Fetal cardiac magnetic resonance imaging of the descending aorta in suspected left-sided cardiac obstructions.

Background: Severe left-sided cardiac obstructions are associated with high morbidity and mortality if not detected in time. The correct prenatal diagnosis of coarctation of the aorta (CoA) is difficult. Fetal cardiac magnetic resonance imaging (CMR) may improve the prenatal diagnosis of complex congenital heart defects. Flow measurements in the ascending aorta could aid in predicting postnatal CoA, but its accurate visualization is challenging. Objectives: To compare the flow in the descending aorta (DAo) and umbilical vein (UV) in fetuses with suspected left-sided cardiac obstructions with and without the need for postnatal intervention and healthy controls by fetal phase-contrast CMR flow. A second objective was to determine if adding fetal CMR to echocardiography (echo) improves the fetal CoA diagnosis. Methods: Prospective fetal CMR phase-contrast flow in the DAo and UV and echo studies were conducted between 2017 and 2022. Results: A total of 46 fetuses with suspected left-sided cardiac obstructions [11 hypoplastic left heart syndrome (HLHS), five critical aortic stenosis (cAS), and 30 CoA] and five controls were included. Neonatal interventions for left-sided cardiac obstructions (n = 23) or comfort care (n = 1 with HLHS) were pursued in all 16 fetuses with suspected HLHS or cAS and in eight (27%) fetuses with true CoA. DAo or UV flow was not different in fetuses with and without need of intervention. However, DAo and UV flows were lower in fetuses with either retrograde isthmic systolic flow [DAo flow 253 (72) vs. 261 (97) ml/kg/min, p = 0.035; UV flow 113 (75) vs. 161 (81) ml/kg/min, p = 0.04] or with suspected CoA and restrictive atrial septum [DAo flow 200 (71) vs. 268 (94) ml/kg/min, p = 0.04; UV flow 89 vs. 159 (76) ml/kg/min, p = 0.04] as well as in those without these changes. Adding fetal CMR to fetal echo predictors for postnatal CoA did not improve the diagnosis of CoA. Conclusion: Fetal CMR-derived DAo and UV flow measurements do not improve the prenatal diagnosis of left-sided cardiac obstructions, but they could be important in identifying fetuses with a more severe decrease in blood flow across the left side of the heart. The physiological explanation may be a markedly decreased left ventricular cardiac output with subsequent retrograde systolic isthmic flow and decreased total DAo flow.

Factors affecting performance of fetal blood T2 measurements for noninvasive estimation of oxygen saturation.

PURPOSE: To ultimately make accurate and precise fetal noninvasive oxygen saturation (sO2 ) measurements by T2 -prepared bSSFP more widely available by systematically assessing error sources in order to potentially reduce perinatal mortality in cardiovascular malformations and fetal growth restriction. METHODS: T2 -prepared bSSFP data were acquired in phantoms; in flowing blood in adults in the superior sagittal sinus, ascending and descending aorta, and main pulmonary artery; and in the fetal descending aorta and umbilical vein. T2 was assessed in relation to T2 two- or three-parameter curve-fitting techniques, SSFP readout, refocusing time delay (τ), constant and pulsatile blood flow, and impact of T1 recovery. Further, fetal T2 and sO2 variability were quantified in the descending aorta and umbilical vein in healthy fetuses and fetuses with cardiovascular malformation (gestational weeks 32-38). RESULTS: In phantoms, three-parameter fitting was accurate irrespective of phase FOV (<4 ms; i.e., <2%), and T2 was overestimated (up to 23 ms/10%; p = 0.001) beyond ±30 Hz off-resonance. In the adult aorta, T2 was underestimated during higher blood flow velocities and pulsatility for τ = 16 ms (-41 ms/-17%; p = 0.008). In fetuses, two-parameter fitting overestimated T2 compared with three-parameter fitting (+33 ms/+18%; p = 0.03). T2 variability was 18 ms/15% in the fetal descending aorta and 28 ms/14% in the umbilical vein. The resulting estimated sO2 variability was ∼10% (15% of sO2 value) in the fetal descending aorta. CONCLUSIONS: Errors due to T2 -fitting techniques, off-resonance, flow velocity, and insufficient T1 recovery between image acquisitions could be mitigated by using three-parameter fitting with included saturation-prepared images approximating infinite T2 -preparation time, adequate shimming covering the fetus and placenta, and by modifying acquisition parameters. Variability in fetal blood T2 and sO2 , however, indicate that it is currently not feasible to use these methods for prediction of disease.

Mild hypothermia attenuates ischaemia/reperfusion injury: insights from serial non-invasive pressure-volume loops.

