Diastolic Filling in Patients After Heart Transplantation Is Impaired Due to an Altered Geometrical Relationship Between the Left Atrium and Ventricle.

BACKGROUND: The geometrical relationship between atrial and ventricular short-axis cross-sectional area determines the hydraulic forces acting on intracardiac blood. This is important for diastolic filling. In patients undergoing heart transplantation (HTx), the left atrium is often enlarged as a result of the standard surgical technique. We hypothesized that diastolic filling in HTx patients is affected by the surgery altering the geometrical relationship between atrium and ventricle. METHODS AND RESULTS: This retrospective, cross-sectional study included 25 HTx patients (median age, 52 [range, 25-70] years), 15 patients with heart failure with reduced ejection fraction (median age, 63 [range, 52-75] years), 15 patients with heart failure with preserved ejection fraction (median age, 74 [range, 56-82] years), and 15 healthy controls (median age, 64 [range, 58-67] years) who underwent cardiac magnetic resonance imaging. Left ventricular, atrial, and total heart volumes (THV) were obtained. Atrioventricular area difference at end diastole and end systole was calculated as the largest ventricular short-axis area minus the largest atrial short-axis area. Left atrial minimum volume normalized for THV (LAmin/THV) was larger in HTx patients (median, 0.13 [range, 0.07-0.19]) compared with controls (median, 0.05 [range, 0.03-0.08], P <0.001), whereas left ventricular volume normalized for THV (left ventricular end-diastolic volume/THV) was similar between HTx and controls (median, 0.19 [range, 0.12-0.24] and median, 0.22 [range, 0.20-0.25], respectively). At end diastole, when atrioventricular area difference reached its largest positive value in controls, 11 HTx patients (44%) had a negative atrioventricular area difference, indicating impaired diastolic filling. CONCLUSIONS: Diastolic filling is impaired in HTx patients due to an altered geometrical relationship between the left atrium and ventricle. When performing cardiac transplantation, a surgical technique that creates a smaller left atrium may improve diastolic filling by aiding hydraulic forces.

Photon-counting computed tomography for paediatric congenital heart defects yields images of high diagnostic quality with low radiation doses at both 70 kV and 90 kV.

BACKGROUND: Photon-counting computed tomography (PCCT) is a new clinical method that may show better diagnostic quality at lower radiation doses than conventional CT. OBJECTIVE: To investigate the diagnostic quality and radiation dose of paediatric cardiovascular PCCT for diagnosis of congenital heart defects at 70 kV and 90 kV. MATERIALS AND METHODS: This retrospective assessment included clinical non-gated paediatric PCCT examinations for assessment of congenital heart defects. Radiation doses were recorded, and overall and specific diagnostic quality (1-4) were scored by four paediatric radiologists. Agreement, differences, and trends were assessed by percent rater agreement, intraclass correlation, Mann-Whitney tests, and Jonckheere-Terpstra tests. RESULTS: Seventy children with congenital heart defects were examined at 70 kV (n = 35; age 2 days-16 years; 63% boys) or 90 kV (n = 35; age 2 days-17 years; 51% boys). All observers gave a median score of 4 (high diagnostic quality) for both 70 kV and 90 kV, with no difference in median values between tube voltages (all P > 0.06). Agreement for overall scores was 66-94% for 70 kV and 60-77% for 90 kV. Agreement for specific scores was 80-97% for 70 kV and 83-89% for 90 kV. Size-dependent dose estimate was 0.68 mGy (0.25-2.02 mGy) for 70 kV and 1.10 mGy (0.58-2.71 mGy; P < 0.001) for 90 kV. Effective dose was 0.30 mSv (0.15-0.82 mSv) for 70 kV and 0.39 mSv (0.22-1.51 mSv; P = 0.01) for 90 kV. CONCLUSION: Paediatric cardiovascular PCCT yields images for congenital heart defects of high diagnostic quality with low radiation dose at both 70 kV and 90 kV.

Fetal growth restriction followed by very preterm birth is associated with smaller kidneys but preserved kidney function in adolescence.

