Brain computed tomography perfusion analysis in HIV-seropositive adults with and without neurocognitive impairment in Nigeria: outcomes and challenges of a pilot study.

Introduction: the significance of cerebrovascular disease in HIV-associated neurocognitive disorder (HAND) in a homogeneous black population has not yet been determined. This incident case-control study used CT perfusion imaging to quantify and compare regional cerebral blood flow parameters in neuro-cognitively impaired and unimpaired HIV+ participants of the Ibadan Cohort on Neuro AIDS (ICON) in Nigeria. Methods: this was an incident case-control study consisting of twenty-seven HIV+ adults, classified based on Frascati criteria into neurocognitive impaired (n=18) and unimpaired (n=9) groups, who had brain computed tomographic perfusion (CTP) with a 64-slice Toshiba T scanner. The standard deviation (SD) of regional mean transit time (MTT), cerebral blood flow (CBF), and cerebral blood volume (CBV) values were calculated for bilateral basal ganglia (BG), frontal, parietal, temporal, and occipital regions from CT perfusion maps. The regional mean values and variability (SD) in the CTP measures were compared in the groups using an independent student t-test. Results: differentially higher variability in the bilateral CBF measures in the parietal (right; OR = 1.14, x̄ =5.61, p=0.041, CI=0.27-11.35/left; OR = 1.16, x̄=7.01, p=0.03, CI=5.6-13.47) and time to peak (TTP) measures in the basal ganglia (right; OR = 3.78, x̄=0.88, p=0.032, CI=0.081-1.67/left; OR = 2.44, x̄=1.48, p=0.020, CI=0.26-2.71) and occipital (right; OR = 2.18, x̄=1.32, p=0.018, CI=0.25-2.38/left; OR = 1.93, x̄=1.08, p=0.034, CI=0.086-2.06) regions were observed in the cognitively impaired group compared to the unimpaired group. Conclusion: the study evidence suggests that alterations in cerebral perfusion implicated in HIV-associated neurocognitive disorder may be possibly demonstrated using CTP, a readily available resource in most African countries saddled with the highest burden of HIV.

The comorbidity of depression and neurocognitive disorder in persons with HIV infection: call for investigation and treatment.

Depression and neurocognitive disorder continue to be the major neuropsychiatric disorders affecting persons with HIV (PWH). The prevalence of major depressive disorder is two to fourfold higher among PWH than the general population (∼6.7%). Prevalence estimates of neurocognitive disorder among PWH range from 25 to over 47% - depending upon the definition used (which is currently evolving), the size of the test battery employed, and the demographic and HIV disease characteristics of the participants included, such as age range and sex distribution. Both major depressive disorder and neurocognitive disorder also result in substantial morbidity and premature mortality. However, though anticipated to be relatively common, the comorbidity of these two disorders in PWH has not been formally studied. This is partly due to the clinical overlap of the neurocognitive symptoms of these two disorders. Both also share neurobehavioral aspects - particularly apathy - as well as an increased risk for non-adherence to antiretroviral therapy. Shared pathophysiological mechanisms potentially explain these intersecting phenotypes, including neuroinflammatory, vascular, and microbiomic, as well as neuroendocrine/neurotransmitter dynamic mechanisms. Treatment of either disorder affects the other with respect to symptom reduction as well as medication toxicity. We present a unified model for the comorbidity based upon deficits in dopaminergic transmission that occur in both major depressive disorder and HIV-associated neurocognitive disorder. Specific treatments for the comorbidity that decrease neuroinflammation and/or restore associated deficits in dopaminergic transmission may be indicated and merit study.

Potential Prognostic Value of Native T1 in Pulmonary Hypertension Patients.

Native T1, extracellular volume fraction (ECV), and late gadolinium enhancement (LGE) characterize myocardial tissue and relate to patient prognosis in a variety of diseases, including pulmonary hypertension. The purpose of this study was to evaluate if left ventricle (LV) fibrosis measurements have prognostic value for cardiac outcomes in pulmonary hypertension subgroups. 54 patients with suspected pulmonary hypertension underwent right-heart catheterization and were classified into pulmonary hypertension subgroups: pre-capillary component (PreCompPH) and isolated post-capillary (IpcPH). Cardiac magnetic resonance imaging (MRI) scans were performed with the acquisition of balanced cine steady-state free precession, native T1, and LGE pulse sequences to measure cardiac volumes and myocardial fibrosis. Associations between cardiac events and cardiac MRI measurements were analyzed within PreCompPH and IpcPH patients. IpcPH: LV native T1 was higher in patients who experienced a cardiac event within two years vs. those who did not. In patients with LV native T1 > 1050 ms, the rate of cardiac events was higher. ECV and quantitative LGE did not differ between groups. PreCompPH: native T1, ECV, and quantitative/qualitative LGE did not differ between patients who experienced a cardiac event within two years vs. those who did not. LV native T1 may have potential value for forecasting cardiac events in IpcPH, but not in PreCompPH, patients.

