Advanced magnetic resonance imaging in human placenta: insights into fetal growth restriction and congenital heart disease.

Placental function plays a crucial role in fetal development, as it serves as the primary interface for delivery of nutrients and oxygen from the mother to fetus. Magnetic resonance imaging (MRI) has significantly improved our ability to visualize and understand the placenta's complex structure and function. This review provides an up-to-date examination of the most common and novel placental MRI techniques. It will also discuss the clinical applications of MRI in diagnosing and monitoring placental insufficiency, as well as its implications for fetal growth restriction (FGR) and congenital heart disease (CHD). Ongoing research using multi-parametric MRI techniques aims to develop novel biomarkers and uncover the relationships between placental parameters and pre-onset diseased states, ultimately contributing to better maternal and fetal health outcomes, which is essential to better guide clinical judgement.

Acute-on-chronic: using magnetic resonance imaging to disentangle the haemodynamic responses to acute and chronic fetal hypoxaemia.

Introduction: The fetal haemodynamic response to acute episodes of hypoxaemia are well characterised. However, how these responses change when the hypoxaemia becomes more chronic in nature such as that associated with fetal growth restriction (FGR), is less well understood. Herein, we utilised a combination of clinically relevant MRI techniques to comprehensively characterize and differentiate the haemodynamic responses occurring during acute and chronic periods of fetal hypoxaemia. Methods: Prior to conception, carunclectomy surgery was performed on non-pregnant ewes to induce FGR. At 108-110 days (d) gestational age (GA), pregnant ewes bearing control (n = 12) and FGR (n = 9) fetuses underwent fetal catheterisation surgery. At 117-119 days GA, ewes underwent MRI sessions where phase-contrast (PC) and T2 oximetry were used to measure blood flow and oxygenation, respectively, throughout the fetal circulation during a normoxia and then an acute hypoxia state. Results: Fetal oxygen delivery (DO2) was lower in FGR fetuses than controls during the normoxia state but cerebral DO2 remained similar between fetal groups. Acute hypoxia reduced both overall fetal and cerebral DO2. FGR increased ductus venosus (DV) and foramen ovale (FO) blood flow during both the normoxia and acute hypoxia states. Pulmonary blood flow (PBF) was lower in FGR fetuses during the normoxia state but similar to controls during the acute hypoxia state when PBF in controls was decreased. Conclusion: Despite a prevailing level of chronic hypoxaemia, the FGR fetus upregulates the preferential streaming of oxygen-rich blood via the DV-FO pathway to maintain cerebral DO2. However, this upregulation is unable to maintain cerebral DO2 during further exposure to an acute episode of hypoxaemia. The haemodynamic alterations required at the level of the liver and lung to allow the DV-FO pathway to maintain cerebral DO2, may have lasting consequences on hepatic function and pulmonary vascular regulation after birth.

Post-Myocardial Infarction Remodeling and Hyperkinetic Remote Myocardium in Sheep Measured by Cardiac MRI Feature Tracking.

