Myocardial strain assessment in the human fetus by cardiac MRI using Doppler ultrasound gating and feature tracking.

OBJECTIVES: Assessment of myocardial strain by feature tracking magnetic resonance imaging (FT-MRI) in human fetuses with and without congenital heart disease (CHD) using cardiac Doppler ultrasound (DUS) gating. METHODS: A total of 43 human fetuses (gestational age 28-41 weeks) underwent dynamic cardiac MRI at 3 T. Cine balanced steady-state free-precession imaging was performed using fetal cardiac DUS gating. FT-MRI was analyzed using dedicated post-processing software. Endo- and epicardial contours were manually delineated from fetal cardiac 4-chamber views, followed by automated propagation to calculate global longitudinal strain (GLS) of the left (LV) and right ventricle (RV), LV radial strain, and LV strain rate. RESULTS: Strain assessment was successful in 38/43 fetuses (88%); 23 of them had postnatally confirmed diagnosis of CHD (e.g., coarctation, transposition of great arteries) and 15 were heart healthy. Five fetuses were excluded due to reduced image quality. In fetuses with CHD compared to healthy controls, median LV GLS (- 13.2% vs. - 18.9%; p < 0.007), RV GLS (- 7.9% vs. - 16.2%; p < 0.006), and LV strain rate (1.4 s-1 vs. 1.6 s-1; p < 0.003) were significantly higher (i.e., less negative). LV radial strain was without a statistically significant difference (20.7% vs. 22.6%; p = 0.1). Bivariate discriminant analysis for LV GLS and RV GLS revealed a sensitivity of 67% and specificity of 93% to differentiate between fetuses with CHD and healthy fetuses. CONCLUSION: Myocardial strain was successfully assessed in the human fetus, performing dynamic fetal cardiac MRI with DUS gating. Our study indicates that strain parameters may allow for differentiation between fetuses with and without CHD. CLINICAL RELEVANCE STATEMENT: Myocardial strain analysis by cardiac MRI with Doppler ultrasound gating and feature tracking may provide a new diagnostic approach for evaluation of fetal cardiac function in congenital heart disease. KEY POINTS: • MRI myocardial strain analysis has not been performed in human fetuses so far. • Myocardial strain was assessed in human fetuses using cardiac MRI with Doppler ultrasound gating. • MRI myocardial strain may provide a new diagnostic approach to evaluate fetal cardiac function.

Rapid MRI Assessment of Long-Axis Strain to Indicate Systolic Dysfunction in Patients With Sickle Cell Disease.

BACKGROUND: Patients with sickle cell disease (SCD) have a unique form of cardiomyopathy. However, left ventricular ejection fraction (LVEF) is often preserved. Monoplanar long-axis strain (LAS) can be assessed from MRI four-chamber views and may be better at detecting mild systolic dysfunction in these patients. PURPOSE: To compare LAS (monoplanar and biplanar) with LVEF as a marker of systolic dysfunction in SCD patients. STUDY TYPE: Retrospective. SUBJECTS: A total of 20 patients with genetically proven SCD (35 MRI examinations), 39 healthy controls, and 124 patients with systemic iron overload (for validation purposes). FIELD STRENGTH/SEQUENCE: 1.5 T/3 T. Cine balanced steady-state free-precession. ASSESSMENT: Rapidly assessed biplanar LAS from four- and two-chamber views was correlated with age and compared to LVEF by two operators. For validation, biplanar LAS was compared to global longitudinal strain (GLS) using MRI feature-tracking in 124 patients with systemic iron overload. STATISTICAL TESTS: Bland-Altman analysis. Wilcoxon-Mann-Whitney test and Spearman-rank correlation (correlation coefficient, rS ). Receiver-operating-characteristic (ROC) curve analysis (area under the curve, AUC). Bivariate discriminant analysis. Significance level: P < 0.01. RESULTS: There was strong correlation between biplanar LAS and GLS using feature tracking (rS  = 0.73). Interoperator agreement showed nonsignificant bias for biplanar LAS (-0.02%; ±95%-agreement interval -2.2%/2.2%, P = 0.9). Biplanar LAS increased significantly with age in controls (rS  = 0.70). In SCD patients, biplanar LAS was better correlated with age than monoplanar LAS (r2  = 0.53, standard error of estimate, SEE = 1.4% vs. r2  = 0.37;SEE = 2.0%). ROC analysis of LVEF, biplanar LAS, and age-adjusted Z-scores Z (LAS(age)) showed AUCs of 0.69, 0.75, and 0.86 for differentiation between SCD patients and controls. Bivariate discriminant analysis of biplanar Z (LAS(age)) and LVEF revealed a sensitivity of 63% and a specificity of 95%. DATA CONCLUSION: Rapidly assessed biplanar LAS demonstrated high diagnostic accuracy and was an indicator of mild systolic dysfunction in patients with SCD. Biplanar LAS provided more precise measurements than monoplanar, and normalization to age increased diagnostic accuracy. EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 2.