Imaging of Brain Structural and Functional Effects in People With Human Immunodeficiency Virus.

Before the introduction of antiretroviral therapy, human immunodeficiency virus (HIV) infection was often accompanied by central nervous system (CNS) opportunistic infections and HIV encephalopathy marked by profound structural and functional alterations detectable with neuroimaging. Treatment with antiretroviral therapy nearly eliminated CNS opportunistic infections, while neuropsychiatric impairment and peripheral nerve and organ damage have persisted among virally suppressed people with HIV (PWH), suggesting ongoing brain injury. Neuroimaging research must use methods sensitive for detecting subtle HIV-associated brain structural and functional abnormalities, while allowing for adjustments for potential confounders, such as age, sex, substance use, hepatitis C coinfection, cardiovascular risk, and others. Here, we review existing and emerging neuroimaging tools that demonstrated promise in detecting markers of HIV-associated brain pathology and explore strategies to study the impact of potential confounding factors on these brain measures. We emphasize neuroimaging approaches that may be used in parallel to gather complementary information, allowing efficient detection and interpretation of altered brain structure and function associated with suboptimal clinical outcomes among virally suppressed PWH. We examine the advantages of each imaging modality and systematic approaches in study design and analysis. We also consider advantages of combining experimental and statistical control techniques to improve sensitivity and specificity of biotype identification and explore the costs and benefits of aggregating data from multiple studies to achieve larger sample sizes, enabling use of emerging methods for combining and analyzing large, multifaceted data sets. Many of the topics addressed in this article were discussed at the National Institute of Mental Health meeting "Biotypes of CNS Complications in People Living with HIV," held in October 2021, and are part of ongoing research initiatives to define the role of neuroimaging in emerging alternative approaches to identifying biotypes of CNS complications in PWH. An outcome of these considerations may be the development of a common neuroimaging protocol available for researchers to use in future studies examining neurological changes in the brains of PWH.

Quantitative Assessment of Regional Pulmonary Transit Times in Pulmonary Hypertension.

BACKGROUND: Pulmonary hypertension (PH) contributes to restricted flow through the pulmonary circulation characterized by elevated mean pulmonary artery pressure acquired from invasive right heart catheterization (RHC). MRI may provide a noninvasive alternative for diagnosis and characterization of PH. PURPOSE: To characterize PH via quantification of regional pulmonary transit times (rPTT). STUDY TYPE: Retrospective. POPULATION: A total of 43 patients (58% female); 24 controls (33% female). RHC-confirmed patients classified as World Health Organization (WHO) subgroups 1-4. FIELD STRENGTH/SEQUENCE: A 1.5 T/time-resolved contrast-enhanced MR Angiography (CE-MRA). ASSESSMENT: CE-MRA data volumes were combined into a 4D matrix (3D resolution + time). Contrast agent arrival time was defined as the peak in the signal-intensity curve generated for each voxel. Average arrival times within a vessel region of interest (ROI) were normalized to the main pulmonary artery ROI (t0 ) for eight regions to define rPTT for all subjects. Subgroup analysis included grouping the four arterial and four venous regions. Intraclass correlation analysis completed for reproducibility. STATISTICAL TESTS: Analysis of covariance with age as covariate. A priori Student's t-tests or Wilcoxon rank-sum test; α = 0.05. Results compared to controls unless noted. Significant without listing P value. ICC ran as two-way absolute agreement model with two observers. RESULTS: PH patients demonstrated elevated rPTT in all vascular regions; average rPTT increase in arterial and venous branches was 0.85 ± 0.15 seconds (47.7%) and 1.0 ± 0.18 seconds (16.9%), respectively. Arterial rPTT was increased for all WHO subgroups; venous regions were elevated for subgroups 2 and 4 (group 1, P = 0.86; group 3, P = 0.32). No significant rPTT differences were found between subgroups (P = 0.094-0.94). Individual vessel ICC values ranged from 0.58 to 0.97. DATA CONCLUSION: Noninvasive assessment of PH using standard-of-care time-resolved CE-MRA can detect increased rPTT in PH patients of varying phenotypes compared to controls. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 3.

