Fetal development relies on a complex circulatory network and accurately assessing the flow distr... more Fetal development relies on a complex circulatory network and accurately assessing the flow distribution is important for understanding pathologies and potential therapies. In this paper, we demonstrate a method for volumetric multidimensional imaging of fetal flow with magnetic resonance imaging (MRI). Fetal application of MRI faces several challenges such as small vascular structures, unpredictable motion, and lack of traditional cardiac gating methods. Here, orthogonal multislice stacks are acquired with accelerated multidimensional radial phase contrast (PC) MRI. Each slice is reconstructed into flow sensitive time-series images (CINEs) with retrospective intraslice motion correction and image-based fetal cardiac gating. CINEs are then combined into a dynamic 3D volume using slice-to-volume reconstruction (SVR) while accounting for interslice spatiotemporal coregistration. Validation of the technique is demonstrated in adult volunteers by comparing mean flows from SVR with 4D ra...
Background: Recent advances in cardiovascular magnetic resonance (CMR) imaging have facilitated C... more Background: Recent advances in cardiovascular magnetic resonance (CMR) imaging have facilitated CINE imaging of the fetal heart. In this work, a preliminary investigation of the utility of multislice CINE CMR for assessing fetal congenital heart disease is performed and compared with echocardiography. Methods and Results: Multislice CINE CMR and echocardiography images were acquired in 25 pregnant women wherein the fetus had a suspected congenital heart defect based on routine obstetric ultrasound. Pathognomonic images were identified for each subject for qualitative comparison of CMR and echocardiography. Quantitative comparison of CMR and echocardiography was then performed by 2 reviewers using a binary scoring of 9 fetal cardiac anatomic features (identifiable/not-identifiable). Pathognomonic images demonstrated the ability of CMR to visualize a variety of congenital heart defects. Overall CMR was able to identify the majority of the 9 assessed fetal cardiac anatomic features (re...
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2017
Hypoxic stress is a common occurrence during human pregnancy, yet little is known about its effec... more Hypoxic stress is a common occurrence during human pregnancy, yet little is known about its effects on the fetal brain. This study examined the fetal hemodynamic responses to chronic hypoxia in an experimental mouse model of chronic maternal hypoxia (11% O from E14.5 to E17.5). Using high-frequency Doppler ultrasound, we found fetal cerebral and ductus venosus blood flow were both elevated by 69% and pulmonary blood flow was decreased by 62% in the fetuses exposed to chronic hypoxia compared to controls. This demonstrates that brain sparing persists during chronic fetal hypoxia and is mediated by "streaming," where highly oxygenated blood preferentially flows through the ductus venosus towards the cerebral circulation, bypassing the liver and the lungs. Consistent with these changes in blood flow, the fetal brain volume measured by MRI is preserved, while the liver and lung volumes decreased compared to controls. However, hypoxia exposed fetuses were rendered vulnerable to...
Until recently, our modern understanding of fetal circulatory physiology has been largely based o... more Until recently, our modern understanding of fetal circulatory physiology has been largely based on invasive measurements made in fetal sheep. However, new MRI technology developed by our group has provided equivalent information about the distribution of blood flow and oxygen transport noninvasively. The initial findings largely confirm prior estimates about the human fetal circulation extrapolated from fetal sheep data and human ultrasound data. Here we describe the hemodynamics of the normal late gestation human fetal circulation by MRI and speculate about what the advent of this technology might mean in terms of the management of fetuses affected by placental insufficiency and congenital heart disease.
American journal of physiology. Regulatory, integrative and comparative physiology, Jan 13, 2017
Phase-contrast cine MRI (PC-MRI) is the gold-standard non-invasive technique for measuring vessel... more Phase-contrast cine MRI (PC-MRI) is the gold-standard non-invasive technique for measuring vessel blood flow and has previously been applied in the human fetal circulation. We aimed to assess the feasibility of using PC-MRI to define the distribution of the fetal circulation in sheep. Fetuses were catheterized at 119-120 days gestation (term, 150 days) and underwent MRI at 123 days gestation under isoflurane anesthesia, ventilated at a FiO of 1.0. PC-MRI was performed using a fetal arterial blood pressure catheter signal for cardiac triggering. Blood flows were measured in the major fetal vessels, including the main pulmonary artery, ascending and descending aorta, superior vena cava, ductus arteriosus, left and right pulmonary arteries, umbilical vein, ductus venosus, and common carotid artery; and were indexed to estimated fetal weight. The combined ventricular output, pulmonary blood flow and flow across the foramen ovale were calculated from vessel flows. Intra-observer, inter-o...