BACKGROUND: Preterm birth and fetal growth restriction (FGR) are associated with structural and functional kidney changes, increasing long-term risk for chronic kidney disease and hypertension. However, recent studies in preterm children are conflicting, indicating structural changes but normal kidney function. This study therefore assessed kidney structure and function in a cohort of adolescents born very preterm with and without verified FGR. METHODS: Adolescents born very preterm with FGR and two groups with appropriate birthweight (AGA) were included; one matched for gestational week at birth and one born at term. Cortical and medullary kidney volumes and T1 and T2* mapping values were assessed by magnetic resonance imaging. Biochemical markers of kidney function and renin-angiotensin-aldosterone system (RAAS) activation were analyzed. RESULTS: Sixty-four adolescents were included (13-16 years; 48% girls). Very preterm birth with FGR showed smaller total (66 vs. 75 ml/m2; p = 0.01) and medullary volume (19 vs. 24 ml/m2; p < 0.0001) compared to term AGA. Corticomedullary volume ratio decreased from preterm FGR (2.4) to preterm AGA (2.2) to term AGA (1.9; p = 0.004). There were no differences in T1 or T2* values (all p ≥ 0.34) or in biochemical markers (all p ≥ 0.12) between groups. CONCLUSIONS: FGR with abnormal fetal blood flow followed by very preterm birth is associated with smaller total kidney and medullary kidney volumes, but not with markers of kidney dysfunction or RAAS activation in adolescence. Decreased total kidney and medullary volumes may still precede a long-term decrease in kidney function, and potentially be used as a prognostic marker. A higher resolution version of the Graphical abstract is available as Supplementary information.

Automatic Segmentation of the Fetus in 3D Magnetic Resonance Images Using Deep Learning: Accurate and Fast Fetal Volume Quantification for Clinical Use.

Magnetic resonance imaging (MRI) provides images for estimating fetal volume and weight, but manual delineations are time consuming. The aims were to (1) validate an algorithm to automatically quantify fetal volume by MRI; (2) compare fetal weight by Hadlock's formulas to that of MRI; and (3) quantify fetal blood flow and index flow to fetal weight by MRI. Forty-two fetuses at 36 (29-39) weeks gestation underwent MRI. A neural network was trained to segment the fetus, with 20 datasets for training and validation, and 22 for testing. Hadlock's formulas 1-4 with biometric parameters from MRI were compared with weight by MRI. Blood flow was measured using phase-contrast MRI and indexed to fetal weight. Bland-Altman analysis assessed the agreement between automatic and manual fetal segmentation and the agreement between Hadlock's formulas and fetal segmentation for fetal weight. Bias and 95% limits of agreement were for automatic versus manual measurements 4.5 ± 351 ml (0.01% ± 11%), and for Hadlock 1-4 vs MRI 108 ± 435 g (3% ± 14%), 211 ± 468 g (7% ± 15%), 106 ± 425 g (4% ± 14%), and 179 ± 472 g (6% ± 15%), respectively. Umbilical venous flow was 406 (range 151-650) ml/min (indexed 162 (range 52-220) ml/min/kg), and descending aortic flow was 763 (range 481-1160) ml/min (indexed 276 (range 189-386) ml/min/kg). The automatic method showed good agreement with manual measurements and saves considerable analysis time. Hadlock 1-4 generally agree with MRI. This study also illustrates the confounding effects of fetal weight on absolute blood flow, and emphasizes the benefit of indexed measurements for physiological assessment.

Non-contrast-enhanced magnetic resonance imaging can be used to assess renal cortical and medullary volumes-A validation study.

BACKGROUND: Magnetic resonance imaging (MRI) biomarkers can diagnose and prognosticate kidney disease. Renal volume validation studies are however scarce, and measurements are limited by use of contrast agent or advanced post-processing. PURPOSE: To validate a widely available non-contrast-enhanced MRI method for quantification of renal cortical and medullary volumes in pigs; investigate observer variability of cortical and medullary volumes in humans; and present reference values for renal cortical and medullary volumes in adolescents. MATERIALS AND METHODS: Cortical and medullary volumes were quantified from transaxial in-vivo water-excited MR images in six pigs and 15 healthy adolescents (13-16years). Pig kidneys were excised, and renal cortex and medulla were separately quantified by the water displacement method. Both limits of agreement by the Bland-Altman method and reference ranges are presented as 2.5-97.5 percentiles. RESULTS: Agreement between MRI and ex-vivo quantification were -7 mL (-10-0 mL) for total parenchyma, -4 mL (-9-3 mL) for cortex, and -2 mL (-7-2 mL) for medulla. Intraobserver variability for pig and human kidneys were <5% for total parenchyma, cortex, and medulla. Interobserver variability for both pig and human kidneys were ≤4% for total parenchyma and cortex, and 6% and 12% for medulla. Reference ranges indexed for body surface area and sex were 54-103 mL/m2 (boys) and 56-103 mL/m2 (girls) for total parenchyma, 39-62 mL/m2 and 36-68 mL/m2 for cortex, and 16-45 mL/m2 and 17-42 mL/m2 for medulla. CONCLUSION: The proposed widely available non-contrast-enhanced MRI method can quantify cortical and medullary renal volumes and can be directly implemented clinically.