Dynamic impairment classification through arrayed comparisons.

The multivariate normative comparison (MNC) method has been used for identifying cognitive impairment. When participants' cognitive brain domains are evaluated regularly, the longitudinal MNC (LMNC) has been introduced to correct for the intercorrelation among repeated assessments of multiple cognitive domains in the same participant. However, it may not be practical to wait until the end of study for diagnosis. For example, in participants of the Multicenter AIDS Cohort Study (MACS), cognitive functioning has been evaluated repeatedly for more than 35 years. Therefore, it is optimal to identify cognitive impairment at each assessment, while the family-wise error rate (FWER) is controlled with unknown number of assessments in future. In this work, we propose to use the difference of consecutive LMNC test statistics to construct independent tests. Frequency modeling can help predict how many assessments each participant will have, so Bonferroni-type correction can be easily adapted. A chi-squared test is used under the assumption of multivariate normality, and permutation test is proposed where this assumption is violated. We showed through simulation and the MACS data that our method controlled FWER below a predetermined level.

Why do humans undergo an adiposity rebound? Exploring links with the energetic costs of brain development in childhood using MRI-based 4D measures of total cerebral blood flow.

BACKGROUND: Individuals typically show a childhood nadir in adiposity termed the adiposity rebound (AR). The AR serves as an early predictor of obesity risk, with early rebounders often at increased risk; however, it is unclear why this phenomenon occurs, which could impede understandings of weight gain trajectories. The brain's energy requirements account for a lifetime peak of 66% of the body's resting metabolic expenditure during childhood, around the age of the AR, and relates inversely to weight gain, pointing to a potential energy trade-off between brain development and adiposity. However, no study has compared developmental trajectories of brain metabolism and adiposity in the same individuals, which would allow a preliminary test of a brain-AR link. METHODS: We used cubic splines and generalized additive models to compare age trajectories of previously collected MRI-based 4D flow measures of total cerebral blood flow (TCBF), a proxy for cerebral energy use, to the body mass index (BMI) in a cross-sectional sample of 82 healthy individuals (0-60 years). We restricted our AR analysis to pre-pubertal individuals (0-12 years, n = 42), predicting that peak TCBF would occur slightly after the BMI nadir, consistent with evidence that lowest BMI typically precedes the nadir in adiposity. RESULTS: TCBF and the BMI showed inverse trajectories throughout childhood, while the estimated age at peak TCBF (5.6 years) was close but slightly later than the estimated age of the BMI nadir (4.9 years). CONCLUSIONS: The timing of peak TCBF in this sample points to a likely concordance between peak brain energetics and the nadir in adiposity. Inverse age trajectories between TCBF and BMI support the hypothesis that brain metabolism is a potentially important influence on early life adiposity. These findings also suggest that experiences influencing the pattern of childhood brain energy use could be important predictors of body composition trajectories.

Aortic Pulse Wave Velocity Evaluated by 4D Flow MRI Across the Adult Lifespan.

BACKGROUND: Evaluation of aortic stiffness by pulse wave velocity (PWV) across the adult lifespan is needed to better understand normal aging in women and men. PURPOSE: To characterize PWV in the thoracic aorta using 4D flow MRI in an age- and sex-stratified cohort of healthy adults. STUDY TYPE: Retrospective. POPULATION: Ninety nine healthy participants (age: 46 ± 15 [19-79] years, 50% female), divided into young adults (<45 years) (N = 48), midlife (45-65 years) (N = 37), and later life (>65 years) (N = 14) groups. FIELD STRENGTH/SEQUENCE: 1.5 T or 3 T, 2D cine bSSFP, 4D flow MRI. ASSESSMENT: Cardiac functional parameters of end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV) and myocardial mass were assessed by 2D cine bSSFP. PWV and aortic blood flow velocity were assessed by 4D flow MRI. Reproducibility of PWV was evaluated in a subset of nine participants. STATISTICAL TESTS: Analysis of variance, Pearson's correlation coefficient (r), linear regression, intraclass correlation coefficient (ICC). A P value < 0.05 was considered statistically significant. RESULTS: PWV increased significantly with age (young adults: 5.4 ± 0.9 m/sec, midlife: 7.2 ± 1.1 m/sec, and later life: 9.4 ± 1.8 m/sec) (r = 0.79, slope = 0.09 m/sec/year). PWV did not differ in women and men in entire sample (P = 0.40) or within age groups (young adults: P = 0.83, midlife: P = 0.17, and later life: P = 0.96). PWV was significantly correlated with EDV (r = -0.29), ESV (r = -0.23), SV (r = -0.28), myocardial mass (r = 0.21), and mean aortic blood flow velocity (r = -0.62). In the test-retest subgroup (N = 9), PWV was 6.7 ± 1.5 [4.4-9.3] m/sec and ICC = 0.75. DATA CONCLUSION: 4D flow MRI quantified higher aortic PWV with age, by approximately 1 m/sec per decade, and significant differences between young adults, midlife and later life. Reproducibility analysis showed good test-retest agreement. Increased PWV was associated with decline in cardiac function and reduced aortic blood flow velocity. This study demonstrates the utility of 4D flow MRI-derived aortic PWV for studying aging. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Legacy effect on neuropsychological function in HIV-infected men on combination antiretroviral therapy.

