Ann B. Ragin

Comparative trial of prednisone plus aspirin versus aspirin alone in the treatment of anticardiolipin antibody-positive obstetric patients

OBJECTIVE We compared the use of aspirin alone with combined therapy (prednisone plus aspirin) in antiphospholipid antibody-positive obstetric patients with prior adverse pregnancy outcome. STUDY DESIGN Thirty-nine patients meeting specific laboratory and clinical inclusion criteria were randomized to receive either combined therapy (prednisone plus low-dose aspirin, n = 17) or aspirin alone (n = 22). The daily aspirin dose was 81 mg; prednisone was begun at 20 mg/day and increased or decreased on the basis of observed changes in serial antibody levels. Perinatal outcomes were compared between groups. Evaluation of treatment-related maternal complications and serial antibody titers was also accomplished. RESULTS Thirty-four randomized subjects were evaluable (prednisone plus low-dose aspirin, n = 12 vs aspirin only, n = 22); no perinatal losses were observed in the study cohort. Preterm delivery was experienced by significantly more patients receiving prednisone plus low-dose aspirin than aspirin only (8/12 vs 3/22, respectively; p = 0.003), and prednisone exposure appeared to be an independent risk factor for preterm birth. CONCLUSIONS The use of prednisone therapy in conjunction with low-dose aspirin does not appear to improve outcome and may provoke obstetric complications in antiphospholipid antibody-positive patients.

Vascular risk factors, HIV serostatus, and cognitive dysfunction in gay and bisexual men

Background: The purpose of this study was to evaluate the relationship between cognitive performance, risk factors for cardiovascular and cerebrovascular disease (CVD), and HIV infection in the era of highly active antiretroviral therapy. Methods: We evaluated the cognitive functions of men enrolled in the cardiovascular disease substudy of the Multicenter AIDS Cohort Study who were aged ≥40 years, with no self-reported history of heart disease or cerebrovascular disease. Results from comprehensive neuropsychological evaluations were used to construct composite scores of psychomotor speed and memory performance. Subclinical CVD was assessed by measuring coronary artery calcium and carotid artery intima-media thickness (IMT), as well as laboratory measures, including total cholesterol, fasting glucose, glycosylated hemoglobin, glomerular filtration rate (estimated), and standardized blood pressure and heart rate measures. Results: After accounting for education, depression, and race, carotid IMT and glomerular filtration rate were significantly associated with psychomotor speed, whereas IMT was associated with memory test performance. HIV serostatus was not significantly associated with poorer cognitive test performance. However, among the HIV-infected individuals, the presence of detectable HIV RNA in plasma was linked to lower memory performance. Conclusions: These findings suggest that HIV infection may not be the most important predictor of cognitive performance among older gay and bisexual men in the post–highly active antiretroviral therapy era, at least among those with access to medical care and to appropriate medications. Medical factors associated with normal aging are significantly associated with performance on neuropsychological tests, and good clinical management of these factors both in HIV-infected individuals and those at risk for infection may have beneficial effects in the short term and could reduce the risk of subsequent cognitive decline.

Subcortical brain atrophy persists even in HAART-regulated HIV disease

The purpose of this study was to determine the pattern and extent of caudate nucleus and putamen atrophy in HIV-infected men with well-controlled immune status and viral replication. 155 men underwent structural brain magnetic resonance imaging; 84 were HIV-infected and 71 were uninfected controls. MRI data were processed using the Fully Deformable Segmentation routine, producing volumes for the right and left caudate nucleus and putamen, and 3-D maps of spatial patterns of thickness. There was significant atrophy in the HIV-infected men in both the caudate and putamen, principally in the anterior regions. The volume of the basal ganglia was inversely associated with the time since first seropositivity, suggesting that either there is a chronic, subclinical process that continues in spite of therapy, or that the extent of the initial insult caused the extent of atrophy.

Quantitative cerebral perfusion using dynamic susceptibility contrast MRI: Evaluation of reproducibility and age- and gender-dependence with fully automatic image postprocessing algorithm

