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Background Doppler echocardiography (echo) is the reference standard for blood flow velocity analysis, and two-dimensional (2-D) phase-contrast magnetic resonance imaging (MRI) is considered the reference standard for quantitative blood flow assessment. However, both clinical standard-of-care techniques are limited by 2-D acquisitions and single-direction velocity encoding and may make them inadequate to assess the complex three-dimensional hemodynamics seen in congenital heart disease. Four-dimensional flow MRI (4-D flow) enables qualitative and quantitative analysis of complex blood flow in the heart and great arteries. Objectives The objectives of this study are to compare 4-D flow with 2-D phase-contrast MRI for quantification of aortic and pulmonary flow and to evaluate the advantage of 4-D flow-based volumetric flow analysis compared to 2-D phase-contrast MRI and echo for peak velocity assessment in children and young adults. Materials and methods Two-dimensional phase-contrast MRI of the aortic root, main pulmonary artery (MPA), and right and left pulmonary arteries (RPA, LPA) and 4-D flow with volumetric coverage of the aorta and pulmonary arteries were performed in 50 patients (mean age: 13.1 ± 6.4 years). Four-dimensional flow analyses included calculation of net flow and regurgitant fraction with 4-D flow analysis planes similarly positioned to 2-D planes. In addition, 4-D flow volumetric assessment of aortic root/ascending aorta and MPA peak velocities was performed and compared to 2-D phase-contrast MRI and echo. Results Excellent correlation and agreement were found between 2-D phase-contrast MRI and 4-D flow for net flow ( r  = 0.97, P  < 0.001) and excellent correlation with good agreement was found for regurgitant fraction ( r  = 0.88, P  < 0.001) in all vessels. Two-dimensional phase-contrast MRI significantly underestimated aortic ( P  = 0.032) and MPA ( P  < 0.001) peak velocities compared to echo, while volumetric 4-D flow analysis resulted in higher (aortic: P  = 0.001) or similar (MPA: P  = 0.98) peak velocities relative to echo. Conclusion Excellent flow parameter agreement between 2-D phase-contrast MRI and 4-D flow and the improved volumetric 4-D flow velocity analysis relative to echo suggests that 4-D flow has the potential to become a clinical alternative to 2-D phase-contrast MRI.

Although environmental lead exposure is associated with significant deficits in cognition, executive functions, social behaviors, and motor abilities, the neuroanatomical basis for these impairments remains poorly understood. In this study, we examined the relationship between childhood lead exposure and adult brain volume using magnetic resonance imaging (MRI). We also explored how volume changes correlate with historic neuropsychological assessments. Volumetric analyses of whole brain MRI data revealed significant decreases in brain volume associated with childhood blood lead concentrations. Using conservative, minimum contiguous cluster size and statistical criteria (700 voxels, unadjusted p < 0.001), approximately 1.2% of the total gray matter was significantly and inversely associated with mean childhood blood lead concentration. The most affected regions included frontal gray matter, specifically the anterior cingulate cortex (ACC). Areas of lead-associated gray matter volume loss were much larger and more significant in men than women. We found that fine motor factor scores positively correlated with gray matter volume in the cerebellar hemispheres; adding blood lead concentrations as a variable to the model attenuated this correlation. Childhood lead exposure is associated with region-specific reductions in adult gray matter volume. Affected regions include the portions of the prefrontal cortex and ACC responsible for executive functions, mood regulation, and decision-making. These neuroanatomical findings were more pronounced for males, suggesting that lead-related atrophic changes have a disparate impact across sexes. This analysis suggests that adverse cognitive and behavioral outcomes may be related to lead's effect on brain development producing persistent alterations in structure. Using a simple model, we found that blood lead concentration mediates brain volume and fine motor function.