Utility of Fetal Cardiovascular Magnetic Resonance for Prenatal Diagnosis of Complex Congenital Heart Defects.

Importance: Prenatal diagnosis of complex congenital heart defects reduces mortality and morbidity in affected infants. However, fetal echocardiography can be limited by poor acoustic windows, and there is a need for improved diagnostic methods. Objective: To assess the clinical utility of fetal cardiovascular magnetic resonance imaging in cases in which fetal echocardiography could not visualize all relevant anatomy. Design, Setting, and Participants: This cohort study was conducted between January 20, 2017, and June 29, 2020, at Skåne University Hospital (Lund, Sweden), a tertiary center for pediatric cardiology and thoracic surgery. Participants were fetuses referred for fetal cardiovascular magnetic resonance examination by a pediatric cardiologist after an inconclusive echocardiograph. Exposures: Fetal cardiovascular magnetic resonance examination requested by the patient's pediatric cardiologist. Main Outcomes and Measures: Any change in patient management because of diagnostic information gained from fetal cardiovascular magnetic resonance imaging. Results: A total of 31 fetuses underwent cardiovascular magnetic resonance examination at a median gestational age of 36 weeks (range, 31-39 weeks). Overall, fetal cardiovascular magnetic resonance imaging had clinical utility, affecting patient management and/or parental counseling in 26 cases (84%). For aortic arch anatomy including signs of coarctation (20 fetuses), fetal cardiovascular magnetic resonance imaging added diagnostic information in 16 cases (80%). For assessment of univentricular vs biventricular outcome in borderline left ventricle, unbalanced atrioventricular septal defect, and pulmonary atresia with intact ventricular septum (15 fetuses), fetal cardiovascular magnetic resonance imaging visualized intracardiac anatomy and ventricular function, allowing assessment of outcome in 13 cases (87%). In 4 fetuses with hypoplastic left heart syndrome, fetal cardiovascular magnetic resonance imaging helped delivery planning in 3 cases (75%). Finally, fetal cardiovascular magnetic resonance imaging provided valuable information for parental counseling in 21 cases (68%). Conclusions and Relevance: In this cohort study, fetal cardiovascular magnetic resonance imaging added clinically useful information to what was available from echocardiography. These findings suggest that fetal CMR has the potential to affect clinical decision-making in challenging cases of congenital heart defects with inconclusive data from echocardiography. Fetal cardiovascular magnetic resonance imaging showed an association with clinical decision-making, including mode of delivery and early postnatal care, as well as with parental counseling.

Hydraulic force is a novel mechanism of diastolic function that may contribute to decreased diastolic filling in HFpEF and facilitate filling in HFrEF.

