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Background: To investigate the ability of a delayed respiratory-navigated, electrocardiographically-gated three-dimensional inversion recovery-prepared flash low angle shot (3D IR FLASH) sequence to evaluate the lower airways in children undergoing routine cardiovascular magnetic resonance (CMR)., Methods: This retrospective study included pediatric patients (0-18 years) who underwent clinical CMR where a delayed 3D IR FLASH sequence was performed between July 2020 and April 2021. The airway image quality and extent of lower airway visibility was graded by two blinded readers using a four-point ordinal scale (0-3). Lower airway anatomical variants and abnormalities were recorded., Results: 180 patients were included with a median age of 11.7 (4.6-15.3) years. 51/180 (28%) were under general anesthesia (GA). Overall, the median grading of airway image quality was 3 (2-3) and extent of lower airway visibility was 3 (3-3). Interrater agreement was almost perfect (κ = 0.867 and κ = 0.956, respectively). Image quality correlated with extent of lower airway visibility (r = 0.62, p < 0.01). Delayed 3D IR FLASH was able to characterize the segmental bronchi in 137/180 (76%) and lobar bronchi in 172/180 (96%) of patients. Lower airway abnormalities were identified in 37/180 (21%) of patients and in 33/129 (26%) with congenital heart disease (CHD). Identified abnormalities included tracheobronchial branching anomalies in 6/180 (3%), abnormal tracheobronchial situs in 6/180 (3%), and extrinsic vascular compression in 25/180 (14%)., Conclusions: Delayed 3D IR FLASH has excellent performance for evaluation of the lower airway anatomy and can simultaneously assess for myocardial late gadolinium enhancement. Lower airway abnormalities are not infrequently seen in children undergoing routine CMR for CHD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: This study compares three-dimensional (3D) high-resolution (HR) late gadolinium enhancement (LGE; 3D HR-LGE) imaging using a respiratory navigated, electrocardiographically-gated inversion recovery gradient echo sequence with conventional LGE imaging using a single-shot phase-sensitive inversion recovery (PSIR) balanced steady-state free precession (bSSFP; PSIR-bSSFP) sequence for routine clinical use in the pediatric population., Methods: Pediatric patients (0-18 years) who underwent clinical cardiovascular magnetic resonance (CMR) with both 3D HR-LGE and single-shot PSIR-bSSFP LGE between January 2018 and June 2020 were included. Image quality (0-4) and detection of LGE in the left ventricle (LV) (per 17 segments), in the right ventricle (RV) (per 3 segments), as endocardial fibroelastosis (EFE), at the hinge points, and at the papillary muscles was analyzed by two blinded readers for each sequence. Ratios of the mean signal intensity of LGE to normal myocardium (LGE:Myo) and to LV blood pool (LGE:Blood) were recorded. Data is presented as median (1st-3rd quartiles). Wilcoxon signed rank test and chi-square analyses were used as appropriate. Inter-rater agreement was analyzed using weighted κ-statistics., Results: 102 patients were included with median age at CMR of 8 (1-13) years-old and 44% of exams performed under general anesthesia. LGE was detected in 55% of cases. 3D HR LGE compared to single-shot PSIR-bSSFP had longer scan time [4:30 (3:35-5:34) vs 1:11 (0:47-1:32) minutes, p < 0.001], higher image quality ratings [3 (3-4) vs 2 (2-3), p < 0.001], higher LGE:Myo [23.7 (16.9-31.2) vs 5.0 (2.9-9.0), p < 0.001], detected more segments of LGE in both the LV [4 (2-8) vs 3 (1-7), p = 0.045] and RV [1 (1-1) vs 1 (0-1), p < 0.001], and also detected more cases of LGE with 13/56 (23%) of patients with LGE only detectable by 3D HR LGE (p < 0.001). 3D HR LGE specifically detected a greater proportion of RV LGE (27/27 vs 17/27, p < 0.001), EFE (11/11 vs 5/11, p = 0.004), and papillary muscle LGE (14/15 vs 4/15, p < 0.001). Inter-rater agreement for the recorded variables ranged from 0.42 to 1.00., Conclusions: 3D HR LGE achieves greater image quality and detects more LGE than conventional single-shot PSIR-bSSFP LGE imaging, and should be considered an alternative to conventional LGE sequences for routine clinical use in the pediatric population., (© 2023. The Author(s).)