AIMS: Mild hypothermia, 32-35°C, reduces infarct size in experimental studies, potentially mediating reperfusion injuries, but human trials have been ambiguous. To elucidate the cardioprotective mechanisms of mild hypothermia, we analysed cardiac performance in a porcine model of ischaemia/reperfusion, with serial cardiovascular magnetic resonance (CMR) imaging throughout 1 week using non-invasive pressure-volume (PV) loops. METHODS AND RESULTS: Normothermia and Hypothermia group sessions (n = 7 + 7 pigs, non-random allocation) were imaged with Cardiovascular magnetic resonance (CMR) at baseline and subjected to 40 min of normothermic ischaemia by catheter intervention. Thereafter, the Hypothermia group was rapidly cooled (mean 34.5°C) for 5 min before reperfusion. Additional CMR sessions at 2 h, 24 h, and 7 days acquired ventricular volumes and ischaemic injuries (unblinded analysis). Stroke volume (SV: -24%; P = 0.029; Friedmans test) and ejection fraction (EF: -20%; P = 0.068) were notably reduced at 24 h in the Normothermia group compared with baseline. In contrast, the decreases were ameliorated in the Hypothermia group (SV: -6%; P = 0.77; EF: -6%; P = 0.13). Mean arterial pressure remained stable in Normothermic animals (-3%, P = 0.77) but dropped 2 h post-reperfusion in hypothermic animals (-18%, P = 0.007). Both groups experienced a decrease and partial recovery pattern for PV loop-derived variables over 1 week, but the adverse effects tended to attenuate in the Hypothermia group. Infarct sizes were 10 ± 8% in Hypothermic and 15 ± 8% in Normothermic animals (P = 0.32). Analysis of covariance at 24 h indicated that hypothermia has cardioprotective properties incremental to reducing infarct size, such as higher external power (P = 0.061) and lower arterial elastance (P = 0.015). CONCLUSION: Using non-invasive PV loops by CMR, we observed that mild hypothermia at reperfusion alleviates the heart's work after ischaemia/reperfusion injuries during the first week and preserves short-term cardiac performance. This hypothesis-generating study suggests hypothermia to have cardioprotective properties, incremental to reducing infarct size. The primary cardioprotective mechanism was likely an afterload reduction acutely unloading the left ventricle.

Fetal 3D cardiovascular cine image acquisition using radial sampling and compressed sensing.

PURPOSE: To explore a fetal 3D cardiovascular cine acquisition using a radial image acquisition and compressed-sensing reconstruction and compare image quality and scan time with conventional multislice 2D imaging. METHODS: Volumetric fetal cardiac data were acquired in 26 volunteers using a radial 3D balanced SSFP pulse sequence. Cardiac gating was performed using a Doppler ultrasound device. Images were reconstructed using a parallel-imaging and compressed-sensing algorithm. Multiplanar reformatting to standard cardiac views was performed before image analysis. Clinical 2D images were used for comparison. Qualitative and quantitative image evaluation were performed by two experienced observers (scale: 1-4). Volumes, mass, and function were assessed. RESULTS: Average scan time for the 3D imaging was 6 min, including one localizer. A 2D imaging stack covering the entire heart including localizer sequences took at least 6.5 min, depending on planning complexity. The 3D acquisition was successful in 7 of 26 subjects (27%). Overall image contrast and perceived resolution were lower in the 3D images. Nonetheless, the 3D images had, on average, a moderate cardiac diagnostic quality (median [range]: 3 [1-4]). Standard clinical 2D acquisitions had a high cardiac diagnostic quality (median [range]: 4 [3, 4]). Cardiac measurements were not different between 2D and 3D images (all p > 0.16). CONCLUSION: The presented free-breathing whole-heart fetal 3D radial cine MRI acquisition and reconstruction method enables retrospective visualization of all cardiac views while keeping examination times short. This proof-of-concept work produced images with diagnostic quality, while at the same time reducing the planning complexity to a single localizer.

Higher blood pressure in adolescent boys after very preterm birth and fetal growth restriction.

BACKGROUND: Although preterm birth predisposes for cardiovascular disease, recent studies in children indicate normal blood pressure and arterial stiffness. This prospective cohort study therefore assessed blood pressure and arterial stiffness in adolescents born very preterm due to verified fetal growth restriction (FGR). METHODS: Adolescents (14 (13-17) years; 52% girls) born very preterm with FGR (preterm FGR; n = 24) and two control groups born with appropriate birth weight (AGA), one in similar gestation (preterm AGA; n = 27) and one at term (term AGA; n = 28) were included. 24-hour ambulatory blood pressure and aortic pulse wave velocity (PWV) and distensibility by magnetic resonance imaging were acquired. RESULTS: There were no group differences in prevalence of hypertension or in arterial stiffness (all p ≥ 0.1). In boys, diastolic and mean arterial blood pressures increased from term AGA to preterm AGA to preterm FGR with higher daytime and 24-hour mean arterial blood pressures in the preterm FGR as compared to the term AGA group. In girls, no group differences were observed (all p ≥ 0.1). CONCLUSIONS: Very preterm birth due to FGR is associated with higher, yet normal blood pressure in adolescent boys, suggesting an existing but limited impact of very preterm birth on cardiovascular risk in adolescence, enhanced by male sex and FGR. IMPACT: Very preterm birth due to fetal growth restriction was associated with higher, yet normal blood pressure in adolescent boys. In adolescence, very preterm birth due to fetal growth restriction was not associated with increased thoracic aortic stiffness. In adolescence, very preterm birth in itself showed an existing but limited effect on blood pressure and thoracic aortic stiffness. Male sex and fetal growth restriction enhanced the effect of preterm birth on blood pressure in adolescence. Male sex and fetal growth restriction should be considered as additional risk factors to that of preterm birth in cardiovascular risk stratification.