Factors associated with homecare coordination and quality of care: a research protocol for a national multi-center cross-sectional study.

INTRODUCTION: The persistent fragmentation of home healthcare reflects inadequate coordination between care providers. Still, while factors at the system (e.g., regulations) and organisational (e.g., work environment) levels crucially influence homecare organisation, coordination and ultimately quality, knowledge of these factors and their relationships in homecare settings remains limited. OBJECTIVES: This study has three aims: [1] to explore how system-level regulations lead to disparities between homecare agencies' structures, processes and work environments; [2] to explore how system- and organisation-level factors affect agency-level homecare coordination; and [3] to explore how agency-level care coordination is related to patient-level quality of care. DESIGN AND METHODS: This study focuses on a national multi-center cross-sectional survey in Swiss homecare settings. It will target 100 homecare agencies, their employees and clients for recruitment, with data collection period planned from January to June 2021. We will assess regulations and financing mechanisms (via public records), agency characteristics (via agency questionnaire data) and homecare employees' working environments and coordination activities, as well as staff- and patient-level perceptions of coordination and quality of care (via questionnaires for homecare employees, clients and informal caregivers). All collected data will be subjected to descriptive and multi-level analyses. DISCUSSION: The first results are expected by December 2021. Knowledge of factors linked to quality of care is essential to plan and implement quality improvement strategies. This study will help to identify modifiable factors at multiple health system levels that might serve as access points to improve coordination and quality of care.

Different topologies in three manganese-µ-azido 1D compounds: magnetic behavior and DFT-quantum Monte Carlo calculations.

The syntheses and structural characterization of three new monodimensional azido-bridged manganese(ii) complexes with empirical formulae [Mn(N3)2(aminopyz)2]n (1), [Mn(N3)2(4-azpy)2]n (2) and [Mn(N3)2(4-Bzpy)2]n (3) (pyz = pyrazine (1,4-diazine)), 4-azpy = 4-azidopyridine and 4-Bzpy = 4-benzoylpyridine) are reported. 1 is a monodimensional compound with double EO azido bridges, 2 is an alternating monodimensional compound with double end-on and double end-to-end azido bridges in the sequence di-EO-di-EE and 3 is a monodimensional compound with double end-on and double end-to-end azido bridges in the sequence di-EO-di-EO-diEO-di-EO-di-EE. The magnetic properties of 1-3 are reported. Periodic DFT calculations were performed to estimate the J values and quantum Monte Carlo simulations were carried out using the calculated J values to check their accuracy in comparison with the experimental magnetic measurements. From this theoretical analysis, two appealing features of the di-EO Mn(ii) compounds can be extracted: first, the exchange coupling becomes more ferromagnetic when the Mn-N-Mn bridging angle becomes larger and the spin density of the bridging nitrogen atoms has an opposite sign to that of the Mn(II) centers.

Pancreatic iron and fat assessment by MRI-R2* in patients with iron overload diseases.

BACKGROUND: To determine the pancreatic iron (R2*) and fat content (FC) in comparison to hepatic and cardiac R2* in patients with iron overload disorders like ß-thalassemia major (TM), Diamond-Blackfan anemia (DBA) or hereditary hemochromatosis. METHODS: R2* rates were assessed in the liver, heart and pancreas of 42 patients with TM, 29 subjects with other iron overload diseases, and 10 controls using an ECG-gated breathhold sequence (12 echo time [TE] = 1.3-25.7 ms, readout repetition time [TR] = 244 ms). Pancreatic R2* and FC were assessed from TE dependent region of interest based signal intensities performing water-fat chemical shift relaxometry and were compared with laboratory parameters (glucose, HbA1c, amylase and lipase). RESULTS: A pancreatic iron gradient from tail (R2* = 122 s(-1) ) to head (R2* = 114 s(-1) , P < 10(-4) ) was found. The close association between cardiac and pancreatic R2* was also confirmed in patients with TM and other iron overload diseases (rs = 0.64, P < 10(-4) ). Receiver operator characteristic analysis (area: 0.89, P < 10(-4) ) identified patients with elevated cardiac iron at a pancreatic R2* cut-off level of 131s(-1) (sensitivity = specificity at 81%). Highest pancreatic R2* (211s(-1) ) and FC (36%) were found in the tail region of diabetic patients with TM. CONCLUSION: Pancreatic tail showed highest R2* rates and fat contents, especially in patients with thalassemia. Besides iron accumulation fatty degeneration might be an additional risk factor for the development of diabetes in ß-thalassemia major, but this hypothesis needs further studies in prediabetic patients.

Quantification of prenatal liver and spleen iron in a sheep model and assessment of iron stores in a human neonate with neonatal hemochromatosis using R2* mapping.