Background: The extent and significance in of cardiac remodeling in Fontan patients are unclear and were the subject of this study., Methods: This retrospective cohort study compared cardiovascular magnetic resonance (CMR) imaging markers of cardiac function, myocardial fibrosis, and hemodynamics in young Fontan patients to controls., Results: Fifty-five Fontan patients and 44 healthy controls were included (median age 14 years (range 7-17 years) vs 13 years (range 4-14 years), p = 0.057). Fontan patients had a higher indexed end-diastolic ventricular volume (EDVI 129 ml/m 2 vs 93 ml/m 2 , p < 0.001), and lower ejection fraction (EF 45% vs 58%, p < 0.001), circumferential (CS - 23.5% vs - 30.8%, p < 0.001), radial (6.4% vs 8.2%, p < 0.001), and longitudinal strain (- 13.3% vs - 24.8%, p < 0.001). Compared to healthy controls, Fontan patients had higher extracellular volume fraction (ECV) (26.3% vs 20.6%, p < 0.001) and native T1 (1041 ms vs 986 ms, p < 0.001). Patients with a dominant right ventricle demonstrated larger ventricles (EDVI 146 ml/m 2 vs 120 ml/m 2 , p = 0.03), lower EF (41% vs 47%, p = 0.008), worse CS (- 20.1% vs - 25.6%, p = 0.003), and a trend towards higher ECV (28.3% versus 24.1%, p = 0.09). Worse EF and CS correlated with longer cumulative bypass (R = - 0.36, p = 0.003 and R = 0.46, p < 0.001), cross-clamp (R = - 0.41, p = 0.001 and R = 0.40, p = 0.003) and circulatory arrest times (R = - 0.42, p < 0.001 and R = 0.27, p = 0.03). T1 correlated with aortopulmonary collateral (APC) flow (R = 0.36, p = 0.009) which, in the linear regression model, was independent of ventricular morphology (p = 0.9) and EDVI (p = 0.2). The composite outcome (cardiac readmission, cardiac reintervention, Fontan failure or any clinically significant arrhythmia) was associated with increased native T1 (1063 ms vs 1026 ms, p = 0.029) and EDVI (146 ml/m 2 vs 118 ml/m 2 , p = 0.013), as well as decreased EF (42% vs 46%, p = 0.045) and worse CS (- 22% vs - 25%, p = 0.029). APC flow (HR 5.5 CI 1.9-16.2, p = 0.002) was independently associated with the composite outcome, independent of ventricular morphology (HR 0.71 CI 0.30-1.69 p = 0.44) and T1 (HR1.006 CI 1.0-1.13, p = 0.07)., Conclusions: Pediatric Fontan patients have ventricular dysfunction, altered myocardial mechanics and increased fibrotic remodeling. Cumulative exposure to cardiopulmonary bypass and increased aortopulmonary collateral flow are associated with myocardial dysfunction and fibrosis. Cardiac dysfunction, fibrosis, and collateral flow are associated with adverse outcomes., (© 2021. The Author(s).)

Background: Cardiovascular magnetic resonance (CMR) late gadolinium enhancement (LGE) requires identification of the normal myocardial nulling time using inversion time (TI)-scout imaging sequence. Although TI-scout images are not primarily used for myocardial assessment, they provide information regarding different signal recovery patterns of normal and abnormal myocardium facilitating identification of LGE in instances where standard LGE images alone are not diagnostic. We aimed to assess the diagnostic performance of TI-scout as compared to that of standard LGE images., Methods: CMR studies with LGE imaging in 519 patients (345 males, 1-17 years) were reviewed to assess the diagnostic performance of LGE imaging in terms of the location of LGE and the pathologic entities. The diagnostic performance of the TI-scout and standard LGE imaging was classified into four categories: (1) equally diagnostic, (2) TI-scout superior to standard LGE, (3) standard LGE superior to TI-scout, and (4) complementary, by the consensus of the two observers., Results: The study cohort consisted of 440 patients with negative LGE and 79 with evidence for LGE. For a negative diagnosis of LGE, TI-scout and standard LGE images were equally diagnostic in 75% of the cases and were complementary in 12%. For patients with LGE, TI-scout images were superior to standard LGE images in 52% of the cases and were complementary in 19%. The diagnostic performance of TI-scout images was superior to that of standard LGE images in all locations. TI-scout images were superior to standard LGE images in 11 of 12 (92%) cases with LGE involving the papillary muscles, in 7 /12 (58%) cases with subendocardial LGE, and in 4/7 (57%) cases with transmural LGE. TI-scout images were particularly useful assessing the presence and extent of LGE in hypertrophic cardiomyopathy (HCM). TI-scout was superior to standard LGE in 6/10 (60%) and was complementary in 3/10 (30%) of the positive cases with HCM., Conclusions: TI-scout images enhance the diagnostic performance of LGE imaging in children.