BACKGROUND: Cardiac MRI feature tracking (FT) allows objective assessment of segmental left ventricular (LV) function following a myocardial infarction (MI), but its utilization in sheep, where interventions can be tested, is lacking. PURPOSE: To apply and validate FT in a sheep model of MI and describe post-MI LV remodeling. STUDY TYPE: Animal model, longitudinal. ANIMAL MODEL: Eighteen lambs (6 months, male, n = 14; female, n = 4; 25.2 ± 4.5 kg). FIELD STRENGTH/SEQUENCE: Two-dimensional balanced steady-state free precession (bSSFP) and 3D inversion recovery fast low angle shot (IR-FLASH) sequences at 3 T. ASSESSMENT: Seven lambs underwent test-retest imaging to assess FT interstudy reproducibility. MI was induced in the remaining 11 by coronary ligation with MRI being undertaken before and 15 days post-MI. Injury size was measured by late gadolinium enhancement (LGE) and LV volumes, LV mass, ejection fraction (LVEF), and wall thickness (LVWT) were measured, with FT measures of global and segmental radial, circumferential, and longitudinal strain. STATISTICAL TESTS: Sampling variability, inter-study, intra and interobserver reproducibility were assessed using Pearson's correlation, Bland-Altman analyses, and intra-class correlation coefficients (ICC). Diagnostic performance of segmental strain to predict LGE was assessed using receiver operating characteristic curve analysis. Significant differences were considered P < 0.05. RESULTS: Inter-study reproducibility of FT was overall good to excellent, with global strain being more reproducible than segmental strain (ICC = 0.89-0.98 vs. 0.77-0.96). MI (4.0 ± 3.7% LV mass) led to LV remodeling, as evident by significantly increased LV volumes and LV mass, and significantly decreased LVWT in injured regions, while LVEF was preserved (54.9 ± 6.9% vs. 55.6 ± 5.7%; P = 0.778). Segmental circumferential strain (CS) correlated most strongly with LGE. Basal and mid- CS increased significantly, while apical CS significantly decreased post-MI. DATA CONCLUSION: FT is reproducible and compensation by hyperkinetic remote myocardium may manifest as overall preserved global LV function. EVIDENCE LEVEL: N/A TECHNICAL EFFICACY: Stage 2.

Fetal Cardiovascular MR Imaging.

Prenatal diagnosis of congenital heart disease allows for appropriate planning of delivery and an opportunity to inform families about the prognosis of the cardiac malformation. On occasion, prenatal therapies may be offered to improve perinatal outcomes. While ultrasound is the primary diagnostic method, advances have led to interest in fetal MRI for its potential to aid in clinical decision-making. This review explores technical innovations and the clinical utility of fetal cardiovascular magnetic resonance (CMR), highlighting its role in diagnosing and planning interventions for complex heart conditions. Future directions include the prediction of perinatal physiology and guidance of delivery planning.

Surgical Melody Mitral Valve: A Paradigm Shift for Infants With Unrepairable Mitral Valve Disease.

BACKGROUND: The Melody valve (Medtronic, Minneapolis, MN) for mitral valve replacement (MVR) (MelodyMVR) has been an effective strategy to treat unrepairable mitral valve disease in small children. This study analyzed survival, durability, and complications of the MelodyMVR strategy. METHODS: Patients who underwent MelodyMVR between 2014 and 2023 were included. Transplant-free survival was analyzed with Kaplan-Meier analysis. The Fine and Gray subdistribution method was applied to quantify the cumulative incidence. RESULTS: Twenty-five patients underwent MelodyMVR. Median age and weight were 6.3 months (interquartile range, 4.4-15.2 months) and 6.36 kg (interquartile range, 4.41-7.57 kg). Fifteen patients (60%) had congenital mitral valve disease and 13 (52%) had dominant mitral regurgitation. The median diameter of the implanted Melody was 16 mm (interquartile range, 14-18 mm). Mortality at 6 months, 1 year, and 5 years was 8.3% (95% CI, 2.2%-29.4%), 12.5% (95% CI, 4.2%-33.9%), and 17.6% (95% CI, 7.0%-40.7%), respectively. Two hospital survivors (8%) required early Melody replacement. Competing risk analysis showed that ∼50% of patients underwent mechanical MVR by 3.5 years after MelodyMVR. Freedom from bleeding and thrombosis at 4 years was 87.5% (95% CI, 74.2%-100%). Eleven patients underwent subsequent mechanical MVR with no deaths. One (9%) required pacemaker implantation after mechanical MVR. CONCLUSIONS: MelodyMVR provides reasonable early and medium-term survival in small children and a high rate of successful bridge to mechanical MVR. MelodyMVR is associated with minimal pacemaker requirement, bleeding, and thrombosis. Early Melody functional deterioration necessitates early repeat MVR, which can be achieved with minimal morbidity and mortality.