A novel approach for quantifying cerebral blood flow (CBF) is proposed that combines the bookend technique of calculating cerebral perfusion with an automatic postprocessing algorithm. The reproducibility of the quantitative CBF (qCBF) measurement in healthy controls (N = 8) showed a higher intraclass correlation coefficient (ICC) and lower coefficient of variation (COV) when calculated with automatic analysis (ICC/COV = 0.90/0.09) than when compared to conventional manual analysis (ICC/COV = 0.58/0.19). Also, the reproducibility in patients (N = 25) was successfully evaluated with the automatic analysis (ICC/COV = 0.81/0.14). In 175 consecutive clinical scans, we found 3.0% and 7.4% of qCBF decrease per decade in white matter (WM) (21.5 ± 6.66 ml/100 g‐min) and gray matter (GM) (49.6 ± 16.2 ml/100 g‐min), respectively. Cerebral blood volume (CBV) showed a significant 3.7% decrease per decade in GM (3.00 ± 0.94 ml/100 g) but not in WM (1.69 ± 0.40 ml/100 g). Mean transit time (MTT) increased by 1.9% and 3.8% per decade in WM (5.04 ± 0.88 s) and GM (4.14 ± 0.80 s), respectively. qCBF and MTT values between males (N = 85) and females (N = 90) were significantly different in GM. Women showed 11% higher qCBF as well as a higher decrease in qCBF with increasing age than men in the whole brain (WB). Our results supported the notion that population average empirical quantification of cerebral perfusion is subject to individual variation as well as age‐ and gender‐dependent variability. Magn Reson Med, 2007.

Prevalence of HIV-associated neurocognitive disorders in the Multicenter AIDS Cohort Study

Objective: To evaluate the frequency of HIV-associated neurocognitive disorder (HAND) in HIV+ individuals and determine whether the frequency of HAND changed over 4 years of follow-up. Methods: The Multicenter AIDS Cohort Study (MACS) is a prospective study of gay/bisexual men. Beginning in 2007, all MACS participants received a full neuropsychological test battery and functional assessments every 2 years to allow for HAND classification. Results: The frequency of HAND for the 364 HIV+ individuals seen in 2007–2008 was 33% and for the 197 HIV+ individuals seen at all time periods during the 2007–2008, 2009–2010, and 2011–2012 periods were 25%, 25%, and 31%, respectively. The overall frequency of HAND increased from 2009–2010 to 2011–2012 (p = 0.048). Over the 4-year study, 77% of the 197 HIV+ individuals remained at their same stage, with 13% showing deterioration and 10% showing improvement in HAND stage. Hypercholesterolemia was associated with HAND progression. A diagnosis of asymptomatic neurocognitive impairment was associated with a 2-fold increased risk of symptomatic HAND compared to a diagnosis of normal cognition. Conclusion: HAND remains common in HIV+ individuals. However, for the majority of HIV+ individuals on combination antiretroviral therapy with systemic virologic suppression, the diagnosis of HAND is not a progressive condition over 4 years of follow-up. Future studies should evaluate longitudinal changes in HAND and specific neurocognitive domains over a longer time period.

Abnormalities in Resting-State Functional Connectivity in Early Human Immunodeficiency Virus Infection

Limited information is available concerning changes that occur in the brain early in human immunodeficiency virus (HIV) infection. This investigation evaluated resting-state functional connectivity, which is based on correlations of spontaneous blood oxygen level-dependent functional magnetic resonance imaging (fMRI) oscillations between brain regions, in 15 subjects within the first year of HIV infection and in 15 age-matched controls. Resting-state fMRI data for each session were concatenated in time across subjects to create a single 4D dataset and decomposed into 36 independent component analysis (ICA) using Multivariate Exploratory Linear Optimized Decomposition into Independent Components. ICA components were back-reconstructed for each subjects 4D data to estimate subject-specific spatial maps using the dual-regression technique. Comparison of spatial maps between HIV and controls revealed significant differences in the lateral occipital cortex (LOC) network. Reduced coactivation in left inferior parietal cortex within the LOC network was identified in the HIV subjects. Connectivity strength within this region correlated with performance on tasks involving visual-motor coordination (Grooved Pegboard and Rey Figure Copy) in the HIV group. The findings indicate prominent changes in resting-state functional connectivity of visual networks early in HIV infection. This network may sustain injury in association with the intense viremia and brain viral invasion before immune defenses can contain viral replication. Resting-state functional connectivity may have utility as a noninvasive neuroimaging biomarker for central nervous system impairment in early HIV infection.

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.

MR imaging to assess immediate response to irreversible electroporation for targeted ablation of liver tissues: preclinical feasibility studies in a rodent model.

PURPOSE To test the hypothesis that magnetic resonance (MR) imaging measurements can be used to immediately detect treated tissue regions after irreversible electroporation (IRE) ablation procedures in rodent liver tissues. MATERIALS AND METHODS All experiments received institutional animal care and use committee approval. In four rats for preliminary studies and 18 rats for formal assessment, MR imaging-compatible electrodes were inserted into the liver and MR imaging-monitored IRE procedures were performed at one of three electrode voltages (1000, 1500, or 2500 V), with T1- and T2-weighted images acquired before and immediately after application of the IRE pulses. MR imaging measurements were compared with both finite element modeling (FEM)-anticipated ablation zones and histologically confirmed ablation zones at necropsy. Intraclass and Spearman correlation coefficients were calculated for statistical comparisons. RESULTS MR imaging measurements permitted immediate depiction of IRE ablation zones that were hypointense on T1-weighted images and hyperintense on T2-weighted images. MR imaging-based measurements demonstrated excellent consistency with FEM-anticipated ablation zones (r > 0.90 and P < .001 for both T1- and T2-weighted images). MR imaging measurements were also highly correlated with histologically confirmed ablation zone measurements (rho > 0.90 and P < .001 for both T1- and T2-weighted images). CONCLUSION MR imaging permits immediate depiction of ablated tissue zones for monitoring of IRE ablation procedures. These measurements could potentially be used during treatment to elicit repeat application of IRE pulses or adjustments to electrode positions to ensure complete treatment of targeted lesions.