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 36 0 (26 5 -40 0 ) 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.

Background: Patients with single ventricle physiology are at increased risk for developing liver fibrosis. Its extent and prevalence in children with bidirectional cavopulmonary connection (BCPC) and Fontan circulation are unclear. Extracellular volume fraction (ECV), derived from cardiovascular magnetic resonance (CMR) and T1 relaxometry, reflect fibrotic remodeling and/or congestion in the liver. The aim of this study was to investigate whether pediatric patients with single ventricle physiology experience increased native T1 and ECV as markers of liver fibrosis/congestion., Methods: Hepatic native T1 times and ECV, using a cardiac short axis modified Look-Locker inversion recovery sequence displaying the liver, were measured retrospectively in children with BCPC- and Fontan circulations and compared to pediatric controls., Results: Hepatic native T1 time were increased in Fontan patients (n = 62, 11.4 ± 4.4 years, T1 762 ± 64 ms) versus BCPC patients (n = 20, 2.8 ± 0.9 years, T1 645 ± 43 ms, p = 0.04). Both cohorts had higher T1 than controls (n = 44, 13.7 ± 2.9 years, T1 604 ± 54 ms, p < 0.001 for both). ECV was 41.4 ± 4.8% in Fontan and 36.4 ± 4.8% in BCPC patients, respectively (p = 0.02). In Fontan patients, T1 values correlated with exposure to cardiopulmonary bypass time (R = 0.3, p = 0.02), systolic and end diastolic volumes (R = 0.3, p = 0.04 for both) and inversely with oxygen saturations and body surface area (R = -0.3, p = 0.04 for both). There were no demonstrable associations of T1 or ECV with central venous pressure or age after Fontan., Conclusion: Fontan and BCPC patients have elevated CMR markers suggestive of hepatic fibrosis and/or congestion, even at a young age. The tissue changes do not appear to be related to central venous pressures., Trial Registration: Retrospectively registered data.

Background: Validating new techniques for fetal cardiovascular magnetic resonance (CMR) is challenging due to random fetal movement that precludes repeat measurements. Consequently, fetal CMR development has been largely performed using physical phantoms or postnatal volunteers. In this work, we present an open-source simulation designed to aid in the development and validation of new approaches for fetal CMR. Our approach, fetal extended Cardiac-Torso cardiovascular magnetic resonance imaging (Fetal XCMR), builds on established methods for simulating CMR acquisitions but is tailored toward the dynamic physiology of the fetal heart and body. We present comparisons between the Fetal XCMR phantom and data acquired in utero, resulting in image quality, anatomy, tissue signals and contrast., Methods: Existing extended Cardiac-Torso models are modified to create maternal and fetal anatomy, combined according to simulated motion, mapped to CMR contrast, and converted to CMR data. To provide a comparison between the proposed simulation and experimental fetal CMR images acquired in utero, images from a typical scan of a pregnant woman are included and simulated acquisitions were generated using matching CMR parameters, motion and noise levels. Three reconstruction (static, real-time, and CINE), and two motion estimation methods (translational motion, fetal heart rate) from data acquired in transverse, sagittal, coronal, and short-axis planes of the fetal heart were performed to compare to in utero acquisitions and demonstrate feasibility of the proposed simulation framework., Results: Overall, CMR contrast, morphologies, and relative proportions of the maternal and fetal anatomy are well represented by the Fetal XCMR images when comparing the simulation to static images acquired in utero. Additionally, visualization of maternal respiratory and fetal cardiac motion is comparable between Fetal XCMR and in utero real-time images. Finally, high quality CINE image reconstructions provide excellent delineation of fetal cardiac anatomy and temporal dynamics for both data types., Conclusion: The fetal CMR phantom provides a new method for evaluating fetal CMR acquisition and reconstruction methods by simulating the underlying anatomy and physiology. As the field of fetal CMR continues to grow, new methods will become available and require careful validation. The fetal CMR phantom is therefore a powerful and convenient tool in the continued development of fetal cardiac imaging.

