Sleep duration and association with cardiometabolic health in adolescents and adults with type 1 diabetes: Results from the BCQR-T1D study.

AIM: Type 1 diabetes (T1D) increases the risk of morbidity and mortality from cardiovascular disease, and insufficient sleep is prevalent. Emerging evidence suggests a link between sleep and cardiometabolic health, but this has not been examined across the lifespan in individuals with T1D. We aimed to examine associations between sleep and cardiometabolic health in adolescents and adults with T1D in a secondary analysis of data from a 4-week double-blind, random-order, placebo-controlled crossover trial of bromocriptine quick release (BCQR) therapy with a 4-week washout in between conditions. MATERIALS AND METHODS: Forty-two adults (19-60 years) and 42 adolescents (12-18 years) with T1D >9 months completed 1 week of home monitoring with wrist-worn actigraphy to estimate sleep duration and continuous glucose monitoring, anthropometrics, arterial stiffness, magnetic resonance imaging (adolescents only), and fasting laboratory testing at each treatment phase. RESULTS: Sixty-two per cent of adolescents and 74% of adults obtained <7 h of sleep per night at baseline. After adjustment for age, sex and diabetes duration, baseline sleep <7 h per night was associated with a higher body mass index, a higher waist circumference, a higher systolic blood pressure, worse arterial stiffness and a lower estimated insulin sensitivity (all p < .05). When examined by age group, associations between sleep duration and cardiometabolic health outcomes remained significant, predominantly for adolescents. In adolescents only, wake time was significantly later (p = .027) and time in bed was significantly longer with BCQR versus placebo (p = .049). CONCLUSIONS: Objectively measured sleep <7 h per night was prevalent in adolescents and adults with T1D and associated with poorer cardiometabolic health markers. Small changes in sleep were seen following BCQR treatment in adolescents only. Sleep may be an important and novel target for improving cardiometabolic health in individuals with T1D.

Consensus Minimum MRI Protocol for the Child With Acute Recurrent or Chronic Pancreatitis.

Imaging plays an important role in the diagnosis and follow-up of children with acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP). Consensus is lacking for a minimum MRI protocol for the child with known or suspected ARP or CP. Lack of standardization contributes to variable diagnostic performance and hampers application of uniform interpretive criteria for clinical diagnosis and multicenter research studies. We convened a working group to achieve consensus for a minimum MRI protocol for children with suspected ARP or CP. The group included eight pediatric radiologists experienced in interpreting MRI for pediatric pancreatitis and one medical pancreatologist and functioned from November 2022 to March 2023. Existing clinical protocols were summarized across sites represented by group members, and commonly used sequences guided the group's discussion. The final consensus minimum MRI protocol includes five noncontrast sequences and two postcontrast sequences (which are required only in select clinical scenarios). The working group also provides recommended acquisition parameters, sequence-specific technical suggestions, and general recommendations for optimal imaging technique. We recommend that all sites imaging children with ARP and CP for clinical care, and particularly those engaged in cooperative group trials for pancreatitis, ensure that their local protocol includes these minimum sequences.

Computed tomographic findings in TBX4 mutation: a common cause of severe pulmonary artery hypertension in children.

BACKGROUND: Mutations in the T-Box 4 (TBX4) gene are a lesser-known cause of heritable pulmonary arterial hypertension (PAH). Patients with heritable PAH typically have worse outcomes when compared with patients with idiopathic PAH, yet little is known about the phenotypical presentation of this mutation. OBJECTIVE: This article reviews the pattern of chest CT findings in pediatric patients with PAH and TBX4 mutations and compares their radiographic presentation with those of age-matched patients with PAH but without TBX4 mutations. MATERIALS AND METHODS: A retrospective chart review of the pulmonary arterial hypertension database was performed. Pediatric patients with PAH-confirmed TBX4 mutations and an available high CT were included. Fifteen (9 females) patients met the inclusion criteria. Fourteen (8 females) age-matched controls with diagnosed PAH but without TBX4 mutations were also evaluated. The median age at diagnosis was 7.4 years (range: 0.1-16.4 years). Demographic information and clinical outcomes were collected. CTs of the chest were reviewed for multiple airway, parenchymal, and structural abnormalities (16 imaging findings in total). Chi-square tests were used to compare the prevalence of each imaging finding in the TBX4 cohort compared to the control group. RESULTS: Patients with TBX-4 mutations had increased presence of peripheral or subpleural irregularity (73% vs 0%, P < 0.01), cystic lucencies (67% vs 7%, P < 0.01), and linear or reticular opacity (53% vs 0%, P < 0.01) compared to the control group. Ground glass opacities, bronchiectasis, and centrilobular nodules were not significantly different between the two patient groups (P > 0.05). CONCLUSION: TBX4 mutations have distinct imaging phenotypes in pediatric patients with PAH. Compared to patients without this mutation, patients with TBX-4 genes typically present with peripheral or subpleural irregularity, cystic lucencies, and linear or reticular opacity.

