Free-breathing pseudo-golden-angle bSSFP cine cardiac MRI for biventricular functional assessment in congenital heart disease.

PURPOSE: To compare standard breath-hold (BH) cine imaging to a radial pseudo-golden-angle free-breathing (FB) technique in congenital heart disease (CHD). METHODS: In this prospective study, short-axis and 4-chamber BH and FB cardiac MRI sequences of 25 participants with CHD acquired at 1.5 Tesla, were quantitatively compared regarding ventricular volumes, function, interventricular septum thickness (IVSD), apparent signal to noise ratio (aSNR), and estimated contrast to noise ratio (eCNR). For qualitative comparison, three image quality criteria (contrast, endocardial edge definition, and artefacts) were rated on a 5-point Likert scale (5: excellent, 1: non-diagnostic). Paired t-Test was used for group comparisons, Bland-Altman analysis for agreement between techniques. Inter-reader agreement was compared using intraclass correlation coefficient. RESULTS: IVSD (BH 7.4 ± 2.1 mm vs FB 7.4 ± 1.9 mm, p =.71), biventricular ejection fraction (left ventricle [LV]: 56.4 ± 10.8% vs 56.1 ± 9.3%, p =.83; right ventricle [RV]: 49.5 ± 8.6% vs 49.7 ± 10.1%, p =.83), and biventricular end diastolic volume (LV: 176.3 ± 63.9 ml vs 173.9 ± 64.9 ml, p =.90; RV: 185.4 ± 63.8 ml vs 189.6 ± 66.6 ml, p =.34) were comparable. Mean measurement time for FB short-axis sequences was 8.1 ± 1.3 compared to 4.4 ± 1.3 min for BH (p <.001). Subjective image quality between sequences was deemed comparable, (4.6 ± 0.6 vs 4.5 ± 0.6, p =.26, for 4-chamber views) with a significant difference regarding short-axis views (4.9 ± 0.3 vs 4.5 ± 0.6, p =.008). aSNR was similar (BH 25.8 ± 11.2 vs FB 22.2 ± 9.5, p =.24), while eCNR was higher for BH (89.1 ± 36.1 vs 68.5 ± 32.1, p =.03). CONCLUSION: FB sequences yielded comparable results to BH regarding image quality, biventricular volumetry, and function, though measurement times were longer. The FB sequence described might be clinically valuable when BHs are insufficiently performed.

Free-breathing high resolution modified Dixon steady-state angiography with compressed sensing for the assessment of the thoracic vasculature in pediatric patients with congenital heart disease.

BACKGROUND: Cardiovascular magnetic resonance angiography (CMRA) is a non-invasive imaging modality of choice in pediatric patients with congenital heart disease (CHD). This study was aimed to evaluate the diagnostic utility of a respiratory- and electrocardiogram-gated steady-state CMRA with modified Dixon (mDixon) fat suppression technique and compressed sensing in comparison to standard first-pass CMRA in pediatric patients with CHD at 3 T. METHODS: In this retrospective single center study, pediatric CHD patients who underwent CMR with first-pass CMRA followed by mDixon steady-state CMRA at 3 T were analyzed. Image quality using a Likert scale from 5 (excellent) to 1 (non-diagnostic) and quality of fat suppression were assessed in consensus by two readers. Blood-to-tissue contrast and quantitative measurements of the thoracic vasculature were assessed separately by two readers. CMRA images were reevaluated by two readers for additional findings, which could be identified only on either one of the CMRA types. Paired Student t test, Wilcoxon test, and intraclass correlation coefficients (ICCs) were used for statistical analysis. RESULTS: 32 patients with CHD (3.3 ± 1.7 years, 13 female) were included. Overall image quality of steady-state mDixon CMRA was higher compared to first-pass CMRA (4.5 ± 0.5 vs. 3.3 ± 0.5; P < 0.001). Blood-to-tissue contrast ratio of steady-state mDixon CMRA was comparable to first-pass CMRA (7.85 ± 4.75 vs. 6.35 ± 2.23; P = 0.133). Fat suppression of steady-state mDixon CMRA was perfect in 30/32 (94%) cases. Vessel diameters were greater in first-pass CMRA compared to steady-state mDixon CMRA with the greatest differences at the level of pulmonary arteries and veins (e.g., right pulmonary artery for reader 1: 10.4 ± 2.4 vs. 9.9 ± 2.3 mm, P < 0.001). Interobserver agreement was higher for steady-state mDixon CMRA for all measurements compared to first-pass CMRA (ICCs > 0.92). In 9/32 (28%) patients, 10 additional findings were identified on mDixon steady-state CMRA (e.g., partial anomalous venous return, abnormalities of coronary arteries, subclavian artery stenosis), which were not depicted using first-pass CMRA. CONCLUSIONS: Steady-state mDixon CMRA offers a robust fat suppression, a high image quality, and diagnostic utility for the assessment of the thoracic vasculature in pediatric CHD patients.