Background: This study assessed the feasibility and acceptability of two common types of exercise training-high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT)-in adults with Crohn's disease (CD)., Methods: In this mixed-methods pilot trial, participants with quiescent or mildly-active CD were randomly assigned 1:1:1 to HIIT, MICT or usual care control, and followed up for 6 months. The HIIT and MICT groups were offered three exercise sessions per week for the first 12 weeks. Feasibility outcomes included rates of recruitment, retention, outcome completion, and exercise attendance. Data were collected on cardiorespiratory fitness (e.g., peak oxygen uptake), disease activity, fatigue, quality of life, adverse events, and intervention acceptability (via interviews)., Results: Over 17 months, 53 patients were assessed for eligibility and 36 (68%) were randomised (47% male; mean age 36.9 [SD 11.2] years); 13 to HIIT, 12 to MICT, and 11 to control. The exercise session attendance rate was 62% for HIIT (288/465) and 75% for MICT (320/429), with 62% of HIIT participants (8/13) and 67% of MICT participants (8/12) completing at least 24 of 36 sessions. One participant was lost to follow-up. Outcome completion rates ranged from 89 to 97%. The mean increase in peak oxygen uptake, relative to control, was greater following HIIT than MICT (2.4 vs. 0.7 mL/kg/min). There were three non-serious exercise-related adverse events, and two exercise participants experienced disease relapse during follow-up., Conclusions: The findings support the feasibility and acceptability of the exercise programmes and trial procedures. A definitive trial is warranted. Physical exercise remains a potentially useful adjunct therapy in CD. [ID: ISRCTN13021107].

Background: To date it has not been possible to obtain a comprehensive 3D assessment of fetal hemodynamics because of the technical challenges inherent in imaging small cardiac structures, movement of the fetus during data acquisition, and the difficulty of fusing data from multiple cardiac cycles when a cardiac gating signal is absent. Here we propose the combination of volumetric velocity-sensitive cardiovascular magnetic resonance imaging ("4D flow" CMR) and a specialized animal preparation (catheters to monitor fetal heart rate, anesthesia to immobilize mother and fetus) to examine fetal sheep cardiac hemodynamics in utero., Methods: Ten pregnant Merino sheep underwent surgery to implant arterial catheters in the target fetuses. Anesthetized ewes underwent 4D flow CMR with acquisition at 3 T for fetal whole-heart coverage with 1.2-1.5 mm spatial resolution and 45-62 ms temporal resolution. Flow was measured in the heart and major vessels, and particle traces were used to visualize circulatory patterns in fetal cardiovascular shunts. Conservation of mass was used to test internal 4D flow consistency, and comparison to standard 2D phase contrast (PC) CMR was performed for validation., Results: Streaming of blood from the ductus venosus through the foramen ovale was visualized. Flow waveforms in the major thoracic vessels and shunts displayed normal arterial and venous patterns. Combined ventricular output (CVO) was 546 mL/min per kg, and the distribution of flows (%CVO) were comparable to values obtained using other methods. Internal 4D flow consistency across 23 measurement locations was established with differences of 14.2 ± 12.1%. Compared with 2D PC CMR, 4D flow showed a strong correlation (R 2  = 0.85) but underestimated flow (bias = - 21.88 mL/min per kg, p < 0.05)., Conclusions: The combination of fetal surgical preparation and 4D flow CMR enables characterization and quantification of complex flow patterns in utero. Visualized streaming of blood through normal physiological shunts confirms the complex mechanism of substrate delivery to the fetal heart and brain. Besides offering insight into normal physiology, this technology has the potential to qualitatively characterize complex flow patterns in congenital heart disease phenotypes in a large animal model, which can support the development of new interventions to improve outcomes in this population.