A hydraulic force generated by blood moving the atrioventricular plane is a novel mechanism of diastolic function. The direction and magnitude of the force is dependent on the geometrical relationship between the left atrium and ventricle and is measured as the short-axis atrioventricular area difference (AVAD). In short, the net hydraulic force acts from a larger area toward a smaller one. It is currently unknown how cardiac remodeling affects this mechanism. The aim of the study was therefore to investigate this diastolic mechanism in patients with pathological or physiological remodeling. Seventy subjects [n = 11 heart failure with preserved ejection fraction (HFpEF), n = 10 heart failure with reduced ejection fraction (HFrEF), n = 7 signs of isolated diastolic dysfunction, n = 10 hypertrophic cardiomyopathy, n = 10 cardiac amyloidosis, n = 18 triathletes, and n = 14 controls] were included. Subjects underwent cardiac MR, and short-axis images of the left atrium and ventricle were delineated. AVAD was calculated as ventricular area minus atrial area and used as an indicator of net hydraulic force. At the onset of diastole, AVAD in HFpEF was -9.2 cm2 (median) versus -4.4 cm2 in controls, P = 0.02. The net hydraulic force was directed toward the ventricle for both but was larger in HFpEF. HFrEF was the only group with a positive median value (11.6 cm2), and net hydraulic force was throughout diastole directed toward the atrium. The net hydraulic force may impede cardiac filling throughout diastole in HFpEF, worsening diastolic dysfunction. In contrast, it may work favorably in patients with dilated ventricles and aid ventricular filling.NEW & NOTEWORTHY It is a previously unrecognized physiological mechanism of the heart that diastolic filling occurs with the help of hydraulics. In patients with heart failure with preserved ejection fraction, atrial dilatation may cause the net hydraulic force to work against cardiac filling, thus further augmenting diastolic dysfunction. In contrast, it may work favorably in patients with dilated ventricles, as in heart failure with reduced ejection fraction.

Changes in left and right ventricular longitudinal function after pulmonary valve replacement in patients with Tetralogy of Fallot.

Timing and indication for pulmonary valve replacement (PVR) in patients with repaired Tetralogy of Fallot (rToF) and pulmonary regurgitation (PR) are uncertain. To improve understanding of pumping mechanics, we investigated atrioventricular coupling before and after surgical PVR. Cardiovascular magnetic resonance was performed in patients (n = 12) with rToF and PR > 35% before and after PVR and in healthy controls (n = 15). Atrioventricular plane displacement (AVPD), global longitudinal peak systolic strain (GLS), atrial and ventricular volumes, and caval blood flows were analyzed. Right ventricular (RV) AVPD and RV free wall GLS were lower in patients before PVR compared with controls (P < 0.0001; P < 0.01) and decreased after PVR (P < 0.0001 for both). Left ventricular AVPD was lower in patients before PVR compared with controls (P < 0.05) and decreased after PVR (P < 0.01). Left ventricular GLS did not differ between patients and controls (P > 0.05). Right atrial reservoir volume and RV stroke volume generated by AVPD correlated in controls (r = 0.93; P < 0.0001) and patients before PVR (r = 0.88; P < 0.001) but not after PVR. In conclusion, there is a clear atrioventricular coupling in patients before PVR that is lost after PVR, possibly because of loss of pericardial integrity. Impaired atrioventricular coupling complicates assessment of ventricular function after surgery using measurements of longitudinal function. Changes in atrioventricular coupling seen in patients with rToF may be energetically unfavorable, and long-term effects of surgery on atrioventricular coupling is therefore of interest. Also, AVPD and GLS cannot be used interchangeably to assess longitudinal function in rToF.NEW & NOTEWORTHY There is a clear atrioventricular coupling in patients with Tetralogy of Fallot (ToF) and pulmonary regurgitation before surgical pulmonary valve replacement (PVR) that is lost after operation, possibly because of loss of pericardial integrity. The impaired atrioventricular coupling complicates assessment of ventricular function after surgery when using measurements of longitudinal function. Left ventricular atrioventricular plane displacement (AVPD) found differences between patients and controls and changes after PVR that longitudinal strain could not detect. This indicates that AVPD and strain cannot be used interchangeably to assess longitudinal function in repaired ToF.

A new vessel segmentation algorithm for robust blood flow quantification from two-dimensional phase-contrast magnetic resonance images.