OBJECTIVE: To determine whether combination antiretroviral therapy (cART) initiation alters the trajectory of cognitive performance in HIV+ men, and whether cognition prior to cART predicts postcART function. DESIGN: Longitudinal cohort study. Multicenter AIDS Cohort Study. METHODS: From an initial set of 3701 men with complete neuropsychological data, men with HIV infection were initially matched with men without infection on cognitive status, race, age, and timeline (T0 defined as cART initiation). Propensity score matching was then used to match pairs on depressive symptoms at T0, education, T0 cognitive scores, and recruitment cohort. There were 506 matched pairs of infected and uninfected men in the final analysis. Mixed effect models were constructed to analyze the trajectories of cognitive functions and to test the effect of cART and HIV on cognitive functions over time. RESULTS: Performance in each cognitive domain did not change following the initiation of cART among HIV-infected men with prior impairment and was comparable to the performance of their matched uninfected men. However, among the infected men who were unimpaired prior to cART, motor function declined significantly faster than it did for uninfected controls. CONCLUSIONS: Cognitive dysfunction is persistent in HIV-infected men and cART does not alter the trajectory of cognitive decline in men who were impaired prior to effective therapy. This suggests that current cognitive impairment in HIV+ men results from a legacy effect, and from factors other than the HIV itself. Furthermore, motor skills may be uniquely vulnerable to the virus, cART, or age-related co-morbidities.

MRA of the Supraaortic Vasculature: Comparison of Gadobutrol and Gadoterate Meglumine at 1.5 T.

BACKGROUND: Gadobutrol (GB) and gadoterate meglumine (GM) are contrast agents used for contrast-enhanced magnetic resonance angiography (CEMRA). Supraaortic vasculature (SAV) CEMRAs are used to evaluate stroke risk and neurologic symptoms. There is a need to compare the SAV CEMRA image quality obtained with GB and GM. PURPOSE: To intra-individually compare MRA images obtained with equimolar GB and GM at 1.5 T in the SAV. STUDY TYPE: Prospective, crossover. POPULATION: Twenty-eight subjects (54 ± 13 years; 17 female). FIELD STRENGTH/SEQUENCE: 1.5 T; three-dimensional (3D) gradient recalled echo. ASSESSMENT: Quantitative image quality was measured by normalized signal intensity (SIn ) [SIn  = SI blood/SD blood] and contrast ratio (CR) [CR = SI blood/SI muscle], determined by an observer (JWC) with 1 year of vascular imaging experience. Three radiologists (AS, PA, and MU) with (5, 5, and 6 years of) vascular imaging experience evaluated image quality by Likert-scale ratings (of image impression, wall conspicuity, and artifact absence). STATISTICAL TESTS: SIn and CR were compared with paired t-tests or Wilcoxon signed-rank tests and Bland-Altman plots. Qualitative ratings were compared with Wilcoxon signed-rank test. RESULTS: No significant difference in SIn was found between GB and GM. CRs with GB were significantly higher than GM at the right common carotid (6.9 ± 2.5 vs. 4.8 ± 1), left internal carotid (7.3 ± 2 vs. 4.4 ± 1.2), right internal carotid (7.7 ± 2.2 vs. 5 ± 1.1), and left vertebral (6.6 ± 2.2 vs. 4.5 ± 1.1) arteries. Bland-Altman plots showed relatively greater differences between GB and GM at higher CRs and SIn s. GM showed significantly higher artifact than GB (3.56 ± 0.52 vs. 3.36 ± 0.46) and significantly lower overall image quality (10.73 ± 1.45 vs. 11.26 ± 1.58) at the left vertebral artery. DATA CONCLUSION: At 1.5 T and equimolar demonstration, GB (0.1 mL/kg, i.e., 0.1 mmol/kg) showed higher CRs in the SAV compared to GM (0.2 mL/kg, i.e., 0.1 mmol/kg) at most vessels. Subjective image quality was not significantly different between the two agents for most vessels. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Evaluation of Pulmonary Hypertension Using 4D Flow MRI.