Purpose: To image multidimensional flow in fetuses using golden-angle radial phase contrast cardiovascular magnetic resonance (PC-CMR) with motion correction and retrospective gating., Methods: A novel PC-CMR method was developed using an ungated golden-angle radial acquisition with continuously incremented velocity encoding. Healthy subjects (n = 5, 27 ± 3 years, males) and pregnant females (n = 5, 34 ± 2 weeks gestation) were imaged at 3 T using the proposed sequence. Real-time reconstructions were first performed for retrospective motion correction and cardiac gating (using metric optimized gating, MOG). CINE reconstructions of multidimensional flow were then performed using the corrected and gated data., Results: In adults, flows obtained using the proposed method agreed strongly with those obtained using a conventionally gated Cartesian acquisition. Across the five adults, bias and limits of agreement were - 1.0 cm/s and [- 5.1, 3.2] cm/s for mean velocities and - 1.1 cm/s and [- 6.5, 4.3] cm/s for peak velocities. Temporal correlation between corresponding waveforms was also high (R~ 0.98). Calculated timing errors between MOG and pulse-gating RR intervals were low (~ 20 ms). First insights into multidimensional fetal blood flows were achieved. Inter-subject consistency in fetal descending aortic flows (n = 3) was strong with an average velocity of 27.1 ± 0.4 cm/s, peak systolic velocity of 70.0 ± 1.8 cm/s and an intra-class correlation coefficient of 0.95 between the velocity waveforms. In one fetal case, high flow waveform reproducibility was demonstrated in the ascending aorta (R = 0.97) and main pulmonary artery (R = 0.99)., Conclusion: Multidimensional PC-CMR of fetal flow was developed and validated, incorporating retrospective motion compensation and cardiac gating. Using this method, the first quantification and visualization of multidimensional fetal blood flow was achieved using CMR.

Background: Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging has enabled the accurate assessment of myocardial infarction (MI). However, LGE CMR has not been performed successfully in the fetus, where it could be useful for animal studies of interventions to promote cardiac regeneration. We believe that LGE imaging could allow us to document the presence, extent and effect of MI in utero and would thereby expand our capacity for conducting fetal sheep MI research. We therefore aimed to investigate the feasibility of using LGE to detect MI in sheep fetuses., Methods: Six sheep fetuses underwent a thoracotomy and ligation of a left anterior descending (LAD) coronary artery branch; while two fetuses underwent a sham surgery. LGE CMR was performed in a subset of fetuses immediately after the surgery and three days later. Early gadolinium enhancement (EGE) CMR was also performed in a subset of fetuses on both days. Cine imaging of the heart was performed to measure ventricular function., Results: The imaging performed immediately after LAD ligation revealed no evidence of infarct on LGE (n=3). Two of four infarcted fetuses (50%) showed hypoenhancement at the infarct site on the EGE images. Three days after the ligation, LGE images revealed a clear, hyper-enhanced infarct zone in four of the five infarcted fetuses (80%). No hyper-enhanced infarct zone was seen on the one sham fetus that underwent LGE CMR. No hypoenhancement could be seen in the EGE images in either the sham (n=1) or the infarcted fetus (n=1). No regional wall motion abnormalities were apparent in two of the five infarcted fetuses., Conclusion: LGE CMR detected the MI three days after LAD ligation, but not immediately after. Using available methods, EGE imaging was less useful for detecting deficits in perfusion. Our study provides evidence for the ability of a non-invasive tool to monitor the progression of cardiac repair and damage in fetuses with MI. However, further investigation into the optimal timing of LGE and EGE scans and improvement of the sequences should be pursued with the aim of expanding our capacity to monitor cardiac regeneration after MI in fetal sheep.

Background: Structured exercise training has been proposed as a useful adjunctive therapy for Crohn's disease by improving immune function and psychological health, reducing fatigue and promoting gains in muscle and bone strength. However, the evidence for exercise in Crohn's disease is sparse, with only a handful of small prospective trials [1, 2], with methodological limitations, including the use of non-randomised and non-controlled study designs and small sample sizes. Here, we describe the protocol for a study that aims to assess the feasibility and acceptability of two common types of exercise training-high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT)-in adults with inactive or mildly active Crohn's disease (CD)., Methods: This is a randomised, controlled, assessor-blinded, feasibility trial with three parallel groups. Forty-five adults with inactive or mildly active Crohn's disease will be randomly assigned 1:1:1 to HIIT, MICT or usual care control. Participants in the HIIT and MICT groups will be invited to undertake three sessions of supervised exercise each week for 12 consecutive weeks. HIIT sessions will consist of ten 1-min intervals of cycling exercise at 90% of peak power output separated by 1 min of active recovery. MICT sessions will involve 30 min of continuous cycling at 35% of peak power output. Participants will be assessed before randomisation and 13 and 26 weeks after randomisation. Feasibility outcomes include rates of recruitment, retention and adherence. Interviews with participants will explore the acceptability of the exercise programmes and study procedures. Clinical/health outcomes include cardiorespiratory fitness, body mass index, resting blood pressure, markers of disease activity (faecal calprotectin and Crohn's Disease Activity Index) and activated T cell cytokine profiles. Study questionnaires include the Inflammatory Bowel Disease Quality of Life Questionnaire, EQ-5D-5L, IBD Fatigue Scale, Hospital and Anxiety Depression Scale, and International Physical Activity Questionnaire., Discussion: This study will provide useful information on the feasibility and acceptability of supervised exercise training in adults with inactive and mildly active Crohn's disease and will inform the design of a subsequent, adequately powered, multi-centre trial., Trial Registration: The trial is registered with the International Standard Randomised Controlled Trial Register (ISRCTN13021107). Date registration assigned was 02/12/2015.