Blood flow measurements in the ascending aorta and pulmonary artery from phase-contrast magnetic resonance images require accurate time-resolved vessel segmentation over the cardiac cycle. Current semi-automatic segmentation methods often involve time-consuming manual correction, relying on user experience for accurate results. The purpose of this study was to develop a semi-automatic vessel segmentation algorithm with shape constraints based on manual vessel delineations for robust segmentation of the ascending aorta and pulmonary artery, to evaluate the proposed method in healthy volunteers and patients with heart failure and congenital heart disease, to validate the method in a pulsatile flow phantom experiment, and to make the method freely available for research purposes. Algorithm shape constraints were extracted from manual reference delineations of the ascending aorta (n = 20) and pulmonary artery (n = 20) and were included in a semi-automatic segmentation method only requiring manual delineation in one image. Bias and variability (bias ± SD) for flow volume of the proposed algorithm versus manual reference delineations were 0·0 ± 1·9 ml in the ascending aorta (n = 151; seven healthy volunteers; 144 heart failure patients) and -1·7 ± 2·9 ml in the pulmonary artery (n = 40; 25 healthy volunteers; 15 patients with atrial septal defect). Interobserver bias and variability were lower (P = 0·008) for the proposed semi-automatic method (-0·1 ± 0·9 ml) compared to manual reference delineations (1·5 ± 5·1 ml). Phantom validation showed good agreement between the proposed method and timer-and-beaker flow volumes (0·4 ± 2·7 ml). In conclusion, the proposed semi-automatic vessel segmentation algorithm can be used for efficient analysis of flow and shunt volumes in the aorta and pulmonary artery.

Fetal iGRASP cine CMR assisting in prenatal diagnosis of complicated cardiac malformation with impact on delivery planning.

Limited visualization of the fetal heart and vessels by fetal ultrasound due to suboptimal fetal position, patient habitus and skeletal calcification may lead to missed diagnosis, overdiagnosis and parental uncertainty. Counselling and delivery planning may in those cases also be tentative. The recent fetal cardiac magnetic resonance (CMR) reconstruction method utilizing tiny golden-angle iGRASP (iterative Golden-angle RAdial Sparse Parallel MRI) allows for cine imaging of the fetal heart for use in clinical practice. This case describes an unbalanced common atrioventricular canal where limited ultrasound image quality and visibility of the aortic arch precluded confirming or ruling out presence of a ventricular septal defect. Need of prostaglandins or neonatal intervention was thus uncertain. Cardiovascular magnetic resonance imaging confirmed ultrasound findings and added value by ruling out a significant ventricular septal defect and diagnosing arch hypoplasia. This confirmed the need of patient relocation for delivery at a paediatric cardiothoracic surgery centre and prostaglandins could be initiated before the standard postnatal ultrasound. The applied CMR method can thus improve diagnosis of complicated fetal cardiac malformation and has direct clinical impact.

Altered biventricular hemodynamic forces in patients with repaired tetralogy of Fallot and right ventricular volume overload because of pulmonary regurgitation.

Intracardiac hemodynamic forces have been proposed to influence remodeling and be a marker of ventricular dysfunction. We aimed to quantify the hemodynamic forces in patients with repaired tetralogy of Fallot (rToF) to further understand the pathophysiological mechanisms as this could be a potential marker for pulmonary valve replacement (PVR) in these patients. Patients with rToF and pulmonary regurgitation (PR) > 20% ( n = 18) and healthy control subjects ( n = 15) underwent MRI, including four-dimensional flow. A subset of patients ( n = 8) underwent PVR and MRI after surgery. Time-resolved hemodynamic forces were quantified using 4D-flow data and indexed to ventricular volume. Patients had higher systolic and diastolic left ventricular (LV) hemodynamic forces compared with control subjects in the lateral-septal/LV outflow tract ( P = 0.011 and P = 0.0031) and inferior-anterior ( P < 0.0001 and P < 0.0001) directions, which are forces not aligned with blood flow. Forces did not change after PVR. Patients had higher RV diastolic forces compared with control subjects in the diaphragm-right ventricular (RV) outflow tract (RVOT; P < 0.001) and apical-basal ( P = 0.0017) directions. After PVR, RV systolic forces in the diaphragm-RVOT direction decreased ( P = 0.039) to lower levels than in control subjects ( P = 0.0064). RV diastolic forces decreased in all directions ( P = 0.0078, P = 0.0078, and P = 0.039) but were still higher than in control subjects in the diaphragm-RVOT direction ( P = 0.046). In conclusion, patients with rToF and PR had LV hemodynamic forces less aligned with intraventricular blood flow compared with control subjects and higher diastolic RV forces along the regurgitant flow direction in the RVOT and that of tricuspid inflow. Remaining force differences in the LV and RV after PVR suggest that biventricular pumping does not normalize after surgery. NEW & NOTEWORTHY Biventricular hemodynamic forces in patients with repaired tetralogy of Fallot and pulmonary regurgitation were quantified for the first time. Left ventricular hemodynamic forces were less aligned to the main blood flow direction in patients compared with control subjects. Higher right ventricular forces were seen along the pulmonary regurgitant and tricuspid inflow directions. Differences in forces versus control subjects remain after pulmonary valve replacement, suggesting that altered biventricular pumping does not normalize after surgery.