PURPOSE: We evaluated the feasibility of prenatal quantification of liver and spleen iron by magnetic resonance imaging (MRI) gradient recalled echo (GRE) measurements of transverse relaxation time (R2*) (MRI-GRE-R2*) in a fetal sheep model and applied the method to a human neonate with suspected neonatal hemochromatosis. METHODS: We subjected 13 fetal sheep to MRI at 1.5 Tesla using a breath-triggered (ewe) multi-echo sequence to determine the transverse relaxation rate (R2*) of the liver and spleen. In the human neonate, we measured the R2* of the liver, spleen, and pancreas on the 30th postgestational day. RESULTS: The median R2* of the fetal sheep liver was 25.6 s(-1) (range 20 to 114 s(-1)) and of the spleen, 40.2 s(-1) (range 20 to 70 s(-1)), and the corresponding median iron concentration in the liver was 0.85 mg/g dry weight (d.w.) and in the spleen, 1.22 mg/gd.w.. R2* rates in the human neonate liver were elevated between 67 s(-1) (average), which corresponded with an iron concentration of 1.9 mg Fe/gd.w., and 126 s(-1) (regional maximum), which corresponded with 3.4 mg Fe/gd.w.. The average pancreatic R2* (72.4 s(-1)) was significantly above normal values, which indicated iron overload. CONCLUSION: We demonstrated the feasibility of prenatal quantification of tissue iron by fetal MRI in this sheep model and successfully quantified iron, including that in the pancreas, in a human neonate to confirm the diagnosis of neonatal hemochromatosis. Transferring the successful approach of quantifying iron in intrauterine tissue in fetal sheep to human pregnancies with suspected fetal siderosis could aid early diagnosis.

Multiscale assessment of treatment efficacy in adults with ADHD: a randomized placebo-controlled, multi-centre study with extended-release methylphenidate.

OBJECTIVES: This trial was performed to test the efficacy and safety of an extended-release formulation of methylphenidate (MPH ER). METHODS: A total of 162 adults with ADHD according to DSM-IV were treated for 8 weeks with either two daily individually body weight-adjusted doses of MPH ER up to 1 mg/kg per day (N = 84) or placebo (N = 78). The primary efficacy outcome was the Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS) 8 weeks after randomization. Secondary efficacy measures were the ADHD Diagnostic Checklist (ADHD-DC), the Conners Adult Attention Deficit Disorder Scale (CAARS-S:L), the Clinical Global Impression (CGI) and the Sheehan Disability Scale (SDS). RESULTS: At week 8 a significantly higher decline of the total WRAADDS score was found in the MPH ER group as compared to the placebo group (P = 0.0003). The rates of responders were 50% in the MPH ER and 18% in the placebo group (P < 0.0001). Furthermore, similar effects were observed for the secondary efficacy variable: ADHD-DC score (P = 0.004), CAARS-S:L score (P = 0.008) and the SDS score (P = 0.017). 50% of the MPH ER group and 24.4% of the placebo group were improved "much" or "very much" according to the CGI rating (P = 0.0001). MPH ER treatment was well tolerated. At week 2 also the mean heart rate was significantly higher in the MPH ER group as compared to the placebo group (P = 0.01). No differences between the study groups were observed regarding mean blood pressure at any visit. CONCLUSIONS: This clinical trial demonstrated statistically significant and clinical relevant effects of MPH ER in adults with ADHD for several self- and investigator-rated ADHD psychopathology and also functional efficacy measures.

Assessment of cardiac iron by MRI susceptometry and R2* in patients with thalassemia.

A magnetic resonance imaging cardiac magnetic susceptometry (MRI-CS) technique for assessing cardiac tissue iron concentration based on phase mapping was developed. Normal control subjects (n=9) and thalassemia patients (n=13) receiving long-term blood transfusion therapy underwent MRI-CS and MRI measurements of the cardiac relaxation rate R2*. Using MRI-CS, subepicardium and subendocardium iron concentrations were quantified exploiting the hemosiderin/ferritin iron specific magnetic susceptibility. The average of subepicardium and subendocardium iron concentrations and R2* of the septum were found to be strongly correlated (r=0.96, P<.0001), and linear regression analysis yielded CIC (microg Fe/g(wet tissue))=(6.4+/-0.4).R2* (septum) (s(-1)) - (120+/-40). The results demonstrated that septal R2* indeed measures cardiac iron level.

Non-invasive assessment of tissue iron overload.

In recent years, there has been increasing interest in non-invasive iron measurement, especially of the liver and heart, in patients with iron overload. Serum ferritin still remains an essential monitoring parameter in intervals between liver iron measurements; however, confounding factors such as inflammation, chelation treatment changes and the specific disease have to be taken into account. Liver iron measurements can now routinely be performed in clinical applications either by quantitative magnetic resonance imaging (MRI) using the transverse magnetic relaxation rate R(2) or R(2)* (1/T(2)*) or by biomagnetic liver susceptometry. For iron measurements in the heart, the single-breathhold multi-echo MRI-R(2)* method has become a standard modality and is now applied in clinical settings beyond research studies. In other tissues like the pancreas, pituitary, and brain, different MRI methods are employed, but their clinical benefit has yet to be proven.