Bicuspid aortic valve (BAV) disease is associated with increased risk of aortopathy. In addition to current intervention guidelines, BAV mediated changes in aortic 3D hemodynamics have been considered as risk stratification measures. We aimed to evaluate the association of 4D flow cardiovascular magnetic resonance (CMR) derived voxel-wise aortic reverse flow with aortic dilation and to investigate the role of aortic valve regurgitation (AR) and stenosis (AS) on reverse flow in systole and diastole. 510 patients with BAV (52 ± 14 years) and 120 patients with trileaflet aortic valve (TAV) (61 ± 11 years) and mid-ascending aorta diameter (MAAD) > 35 mm who underwent CMR including 4D flow CMR were retrospectively included. An age and sex-matched healthy control cohort (n = 25, 49 ± 12 years) was selected. Voxel-wise reverse flow was calculated in the aorta and quantified by the mean reverse flow in the ascending aorta (AAo) during systole and diastole. BAV patients without AS and AR demonstrated significantly increased systolic and diastolic reverse flow (222% and 13% increases respectively, p < 0.01) compared to healthy controls and also had significantly increased systolic reverse flow compared to TAV patients with aortic dilation (79% increase, p < 0.01). In patients with isolated AR, systolic and diastolic AAo reverse flow increased significantly with AR severity (c = − 83.2 and c = − 205.6, p < 0.001). In patients with isolated AS, AS severity was associated with an increase in both systolic (c = − 253.1, p < 0.001) and diastolic (c = − 87.0, p = 0.02) AAo reverse flow. Right and left/right and non-coronary fusion phenotype showed elevated systolic reverse flow (> 17% increase, p < 0.01). Right and non-coronary fusion phenotype showed decreased diastolic reverse flow (> 27% decrease, p < 0.01). MAAD was an independent predictor of systolic (p < 0.001), but not diastolic, reverse flow (p > 0.1). 4D flow CMR derived reverse flow associated with BAV was successfully captured even in the absence of AR or AS and in comparison to TAV patients with aortic dilation. Diastolic AAo reverse flow increased with AR severity while AS severity strongly correlated with increased systolic reverse flow in the AAo. Additionally, increasing MAAD was independently associated with increasing systolic AAo reverse flow. Thus, systolic AAo reverse flow may be a valuable metric for evaluating disease severity in future longitudinal outcome studies.

Four-dimensional (4D) flow MRI has shown promise for the assessment of aortic hemodynamics. However, data analysis traditionally requires manual and time-consuming human input at several stages. This limits reproducibility and affects analysis workflows, such that large-cohort 4D flow studies are lacking. Here, a fully automated artificial intelligence (AI) 4D flow analysis pipeline was developed and evaluated in a cohort of over 350 subjects. The 4D flow MRI analysis pipeline integrated a series of previously developed and validated deep learning networks, which replaced traditionally manual processing tasks (background-phase correction, noise masking, velocity anti-aliasing, aorta 3D segmentation). Hemodynamic parameters (global aortic pulse wave velocity (PWV), peak velocity, flow energetics) were automatically quantified. The pipeline was evaluated in a heterogeneous single-center cohort of 379 subjects (age = 43.5 ± 18.6 years, 118 female) who underwent 4D flow MRI of the thoracic aorta (n = 147 healthy controls, n = 147 patients with a bicuspid aortic valve [BAV], n = 10 with mechanical valve prostheses, n = 75 pediatric patients with hereditary aortic disease). Pipeline performance with BAV and control data was evaluated by comparing to manual analysis performed by two human observers. A fully automated 4D flow pipeline analysis was successfully performed in 365 of 379 patients (96%). Pipeline-based quantification of aortic hemodynamics was closely correlated with manual analysis results (peak velocity: r = 1.00, p < 0.001; PWV: r = 0.99, p < 0.001; flow energetics: r = 0.99, p < 0.001; overall r ≥ 0.99, p < 0.001). Bland–Altman analysis showed close agreement for all hemodynamic parameters (bias 1–3%, limits of agreement 6–22%). Notably, limits of agreement between different human observers’ quantifications were moderate (4–20%). In addition, the pipeline 4D flow analysis closely reproduced hemodynamic differences between age-matched adult BAV patients and controls (median peak velocity: 1.74 m/s [automated] or 1.76 m/s [manual] BAV vs. 1.31 [auto.] vs. 1.29 [manu.] controls, p < 0.005; PWV: 6.4–6.6 m/s all groups, any processing [no significant differences]; kinetic energy: 4.9 μJ [auto.] or 5.0 μJ [manu.] BAV vs. 3.1 μJ [both] control, p < 0.005). This study presents a framework for the complete automation of quantitative 4D flow MRI data processing with a failure rate of less than 5%, offering improved measurement reliability in quantitative 4D flow MRI. Future studies are warranted to reduced failure rates and evaluate pipeline performance across multiple centers.