Reference Values for Fetal Cardiac Dimensions, Volumes, Ventricular Function and Left Ventricular Longitudinal Strain Using Doppler Ultrasound Gated Cardiac Magnetic Resonance Imaging in Healthy Third Trimester Fetuses.

BACKGROUND: Recent advances in hardware and software permit the use of cardiac MRI of late gestation fetuses, however there is a paucity of MRI-based reference values. PURPOSE: To provide initial data on fetal cardiac MRI-derived cardiac dimensions, volumes, ventricular function, and left ventricular longitudinal strain in healthy developing fetuses >30 weeks gestational age. STUDY TYPE: Prospective. POPULATION: Twenty-five third trimester (34 ± 1 weeks, range of 32-37 weeks gestation) women with healthy developing fetuses. FIELD STRENGTH/SEQUENCE: Studies were performed at 1.5 T and 3 T. Cardiac synchronization was achieved with a Doppler ultrasound device. The protocol included T2 single shot turbo spin echo stacks for fetal weight and ultrasound probe positioning, and multiplanar multi-slice cine balanced steady state free precession gradient echo sequences. ASSESSMENT: Primary analyses were performed by a single observer. Weight indexed right ventricular (RV) and left ventricular (LV) volumes and function were calculated from short axis (SAX) stacks. Cardiac dimensions were calculated from the four-chamber and SAX stacks. Single plane LV longitudinal strain was calculated from the four-chamber stack. Interobserver variability was assessed in 10 participants. Cardiac MRI values were compared against available published normative fetal echocardiogram data using z-scores. STATISTICAL TESTS: Mean and SDs were calculated for baseline maternal/fetal demographics, cardiac dimensions, volumes, ventricular function, and left ventricular longitudinal strain. Bland-Altman and intraclass correlation coefficient analysis was performed to test interobserver variability. RESULTS: The mean gestational age was 34 ± 1.4 weeks. The mean RV and LV end diastolic volumes were 3.1 ± 0.6 mL/kg and 2.4 ± 0.5 mL/kg respectively. The mean RV cardiac output was 198 ± 49 mL/min/kg while the mean LV cardiac output was 173 ± 43 mL/min/kg. DATA CONCLUSION: This paper reports initial reference values obtained by cardiac MRI in healthy developing third trimester fetuses. MRI generally resulted in slightly larger indexed values (by z-score) compared to reports in literature using fetal echocardiography. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

Abnormal flow conduction through pulmonary arteries is associated with right ventricular volume and function in patients with repaired tetralogy of Fallot: does flow quality affect afterload?

OBJECTIVES: Flow through the proximal pulmonary arteries (PAs) of patients with repaired Tetralogy of Fallot (TOF) is known to be highly disordered and associated with significant regurgitation. The purpose of this study was to evaluate 4D-Flow MRI-derived viscous energy loss [Formula: see text])-as a result of non-efficient flow propagation, and relate this parameter to standard right ventricular (RV) size and function markers in patients with repaired TOF. METHODS: Thirty-five patients with TOF and 14 controls underwent comprehensive 4D-Flow MRI evaluation for qualitative flow analysis and to calculate [Formula: see text] in the main and right pulmonary arteries. Sampled [Formula: see text] indices were correlated with the MRI-derived RV size and functional indices. RESULTS: All patients with TOF exhibited abnormal, supra-physiologic helical/vortical formations in the PAs. Patients with TOF had significantly increased peak systolic [Formula: see text] (8.0 vs 0.5 mW, p < 0.001), time-averaged [Formula: see text] (2.5 vs. 0.2 mW, p < 0.001), and peak systolic [Formula: see text] indexed to stroke volume (0.082 vs. 0.012 mW/mL, p < 0.001). [Formula: see text] indexed to stroke volume correlated with the RV end-diastolic volume (R = 0.68, p < 0.001), end-systolic volume (R = 0.62, p < 0.001), ejection fraction (R = -0.45, p = 0.002), and cardiac index (R = 0.45, p = 0.002). The mean estimated energy loss due to [Formula: see text] with regard to input RV mechanical power was 4.7%. CONCLUSION: This study demonstrates that patients with repaired TOF have highly abnormal flow conduction through the PAs which result into extensive viscous energy loss. This significant flow-mediated energy loss is associated with the RV volume and function, and might represent considerable loss of mechanical power generated by each cardiac cycle. Future studies are required to assess whether the abnormal flow conduction adds to the RV afterload and remodeling. KEY POINTS: • Abnormal flow patterns through proximal pulmonary arteries in patients with TOF are associated with excessive viscous energy loss. • Inefficient flow conduction is associated with the RV dilation and reduced function and might contribute to the RV adaptive remodeling.

Estimation of glomerular filtration rate in a pediatric population using non-contrast kidney phase contrast magnetic resonance imaging.