Echocardiographic assessment of cardiovascular physiology of preterm miniature piglets supported with a pumped artificial placenta system.

OBJECTIVES: We evaluated fetal cardiovascular physiology and mode of cardiac failure in premature miniature piglets on a pumped artificial placenta (AP) circuit. METHODS: Fetal pigs were cannulated via the umbilical vessels and transitioned to an AP circuit composed of a centrifugal pump and neonatal oxygenator and maintained in a fluid-filled biobag. Echocardiographic studies were conducted to measure ventricular function, umbilical blood flow, and fluid status. In utero scans were used as control data. RESULTS: AP fetuses (n = 13; 102±4d gestational age [term 115d]; 616 ± 139 g [g]; survival 46.4 ± 46.8 h) were tachycardic and hypertensive with initially supraphysiologic circuit flows. Increased myocardial wall thickness was observed. Signs of fetal hydrops were present in all piglets. Global longitudinal strain (GLS) measurements increased in the left ventricle (LV) after transition to the circuit. Right ventricle (RV) and LV strain rate decreased early during AP support compared with in utero measurements but recovered toward the end of the experiment. Fetuses supported for >24 h had similar RV GLS to in utero controls and significantly higher GLS compared to piglets surviving only up to 24 h. CONCLUSIONS: Fetuses on a pump-supported AP circuit experienced an increase in afterload, and redistribution of blood flow between the AP and systemic circulations, associated with elevated end-diastolic filling pressures. This resulted in heart failure and hydrops. These preterm fetuses were unable to tolerate the hemodynamic changes associated with connection to the current AP circuit. To better mimic the physiology of the native placenta and preserve normal fetal cardiovascular physiology, further optimization of the circuit will be required.

Maternal tadalafil treatment does not increase uterine artery blood flow or oxygen delivery in the pregnant ewe.

Increasing placental perfusion (PP) could improve outcomes of growth-restricted fetuses. One way of increasing PP may be by using phosphodiesterase (PDE)-5 inhibitors, which induce vasodilatation of vascular beds. We used a combination of clinically relevant magnetic resonance imaging (MRI) techniques to characterize the impact that tadalafil infusion has on maternal, placental and fetal circulations. At 116-117 days' gestational age (dGA; term, 150 days), pregnant ewes (n = 6) underwent fetal catheterization surgery. At 120-123 dGA ewes were anaesthetized and MRI scans were performed during three acquisition windows: a basal state and then ∼15-75 min (TAD 1) and ∼75-135 min (TAD 2) post maternal administration (24 mg; intravenous bolus) of tadalafil. Phase contrast MRI and T2 oximetry were used to measure blood flow and oxygen delivery. Placental diffusion and PP were assessed using the Diffusion-Relaxation Combined Imaging for Detailed Placental Evaluation-'DECIDE' technique. Uterine artery (UtA) blood flow when normalized to maternal left ventricular cardiac output (LVCO) was reduced in both TAD periods. DECIDE imaging found no impact of tadalafil on placental diffusivity or fetoplacental blood volume fraction. Maternal-placental blood volume fraction was increased in the TAD 2 period. Fetal D O 2 ${D_{{{\mathrm{O}}_2}}}$ and V ̇ O 2 ${\dot V_{{{\mathrm{O}}_2}}}$ were not affected by maternal tadalafil administration. Maternal tadalafil administration did not increase UtA blood flow and thus may not be an effective vasodilator at the level of the UtAs. The increased maternal-placental blood volume fraction may indicate local vasodilatation of the maternal intervillous space, which may have compensated for the reduced proportion of UtA D O 2 ${D_{{{\mathrm{O}}_2}}}$ .

Recent advances in multimodal imaging in tetralogy of fallot and double outlet right ventricle.