Background: To develop and evaluate a reconstruction framework for high resolution time-resolved CMR of the fetal heart in the presence of motion., Methods: Data were acquired using a golden angle radial trajectory in seven fetal subjects and reconstructed as real-time images to detect fetal movement. Data acquired during through-plane motion were discarded whereas in-plane motion was corrected. A fetal cardiac gating signal was extracted to sort the corrected data by cardiac phase, allowing reconstruction of cine images. The quality of motion corrected images and the effect of data undersampling were quantified using separate expressions for spatial blur and image error., Results: Motion corrected reordered cine reconstructions (127 slices) showed improved image quality relative to both uncorrected cines and corresponding real-time images across a range of root-mean-squared (RMS) displacements (0.3-3.7 mm) and fetal heart rates (119-176 bpm). The relative spatial blur between cines with and without motion correction increased with in-plane RMS displacement leading to an effective decrease in the effective spatial resolution for images without motion correction. Image error between undersampled and reference images was less than 10% for reconstructions using 750 or more spokes, yielding a minimum acceptable scan time of approximately 4 s/slice during quiescent through plane motion., Conclusions: By rejecting data corrupted by through-plane motion, and correcting data corrupted by in-plane translation, the proposed reconstruction framework accounts for common sources of motion artifact (gross fetal movement, maternal respiration, fetal cardiac contraction) to produce high quality images of the fetal heart.

Background: Unfavorable left ventricular (LV) remodelling may be associated with adverse outcomes after Tetralogy of Fallot (TOF) repair. We sought to assess T1 cardiovascular magnetic resonance (CMR) markers of diffuse LV myocardial fibrosis in children after TOF repair, and associated factors., Methods: In this prospective, cross-sectional study, native (=non-contrast) T1 times and extracellular volume fraction (ECV) were quantified in the LV myocardium using CMR. Results were related to ventricular volumes and function, degree of pulmonary regurgitation, as well as surgical characteristics, and exercise capacity., Results: There was no difference in native T1 times or ECV between 31 TOF patients (age at CMR 13.9 ± 2.4 years, 19 male) and 15 controls (age at CMR 13.4 ± 2.6 years, 7 male). Female TOF patients had higher ECVs than males (25.2 ± 2.9 % versus 22.7 ± 3.3 %, p < 0.05). In the patient group, higher native T1 and ECV correlated with higher Z-Scores of right and left ventricular end-diastolic volumes, but not with reduced left and right ventricular ejection fraction or higher pulmonary regurgitation fraction. Longer cardiopulmonary bypass and aortic cross clamp times at surgery correlated with increased native T1 times and ECVs (r = 0.48, p < 0.05 and r = 0.65, p < 0.01, respectively). Maximum workload (percent of predicted for normal) correlated inversely with ECV (r = -0.62, p < 0.05). Higher native T1 times correlated with worse LV longitudinal (r = 0.50, p < 0.05) and mid short axis circumferential strain (r = 0.38, p < 0.05)., Conclusions: As compared to controls, TOF patients did not express higher markers of diffuse fibrosis. Longer cardiopulmonary bypass and aortic cross clamp times at surgery as well as biventricular enlargement and reduced exercise tolerance are associated with markers of diffuse myocardial fibrosis after TOF repair. Female patients have higher markers of diffuse myocardial fibrosis than males.