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.

Super-Resolution Cine Image Enhancement for Fetal Cardiac Magnetic Resonance Imaging.

BACKGROUND: Fetal cardiac magnetic resonance imaging (MRI) improves the diagnosis of congenital heart defects, but is sensitive to fetal motion due to long image acquisition time. This may be overcome with faster image acquisition with low resolution, followed by image enhancement to provide clinically useful images. PURPOSE: To combine phase-encoding undersampling with super-resolution neural networks to achieve high-resolution fetal cine cardiac MR images with short acquisition time. STUDY TYPE: Prospective. SUBJECTS: Twenty-eight fetuses (gestational week 36 [interquartile range 33-38 weeks]). FIELD STRENGTH/SEQUENCE: 1.5 T, balanced steady-state free precession (bSSFP) cine sequence. ASSESSMENT: Images were acquired using fully sampled Doppler ultrasound-gated clinical bSSFP cine as reference, with equivalent cine sequences with decreased phase-encoding resolution (25%, 33%, and 50% of clinical standard). Two super-resolution methods based on convolutional neural networks were proposed and evaluated (phasrGAN and phasrresnet). Data were partitioned into training (36 cine slices), validation (3 cine slices), and test sets (67 cine slices) without overlap. Conventional reconstruction methods using bicubic interpolation and k-space zeropadding were used for comparison. Three blinded observers scored image quality between 1 and 10. STATISTICAL TESTS: Image scores are reported as median [interquartile range] and were compared using Mann-Whitney's nonparametric test with P < 0.05 showing statistically significant differences. RESULTS: Both proposed methods showed no significant difference in image quality compared to clinical images (8 [7-8.5]) down to 33% (phasrGAN 8 [6.5-8]; phasrresnet 8 [7-8], all P ≥ 0.19) phase-encoding resolution, i.e., up to three times faster image acquisition, whereas bicubic interpolation and k-space zeropadding showed significantly lower quality for 33% phase-encoding resolution (both 7 [6-8]). DATA CONCLUSION: Super-resolution enhancement can be used for fetal cine cardiac MRI to reduce image acquisition time while maintaining image quality. This may lead to an improved success rate for fetal cine MR imaging, as the impact of fetal motion is lessened by shortened acquisitions. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.

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.

Quantification of blood flow in the fetus with cardiovascular magnetic resonance imaging using Doppler ultrasound gating: validation against metric optimized gating.

INTRODUCTION: Fetal cardiovascular magnetic resonance (CMR) imaging is used clinically and for research, but has been previously limited due to lack of direct gating methods. A CMR-compatible Doppler ultrasound (DUS) gating device has resolved this. However, the DUS-gating method is not validated against the current reference method for fetal phase-contrast blood flow measurements, metric optimized gating (MOG). Further, we investigated how different methods for vessel delineation affect flow volumes and observer variability in fetal flow acquisitions. AIMS: To 1) validate DUS gating versus MOG for quantifying fetal blood flow; 2) assess repeatability of DUS gating; 3) assess impact of region of interest (ROI) size on flow volume; and 4) compare time-resolved and static delineations for flow volume and observer variability. METHODS: Phase-contrast CMR was acquired in the fetal descending aorta (DAo) and umbilical vein by DUS gating and MOG in 22 women with singleton pregnancy in gestational week 360 (265-400) with repeated scans in six fetuses. Impact of ROI size on measured flow was assessed for ROI:s 50-150% of the vessel diameter. Four observers from two centers provided time-resolved and static delineations. Bland-Altman analysis was used to determine agreement between both observers and methods. RESULTS: DAo flow was 726 (348-1130) ml/min and umbilical vein flow 366 (150-782) ml/min by DUS gating. Bias±SD for DUS-gating versus MOG were - 45 ± 122 ml/min (-6 ± 15%) for DAo and 19 ± 136 ml/min (2 ± 24%) for umbilical vein flow. Repeated flow measurements in the same fetus showed similar volumes (median CoV = 11% (DAo) and 23% (umbilical vein)). Region of interest 50-150% of vessel diameter yielded flow 35-120%. Bias±SD for time-resolved versus static DUS-gated flow was 33 ± 39 ml/min (4 ± 6%) for DAo and 11 ± 84 ml/min (2 ± 15%) for umbilical vein flow. CONCLUSIONS: Quantification of blood flow in the fetal DAo and umbilical vein using DUS-gated phase-contrast CMR is feasible and agrees with the current reference method. Repeatability was generally high for CMR fetal blood flow assessment. An ROI similar to the vessel area or slightly larger is recommended. A static ROI is sufficient for fetal flow quantification using currently available CMR sequences.

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.