To evaluate k–t accelerated 3D cine b-SSFP (balanced steady state free precession) as magnetic resonance imaging (MRI) technique for aortic annular area measurement in transcatheter aortic valve replacement (TAVR) planning compared to computed tomography angiography (CTA) and other non-contrast MRI sequences with reduced imaging time and without contrast administration. 6 volunteers and 7 TAVR candidates were prospectively enrolled. The volunteers underwent an MRI while TAVR candidates underwent an MRI and CTA. The following non-contrast MRI sequences were obtained at the level of the aortic root: 2D cine b-SSFP [GRAPPA (GeneRalized Autocalibrating Partially Parallel Acquisitions), R = 2], 3D cine b-SSFP [GRAPPA R = 2], navigator triggered 3D b-SSFP MRA [GRAPPA, R = 2] and k–t accelerated 3D cine b-SSFP [PEAK GRAPPA, R = 5]. Qualitative analysis and aortic annular area measurements in systole and diastole were obtained. k–t accelerated 3D cine b-SSFP provided image quality that is acceptable for confident diagnosis with very good interrater agreement. There was no statistically significant difference in aortic annular measurements between k–t accelerated 3D cine b-SSFP and CTA or other MRI sequences (p > 0.05). Bland–Altman analysis showed no systemic difference of annular area measurements between k–t accelerated 3D cine b-SSFP and each of the other techniques. There was excellent inter-rater agreement on aortic annular area measurements during systolic (ICC = 0.976, p < 0.001) and diastolic (ICC = 0.971, p < 0.001) phases using k–t accelerated 3D cine b-SSFP. K–t accelerated 3D cine b-SSFP is a promising alternative for the assessment of annular sizing in pre-TAVR evaluation while offering a reasonable combination of imaging parameters during one breath-hold.

Objectives: Clinical management decisions surrounding ascending aorta (AAo) dilation in bicuspid aortic valve (BAV) disease benefit from personalized predictive tools. 4D-flow MRI may provide patient-specific markers reflective of BAV-associated aortopathy. This study aims to explore novel 4D-flow MRI parametric voxel-by-voxel forward flow, reverse flow, kinetic energy and stasis in BAV disease. We hypothesize that novel parametric voxel-by-voxel markers will be associated with aortic dilation and referral for surgery and can enhance our understanding of BAV hemodynamics beyond standard metrics. Methods: A total of 96 subjects (73 BAV patients, 23 healthy controls) underwent MRI scan. Healthy controls had no known cardiovascular disease. Patients were clinically referred for AAo dilation assessment. Indexed diameters were obtained by dividing the aortic diameter by the patient’s body surface area. Patients were followed for the occurrence of aortic surgery. 4D-flow analysis was performed by a single observer in five regions: left ventricular outflow tract (LVOT), AAo, arch, proximal descending aorta (PDAo), and distal descending aorta (DDAo). In each region peak velocity, kinetic energy (KE), forward flow (FF), reverse flow (RF), and stasis were measured on a voxel-by-voxel basis. T-tests (or non-parametric equivalent) compared flow parameters between cohorts. Univariate and multivariate analyses explored associations between diameter and parametric voxel-by-voxel parameters. Results: Compared to controls, BAV patients showed reduced stasis ( p < 0.01) and increased RF and FF ( p < 0.01) throughout the aorta, and KE remained similar. In the AAo, indexed diameter correlated with age (R = 0.326, p = 0.01), FF (R = −0.648, p < 0.001), RF (R = −0.441, p < 0.001), and stasis (R = −0.288, p < 0.05). In multivariate analysis, FF showed a significant inverse association with AAo indexed diameter, independent of age. During a median 179 ± 180 days of follow-up, 23 patients (32%) required aortic surgery. Compared to patients not requiring surgery, they showed increased KE and peak velocity in the proximal aorta ( p < 0.01), accompanied by increased RF and reduced stasis throughout the entire aorta ( p < 0.01). Conclusion: Novel voxel-by-voxel reverse flow and stasis were altered in BAV patients and are associated with aortic dilation and surgical treatment.