Background: Phase contrast cardiovascular magnetic resonance (PC CMR) has emerged as a clinical tool for blood flow quantification but its use in the foetus has been hampered by the need for gating with the foetal heart beat. The previously described metric optimized gating (MOG) technique has been successfully used to measure foetal blood flow in late gestation foetuses on a 1.5 T CMR magnet. However, there is increasing interest in performing foetal cardiac imaging using 3.0 T CMR. We describe our pilot investigation of foetal blood flow measured using 3.0 T CMR., Methods: Foetal blood flows were quantified in 5 subjects at late gestational age (35-38 weeks). Three were normal pregnancies and two were pregnancies with ventricular size discrepancy. Data were obtained at 1.5 T and 3.0 T using a previously described PC CMR protocol. After reconstruction using MOG, blood flow was quantified independently by two observers. Intra- and inter-observer reproducibility of flow measurements at the two field strengths was assessed by Pearson correlation coefficient (R(2)), linear regression and Bland Altman analysis., Results: PC CMR flow measurements were obtained in 36 of 40 target vessels. Strong intra-observer agreement was obtained between measurements at each field strength (R(2) = 0.78, slope = 0.83 ± 0.11), with a mean bias of -1 ml/min/kg and 95% confidence limits of ±71 ml/min/kg. Inter-observer agreement was similarly high for measurements at both 1.5 T (R(2) = 0.86, slope = 0.95 ± 0.13, bias = 6 ± 52 ml/min/kg) and 3.0 T (R(2) = 0.88, slope = 0.94 ± 0.13, bias = 4 ± 47 ml/min/kg). Across all PC CMR measurements, SNR per pixel was expectedly higher at 3.0 T relative to 1.5 T (165 ± 50%). The relative differences in flow measurements between observers were low (range: 4-16%) except for pulmonary blood flow which showed much higher variability at 1.5 T (34%) versus that at 3.0 T (11%). This was attributed to the poorly visualized, small pulmonary vessels at 1.5 T, which made delineation inconsistent between observers., Conclusions: This is the first pilot study to measure foetal blood flow using PC CMR at 3.0 T. The flow data obtained were in good correlation with those measured at 1.5 T, both within and between observers. With increased SNR at 3.0 T, smaller pulmonary vessels were better visualized which improved inter-observer agreement of associated flows.

Congenital heart diseases causing significant hemodynamic and functional consequences require surgical repair. Understanding of the precise surgical anatomy is often challenging and can be inadequate or wrong. Modern high resolution imaging techniques and 3D printing technology allow 3D printing of the replicas of the patient's heart for precise understanding of the complex anatomy, hands-on simulation of surgical and interventional procedures, and morphology teaching of the medical professionals and patients. CT or MR images obtained with ECG-gating and breath-holding or respiration navigation are best suited for 3D printing. 3D echocardiograms are not ideal but can be used for printing limited areas of interest such as cardiac valves and ventricular septum. Although the print materials still require optimization for representation of cardiovascular tissues and valves, the surgeons find the models suitable for practicing closure of the septal defects, application of the baffles within the ventricles, reconstructing the aortic arch, and arterial switch procedure. Hands-on surgical training (HOST) on models may soon become a mandatory component of congenital heart disease surgery program. 3D printing will expand its utilization with further improvement of the use of echocardiographic data and image fusion algorithm across multiple imaging modalities and development of new printing materials. Bioprinting of implants such as stents, patches and artificial valves and tissue engineering of a part of or whole heart using the patient's own cells will open the door to a new era of personalized medicine.

