significantly increased diameter or decreased velocity with age in some of the scans. This study suggests that early PA alterations that are discriminative of disease state and age might be detectable in human cerebral white matter with 7 T MRI in vivo.

Prospective motion correction and automatic segmentation of penetrating arteries in phase contrast MRI at 7 T.

PURPOSE: To develop a prospective motion correction (MC) method for phase contrast (PC) MRI of penetrating arteries (PAs) in centrum semiovale at 7 T and to evaluate its performance using automatic PA segmentation. METHODS: Head motion was monitored and corrected during the scan based on fat navigator images. Two convolutional neural networks (CNN) were developed to automatically segment PAs and exclude surface vessels. Real-life scans with MC and without MC (NoMC) were performed to evaluate the MC performance. Motion score was calculated from the ranges of translational and rotational motion parameters. MC versus NoMC pairs with similar motion scores during MC and NoMC scans were compared. Data corrupted by motion were reacquired to further improve PA visualization. RESULTS: PA counts (NPA ) and PC and magnitude contrasts (MgC) relative to neighboring tissue were significantly correlated with motion score and were higher in MC than NoMC images at motion scores above 0.5-0.8 mm. Data reacquisition further increased PC but had no significant effect on NPA and MgC. CNNs had higher sensitivity and Dice similarity coefficient for detecting PAs than a threshold-based method. CONCLUSIONS: Prospective MC can improve the count and contrast of segmented PAs in the presence of severe motion. CNN-based PA segmentation has improved performance in delineating PAs than the threshold-based method.

Morphology of perivascular spaces and enclosed blood vessels in young to middle-aged healthy adults at 7T: Dependences on age, brain region, and breathing gas.

Perivascular spaces (PVSs) are fluid-filled spaces surrounding penetrating blood vessels in the brain and are an integral pathway of the glymphatic system. A PVS and the enclosed blood vessel are commonly visualized as a single vessel-like complex (denoted as PVSV) in high-resolution MRI images. Quantitative characterization of the PVSV morphology in MRI images in healthy subjects may serve as a reference for detecting disease related PVS and/or blood vessel alterations in patients with brain diseases. To this end, we evaluated the age dependences, spatial heterogeneities, and dynamic properties of PVSV morphological features in 45 healthy subjects (21-55 years old), using an ultra-high-resolution three-dimensional transverse relaxation time weighted MRI sequence (0.41 â€‹× â€‹0.41 â€‹× â€‹0.4 â€‹mm3) at 7T. Quantitative PVSV parameters, including apparent diameter, count, volume fraction (VF), and relative contrast to noise ratio (rCNR) were calculated in the white matter and subcortical structures. Dynamic changes were induced by carbogen breathing which are known to induce vasodilation and increase the blood oxygenation level in the brain. PVSV count and VF significantly increased with age in basal ganglia (BG), so did rCNR in BG, midbrain, and white matter (WM). Apparent PVSV diameter also showed a positive association with age in the three brain regions, although it did not reach statistical significance. The PVSV VF and count showed large inter-subject variations, with coefficients of variation ranging from 0.17 to 0.74 after regressing out age and gender effects. Both apparent diameter and VF exhibited significant spatial heterogeneity, which cannot be explained solely by radio-frequency field inhomogeneities. Carbogen breathing significantly increased VF in BG and WM, and rCNR in thalamus, BG, and WM compared to air breathing. Our results are consistent with gradual dilation of PVSs with age in healthy adults. The PVSV morphology exhibited spatial heterogeneity and large inter-subject variations and changed during carbogen breathing compared to air breathing.

MR fingerprinting enables quantitative measures of brain tissue relaxation times and myelin water fraction in the first five years of life.

Quantitative assessments of normative brain development using MRI are of critical importance to gain insights into healthy neurodevelopment. However, quantitative MR imaging poses significant technical challenges and requires prohibitively long acquisition times, making it impractical for pediatric imaging. This is particularly relevant for healthy subjects, where imaging under sedation is not clinically indicated. MR Fingerprinting (MRF), a novel MR imaging framework, provides rapid, efficient, and simultaneous quantification of multiple tissue properties. In this study, a 2D MR Fingerprinting method was developed that achieves a spatial resolution of 1 × 1 × 3 mm3 with rapid and simultaneous quantification of T1, T2 and myelin water fraction (MWF). Phantom experiments demonstrated that accurate measurements of T1 and T2 relaxation times were achieved over a wide range of T1 and T2 values. MRF images were acquired cross-sectionally from 28 typically developing children, 0 to five years old, who were enrolled in the UNC/UMN Baby Connectome Project. Differences associated with age of R1 (=1/T1), R2 (=1/T2) and MWF were obtained from several predefined white matter regions. Both R1 and R2 exhibit a marked increase until ∼20 months of age, followed by a slower increase for all WM regions. In contrast, the MWF remains at a negligible level until ∼6 months of age for all predefined ROIs and gradually increases afterwards. Depending on the brain region, rapid increases are observed between 6 and 12 months to 6-18 months, followed by a slower pace of increase in MWF. Neither relaxivities nor MWF were significantly different between the left and right hemispheres. However, regional differences in age-related R1 and MWF measures were observed across different white matter regions. In conclusion, our results demonstrate that the MRF technique holds great potential for multi-parametric assessments of normative brain development in early childhood.

El cáncer como metáfora de muerte o como opción para resignificar la vida: narrativas en la construcción de la experiencia familiar y su relación con el afrontamiento del cáncer de un hijo menor de edad / The cancer like metaphor of death or option stops to resignificar the life: narratives in the construction of the familiar experience and its relation with the facing of cancer of a minor son

Este artículo presenta el trabajo de investigación–intervencióndesde un enfoque sistémico-narrativoconstruccionista,sobre la construcción narrativa familiary personal de la experiencia del cáncer en un hijomenor de edad y el papel en el afrontamiento de la enfermedad,en relación con la dinámica e identidad familiar,en la interacción con el contexto de salud (serviciode oncohematología pediátrica del Hospital de la Misericordiade Bogotá) y el marco cultural narrativo sobrela enfermedad. Partiendo del supuesto de que la experienciahumana es organizada en las narrativas quelas personas construyen en la interacción lingüística conlos otros, se trabajó con tres familias con un hijo menordiagnosticado con cáncer, participando, junto con elequipo de salud tratante, en escenarios conversacionalesy reflexivos que permitieron evocar, comprender y movilizarnarrativas dominantes sobre la experiencia delcáncer que operaban como obstáculos en el proceso demisafrontamientofamiliar. Se identifica en la construcción narrativa de la experienciadel cáncer, que el diagnóstico y su implicación negativa para lavida familiar y personal, era vivido como una experiencia y un afrontamientoparalizante. Por el contrario, la identificación y co-construcciónconversacional de relatos de recursos propios en la identidad familiar ypersonal facilitaba la generación de narrativas alternas posibilitadoras denuevas formas de afrontamiento de la experiencia vivida...