BACKGROUND: Cardiac magnetic resonance imaging (MRI) is becoming an alternative to right heart catheterization (RHC) for evaluating pulmonary hypertension (PH). A need exists to further evaluate cardiac MRI's ability to characterize PH. PURPOSE: To evaluate the potential for four-dimensional (4D) flow MRI-derived pulmonary artery velocities to characterize PH. STUDY TYPE: Prospective case-control. POPULATION: Fifty-four PH patients (56% female); 25 controls (36% female). FIELD STRENGTH/SEQUENCE: 1.5 T; gradient recalled echo 4D flow and balanced steady-state free precession cardiac cine. ASSESSMENT: RHC was used to derive patients' pulmonary vascular resistance (PVR). 4D flow measured blood velocities at the main, left, and right pulmonary arteries (MPA, LPA, and RPA); cine measured ejection fraction, end diastolic, and end systolic volumes (EF, EDV, and ESV). EDV and ESV were normalized (indexed) to body surface area (ESVI and EDVI). Parameters were evaluated between, and within, PH subgroups: pulmonary arterial hypertension (PAH); PH due to left heart disease (PH-LHD)/chronic lung disease (PH-CLD)/or chronic thrombo-emboli (CTE-PH). STATISTICAL TESTS: Analysis of variance and Kruskal-Wallis tests compared parameters between subgroups. Pearson's r assessed velocity, PVR, and volume correlations. Significance definition: P < 0.05. RESULTS: PAH peak and mean velocities were significantly lower than in controls at the LPA (36 ± 12 cm/second and 20 ± 4 cm/second vs. 59 ± 15 cm/second and 32 ± 9 cm/second). At the RPA, mean velocities were significantly lower in PAH vs. controls (27 ± 6 cm/second vs. 40 ± 9 cm/second). Peak velocities significantly correlated with right ventricular EF at the MPA (r = 0.286), RPA (r = 0.400), and LPA (r = 0.401). Peak velocity significantly correlated with right ventricular ESVI at the RPA (r = -0.355) and LPA (r = -0.316). Significant correlations between peak velocities and PVR were moderate at the LPA in PAH (r = -0.641) and in PH-LHD (r = -0.606) patients, and at the MPA in PH-CLD (r = -0.728). CTE-PH showed non-significant correlations between peak velocity and PVR at all locations. DATA CONCLUSION: Preliminary findings suggest 4D flow can identify PAH and track PVR changes. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 5.

Longitudinal 5-year prediction of cognitive impairment among men with HIV disease.

BACKGROUND: Although combination antiretroviral therapy reduced the prevalence of HIV-associated dementia, milder syndromes persist. Our goals were to predict cognitive impairment of the Multicenter AIDS Cohort Study (MACS) participants 5 years ahead and from a large pool of factors, select the ones that mostly contributed to our predictions. DESIGN: Longitudinal, natural and treated history of HIV infection among MSM. METHODS: The MACS is a longitudinal study of the natural and treated history of HIV disease in MSM; the neuropsychological substudy aims to characterize cognitive disorders in men with HIV disease. RESULTS: We modeled on an annual basis the risk of cognitive impairment 5 years in the future. We were able to predict cognitive impairment at individual level with high precision and overperform default methods. We found that while a diagnosis of AIDS is a critical risk factor, HIV infection per se does not necessarily convey additional risk. Other infectious processes, most notably hepatitis B and C, are independently associated with increased risk of impairment. The relative importance of an AIDS diagnosis diminished across calendar time. CONCLUSION: Our prediction models are a powerful tool to help clinicians address dementia in early stages for MACS paticipants. The strongest predictors of future cognitive impairment included the presence of clinical AIDS and hepatitis B or C infection. The fact that the pattern of predictive power differs by calendar year suggests a clinically critical change to the face of the epidemic.

Evaluation of image quality of wideband single-shot late gadolinium-enhancement MRI in patients with a cardiac implantable electronic device.