Dynamic fetal cardiovascular magnetic resonance imaging using Doppler ultrasound gating.

BACKGROUND: Fetal cardiovascular magnetic resonance (CMR) imaging may provide a valuable adjunct to fetal echocardiography in the evaluation of congenital cardiovascular pathologies. However, dynamic fetal CMR is difficult due to the lack of direct in-utero cardiac gating. The aim of this study was to investigate the effectiveness of a newly developed Doppler ultrasound (DUS) device in humans for fetal CMR gating. METHODS: Fifteen fetuses (gestational age 30-39 weeks) were examined using 1.5 T CMR scanners at three different imaging sites. A newly developed CMR-compatible DUS device was used to generate gating signals from fetal cardiac motion. Gated dynamic balanced steady-state free precession images were acquired in 4-chamber and short-axis cardiac views. Gating signals during data acquisition were analyzed with respect to trigger variability and sensitivity. Image quality was assessed by measuring endocardial blurring (EB) and by image evaluation using a 4-point scale. Left ventricular (LV) volumetry was performed using the single-plane ellipsoid model. RESULTS: Gating signals from the fetal heart were detected with a variability of 26 ± 22 ms and a sensitivity of trigger detection of 96 ± 4%. EB was 2.9 ± 0.6 pixels (4-chamber) and 2.5 ± 0.1 pixels (short axis). Image quality scores were 3.6 ± 0.6 (overall), 3.4 ± 0.7 (mitral valve), 3.4 ± 0.7 (foramen ovale), 3.6 ± 0.7 (atrial septum), 3.7 ± 0.5 (papillary muscles), 3.8 ± 0.4 (differentiation myocardium/lumen), 3.7 ± 0.5 (differentiation myocardium/lung), and 3.9 ± 0.4 (systolic myocardial thickening). Inter-observer agreement for the scores was moderate to very good (kappa 0.57-0.84) for all structures. LV volumetry revealed mean values of 2.8 ± 1.2 ml (end-diastolic volume), 0.9 ± 0.4 ml (end systolic volume), 1.9 ± 0.8 ml (stroke volume), and 69.1 ± 8.4% (ejection fraction). CONCLUSION: High-quality dynamic fetal CMR was successfully performed using a newly developed DUS device for direct fetal cardiac gating. This technique has the potential to improve the utility of fetal CMR in the evaluation of congenital pathologies.

The effect of initial teaching on evaluation of left ventricular volumes by cardiovascular magnetic resonance imaging: comparison between complete and intermediate beginners and experienced observers.

BACKGROUND: High reproducibility and low intra- and interobserver variability are important strengths of cardiac magnetic resonance (CMR). In clinical practice a significant learning curve may however be observed. Basic CMR courses offer an average of 1.4 h dedicated to lecturing and demonstrating left ventricular (LV) function analysis. The purpose of this study was to evaluate the effect of initial teaching on complete and intermediate beginners' quantitative measurements of LV volumes and function by CMR. METHODS: Standard clinical cine CMR sequences were acquired in 15 patients. Five observers (two complete beginners, one intermediate, two experienced) measured LV volumes. Before initial evaluation beginners read the SCMR guidelines on CMR analysis. After initial evaluation, beginners participated in a two-hour teaching session including cases and hands-on training, representative for most basic CMR courses, after which it is uncertain to what extent different centres provide continued teaching and feedback in-house. Dice Similarity Coefficient (DSC) assessed delineations. Agreement, accuracy, precision, repeatability and reliability were assessed by Bland-Altman, coefficient of variation, and intraclass correlation coefficient methods. RESULTS: Endocardial DSC improved after teaching (+0.14 ± 0.17;p < 0.001) for complete beginners. Low intraobserver variability was found before and after teaching, however with wide limits of agreement. Beginners underestimated volumes by up to 44 ml (EDV), 27 ml (ESV) and overestimated LVM by up to 53 g before teaching, improving to an underestimation of up to 9 ml (EDV), 7 ml (ESV) and an overestimation of up to 30 g (LVM) after teaching. For the intermediate beginner, however, accuracy was quite high already before teaching. CONCLUSIONS: Initial teaching to complete beginners increases accuracy for assessment of LV volumes, however with high bias and low precision even after standardised teaching as offered in most basic CMR courses. Even though the intermediate beginner showed quite high accuracy already before teaching, precision did generally not improve after standardised teaching. To maintain CMR as a technique known for high accuracy and reproducibility and low intra- and inter-observer variability for quantitative measurements, internationally standardised training should be encouraged including high-quality feedback mechanisms. Objective measurements of training methods, training duration and, above all, quality of assessments are required.