Magnetic resonance imaging of the pancreas at 3.0 tesla: qualitative and quantitative comparison with 1.5 tesla.

Objectives:We sought to perform a preliminary comparison of signal-to-noise ratio (SNR) and image quality for magnetic resonance imaging (MRI) of the pancreas at 1.5 and 3 T. Materials and Methods:Two imaging cohorts were studied using a T2-weighted, single-shot fast spin-echo pulse sequence and a T1-weighted, fat-suppressed 3D gradient-echo pulse sequence. In the first cohort, 4 subjects were imaged using identical imaging parameters before and after contrast administration at 1.5 and 3.0 T. The SNR was quantified for the pancreas as well as for the liver, spleen, and muscle. In a second cohort of 12 subjects in whom the receiver bandwidth was adjusted for field strength, SNR measurements and qualitative rankings of image quality were performed. Results:In the study cohort using identical imaging parameters at both magnetic field strengths, the mean (SD) ratios of SNR at 3.0 to 1.5 T of the single-shot fast spin-echo images for the pancreas, liver, spleen, and muscle were 1.63 (0.39), 1.82 (0.39), 1.45 (0.18), 2.01 (0.16), respectively. For the precontrast fat-suppressed 3D gradient-echo sequence, the corresponding ratios were 1.28 (0.29), 1.26 (0.30), 1.16 (0.27), and 1.76 (0.45), respectively; for the arterial phase, the corresponding ratios were 2.02 (0.28), 1.60 (0.42), 1.47 (0.26), and 1.94 (0.32), respectively; and for the delayed postcontrast phase, the corresponding ratios were 1.63 (0.51), 2.01 (0.25), 1.66 (0.06), and 2.31 (0.47), respectively. The SNR benefit of 3.0 T was significantly greater on contrast-enhanced as compared with noncontrast T1-weighted 3D gradient-echo images. In the second study cohort, SNR was superior at 3.0 T, although the use of a reduced readout bandwidth at 1.5 T substantially diminished the advantage of the higher field system. With qualitative comparison of images obtained at the 2 magnetic field strengths, the fat-suppressed 3D gradient-echo images obtained at 3.0 T were preferred, whereas the single shot fast spin-echo images obtained at 1.5 T were preferred because of better signal homogeneity. Conclusions:Our results in a small cohort of volunteers and patients demonstrate a marked improvement in SNR at 3.0 T compared with 1.5 T (by a factor of 2 in some cases) when identical imaging parameters were used. The SNR advantage at 3.0 T is diminished but persists when the receiver bandwidth is adjusted for magnetic field strength. The results suggest that 3.0 T may offer promise for improved body MRI, although further technical development to optimize SNR and improve signal homogeneity will be needed before its full potential can be achieved.

Disease burden in HIV-associated cognitive impairment: A study of whole-brain imaging measures

Objective: To study whole-brain MR measures derived from diffusion tensor imaging and magnetization transfer imaging (MTI) for the in vivo assessment of cumulative neuropathologic changes in HIV and to evaluate the quantitative imaging strategies with respect to cognitive status measures including the severity of dementia and the degree of impairment in specific cognitive domains including attention, memory, constructional abilities, and motor speed. Methods: Quantitative whole-brain measurements, including fractional anisotropy (FA), apparent diffusion coefficient (ADC), and magnetization transfer ratio (MTR), were derived from histograms and compared in HIV and control participants. Relationships between the MR and cognitive status measures were examined. Results: Whole-brain FA and MTR were reduced in patients with HIV and correlated with dementia severity. Whole-brain MTR and ADC were correlated with psychomotor deficits. Evaluation of relationships between the studied MR measures indicated a correlation between ADC and MTR; FA was not correlated with either ADC or MTR. Conclusions: Findings from this investigation support the use of quantitative whole-brain MR measures for evaluation of disease burden in HIV. Reductions in whole-brain fractional anisotropy and magnetization transfer ratio (MTR) distinguished HIV and control subjects, and these measures were associated with dementia severity. Relationships were identified between whole-brain MTR and apparent diffusion coefficient and psychomotor deficits. Combining these quantitative strategies in neuroimaging examinations may provide more comprehensive information concerning ongoing changes in the brains of HIV patients.