Using a mock board of pharmacy disciplinary hearing to teach concepts related to administrative law, addiction, empathy, and professionalism.

BACKGROUND AND PURPOSE: The purpose of this project was to impact pharmacy students' personal and professional development through simulation of a board of pharmacy disciplinary hearing regarding addiction. EDUCATIONAL ACTIVITY AND SETTING: The mock board hearing was conducted as part of the required curriculum. Faculty obtained materials from a prior board hearing. The actual respondent, lawyer, former executive director, and a board agent participated. Students served as board members and president, asked questions of the witnesses, and deliberated per board procedure. After the event, student learning and perceptions were assessed through knowledge-based, opinion-based questions, and open-ended questions. FINDINGS: Of the 141 students who attended the event, 97% completed the assessment. The average score on the knowledge-based questions was 95%. Ratings of perceptions and reflections of the experience were used in tandem to understand the experience. In general, students indicated the experience was positive and impactful towards their education. Students indicated they felt that the experience allowed them to better understand addiction and empathize with someone called before the board. In fact, there were fundamental differences in perceptions regarding the "addicted person," going from a penalizing and stigmatized perspective to one of caring and compassion. SUMMARY: Students were knowledgeable about the board and its regulatory process after the event. More than knowledge, students indicated fundamental changes in their views of addiction. Other institutions may consider implementing similar exercises to engender empathy and professionalism regarding drug addiction and regulatory compliance.

Integrated Safety Assessment of 2'-O-Methoxyethyl Chimeric Antisense Oligonucleotides in NonHuman Primates and Healthy Human Volunteers.

The common chemical and biological properties of antisense oligonucleotides provide the opportunity to identify and characterize chemical class effects across species. The chemical class that has proven to be the most versatile and best characterized is the 2'-O-methoxyethyl chimeric antisense oligonucleotides. In this report we present an integrated safety assessment of data obtained from controlled dose-ranging studies in nonhuman primates (macaques) and healthy human volunteers for 12 unique 2'-O-methoxyethyl chimeric antisense oligonucleotides. Safety was assessed by the incidence of safety signals in standardized laboratory tests for kidney and liver function, hematology, and complement activation; as well as by the mean test results as a function of dose level over time. At high doses a number of toxicities were observed in nonhuman primates. However, no class safety effects were identified in healthy human volunteers from this integrated data analysis. Effects on complement in nonhuman primates were not observed in humans. Nonhuman primates predicted safe doses in humans, but over predicted risk of complement activation and effects on platelets. Although limited to a single chemical class, comparisons from this analysis are considered valid and accurate based on the carefully controlled setting for the specified study populations and within the total exposures studied.

Anatomical and functional assessment of the intra-atrial lateral tunnel in the Fontan circulation.

OBJECTIVES: In patients after completion of the total cavopulmonary connection (TCPC) with an intra-atrial lateral tunnel, deviations of the tunnel from an ideal straight tubular shape were observed. However, little is known about frequency and adverse effects of such shape deviations. We sought to analyse tunnel anatomy, dimensions and blood flow using cardiac magnetic resonance imaging (CMR). METHODS: Fifty-four patients with hypoplastic left heart syndrome (HLHS; mean age 6.0 ± 2.4 years) underwent CMR with gradient-echo cine sequences, 2D- and 3D-phase-contrast imaging. We analysed anatomy, diameters, cross-sectional areas, volumes and blood flow of the tunnel. RESULTS: Twenty-five patients had a tubular tunnel. In 29 patients, bulging and/or narrowing of the tunnel were present. Cross-sectional areas and volumes of the tunnel were not significantly different between the two groups. There were also no differences for the mean blood flow and the mean and maximal flow velocity (P = 0.05-0.6). In all the patients, the normalized tunnel volume was related to age (r = 0.44; P = 0.002) and body surface area (BSA; r = 0.42; P = 0.005). The mean tunnel blood flow correlated with age (r = 0.73; P = 0.001) and BSA (r = 0.83; P < 0.0001). CONCLUSIONS: A considerable percentage of patients with an intra-atrial lateral tunnel develop mild deviations of the tunnel from ideal tubular shape. The correlation between tunnel volume and mean blood flow with age and BSA suggests that the capacity of the tunnel adjusts to body growth, independent of tunnel shapes that deviate from a fluid-dynamically favourable shape. Follow-up CMRs are needed to detect long-term effects of irregular tunnel shapes on flow dynamics.