BACKGROUND: Glomerular filtration rate (GFR) is a key measure of kidney function but often inaccurately ascertained by serum creatinine and cystatin C in pediatrics. In this pilot trial, we evaluated the relationship between GFR calculated by using phase-contrast MRI (PC-MRI) biomarkers and GFR by 125I-iothalamate clearance in youth undergoing bone marrow transplantation (BMT). METHODS: A total of twenty-one pediatric BMT candidates (8-21 years of age) were recruited for a research kidney PC-MRI. After completion of 125I-iothalamate clearance, same-day PC-MRI measurements were completed of the kidney circulation without a gadolinium-based contrast agent. MRI included a non-contrast balanced-SSFP-triggered angiography to position ECG-gated breath-held 2D PC-MRI flow measurements (1.2 × 1.2 × 6 mm3). A multivariate model of MRI biomarkers estimating GFR (GFR-MRI) was selected using the elastic net approach. RESULTS: The GFR-MRI variables selected by elastic net included average heart rate during imaging (bpm), peak aorta flow below the kidney artery take-offs (ml/s), average kidney artery blood flow, average peak kidney vein blood flow, and average kidney vein blood flow (ml/s). The GFR-MRI model demonstrated strong agreement with GFR by 125I-iothalamate (R2 = 0.65), which was stronger than what was observed with eGFR by the full age spectrum and Chronic Kidney Disease in Children under 25 (CKiD U25) approaches. CONCLUSION: In this pilot study, noninvasive GFR-MRI showed strong agreement with gold standard GFR in youth scheduled for BMT. Further work is needed to evaluate whether non-contrast GFR-MRI holds promise to become a superior alternative to eGFR and GFR by clearance techniques. A higher resolution version of the Graphical abstract is available as Supplementary information.

Unexpected extracardiac findings in cardiac computed tomography from neonates to young adults.

BACKGROUND: Modern CT scanners with lower radiation doses have resulted in large numbers of cardiac CTs being performed in children. As seen in adults, pediatric cardiac CT has the potential to demonstrate extracardiac variants and pathology that can occur in conjunction with congenital heart disease (CHD). Prior publications demonstrated a high incidence of extracardiac findings in various locations but the prevalence of urgent unexpected extracardiac findings in children is unknown. OBJECTIVE: The purpose of this study was to describe the incidence, distribution and clinical significance of the extracardiac findings on pediatric cardiac CT at a tertiary referral center. MATERIALS AND METHODS: We reviewed all reports (n = 648) for 554 children through young adults who received a cardiac CT study between Jan. 2, 2018, and March 10, 2020, at our tertiary referral pediatric hospital. We interrogated CT reports for extracardiac findings and categorized them by system (airway, pulmonary, abdomen, malpositioned lines and musculoskeletal). We then subclassified each of these findings by level of clinical importance based upon the need for intervention or treatment into low, medium or high importance. High-importance findings were confirmed with a focused chart review. If a patient had more than one CT with a persistent extracardiac finding, the finding was only counted once. RESULTS: We identified 562 individual extracardiac findings, with one or more extracardiac findings present in 91% of the study population. Extracardiac findings with high clinical importance, requiring urgent attention or intervention, were present in 10% (57/554) of cases. The most common location of extracardiac findings was pulmonary (50%; 280/562), followed by airway (22%; 125/562) and abdomen (9%; 52/562). CONCLUSION: Unexpected highly important extracardiac findings were found in 10% of patients. Therefore, extracardiac structures should be scrutinized for the timely identification of potentially highly important findings.

Computed tomographic parenchymal lung findings in premature infants with pulmonary vein stenosis.

BACKGROUND: Developmental pulmonary vein pulmonary vein stenosis in the setting of prematurity is a rare and poorly understood condition. Diagnosis can be challenging in the setting of chronic lung disease of prematurity. High-resolution non-contrast chest computed tomography (CT) is the conventional method of evaluating neonates for potential structural changes contributing to severe lung dysfunction and pulmonary hypertension but may miss pulmonary venous stenosis due to the absence of contrast and potential overlap in findings between developmental pulmonary vein pulmonary vein stenosis and lung disease of prematurity. OBJECTIVE: To describe the parenchymal changes of pediatric patients with both prematurity and pulmonary vein stenosis, correlate them with venous disease and to describe the phenotypes associated with this disease. MATERIALS AND METHODS: A 5-year retrospective review of chest CT angiography (CTA) imaging in patients with catheterization-confirmed pulmonary vein stenosis was performed to identify pediatric patients (< 18 years) who had a history of prematurity (< 35 weeks gestation). Demographic and clinical data associated with each patient were collected, and the patients' CTAs were re-reviewed to evaluate pulmonary veins and parenchyma. Patients with post-operative pulmonary vein stenosis and those with congenital heart disease were excluded. Data was analyzed and correlated for descriptive purposes. RESULTS: A total of 17 patients met the inclusion criteria (12 female, 5 male). All had pulmonary hypertension. There was no correlation between mild, moderate, and severe grades of bronchopulmonary dysplasia and the degree of pulmonary vein stenosis. There was a median of 2 (range 1-4) diseased pulmonary veins per patient. In total, 41% of the diseased pulmonary veins were atretic. The right upper and left upper lobe pulmonary veins were the most frequently diseased (n = 13/17, 35%, n = 10/17, 27%, respectively). Focal ground glass opacification, interlobular septal thickening, and hilar soft tissue enlargement were always associated with the atresia of an ipsilateral vein. CONCLUSION: Recognition of the focal parenchymal changes that imply pulmonary vein stenosis, rather than chronic lung disease of prematurity changes, may improve the detection of a potentially treatable source of pulmonary hypertension, particularly where nonangiographic studies result in a limited direct venous assessment.