Introduction: We previously demonstrated that a single-chain fragment variable (scFv) specific to collagen type II (CII) posttranslationally modified by reactive oxygen species (ROS) can be used to target anti-inflammatory therapeutics specifically to inflamed arthritic joints. The objective of the present study was to demonstrate the superior efficacy of anti-inflammatory cytokines when targeted to inflamed arthritic joints by the anti-ROS modified CII (anti-ROS-CII) scFv in a mouse model of arthritis., Methods: Viral interleukin-10 (vIL-10) was fused to anti-ROS-CII scFv (1-11E) with a matrix-metalloproteinase (MMP) cleavable linker to create 1-11E/vIL-10 fusion. Binding of 1-11E/vIL-10 to ROS-CII was determined by enzyme-linked immunosorbent assay (ELISA), Western blotting, and immune-staining of arthritic cartilage, whereas vIL-10 bioactivity was evaluated in vitro by using an MC-9 cell-proliferation assay. Specific in vivo localization and therapeutic efficacy of 1-11E/vIL-10 was tested in the mouse model of antigen-induced arthritis., Results: 1-11E/vIL-10 bound specifically to ROS-CII and to damaged arthritic cartilage. Interestingly, the in vitro vIL-10 activity in the fusion protein was observed only after cleavage with MMP-1. When systemically administered to arthritic mice, 1-11E/vIL-10 localized specifically to the arthritic knee, with peak accumulation observed after 3 days. Moreover, 1-11E/vIL-10 reduced inflammation significantly quicker than vIL-10 fused to the control anti-hen egg lysozyme scFv (C7/vIL10)., Conclusions: Targeted delivery of anti-inflammatory cytokines potentiates their anti-arthritic action in a mouse model of arthritis. Our results further support the hypothesis that targeting biotherapeutics to arthritic joints may be extended to include anti-inflammatory cytokines that lack efficacy when administered systemically.

Background: The distribution of blood flow in fetuses with congenital heart disease (CHD) is likely to influence fetal growth, organ development, and postnatal outcome, but has previously been difficult to study. We present the first measurements of the distribution of the fetal circulation in left-sided CHD made using phase contrast cardiac magnetic resonance (CMR)., Methods: Twenty-two fetuses with suspected left-sided CHD and twelve normal controls underwent fetal CMR and echocardiography at a mean of 35 weeks gestation (range 30-39 weeks)., Results: Fetuses with left-sided CHD had a mean combined ventricular output 19% lower than normal controls (p < 0.01). In fetuses with left-sided CHD with pulmonary venous obstruction, pulmonary blood flow was significantly lower than in those with left-sided CHD without pulmonary venous obstruction (p < 0.01). All three fetuses with pulmonary venous obstruction had pulmonary lymphangectasia by fetal CMR and postnatal histology. Fetuses with small but apex forming left ventricles with left ventricular outflow tract or aortic arch obstruction had reduced ascending aortic and foramen ovale flow compared with normals (p < 0.01). Fetuses with left-sided CHD had more variable superior vena caval flows than normal controls (p < 0.05). Six fetuses with CHD had brain weights at or below the 5th centile for gestational age, while none of the fetuses in the normal control group had brain weights below the 25th centile., Conclusions: Measurement of the distribution of the fetal circulation in late gestation left-sided CHD is feasible with CMR. We demonstrated links between fetal blood flow distribution and postnatal course, and examined the relationship between fetal hemodynamics and lung and brain development. CMR enhances our understanding of pathophysiology of the fetal circulation and, with more experience, may help with the planning of perinatal management and fetal counselling.

Background: We present the first phase contrast (PC) cardiovascular magnetic resonance (CMR) measurements of the distribution of blood flow in twelve late gestation human fetuses. These were obtained using a retrospective gating technique known as metric optimised gating (MOG)., Methods: A validation experiment was performed in five adult volunteers where conventional cardiac gating was compared with MOG. Linear regression and Bland Altman plots were used to compare MOG with the gold standard of conventional gating. Measurements using MOG were then made in twelve normal fetuses at a median gestational age of 37 weeks (range 30-39 weeks). Flow was measured in the major fetal vessels and indexed to the fetal weight., Results: There was good correlation between the conventional gated and MOG measurements in the adult validation experiment (R=0.96). Mean flows in ml/min/kg with standard deviations in the major fetal vessels were as follows: combined ventricular output (CVO) 540 ± 101, main pulmonary artery (MPA) 327 ± 68, ascending aorta (AAo) 198 ± 38, superior vena cava (SVC) 147 ± 46, ductus arteriosus (DA) 220 ± 39,pulmonary blood flow (PBF) 106 ± 59,descending aorta (DAo) 273 ± 85, umbilical vein (UV) 160 ± 62, foramen ovale (FO)107 ± 54. Results expressed as mean percentages of the CVO with standard deviations were as follows: MPA 60 ± 4, AAo37 ± 4, SVC 28 ± 7, DA 41 ± 8, PBF 19 ± 10, DAo50 ± 12, UV 30 ± 9, FO 21 ± 12., Conclusion: This study demonstrates how PC CMR with MOG is a feasible technique for measuring the distribution of the normal human fetal circulation in late pregnancy. Our preliminary results are in keeping with findings from previous experimental work in fetal lambs.