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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.

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.To characterize PH via quantification of regional pulmonary transit times (rPTT).Retrospective.A total of 43 patients (58% female); 24 controls (33% female). RHC-confirmed patients classified as World Health Organization (WHO) subgroups 1-4.A 1.5 T/time-resolved contrast-enhanced MR Angiography (CE-MRA).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 (tAnalysis 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.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.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.1 TECHNICAL EFFICACY: Stage 3.

Evaluation of aortic stiffness by pulse wave velocity (PWV) across the adult lifespan is needed to better understand normal aging in women and men.To characterize PWV in the thoracic aorta using 4D flow MRI in an age- and sex-stratified cohort of healthy adults.Retrospective.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.1.5 T or 3 T, 2D cine bSSFP, 4D flow MRI.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.Analysis of variance, Pearson's correlation coefficient (r), linear regression, intraclass correlation coefficient (ICC). A P value 0.05 was considered statistically significant.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 = 0.75.4D 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.2 TECHNICAL EFFICACY: Stage 2.

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.To intra-individually compare MRA images obtained with equimolar GB and GM at 1.5 T in the SAV.Prospective, crossover.Twenty-eight subjects (54 ± 13 years; 17 female).1.5 T; three-dimensional (3D) gradient recalled echo.Quantitative image quality was measured by normalized signal intensity (SISINo significant difference in SIAt 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.2 TECHNICAL EFFICACY: Stage 2.

BackgroundIndividuals 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.MethodsWe 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.ResultsTCBF 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).ConclusionsThe 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.

Network analysis of human brain connectivity is critically important for understanding brain function and disease states. Embedding a brain network as a whole graph instance into a meaningful low-dimensional representation can be used to investigate disease mechanisms and inform therapeutic interventions. Moreover, by exploiting information from multiple neuroimaging modalities or views, we are able to obtain an embedding that is more useful than the embedding learned from an individual view. Therefore, multi-view multi-graph embedding becomes a crucial task. Currently only a few studies have been devoted to this topic, and most of them focus on vector-based strategy which will cause structural information contained in the original graphs lost. As a novel attempt to tackle this problem, we propose Multi-view Multi-graph Embedding M2E by stacking multi-graphs into multiple partially-symmetric tensors and using tensor techniques to simultaneously leverage the dependencies and correlations among multi-view and multi-graph brain networks. Extensive experiments on real HIV and bipolar disorder brain network datasets demonstrate the superior performance of M2E on clustering brain networks by leveraging the multi-view multi-graph interactions.

The purpose of this study was to characterize brain volumetric differences in HIV seropositive and seronegative men and to determine effects of age, cardiovascular risk, and HIV infection on structural integrity.Magnetic resonance imaging was used to acquire high-resolution neuroanatomic data in 160 men aged 50 years and over, including 84 HIV seropositive and 76 seronegative controls. Voxel-based morphometry was used to derive volumetric measurements at the level of the individual voxel. Data from a detailed neuropsychological test battery were recombined into four summary scores representing psychomotor speed, visual memory, verbal memory, and verbal fluency.Both age and HIV status had a significant effect on both gray matter (GM) and white matter (WM) volume. The age-related GM atrophy was primarily in the superior temporal and inferior frontal regions; the HIV-related GM loss included the posterior and inferior temporal lobes, the parietal lobes, and the cerebellum. Among all subjects, the performance on neuropsychological tests, as indexed by a summary variable, was related to the volume of both the GM and WM. Contrary to our predictions, the CVD variables were not linked to brain volume in statistically adjusted models.In the post-HAART era, having HIV infection is still linked to atrophy in both GM and WM. Secondly, advancing age, even in this relatively young cohort, is also linked to changes in GM and WM volume. Thirdly, CNS structural integrity is associated with overall cognitive functions, regardless of the HIV infection status of the study volunteers.

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. Electronic supplementary material The online version of this article (doi:10.1007/s11682-011-9113-8) contains supplementary material, which is available to authorized users.

Background: Endomyocardial biopsy (EMB) is the current gold standard to monitor patients for heart transplant rejection. Quantification of myocardial T2 relaxation time using cardiac magnetic resonance (CMR) has been shown to have high sensitivity and specificity to detect rejection episodes. In this study, we evaluated the prognostic value of myocardial T2 to predict adverse cardiovascular outcomes during 5-year follow-up after initial CMR. Methods: 49 cardiac transplant patients (mean age, 48 ± 14 years; 65% male) were recruited from a single institution. CMR at 1.5T was performed in all patients, with subsequent quantifications of regional and global myocardial T2. Clinical data was gathered post-CMR over a 5-year period. EMBs were graded according to the International Society of Heart & Lung Transplantation criteria. Rejection episodes were defined by EMB ≥ 2R, new onset heart failure (HF), LV ejection fraction < 40%, or death. Adverse cardiovascular events gathered included coronary artery disease, cardiomyopathies, arrhythmias, and different types of HFs. Multivariable logistic regression and Kaplan-Meier analysis was performed to measure the prognostic value of myocardial T2. Results: Myocardial T2 was found to increase with worsening EMB grade from 53.0 ms (0R, no rejection) to 59.9 ms (3R, severe rejection). ROC analysis using two groups (EMBs ≤ 1R and ≥ 2R) showed T2 = 55.0 ms to have the highest specificity and sensitivity. In multivariable analysis that considered T2 measures, age, length of surgery, donor ischemic time, and BMI, both peak T2 (p = 0.038) and septal T2 (p = 0.035) were significant predictors of EMB grade ≥ 2R. Kaplan-Meier analysis showed a significant higher probability of developing EMB ≥ 2R, new onset HF, or death with a global T2 ≥ 55 (p = 0.02). Adverse cardiovascular outcomes of systolic HF, acute systolic HF, and chronic diastolic HF had a higher probability of developing in patients with global T2 ≥ 55 (p = 0.01, p = 0.01, and p < 0.01, respectively). Conclusions: CMR T2 quantification demonstrated prognostic value for all-cause rejection and various types of HFs in cardiac transplant patients. These findings suggest that CMR may be a suitable modality to non-invasively monitor cardiac transplant patients for rejection.