Understanding of regression in autism has been hampered by variability in parental and clinical recognition and reporting of lost skills. This study introduced an instrument, the Regression Supplement Form, intended to supplement the Autism Diagnosis Interview-Revised and yield precise information about the types and timing of regression and events concurrent with loss and regain of skills. Data were collected from parents of 44 children (38 male, 6 female; mean age = 6 years) with Autistic Spectrum Disorder (37 Autistic Disorder, 7 Pervasive Developmental Disorder-Not Otherwise Specified). Parental responses on the Autism Diagnosis Interview-Revised indicated loss of skills during early development. The profile of regression that emerged included loss of skills between 18 and 21 months, on average, with language-only regression less common than loss of other, nonlanguage skills only or of full regression (loss of language and other skills). The onset of regression typically was gradual in nonlanguage areas and split between gradual and sudden loss for language skills. Some of the children were developing atypically before they lost other, nonlanguage skills, that is, their age at first words was delayed until age 2 years or older. Parents tended to attribute loss to medical factors such as immunizations. Many of the children regained some of the lost skills when they were 3.5-5 years of age, with therapeutic and instructional interventions given credit for the regain.

Abused mothers and their school-aged children who recently entered domestic violence emergency shelters were assessed by individual interview and psychometric measures. Children had positive views of the shelter residence. Mothers and children reported high-quality relationships with each other. Children came from highly violent homes, and the majority had attempted to intervene in the interadult violence. Hierarchical multiple regressions were conducted on child PTSD symptoms, child behavior problems, and maternal depression, anxiety, and anger. Child PTSD symptoms were associated with amount of physical violence. Child behavioral problems were related to mother anxiety and anger. The predictors of maternal emotional distress varied. Depression was associated with sexual abuse, child physical intervention, and quality of mother-child relationship; anxiety was related to witnessing child abuse, child age, and child internalizing behaviors; anger was associated with abuse-related injuries, violence frequency, and child internalizing behaviors. Augmentation of shelter-based interventions for children's trauma, maternal emotional distress, and parenting are discussed.

The early social and communicative development of very young siblings of children with autism spectrum disorder (ASD) is the focus of the current study. Three groups of children were included: (1) young children diagnosed with ASD, (2) younger siblings in families with a somewhat older child with ASD, and (3) young typically developing children. All children participated in a videotaped, structured interactional procedure called the Early Social Communication Scales (ESCS; [Mundy & Hogan, 1996, A Preliminary Manual for the Abridged Early Social Communication Scales (ESCS) Unpublished manual, University of Miami]). Very young siblings were compared to young children with a diagnosed autism spectrum disorder and to a group of young typically developing children. Results indicated that, on three of four of the ESCS subscales, the social communicative behaviors of the younger siblings differed from those of the typically developing children but not from the behaviors displayed by the ASD group. Genetic vulnerability for ASD among siblings and characteristics of family interaction may explain the level of impairment observed in the very young siblings of children with autism spectrum disorders.