Segmentation of the Aorta and Pulmonary Arteries Based on 4D Flow MRI in the Pediatric Setting Using Fully Automated Multi-Site, Multi-Vendor, and Multi-Label Dense U-Net.

BACKGROUND: Automated segmentation using convolutional neural networks (CNNs) have been developed using four-dimensional (4D) flow magnetic resonance imaging (MRI). To broaden usability for congenital heart disease (CHD), training with multi-institution data is necessary. However, the performance impact of heterogeneous multi-site and multi-vendor data on CNNs is unclear. PURPOSE: To investigate multi-site CNN segmentation of 4D flow MRI for pediatric blood flow measurement. STUDY TYPE: Retrospective. POPULATION: A total of 174 subjects across two sites (female: 46%; N = 38 healthy controls, N = 136 CHD patients). Participants from site 1 (N = 100), site 2 (N = 74), and both sites (N = 174) were divided into subgroups to conduct 10-fold cross validation (10% for testing, 90% for training). FIELD STRENGTH/SEQUENCE: 3 T/1.5 T; retrospectively gated gradient recalled echo-based 4D flow MRI. ASSESSMENT: Accuracy of the 3D CNN segmentations trained on data from single site (single-site CNNs) and data across both sites (multi-site CNN) were evaluated by geometrical similarity (Dice score, human segmentation as ground truth) and net flow quantification at the ascending aorta (Qs), main pulmonary artery (Qp), and their balance (Qp/Qs), between human observers, single-site and multi-site CNNs. STATISTICAL TESTS: Kruskal-Wallis test, Wilcoxon rank-sum test, and Bland-Altman analysis. A P-value <0.05 was considered statistically significant. RESULTS: No difference existed between single-site and multi-site CNNs for geometrical similarity in the aorta by Dice score (site 1: 0.916 vs. 0.915, P = 0.55; site 2: 0.906 vs. 0.904, P = 0.69) and for the pulmonary arteries (site 1: 0.894 vs. 0.895, P = 0.64; site 2: 0.870 vs. 0.869, P = 0.96). Qs site-1 medians were 51.0-51.3 mL/cycle (P = 0.81) and site-2 medians were 66.7-69.4 mL/cycle (P = 0.84). Qp site-1 medians were 46.8-48.0 mL/cycle (P = 0.97) and site-2 medians were 76.0-77.4 mL/cycle (P = 0.98). Qp/Qs site-1 medians were 0.87-0.88 (P = 0.97) and site-2 medians were 1.01-1.03 (P = 0.43). Bland-Altman analysis for flow quantification found equivalent performance. DATA CONCLUSION: Multi-site CNN-based segmentation and blood flow measurement are feasible for pediatric 4D flow MRI and maintain performance of single-site CNNs. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Coronary computed tomography angiography in children.

Imaging the coronary arteries of children, with their faster heart rates, small vessel size and common inability to lie still or breath-hold, has been a major challenge. With numerous advances in technology, CT examinations can now be performed quickly, often with children free-breathing and with much lower radiation doses than previously. This has led to increased use in children. Care must be taken with technique and choice of electrocardiogram (ECG)-gating technique to obtain adequate imaging for a diagnosis while keeping radiation dose as low as reasonably achievable (ALARA). In this paper, we discuss techniques and tips for CT imaging of the coronary arteries in children, including use of dual-source- and ultrawide-detector CT scanners.

Free-breathing magnetic resonance imaging with radial k-space sampling for neonates and infants to reduce anesthesia.