Automatic T2* determination for quantification of iron load in heart and liver: a comparison between automatic inline Maximum Likelihood Estimate and the truncation and offset methods.

PURPOSE: To validate ironload T2* by automatic inline Maximum Likelihood Estimate (MLE) with k-space Rician noise correction, against the manual and automated truncation, as well as offset methods, in phantoms and in heart and liver in patients. METHODS: Twenty-five patients and an iron-oxide phantom were scanned at 1.5T using 2 multi-echo gradient-echo sequences. All parameters were identical (voxel 2-3 × 2-3 × 10 mm3 , 10 echoes, TR = 26 ms, FA = 20°, BW = 833 Hz, SENSE = 2) except for TE (cardiac: TE1  = 2·5 ms, ΔTE = 2·5 ms; liver: TE1  = 1·2 ms, ΔTE = 1·5 ms). Phantoms were scanned at 1 and 32 signal averages (NSA), with NSA32 representing low-noise reference. RESULTS: Phantoms: MLE showed low variability between NSA1 and NSA32 (0·02 ± 0·29 ms, CI ±0·21 ms). Between methods, no difference was shown (MLE versus all: <0·31 ms, CI < ±0·35 ms). PATIENTS: No differences were found between methods in heart (MLE versus all: <-0·22 ms, CI < ±0·75 ms) or liver (MLE versus all: <0·12 ms, CI < ±0·26 ms). CONCLUSIONS: The automatic inline MLE method is comparable to the general reference standards for determining cardiac and liver T2* for ironload in man. An automatic inline method may simplify ironload assessment, particularly in centres seeing fewer cases.

Validation of a new T2* algorithm and its uncertainty value for cardiac and liver iron load determination from MRI magnitude images.

PURPOSE: To validate an automatic algorithm for offline T2* measurements, providing robust, vendor-independent T2*, and uncertainty estimates for iron load quantification in the heart and liver using clinically available imaging sequences. METHODS: A T2* region of interest (ROI)-based algorithm was developed for robustness in an offline setting. Phantom imaging was performed on a 1.5 Tesla system, with clinically available multiecho gradient-recalled-echo (GRE) sequences for cardiac and liver imaging. A T2* single-echo GRE sequence was used as reference. Simulations were performed to assess accuracy and precision from 2000 measurements. Inter- and intraobserver variability was obtained in a patient study (n = 23). RESULTS: Simulations: Accuracy, in terms of the mean differences between the proposed method and true T2* ranged from 0-0.73 ms. Precision, in terms of confidence intervals of repeated measurements, was 0.06-4.74 ms showing agreement between the proposed uncertainty estimate and simulations. Phantom study: Bias and variability were 0.26 ± 4.23 ms (cardiac sequence) and -0.23 ± 1.69 ms (liver sequence). Patient study: Intraobserver variability was similar for experienced and inexperienced observers (0.03 ± 1.44 ms versus 0.16 ± 2.33 ms). Interobserver variability was 1.0 ± 3.77 ms for the heart and -0.52 ± 2.75 ms for the liver. CONCLUSION: The proposed algorithm was shown to provide robust T2* measurements and uncertainty estimates over the range of clinically relevant T2* values. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance.

Epidemiology of acute knee injuries seen at the Emergency Department at Umeå University Hospital, Sweden, during 15 years.