PURPOSE OF REVIEW: In the ever-evolving field of medical imaging, this review highlights significant advancements in preoperative and postoperative imaging for Tetralogy of Fallot (TOF) and double outlet right ventricle (DORV) over the past 18 months. RECENT FINDINGS: This review showcases innovations in echocardiography such as 3D speckle tracking echocardiography (3DSTE) for assessing right ventricle-pulmonary artery coupling (RVPAC) and Doppler velocity reconstruction (DoVeR) for intracardiac flow fields evaluation. Furthermore, advances in assessment of cardiovascular anatomy using computed tomography (CT) improve the integration of imaging in ablation procedures. Additionally, the inclusion of cardiac magnetic resonance (CMR) parameters as risk score predictors for morbidity, and mortality and for timing of pulmonary valve replacement (PVR) indicates its significance in clinical management. The utilization of 4D flow techniques for postoperative hemodynamic assessment promises new insights into pressure mapping. Lastly, emerging technologies such as 3D printing and 3D virtual reality are expected to improve image quality and surgical confidence in preoperative planning. SUMMARY: Developments in multimodality imaging in TOF and DORV are poised to shape the future of clinical practice in this field.

Fetal Hemodynamics, Early Survival, and Neurodevelopment in Patients With Cyanotic Congenital Heart Disease.

BACKGROUND: Fetuses with cyanotic congenital heart disease (CHD) exhibit profound fetal circulatory disturbances that may affect early outcomes. OBJECTIVES: This study sought to investigate the relationship between fetal hemodynamics and early survival and neurodevelopmental (ND) outcomes in patients with cyanotic CHD. METHODS: In this longitudinal observational study, fetuses with cyanotic CHD underwent late gestational fetal cardiovascular magnetic resonance (CMR) to measure vessel blood flow and oxygen content. Superior vena cava (SVC) flow was used as a proxy for cerebral blood flow. Primary outcomes were 18-month mortality and Bayley Scales of Infant Development-III assessment. RESULTS: A total of 144 fetuses with cyanotic CHD were assessed. By 18 months, 18 patients (12.5%) died. Early mortality was associated with reduced combined ventricular output (P = 0.01), descending aortic flow (P = 0.04), and umbilical vein flow (P = 0.03). Of the surviving patients, 71 had ND outcomes assessed. Cerebral oxygen delivery was the fetal hemodynamic variable most strongly associated with cognitive, language, and motor outcomes (P < 0.05). Fetal SVC flow was also associated with cognitive, language, and motor outcomes (P < 0.01), and it remained an independent predictor of cognitive (P = 0.002) and language (P = 0.04) outcomes after adjusting for diagnosis. Diminished SVC flow also performed better than other fetal CMR and echocardiographic predictors of cognitive ND delay (receiver-operating characteristic curve area: 0.85; SE 0.05). CONCLUSIONS: Among fetuses with cyanotic CHD, diminished fetal combined ventricular output is associated with mortality, whereas cerebral blood flow and oxygen delivery are associated with early cognitive, language, and motor development at 18 months of age. These results support the inclusion of fetal CMR to help identify patients at risk of adverse ND outcomes.

Pulmonary Vascular Regulation in the Fetal and Transitional Lung.

Fetal lungs have fewer and smaller arteries with higher pulmonary vascular resistance (PVR) than a newborn. As gestation advances, the pulmonary circulation becomes more sensitive to changes in pulmonary arterial oxygen tension, which prepares them for the dramatic drop in PVR and increase in pulmonary blood flow (PBF) that occur when the baby takes its first few breaths of air, thus driving the transition from fetal to postnatal circulation. Dynamic and intricate regulatory mechanisms control PBF throughout development and are essential in supporting gas exchange after birth. Understanding these concepts is crucial given the role the pulmonary vasculature plays in the development of complications with transition, such as in the setting of persistent pulmonary hypertension of the newborn and congenital heart disease. An improved understanding of pulmonary vascular regulation may reveal opportunities for better clinical management.