BACKGROUND: Conventional chest and abdominal MRI require breath-holds to reduce motion artifacts. Neonates and infants require general anesthesia with intubation to enable breath-held acquisitions. OBJECTIVE: We aimed to validate a free-breathing approach to reduce general anesthesia using a motion-insensitive radial acquisition with respiratory gating. MATERIALS AND METHODS: We retrospectively enrolled children <3 years old who were referred for MRI of the chest or abdomen. They were divided into two groups according to MRI protocol: (1) breath-held scans under general anesthesia with T2-weighted single-shot fast spin-echo (SSFSE) and contrast-enhanced T1-weighted modified Dixon, and (2) free-breathing scans using radial sequences (T2-W MultiVane XD and contrast-enhanced T1-W three-dimensional [3-D] Vane XD). Two readers graded image quality and motion artifacts. RESULTS: We included 23 studies in the free-breathing cohort and 22 in the breath-hold cohort. The overall imaging scores for the free-breathing radial T2-W sequence were similar to the scores for the breath-held T2-W SSFSE sequence (chest, 3.6 vs. 3.2, P=0.07; abdomen, 3.9 vs. 3.7, P=0.66). The free-breathing 3-D radial T1-W sequence also had image quality scores that were similar to the breath-held T1-W sequence (chest, 4.0 vs. 3.0, P=0.06; abdomen, 3.7 vs. 3.9, P=0.15). Increased motion was seen in the abdomen on the radial T2-W sequence (P<0.001), but increased motion was not different in the chest (P=0.73) or in contrast-enhanced T1-W sequences (chest, P=0.39; abdomen, P=0.15). The mean total sequence time was longer in free-breathing compared to breath-held exams (P<0.01); however, this did not translate to longer overall exam times (P=0.94). CONCLUSION: Motion-insensitive radial sequences used for infants and neonates were of similar image quality to breath-held sequences and had decreased sedation and intubation.

Higher Mortality in Pediatric Liver Transplant Candidates With Sarcopenia.

Little is known about the impact of sarcopenia (reduced muscle mass and function) in pediatric chronic liver disease. We compared psoas muscle surface area (PMSA), measured at the 4th lumbar vertebrae, in children listed for liver transplantation (LT) to that of healthy controls and studied the impact of sarcopenia on transplant-associated outcomes. The effect of PMSA (raw value and z score) on survival was studied using multivariable proportional hazards, whereas the impact of PMSA on other transplant-associated outcomes was assessed by multivariable linear or logistic regression. The correlation of PMSA with anthropometric values and markers of disease severity was studied using Spearman's rank-order correlation. Mean PMSA was significantly lower in LT candidates (n = 57, 699.4 ± 591.9 mm2 [mean ± SD]) than controls (n = 53, 1052.9 ± 960.7 mm2 ; P = 0.02). For LT candidates, there was an increased risk of death (either while on the waiting list or following transplantation) with lower PMSA (hazard ratio [HR], 1.6 per 100 mm2 [P = 0.03]; 95% confidence interval [CI], 1.1-2.8), amounting to a 4.9 times higher risk of death for every 1 unit decrease in PMSA z score (HR, 4.9 [P = 0.05], 95% CI, 1.2-34.5), adjusting for age and sex. PMSA did not correlate with posttransplant length of intubation, hospital length of stay, or perioperative complications. PMSA also did not correlate with calculated (r = 0.10, P = 0.60) or appealed Model for End-Stage Liver Disease/Pediatric End-Stage Liver Disease scores (r = 0.10, P = 0.69). Pediatric LT candidates have a significant reduction in muscle compared with controls. LT candidates with lower PMSA experience significant increases in mortality. As such, sarcopenia may provide a novel indicator of disease severity in children with chronic liver disease.

Pediatric Metastatic Cardiac Angiosarcoma Successfully Treated With Multimodal Therapy: Case Report and Review of Literature.

Cardiac angiosarcoma (AS) is an extremely rare, malignant vascular tumor with <10 cases reported in the pediatric literature. Prognosis is dismal with overall survival often <1 year from initial diagnosis. In this report, we present the case of a 10-year-old boy with metastatic cardiac AS who is currently alive and is the longest pediatric survivor of metastatic cardiac AS reported in the literature. This is the only published pediatric case to successfully use a combination of surgical resection, conventional chemotherapy, radiation and targeted therapies including bevacizumab and pazopanib for metastatic cardiac AS.

Magnetic resonance imaging findings following button battery ingestion.