INTRODUCTION: While wideband segmented, breath-hold late gadolinium-enhancement (LGE) cardiovascular magnetic resonance (CMR) has been shown to suppress image artifacts associated with cardiac-implanted electronic devices (CIEDs), it may produce image artifacts in patients with arrhythmia and/or dyspnea. Single-shot LGE is capable of suppressing said artifacts. We sought to compare the performance of wideband single-shot free-breathing LGE against the standard and wideband-segmented LGEs in CIED patients. METHODS AND RESULTS: We retrospectively identified all 54 consecutive patients (mean age: 61 ± 15 years; 31% females) with CIED who had undergone CMR with standard segmented, wideband segmented, and/or wideband single-shot LGE sequences as part of quality assurance for determining best clinical practice at 1.5 T. Two raters independently graded the conspicuity of myocardial scar or normal myocardium and the presence of device artifact level on a 5-point Likert scale (1: worst; 3: acceptable; 5: best). Summed visual score (SVS) was calculated as the sum of conspicuity and artifact scores (SVS ≥ 6 defined as diagnostically interpretable). Median conspicuity and artifact scores were significantly better for wideband single-shot LGE (F = 24.2, p < .001) and wideband-segmented LGE (F = 20.6, p < .001) compared to standard-segmented LGE. Among evaluated myocardial segments, 72% were deemed diagnostically interpretable-defined as SVS ≥ 6-for standard-segmented LGE, 89% were deemed diagnostically interpretable for wideband-segmented LGE, and 94% segments were deemed diagnostically interpretable for wideband single-shot LGE. CONCLUSIONS: Wideband single-shot LGE and wideband-segmented LGE produced similarly improved image quality compared to standard LGE.

Brain structural correlates of trajectories to cognitive impairment in men with and without HIV disease.

There are distinct trajectories to cognitive impairment among participants in the Multicenter AIDS Cohort Study (MACS). Here we analyzed the relationship between regional brain volumes and the individual trajectories to impairment in a subsample (n = 302) of the cohort. 302 (167 HIV-infected; mean age = 55.7 yrs.; mean education: 16.2 yrs.) of the men enrolled in the MACS MRI study contributed data to this analysis. We used voxel-based morphometry (VBM) to segment the brain images to analyze gray and white matter volume at the voxel-level. A Mixed Membership Trajectory Model had previously identified three distinct profiles, and each study participant had a membership weight for each of these three trajectories. We estimated VBM model parameters for 100 imputations, manually performed the post-hoc contrasts, and pooled the results. We examined the associations between brain volume at the voxel level and the MMTM membership weights for two profiles: one considered "unhealthy" and the other considered "Premature aging." The unhealthy profile was linked to the volume of the posterior cingulate gyrus/precuneus, the inferior frontal cortex, and the insula, whereas the premature aging profile was independently associated with the integrity of a portion of the precuneus. Trajectories to cognitive impairment are the result, in part, of atrophy in cortical regions linked to normal and pathological aging. These data suggest the possibility of predicting cognitive morbidity based on patterns of CNS atrophy.

Left ventricular extracellular volume expansion does not predict recurrence of atrial fibrillation following catheter ablation.

INTRODUCTION: A recent study reported that diffuse left ventricular (LV) fibrosis is a predictor of atrial fibrillation (AF) recurrence following catheter ablation, by measuring postcontrast cardiac T1 (an error prone metric as per the 2017 Society for Cardiovascular Magnetic Resonance consensus statement) using an inversion-recovery pulse sequence (an error prone method in arrhythmia) in AF ablation candidates. The purpose of this study was to verify the prior study, by measuring extracellular volume (ECV) fraction (an accurate metric) using a saturation-recovery pulse sequence (accurate method in arrhythmia). METHODS AND RESULTS: This study examined 100 AF patients (mean age = 62 ± 11 years, 69 males and 31 females, 67 paroxysmal [pAF] and 33 persistent [peAF]) who underwent a preablation cardiovascular magnetic resonance (CMR) exam. LV ECV and left atrial (LA) and LV functional parameters were quantified using standard analysis methods. During an average follow-up period of 457 ± 261 days with 4 ± 3 rhythm checks per patient, 72 patients maintained sinus rhythm. Between those who maintained sinus rhythm (n = 72) and those who reverted to AF (n = 28), the only clinical characteristic that was significantly different was age (60 ± 12 years vs 66 ± 9 years); for CMR metrics, neither mean LV ECV (25.1 ± 3.3% vs 24.7 ± 3.7%), native LV T1 (1093.8 ± 73.5 ms vs 1070.2 ± 115.9 ms), left ventricular ejection fraction (54.1 ± 11.2% vs 55.7 ± 7.1%), nor LA end diastolic volume/body surface area (42.4 ± 14.8 mL/m2 vs 43.4 ± 19.6 mL/m2 ) were significantly different (P ≥ .23). According to Cox regression tests, none of the clinical and imaging variables predict AF recurrence. CONCLUSION: Neither LV ECV nor other CMR metrics predict recurrence of AF following catheter ablation.