Two different surgical techniques are used to repair anomalous pulmonary venous connection or pul... more Two different surgical techniques are used to repair anomalous pulmonary venous connection or pulmonary vein (PV) stenosis: the classic repair (CR) and the sutureless repair (SR). The purpose of this study was to compare the prevalence of PV stenosis between the two surgical approaches. Patients were prospectively recruited irrespective of symptoms or previous imaging findings. Cardiac magnetic resonance imaging and echocardiography were performed in a blinded fashion on the same day. Twenty-five patients (13 male) after PV repair completed the study. Twelve patients had undergone CR and 13 SR (in 1 patient as a reoperation after CR). The median age at operation was 2 months (range: 1 day to 5 years) and was similar for both groups; the median age at the time of cardiac magnetic resonance was 9 years (range: 6 to 17 years) and 9 years (range: 6 to 14 years) for the CR and SR, respectively. Four patients had PV stenosis. All 4 patients had had total anomalous pulmonary venous connect...
European heart journal cardiovascular Imaging, Jan 25, 2018
The objective of this study was to quantify imaging markers of myocardial fibrosis and assess myo... more The objective of this study was to quantify imaging markers of myocardial fibrosis and assess myocardial function in long-term transposition of the great arteries survivors after the arterial switch operation (ASO). Paediatric ASO patients were prospectively studied by cardiac magnetic resonance imaging, including first-pass myocardial perfusion, late gadolinium enhancement, and T1 relaxometry, as well as echocardiography for left ventricular (LV) systolic and diastolic function including strain analysis, with comparison to healthy controls. Thirty ASO patients (mean age 15.4 ± 2.9 years vs. 14.1 ± 2.6 years in 28 controls, P = 0.04) were included. Patients had normal LV ejection fraction (EF) (57 ± 5% vs. 59 ± 5%, P = 0.07), but end-diastolic and end-systolic volumes were increased (104 ± 20 mL/m2 vs. 89 ± 10 mL/m2, P < 0.01 and 46 ± 13 mL/m2 vs. 36 ± 7 mL/m2, P < 0.01, respectively). Longitudinal strain at two-, three-, and four-chamber levels of the LV were lower in ASO pat...
Congenital heart diseases causing significant hemodynamic and functional consequences require sur... more 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.
To characterize the magnetic susceptibility and relaxation times (T1 and T2 ) of fetal blood at 3... more To characterize the magnetic susceptibility and relaxation times (T1 and T2 ) of fetal blood at 3 T as a function of the hematocrit (Hct) and oxygen saturation (sO2 ). Susceptibility and relaxometry measurements were performed on cord blood specimens (N = 90, derived from six caesarean deliveries) with a range of hematocrits and oxygen saturations (0.09 < Hct < 0.82, 7 < sO2 < 100%). To obtain simple, analytic relationships between MRI properties and blood properties, data were fit to established two-compartment (plasma and erythrocytes) models. Two-compartment models effectively described the cord blood data. The root-mean-squared deviation between the model and the data was 6.3, 10.3, and 1.3% for fits to T1 , T2 , and susceptibility measurements. Relaxometry data and estimated T1 and T2 model parameters were generally consistent with those reported in cord blood at 1.5 T and comparable to published values for adult blood. Notably, the measured value of Δχdeo , the su...
American Journal of Obstetrics and Gynecology, 2017
How to cite TSpace items Always cite the published version, so the author(s) will receive recogni... more How to cite TSpace items Always cite the published version, so the author(s) will receive recognition through services that track citation counts, e.g. Scopus. If you need to cite the page number of the author manuscript from TSpace because you cannot access the published version, then cite the TSpace version in addition to the published version using the permanent URI (handle) found on the record page. This article was made openly accessible by U of T Faculty. Please tell us how this access benefits you. Your story matters.
Journal of Cardiovascular Magnetic Resonance, 2017
Background: Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging has... more 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 noninvasive 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.
Chronic fetal hypoxia is one of the most common complications of pregnancy and is known to cause ... more Chronic fetal hypoxia is one of the most common complications of pregnancy and is known to cause fetal growth restriction. r The structural adaptations of the placental vasculature responsible for growth restriction with chronic hypoxia are not well elucidated. r Using a mouse model of chronic maternal hypoxia in combination with micro-computed tomography and scanning electron microscopy, we found several placental adaptations that were beneficial to fetal growth including capillary expansion, thinning of the interhaemal membrane and increased radial artery diameters, resulting in a large drop in total utero-placental vascular resistance. r One of the mechanisms used to achieve the rapid increase in capillaries was intussusceptive angiogenesis, a strategy used in human placental development to form terminal gas-exchanging villi. r These results contribute to our understanding of the structural mechanisms of the placental vasculature responsible for fetal growth restriction and provide a baseline for understanding adaptive physiological responses of the placenta to chronic hypoxia.
Purpose To estimate reference ranges for blood flow volume (BFV) in major splanchnic, thoracoabdo... more Purpose To estimate reference ranges for blood flow volume (BFV) in major splanchnic, thoracoabdominal, and neck vessels by using phase-contrast magnetic resonance (MR) imaging in children and young adults in fasting and postprandial states. Materials and Methods In this institutional research ethics board-approved prospective study, healthy volunteers underwent phase-contrast MR imaging in a fasting state and again after a standardized meal. BFV values were reported as medians and ranges, and postmeal to premeal BFV ratios were calculated. BFVs in volunteers divided into two groups according to age (≤18 years old and >18 years old) were compared by using the Mann-Whitney test adjusted for multiple comparisons. Linear regression for internal validation of BFV and Pearson correlation and Bland-Altman analysis for interobserver agreement were used. Results Reference ranges for BFVs were estimated in 39 volunteers (23 male and 16 female; mean age, 21.2 years ± 8.5; range, 9-40 years...
Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance, Jan 26, 2016
Unfavorable left ventricular (LV) remodelling may be associated with adverse outcomes after Tetra... more 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. 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. 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,...
We propose an analytical method for calculating blood hematocrit (Hct) and oxygen saturation (sO2... more We propose an analytical method for calculating blood hematocrit (Hct) and oxygen saturation (sO2 ) from measurements of its T1 and T2 relaxation times. Through algebraic substitution, established two-compartment relationships describing R1=T1-1 and R2=T2-1 as a function of hematocrit and oxygen saturation were rearranged to solve for Hct and sO2 in terms of R1 and R2 . Resulting solutions for Hct and sO2 are the roots of cubic polynomials. Feasibility of the method was established by comparison of Hct and sO2 estimates obtained from relaxometry measurements (at 1.5 Tesla) in cord blood specimens to ground-truth values obtained by blood gas analysis. Monte Carlo simulations were also conducted to assess the effect of T1 , T2 measurement uncertainty on precision of Hct and sO2 estimates. Good agreement was observed between estimated and ground-truth blood properties (bias = 0.01; 95% limits of agreement = ±0.13 for Hct and sO2 ). Considering the combined effects of biological variabi...
Myocardial fibrosis is linked with adverse clinical outcomes in adults after tetralogy of Fallot ... more Myocardial fibrosis is linked with adverse clinical outcomes in adults after tetralogy of Fallot repair (rTOF). Native T1 times (T1) by cardiac magnetic resonance have been shown to be a surrogate marker of diffuse myocardial fibrosis. The objective was to quantify native T1 in children post-rTOF and to evaluate their relationship with surgical, imaging, and clinical factors. A retrospective cross-sectional study was performed. Midventricular native T1 were obtained in 100 children post-rTOF using a modified look-locker inversion recovery cardiac magnetic resonance sequence and compared with 35 pediatric controls. rTOF patients, aged 13.0±2.9 years, had higher indexed right ventricular (RV) end-diastolic (range 85-326 mL/m(2), mean 148 mL/m(2)) volumes, and lower RV and left ventricular (LV) ejection fractions compared with controls. RV, but not LV, T1 were higher in patients than in controls (1031±74 versus 954±32 ms, P<0.001) and female patients had higher RV T1 compared with m...
Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance, Jan 20, 2017
To develop and evaluate a reconstruction framework for high resolution time-resolved CMR of the f... more To develop and evaluate a reconstruction framework for high resolution time-resolved CMR of the fetal heart in the presence of motion. 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. 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 correct...
To develop and validate a method for accelerated time-resolved imaging of the fetal heart using a... more To develop and validate a method for accelerated time-resolved imaging of the fetal heart using a combination of compressed sensing (CS) and metric optimized gating (MOG). Joint optimization of CS and MOG reconstructions was used to suppress competing artifact from random undersampling and ungated cardiac motion. Retrospectively and prospectively undersampled adult and fetal data were used to validate the proposed reconstruction algorithm qualitatively based on visual assessment, and quantitatively based on reconstruction error, blur, and MOG timing error. Excellent agreement was observed between the fully sampled and retrospectively undersampled reconstructions, up to an undersampling factor of four. Visually, differences between ECG and MOG reconstructions of adult data were negligible. This was consistent with quantitative comparisons of reconstruction error (RMSEECG = 0.07-0.13; RMSEMOG = 0.08-0.13), and image blur (BECG = 1.03-1.20; BMOG = 1.03-1.20). The calculated MOG tim...
To characterize the MRI relaxation properties of human umbilical cord blood at 1.5 Tesla. Relaxom... more To characterize the MRI relaxation properties of human umbilical cord blood at 1.5 Tesla. Relaxometry measurements were performed on cord blood specimens (N = 88, derived from six caesarean deliveries) spanning a broad range of hematocrits (Hct = 0.19-0.76) and oxygen saturations (sO2 = 4-100%), to characterize the dependence of T1 and T2 on these blood properties. Adult blood data (N = 31 specimens, derived from two volunteers) were similarly studied to validate our experimental methods by comparison with existing literature. Using biophysical models previously developed for adult blood, new model parameters were estimated, which relate Hct and sO2 to the observed cord blood relaxation times. Fitted biophysical models explained more than 90% of the variation in T1 and T2 . In general, T2 relaxation times of cord blood were longer (by up to 35%) than those of adult blood, whereas T1 relaxation times were slightly shorter (by up to 10%). The models and fitted parameters presented her...
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