BACKGROUND: Lithium button battery ingestions have been increasing in frequency since the early 2000s and can develop severe and sometimes fatal complications from caustic injury even after rapid battery removal. To aid in clinical decision-making, we began obtaining magnetic resonance imaging (MRI)/MR angiography in these patients. OBJECTIVE: Our goal was to review MRI/MR angiography imaging in button battery ingestion cases and compare with other imaging, clinical data and outcomes in these patients. MATERIALS AND METHODS: In this retrospective institutional-review-board-approved study, we reviewed all button battery ingestion cases with MRI from April 2012 to September 2018. Clinical data, endoscopic findings and all imaging studies were rereviewed. MRIs were evaluated for inflammation, blooming artifact and complications including vascular injury, tracheoesophageal fistula, esophageal perforation and spondylodiscitis, and compared to endoscopy, esophagram and bronchoscopy. RESULTS: Twenty-three patients with button battery ingestions had a total of 51 MRI/MR angiograms. Seventy percent of the cohort was male with a median age of 2 years (range: 0.94-17 years). Severe complications were found in 48% of patients (11/23), including esophageal perforation (n=11), tracheoesophageal fistula (n=3) and spondylodiscitis (n=1). No patients had vascular injury. Cervical location of the battery was significantly associated with severe complications (10/11 cases). The length of the blooming artifact was greater than 2 cm in those with severe complications and, in most cases, <2 cm in those without severe complications. All complications were seen on initial screening MR exam with serial exams showing decreased inflammation. CONCLUSION: MRI/MR angiography can provide valuable information about complications, including esophageal perforation, tracheoesophageal fistula and spondylodiscitis. Decreasing inflammation surrounding the esophagus and vasculature is believed to be clinically reassuring and aids in managing button battery ingestion patients.

Use of compressed sensing to reduce scan time and breath-holding for cardiac cine balanced steady-state free precession magnetic resonance imaging in children and young adults.

BACKGROUND: Conventional pediatric volumetric MRI acquisitions of a short-axis stack typically require multiple breath-holds under anesthesia. OBJECTIVE: Here, we aimed to validate a vendor-optimized compressed-sensing approach to reduce scan time during short-axis balanced steady-state free precession (bSSFP) cine imaging. MATERIALS AND METHODS: Imaging was performed in 28 patients (16±9 years) in this study on a commercial 3-tesla (T) scanner using retrospective electrocardiogram-gated cine bSSFP. Cine short-axis images covering both ventricles were acquired with conventional parallel imaging and a vendor-optimized parallel imaging/compressed-sensing approach. Qualitative Likert scoring for blood-myocardial contrast, edge definition, and presence of artifact was performed by two experienced radiologists. Quantitative comparisons were performed including biventricular size and function. A paired t-test was used to detect significant differences (P<0.05). RESULTS: Scan duration was 7±2 s/slice for conventional imaging (147±33 s total) vs. 4±2 s/slice for compressed sensing (83±28 s total). No significant differences were found with qualitative image scores for blood-myocardial contrast, edge definition, and presence of artifact. No significant differences were found in volumetric analysis between the two sequences. The number of breath-holds was 10±4 for conventional imaging and 5±3 for compressed sensing. CONCLUSION: Compressed sensing allowed for a 50% reduction in the number of breath-holds and a 43% reduction in the total scan time without differences in the qualitative or quantitative measurements as compared to the conventional technique.

Flow profile characteristics in Fontan circulation are associated with the single ventricle dilation and function: principal component analysis study.

The Fontan circulation is characterized as a nonpulsatile flow propagation without a pressure-generating ventricle. However, flow through the Fontan circulation still exhibits oscillatory waves as a result of pressure changes generated by the systemic single ventricle. Identification of discrete flow patterns through the Fontan circuit may be important to understand single ventricle performance. Ninety-seven patients with Fontan circulation underwent phase-contrast MRI of the right pulmonary artery, yielding subject-specific flow waveforms. Principal component (PC) analysis was performed on preprocessed flow waveforms. Principal components were then correlated with standard MRI indices of function, volume, and aortopulmonary collateral flow. The first principal component (PC) described systolic versus diastolic-dominant flow through the Fontan circulation, accounting for 31.3% of the variance in all waveforms. The first PC correlated with end-diastolic volume (R = 0.34, P = 0.001), and end-systolic volume (R = 0.30, P = 0.003), cardiac index (R = 0.51, P < 0.001), and the amount of aortopulmonary collateral flow (R = 0.25, P = 0.027)-lower ventricular volumes and a smaller volume of collateral flow-were associated with diastolic-dominant cavopulmonary flow. The second PC accounted for 19.5% of variance and described late diastolic acceleration versus deceleration and correlated with ejection fraction-diastolic deceleration was associated with higher ejection fraction. Principal components describing the diastolic flow variations in pulmonary arteries are related to the single ventricle function and volumes. Particularly, diastolic-dominant flow without late acceleration appears to be related to preserved ventricular volume and function, respectively.NEW & NOTEWORTHY The exact physiological significance of flow oscillations of phasic and temporal flow variations in Fontan circulation is unknown. With the use of principal component analysis, we discovered that flow variations in the right pulmonary artery of Fontan patients are related to the single ventricle function and volumes. Particularly, diastolic-dominant flow without late acceleration appears to be related to more ideal ventricular volume and systolic function, respectively.

Novel measures of left ventricular electromechanical discoordination predict clinical outcomes in children with pulmonary arterial hypertension.