Cross-sectional analysis of cognitive function using multivariate normative comparisons in men with HIV disease.

BACKGROUND: Prevalence estimates of cognitive impairment in HIV disease vary widely. Here we used multivariate normative comparison (MNC) with identify individuals with impaired cognition, and to compare the results with those using the Frascati and Gisslén criteria. METHODS: The current project used data collected before October 2014 from bisexual/gay men from the Multicenter AIDS Cohort Study. A total of 2904 men (mean age 39.7 years, 52.7% seropositive) had complete data in six cognitive domains at their first neuropsychological evaluation. T-scores were computed for each domain and the MNC was applied to detect impairment among seronegative and seropositive groups. RESULTS: The MNC classified 6.26% of seronegative men as being impaired using a predetermined 5% false discovery rate. By contrast, the Frascati and the Gisslén criteria identified 24.54 and 11.36% of seronegative men as impaired. For seropositive men, the percentage impairment was 7.45, 25.73, and 11.69%, respectively, by the MNC, Frascati and Gisslén criteria. When we used seronegative men without medical comorbidities as the control group, the MNC, the Frascati and the Gisslén criteria identified 5.05, 27.07, and 4.21% of the seronegative men, and 4.34, 30.95, and 4.48% of the seropositive men as having cognitive impairment. For each method, serostatus was not associated with cognitive impairment. CONCLUSION: The MNC controls the false discovery rate and therefore avoids the low specificity that characterizes the Frascati and Gisslén criteria. More research is needed to evaluate the sensitivity of the MNC method in a seropositive population that may be sicker and older than the current study sample and that includes women.

Neuropsychological changes in efavirenz switch regimens.

BACKGROUND: Efavirenz is associated with side effects involving the central nervous system. However, it remains largely unknown whether switching off EFV improves neuropsychological performance. METHODS: We utilized data from the Multicenter AIDS Cohort Study (MACS). Participants were categorized by their use of EFV: never on EFV (No EFV), continuously on EFV (No Switch-OFF) and on EFV and then switched off (Switch-OFF). Baseline time points were defined as visits when first neuropsychological data were available. In Analysis 1, we compared neuropsychological and Center for Epidemiological Studies-Depression Scale (CES-D) scores before and after EFV switch in Switch-OFF group, aligning participants at the time of switch. Analysis 2 evaluated trajectory of neuropsychological/CES-D score among the three groups. RESULTS: This analysis included 1989 HIV-seropositive participants with neuropsychological data (1675 in No EFV, 44 in No Switch-OFF, and 270 in Switch-OFF group). At baseline, participants had a median age of 37 years, median CD4 cell count 442 cells/µl, and 22.9% viral suppression rate. In Analysis 1, neuropsychological and CES-D scores did not show clinically significant changes over 2 years prior to and 4 years after switch in Switch-OFF group. In Analysis 2, trends in neuropsychological and CES-D scores in the three different groups did not show significant differences during a median of 3.2 years of follow-up. CONCLUSION: Discontinuation of EFV is not associated with changes in neuropsychological performance or severity of depression in men. Furthermore, we did not observe differences among participants who were never on EFV, continuously on EFV, and on EFV and then switched off.

Accelerated, first-pass cardiac perfusion pulse sequence with radial k-space sampling, compressed sensing, and k-space weighted image contrast reconstruction tailored for visual analysis and quantification of myocardial blood flow.