PURPOSE: To describe the incidence and injury distribution of knee injuries in the general population of a European setting. METHODS: Retrospective study of all knee injuries registered at the Emergency Department at Umeå University Hospital, Sweden, during 1995-2009 in relation to age, sex, diagnosis, location and activity at the time of injury, mechanism of injury, and treatment and/or follow-up plan. RESULTS: During 1995-2009, 12,663 knee injuries were registered, 8% of all injuries. The incidence of knee injuries resulting in a visit to the Emergency Department was six cases per 1,000 person years. One-third of all injuries occurred during sports. And 30% were 15-24 years. More men than women were injured during sporting activities and women were mostly injured during transportation. CONCLUSION: Knee injuries in a general population are common and the injury distribution varies with age and sex. Sports activities and young age were prominent features of the injured population. LEVEL OF EVIDENCE: IV.

Initial results of inflammatory response, matrix remodeling, and reactive oxygen species following PCI in acute ischemic myocardial injury in man.

BACKGROUND: Neutrophils and reactive oxygen species (ROS) are suggested to be involved in irreversible myocardial reperfusion injury and stunning. We investigated the relations between circulating biochemical markers and myocardium at risk (MaR), myocardial infarct (MI) size, salvage, and recovery of function in man. METHODS AND RESULTS: In patients undergoing PCI serial blood samples were acquired for markers of inflammatory response (myeloperoxidase [MPO], neutrophil-gelatinase-associated lipocalin [NGAL], interleukins 6 and 8 [IL-6/8], tumor necrosis factor-a [TNF-a], high-sensitive C-reactive protein [hsCRP]), matrix remodeling (matrixmetalloproteinase-9 [MMP-9]) and ROS (malondialdehyde [MDA], isoprostane [IsoP]). Samples were obtained before PCI and 1.5, 3, and 24 hours after reperfusion. Myocardial perfusion SPECT (MPS) was used to assess MaR. Late gadolinum-enhanced cardiac magnetic resonance imaging was performed for regional function in the acute setting, at 1 week and 6 months, and at 1 week also for MI size. Sixteen patients (15 men; 42-78 years) were enrolled, 12 of whom underwent MPS. Peak and cumulative NGAL and cumulative MMP-9 showed inverse correlations to MaR. No correlation was found for MI size. Peak MPO correlated inversely to salvage and to recovery of regional function in the infarcted segments at 1 week and 6 months. CONCLUSIONS: This is the first study in man to show inverse relations between circulating NGAL and MMP-9 and MaR. The current results do not support that ROS has a role in stunning in man. MI size showed no significant correlation to any parameter, challenging inflammatory treatment in reperfusion.

Dissociation of the Inflammatory Reaction following PCI for Acute Myocardial Infarction.

OBJECTIVES: Neutrophils are activated and infiltrate the myocardium after ischemia and reperfusion. The involvement of neutrophils in irreversible reperfusion injury is suggested by numerous experimental studies. The aim of this study was to investigate markers of neutrophil activation following reperfusion of acute myocardial infarction (AMI) accomplished with percutaneous coronary intervention (PCI) and their relationship to markers of lipid peroxidation, cytokines and highly-sensitive C-reactive protein (hsCRP). DESIGN: Non-consecutive patients with their first myocardial infarction were evaluated. Setting. University hospital as primary referral center, single center. PATIENTS AND METHODS: Forty-nine patients with AMI were evaluated. All were treated with primary PCI and infusion of abciximab. Reperfusion was verified by angiography. Blood samples for analyses of myeloperoxidase (MPO), neutrophil gelatinase-associated lipocalin (NGAL), matrix metalloproteinase-9 (MMP-9), malondialdehyde (MDA), 8-isoprostane-prostaglandin F2alpha (Iso-P), interleukin 6 (IL-6), interleukin 8 (IL-8), tumor necrosis factoralpha (TNFalpha), hsCRP, creatine kinase-monobasic fraction (CK-MB) and troponin-T (TnT) were obtained at baseline with the occluded coronary vessel, and subsequently after verified reperfusion at 1.5, 3 and 24 hours. RESULTS: Significant increases in MMP-9, IL-6, IL-8, TNFalpha and hsCRP were observed, and a significant decrease in MPO and MDA was also observed over the same period. No significant changes in Iso-P and NGAL were found. CONCLUSION: We found a dissociation of the inflammatory reaction after PCI for AMI: a decrease of markers of neutrophil activation and MDA, but an increase in cytokines and hsCRP. An antineutrophil effect of the PCI procedure including treatment with abciximab, an antiplatelet drug and a modulator of inflammation, is conceivable.