Adverse ventricle-ventricle interaction and resultant left ventricular (LV) dysfunction are a recognized pathophysiological component of disease progression in pulmonary arterial hypertension (PAH) and can be associated with electrical and mechanical dyssynchrony. The purpose of this study was to investigate the clinical and mechanistic implications of LV electromechanical dyssynchrony in children with PAH by using novel systolic stretch and diastolic relaxation discoordination indexes derived noninvasively from cardiac MRI (CMR). In children with PAH referred for CMR (n = 64) and healthy controls (n = 20), we calculated two novel markers of ventricular discoordination, systolic stretch fraction (SSF) and diastolic relaxation fraction (DRF). SSF and DRF were evaluated with respect to 1) electrical dyssynchrony, 2) functional status, and 3) composite clinical outcomes. SSF was increased in patients with PAH compared with controls (P = 0.004). There was no difference in DRF between PAH and control groups. There were no differences between groups in standard mechanical dyssynchrony and LV global circumferential strain. Increased SSF was associated with greater electrical dyssynchrony (QRS duration) as well as worse WHO functional class. SSF, DRF, mechanical dyssynchrony, and right ventricular (RV) volumes were prognostic for worse clinical outcomes. LV dyssynchrony indexes are altered in pediatric patients with PAH compared with controls in proportion with greater degrees of RV dilation. Patients with PAH with greater dyssynchrony have worse clinical outcomes. RV-induced increased LV electromechanical dyssynchrony therefore may be an important link in the causal pathway from PAH to clinically significant LV dysfunction. Since dyssynchrony could precede overt LV dysfunction, addition of ventricular synchrony analysis to CMR postprocessing protocols may be of clinical benefit.NEW & NOTEWORTHY We demonstrate that left ventricular discoordination indexes are altered in pediatric patients with pulmonary arterial hypertension compared with controls and pediatric patients with pulmonary arterial hypertension with greater dyssynchrony have worse clinical outcomes. Furthermore, there is evidence for the mechanism of right ventricular-induced left ventricular discoordination to include a combination of delayed early systolic electromechanical activation, late-systolic septal shift, and prolonged, postsystolic septal thickening.

Visualization of proximal coronary arteries on high-pitch electrocardiogram-triggered computed tomography in pediatric congenital heart disease: effects of heart rate and body surface area.

BACKGROUND: As CT technology has advanced, techniques for pediatric cardiac CT in congenital heart disease have evolved from retrospective electrocardiography (ECG)-gating with relatively high radiation doses to lower-dose prospective ECG-gating and even single-beat gated scans. Despite these advances, coronary artery imaging in children remains challenging because of their small vessel size and high heart rates, often necessitating retrospective gating. OBJECTIVE: Evaluate coronary artery visualization in pediatric patients (<20 years) who underwent low-dose high-pitch ECG-triggered scans and stratify the probability of coronary artery visualization based upon heart rate and body surface area (BSA). MATERIALS AND METHODS: Two hundred eleven high-pitch ECG-triggered studies from April 2014 to November 2017 were reviewed by two pediatric cardiac imagers in this retrospective study. Patient age, gender, BSA, average heart rate, heart rate variability and use of general anesthesia were recorded as well as dose-length product (DLP) and volumetric CT dose index (CTDIvol). We assessed the coronary artery score using a 5-point scale, with score of ≥3 considered of diagnostic quality. We performed multivariate statistical analysis including logistic regression to analyze effects of heart rate and BSA. RESULTS: Patient age range was 1 day to 19 years (median age 3 years). Heart rate range was 49-188 beats per minute (bpm; median 122 bpm) and BSA range was 0.15-2.07 m2 (median 0.53 m2). The origin and proximal coronary arteries were confidently seen (score ≥3) in 61% of studies in this cohort. Coronary artery visualization scores further increased with increased BSA (P<0.002) and with decreased heart rate (P<0.001). At heart rates <100 bpm or in patients with BSA>0.58, adequate coronary artery visualization was present 72% of the time. CONCLUSION: While in many patients the coronary artery origins are visualized using high-pitch ECG-triggered technique, the importance of coronary artery visualization needs to be weighed with the radiation dose penalty in individual patients to achieve optimal imaging.

Metformin Improves Insulin Sensitivity and Vascular Health in Youth With Type 1 Diabetes Mellitus.

