Hongyan Du

Structural brain alterations can be detected early in HIV infection.

Objective: Brain changes occurring early in HIV infection are not well characterized. The Chicago Early HIV Infection Study aimed to evaluate the presence and extent of structural brain alterations using quantitative MRI. Methods: Forty-three HIV and 21 control subjects were enrolled. Mean length of infection was estimated as less than 1 year based on assay results. High-resolution neuroanatomical images were acquired. Automated image analysis was used to derive measurements for total brain, ventricular volume, and for tissue classes (total and cortical gray matter, white matter, and CSF). A separate image analysis algorithm was used to calculate measurements for individual brain regions. Cognitive function was assessed by neuropsychological evaluation. Results: Reductions were quantified in total (p = 0.0547) and cortical (p = 0.0109) gray matter in the HIV group. Analysis of individual brain regions with a separate image analysis algorithm revealed consistent findings of reductions in cerebral cortex (p = 0.042) and expansion of third ventricle (p = 0.046). The early HIV group also demonstrated weaker performance on several neuropsychological tests, with the most pronounced difference in psychomotor speed (p = 0.001). Conclusions: This cross-sectional brain volumetric study indicates structural alterations early in HIV infection. The findings challenge the prevailing assumption that the brain is spared in this period. Revisiting the question of the brains vulnerability to processes unfolding in the initial virus-host interaction and the early natural history may yield new insights into neurologic injury in HIV infection and inform neuroprotection strategies.

Brain alterations within the first 100 days of HIV infection

Brain involvement is a serious complication of HIV infection. The earliest changes in the brain, which represents an anatomic site for viral persistence, are largely unknown.

Value of precontrast T1 for dGEMRIC of native articular cartilage

To evaluate if the difference between pre‐ and post‐Gd‐DTPA2‐ relaxation rate (ΔR1) provides better differentiation of osteoarthritic patients (OA) from healthy subjects (HS) with dGEMRIC, as compared to post‐Gd‐DTPA2‐ spin‐lattice relaxation time (T1Gd).

Intrarenal oxygenation by blood oxygenation level-dependent MRI in contrast nephropathy model: effect of the viscosity and dose.

To compare the effects of osmolality versus viscosity of radio‐contrast media on intra‐renal oxygenation as determined by blood oxygenation level‐dependent (BOLD) MRI in a model of contrast induced nephropathy (CIN).

Matrix metalloproteinase levels in early HIV infection and relation to in vivo brain status

Matrix metalloproteinases (MMPs) have been implicated in human immunodeficiency virus (HIV)-associated neurological injury; however, this relationship has not been studied early in infection. Plasma levels of MMP-1, MMP-2, MMP-7, MMP-9, and MMP-10 measured using Luminex technology (Austin, TX, USA) were compared in 52 HIV and 21 seronegative participants of the Chicago Early HIV Infection study. MMP levels were also examined in HIV subgroups defined by antibody reactivity, viremia, and antiretroviral status, as well as in available cerebrospinal fluid (CSF) samples (nu2009=u20099). MMPs were evaluated for patterns of relationship to cognitive function and to quantitative magnetic resonance measurements of the brain derived in vivo. Plasma MMP-2 levels were significantly reduced in early HIV infection and correlated with altered white matter integrity and atrophic brain changes. MMP-9 levels were higher in the treated subgroup than in the naïve HIV subgroup. Only MMP-2 and MMP-9 were detected in the CSF; CSF MMP-2 correlated with white matter integrity and with volumetric changes in basal ganglia. Relationships with cognitive function were also identified. MMP-2 levels in plasma and in CSF correspond to early changes in brain structure and function. These findings establish a link between MMPs and neurological status previously unidentified in early HIV infection.

A Comparative Evaluation of Quantitative Neuroimaging Measurements of Brain Status in HIV Infection

Diffusion tensor imaging (DTI), magnetization transfer imaging (MT) and automated brain volumetry were used to summarize brain involvement in human immunodeficiency virus (HIV) infection. A multiparametric neuroimaging protocol was implemented at 1.5 T in 10 HIV+ and 24 controls. Various summary parameters were calculated based on DTI, MT, and automated brain volumetry. The magnitude of the difference, as well as the between-group discrimination, was determined for each measure. Bivariate correlations were computed and redundancy among imaging parameters was examined by principal factor analysis. Significant or nearly significant differences were found for most measures. Large Cohens d effect sizes were indicated for mean diffusivity (MD), fractional anisotropy (FA), magnetization transfer ratio (MTR) and gray matter volume fraction (GM). Between-group discrimination was excellent for FA and MTR and acceptable for MD. Correlations among all imaging parameters could be explained by three factors, possibly reflecting general atrophy, neuronal loss, and alterations. This investigation supports the utility of summary measurements of brain involvement in HIV infection. The findings also support assumptions concerning the enhanced sensitivity of DTI and MT to atrophic as well as alterations in the brain. These findings are broadly generalizable to brain imaging studies of physiological and pathological processes.

Marked relationship between matrix metalloproteinase 7 and brain atrophy in HIV infection.

Circulating levels of matrix metalloproteinases (MMP-1 and 7) have been found to correlate with the severity of brain injury in HIV-infected subjects. This study used high-resolution neuroanatomic imaging and automated segmentation algorithms to clarify this relationship. Both metalloproteinases were significantly correlated with increased cerebrospinal fluid volume fraction. Comprehensive brain volumetric analysis revealed a more marked relationship with atrophy for MMP-7, which was significantly correlated with neural injury in multiple brain regions and nearly all ventricular measurements. MMP-7 was also correlated with measures of virologic and cognitive status.

Intra-renal oxygenation in rat kidneys during water loading: Effects of cyclooxygenase (COX) inhibition and nitric oxide (NO) donation

To evaluate intra‐renal oxygenation by blood oxygenation level dependent (BOLD) MRI in rat kidneys during water loading and to investigate if the NO donating moiety in naproxcinod could compensate for the effect of cyclooxygenase (COX) inhibition of naproxen.

Sub-Millimeter Isotropic MRI for Segmentation of Subcortical Brain Regions and Brain Visualization

To evaluate a rapid sub‐millimeter isotropic spoiled gradient‐echo (nonselective SPGR) to facilitate the brain subcortical segmentation and the visualization of brain volume compared with the commonly accepted inversion recovery‐prepared SPGR (SPGR‐IR) technique.

Comprehensive brain analysis with automated high-resolution magnetization transfer measurements

To enhance the reliability and spatial resolution of magnetization transfer ratio (MTR) measurements for interrogation of subcortical brain regions with an automated volume of interest (VOI) approach.