Antenatal diagnosis, neonatal brain volumes, and neurodevelopment in transposition of the great arteries.

AIM: To examine whether antenatal diagnosis modifies relationships between neonatal brain volumes and 18-month neurodevelopmental outcomes in children with transposition of the great arteries (TGA). METHOD: In a retrospective cohort of 139 children with TGA (77 antenatally diagnosed), we obtained total brain volumes (TBVs) on pre- (n = 102) and postoperative (n = 112) magnetic resonance imaging. Eighteen-month neurodevelopmental outcomes were assessed using the Bayley Scales of Infant and Toddler Development, Third Edition. Generalized estimating equations with interaction terms were used to determine whether antenatal diagnosis modified associations between TBVs and neurodevelopmental outcomes accounting for postmenstrual age at scan, brain injury, and ventricular septal defect. RESULTS: Infants with postnatal diagnosis had more preoperative hypotension (35% vs 14%, p = 0.004). The interactions between antenatal diagnosis and TBVs were significantly related to cognitive (p = 0.003) outcomes. Specifically, smaller TBVs were associated with lower cognitive scores in infants diagnosed postnatally; this association was attenuated in those diagnosed antenatally. INTERPRETATION: Antenatal diagnosis modifies associations between neonatal brain volume and 18-month cognitive outcome in infants with TGA. These findings suggest that antenatal diagnosis may be neuroprotective, possibly through improved preoperative clinical status. These data highlight the need to improve antenatal diagnosis rates. WHAT THIS PAPER ADDS: Antenatal diagnosis of transposition of the great arteries modified relationships between neonatal brain volume and neurodevelopment. Smaller brain volumes related to poorer cognitive scores with postnatal diagnosis only. There was more preoperative hypotension in the postnatal diagnosis group.

Biventricular Repair in Borderline Left Hearts: Insights From Cardiac Magnetic Resonance Imaging.

Background: Cardiac magnetic resonance imaging (CMR) may augment 2-dimensional (2D) echocardiography in decision-making for biventricular repair in borderline hypoplastic left hearts. Objectives: This study evaluates: 1) the relationship between 2D echocardiography and CMR; 2) imaging variables affecting assignment to biventricular vs non-biventricular management; and 3) variables affecting transplant-free biventricular survival. Methods: We reviewed clinical, echocardiographic, and CMR data in 67 infants, including CMR-determined ascending aortic (AAo) flow and comparable left ventricular end-diastolic volume indexed (LVEDVi) by 2D-echocardiography and CMR. Results: Treatment assignment to biventricular repair was either direct (BV, n = 45) or with a bridging hybrid procedure (H1-BV, n = 12). Echocardiographic LVEDVi was <20 mL/m2 in 83% of biventricular repair infants and underestimated CMR-LVEDVi by 16.8 mL/m2. AAo flows had no/weak correlation with aortic and mitral valve z-scores or LVEDVi. AAo flows differed between BV, H1-BV, and single-ventricle groups (median): 2.1, 1.7, and 0.7 L/min/m2, respectively. Important variables for treatment assignment were presence of endocardial fibroelastosis, AAo flow, and mitral valve z-score. Biventricular repair was achieved in 54. The median follow-up was 8.0 (0.1-16.4) years. Transplant-free biventricular survival was 96%, 82%, and 77% at 1, 5, and 10 years, respectively. Patients without aortic coarctation repair were at higher risk of death, transplantation, or single-ventricle conversion (HR: 54.3; 95% CI: 6.3-47.1; P < 0.001) during follow-up. AAo flow had a smaller nonlinear effect with hazard ratio increasing at lower flows. Conclusions: Historical 2D echocardiographic criteria would have precluded many patients from successful biventricular repair. AAo flow, an integrative index of left heart performance, was important in assigning patients to a biventricular circulation and affected survival. Biventricular survival was strongly associated with the need for aortic coarctation repair.