PURPOSE: To develop an accelerated cardiac perfusion pulse sequence and test whether it is capable of increasing spatial coverage, generating high-quality images, and enabling quantification of myocardial blood flow (MBF). METHODS: We implemented an accelerated first-pass cardiac perfusion pulse sequence by combining radial k-space sampling, compressed sensing (CS), and k-space weighted image contrast (KWIC) filtering. The proposed and clinical standard pulse sequences were evaluated in a randomized order in 13 patients at rest. For visual analysis, 3 readers graded the conspicuity of wall enhancement, artifact, and noise level on a 5-point Likert scale (overall score index = sum of 3 individual scores). Resting MBF was calculated using a Fermi function model with and without KWIC filtering. Mean visual scores and MBF values were compared between sequences using appropriate statistical tests. RESULTS: The proposed pulse sequence produced greater spatial coverage (6-8 slices) with higher spatial resolution (1.6 × 1.6 × 8 mm3 ) and shorter readout duration (78 ms) compared to clinical standard (3-4 slices, 3 × 3 × 8 mm3 , 128 ms, respectively). The overall image score index between accelerated (11.1 ± 1.3) and clinical standard (11.2 ± 1.3) was not significantly different (P = 0.64). Mean resting MBF values with KWIC filtering (0.9-1.2 mL/g/min across different slices) were significantly lower (P < 0.0001) than those without KWIC filtering (3.1-4.3 mL/g/min) and agreed better with values reported in literature. CONCLUSION: An accelerated, first-pass cardiac perfusion pulse sequence with radial k-space sampling, CS, and KWIC filtering is capable of increasing spatial coverage, generating high-quality images, and enabling quantification of MBF.

Neuropsychological phenotypes among men with and without HIV disease in the multicenter AIDS cohort study.

OBJECTIVE: Mild forms of HIV-associated neurocognitive disorder (HAND) remain prevalent in the combination antiretroviral therapy (cART) era. This study's objective was to identify neuropsychological subgroups within the Multicenter AIDS Cohort Study (MACS) based on the participant-based latent structure of cognitive function and to identify factors associated with subgroups. DESIGN: The MACS is a four-site longitudinal study of the natural and treated history of HIV disease among gay and bisexual men. METHODS: Using neuropsychological domain scores, we used a cluster variable selection algorithm to identify the optimal subset of domains with cluster information. Latent profile analysis was applied using scores from identified domains. Exploratory and posthoc analyses were conducted to identify factors associated with cluster membership and the drivers of the observed associations. RESULTS: Cluster variable selection identified all domains as containing cluster information except for Working Memory. A three-profile solution produced the best fit for the data. Profile 1 performed below average on all domains, Profile 2 performed average on executive functioning, motor, and speed and below average on learning and memory, Profile 3 performed at or above average across all domains. Several demographic, cognitive, and social factors were associated with profile membership; these associations were driven by differences between Profile 1 and the other profiles. CONCLUSION: There is an identifiable pattern of neuropsychological performance among MACS members determined by all domains except Working Memory. Neither HIV nor HIV-related biomarkers were related with cluster membership, consistent with other findings that cognitive performance patterns do not map directly onto HIV serostatus.

HIV disease and diabetes interact to affect brain white matter hyperintensities and cognition.

BACKGROUND: Since the onset of combination antiretroviral therapy use, the incidence of HIV-associated dementia and of HIV encephalitis has fallen dramatically. The present study investigates the extent of white matter hyperintensities (WMHs) among individuals with HIV disease, and factors that predict their presence and their impact on psychomotor speed. METHODS: A total of 322 men participating in the Multicenter AIDS Cohort Study (185 HIV-infected, age: 57.5 ±â€Š6.0) underwent MRI scans of the brain. T1-weighted magnetization-prepared rapid gradient-echo (MP-RAGE) and T2-weighted Fluid Attenuated Inversion Recovery (FLAIR) images were obtained and processed using an automated method for identifying and measuring WMHs. WMH burden was expressed as the log10 transformed percentage of total white matter. RESULTS: There were no significant associations between WMHs and HIV disease. However, the extent of WMHs was predicted by age more than 60 (ß = 0.17), non-white race (ß = 0.14), glomerular filtration rate (ß = -0.11), and the presence of diabetes (ß = 0.12). There were no interactions between HIV status and age (ß = -0.03) or between age and diabetes (ß = 0.07). However, the interaction between HIV infection and diabetes was significant (ß = 0.26). The extent of WMHs was significantly associated with performance on measures of psychomotor speed (ß = 0.15). CONCLUSION: In today's therapeutic environment, in HIV-infected and HIV seronegative individuals, those factors which affect the cerebrovasculature are the best predictors of WMHs. Diabetes has a specific impact among HIV-infected, but not uninfected, men, suggesting the need for more aggressive treatment even in the prediabetes state, especially as WMHs affect cognitive functions.