BACKGROUND: Cardiovascular disease is the leading cause of mortality in type 1 diabetes mellitus (T1DM) and relates strongly to insulin resistance (IR). Lean and obese adolescents with T1DM have marked IR. Metformin improves surrogate markers of IR in T1DM, but its effect on directly measured IR and vascular health in youth with T1DM is unclear. We hypothesized that adolescents with T1DM have impaired vascular function and that metformin improves this IR and vascular dysfunction. METHODS: Adolescents with T1DM and control participants underwent magnetic resonance imaging of the ascending (AA) and descending aorta to assess pulse wave velocity, relative area change, and maximal (WSSMAX) and time-averaged (WSSTA) wall shear stress. Participants with T1DM also underwent assessment of carotid intima-media thickness by ultrasound, brachial distensibility by DynaPulse, fat and lean mass by dual-energy x-ray absorptiometry, fasting laboratories after overnight glycemic control, and insulin sensitivity by hyperinsulinemic-euglycemic clamp (glucose infusion rate/insulin). Adolescents with T1DM were randomized 1:1 to 3 months of 2000 mg metformin or placebo daily, after which baseline measures were repeated. RESULTS: Forty-eight adolescents with T1DM who were 12 to 21 years of age (40% body mass index [BMI] ≥90th percentile; 56% female) and 24 nondiabetic control participants of similar age, BMI, and sex distribution were enrolled. Adolescents with T1DM demonstrated impaired aortic health compared with control participants, including elevated AA and descending aorta pulse wave velocity, reduced AA and descending aorta relative area change, and elevated AA and descending aorta WSSMAX and WSSTA. Adolescents with T1DM in the metformin versus placebo group had improved glucose infusion rate/insulin (12.2±3.2 [mg·kg-1·min-1]/µIU/µL versus -2.4±3.6 [mg·kg-1·min-1]/µIU/µL, P=0.005; 18.6±4.8 [mg·lean kg-1·min-1]/µIU/µL versus -3.4±5.6 [mg·lean kg-1·min-1]/µIU/µL, P=0.005) and reduced weight (-0.5±0.5 kg versus 1.6±0.5 kg; P=0.004), BMI (-0.2±0.15 kg/m2 versus 0.4±0.15 kg/m2; P=0.005), and fat mass (-0.7±0.3 kg versus 0.6±0.4 kg; P=0.01). Glucose infusion rate/insulin also improved in normal-weight participants (11.8±4.4 [mg·kg-1·min-1]/µIU/µL versus -4.5±4.4 [mg·kg-1·min-1]/µIU/µL, P=0.02; 17.6±6.7 [mg·lean kg-1·min-1]/µIU/µL versus -7.0±6.7 [mg·lean kg-1·min-1]/µIU/µL, P=0.02). The metformin group had reduced AA WSSMAX (-0.3±0.4 dyne/cm2 versus 1.5±0.5 dyne/cm2; P=0.03), AA pulse wave velocity (-1.1±1.20 m/s versus 4.1±1.6 m/s; P=0.04), and far-wall diastolic carotid intima-media thickness (-0.04±0.01 mm versus -0.00±0.01 mm; P=0.049) versus placebo. CONCLUSIONS: Adolescents with T1DM demonstrate IR and impaired vascular health compared with control participants. Metformin improves IR, regardless of baseline BMI, and BMI, weight, fat mass, insulin dose, and aortic and carotid health in adolescents with T1DM. Metformin may hold promise as a cardioprotective intervention in T1DM. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01808690.

Differences in pulmonary arterial flow hemodynamics between children and adults with pulmonary arterial hypertension as assessed by 4D-flow CMR studies.

Despite different developmental and pathological processes affecting lung vascular remodeling in both patient populations, differences in 4D MRI findings between children and adults with PAH have not been studied. The purpose of this study was to compare flow hemodynamic state, including flow-mediated shear forces, between pediatric and adult patients with PAH matched by severity of pulmonary vascular resistance index (PVRi). Adults (n = 10) and children (n = 10) with PAH matched by pulmonary vascular resistance index (PVRi) and healthy adult (n = 10) and pediatric (n = 10) subjects underwent comprehensive 4D-flow MRI to assess peak systolic wall shear stress (WSSmax) measured in the main (MPA), right (RPA), and left pulmonary arteries (LPA), viscous energy loss (EL) along the MPA-RPA and MPA-LPA tract, and qualitative analysis of secondary flow hemodynamics. WSSmax was decreased in all pulmonary vessels in children with PAH when compared with the same age group (all P < 0.05). Similarly, WSSmax was decreased in all pulmonary vessels in adult PAH patients when compared with healthy adult subjects (all P < 0.01). Average EL was increased in adult patients with PAH when compared with the same age group along both MPA-RPA (P = 0.020) and MPA-LPA (P = 0.025) tracts. There were no differences in EL indices between adults and pediatric patients. Children and adult patients with PAH have decreased shear hemodynamic forces. However, pathological flow hemodynamic formations appear to be more consistent in adult patients, whereas flow hemodynamic abnormalities appear to be more variable in children with PAH for comparable severity of PVRi. NEW & NOTEWORTHY Both children and adult patients with PAH have decreased shear hemodynamic forces inside the pulmonary arteries associated with the degree of vessel dilation and stiffness. These differences also exist between healthy normotensive children and adults. However, pathological flow hemodynamic formations appear to more uniform in adult patients, whereas in children with PAH flow, hemodynamic abnormalities appear to be more variable. Pathological flow formations appear not to have a major effect on viscous energy loss associated with the flow conduction through proximal pulmonary arteries.