Assessing Aortic Motion with Automated 3D Cine Balanced SSFP MRI Segmentation.

PURPOSE: To apply free-running three-dimensional (3D) cine balanced steady state free precession (bSSFP) CMR framework in combination with AI segmentations to quantify time-resolved aortic displacement, diameter and diameter change. METHODS: In this prospective study, we implemented a free-running 3D cine bSSFP sequence with scan time of about 4minutes facilitated by pseudo-spiral Cartesian undersampling and compressed-sensing reconstruction. Automated segmentation of all cardiac timeframes was applied through the use of nnU-Net. Dynamic 3D motion maps were created for three repeated scans per volunteer, leading to the detailed quantification of motion, as well as the measurement and change in diameter of the ascending aorta. RESULTS: A total of 14 adult healthy volunteers (median age, 28 years (IQR: 26.0-31.3), 6 female) were included. Automated segmentation compared to manual segmentation of the aorta test set showed a Dice score of 0.93 ± 0.02. The median (interquartile range) over all volunteers for the largest maximum and mean ascending aorta (AAo) displacement in the first scan was 13.0 (4.4) mm and 5.6 (2.4) mm, respectively. Peak mean diameter in the AAo was 25.9 (2.2) mm and peak mean diameter change was 1.4 (0.5) mm. The maximum individual variability over the three repeated scans of maximum and mean AAo displacement was 3.9 (1.6) mm and 2.2 (0.8) mm, respectively. The maximum individual variability of mean diameter and diameter change were 1.2 (0.5) mm and 0.9 (0.4) mm. CONCLUSION: A free-running 3D cine bSSFP CMR scan with a scan time of four minutes combined with an automated nnU-net segmentation consistently captured the aorta's cardiac motion-related 4D displacement, diameter, and diameter change.

Effects of resveratrol on aortic growth in patients with Marfan syndrome: a single-arm open-label multicentre trial.

BACKGROUND: Resveratrol, a dietary supplement that intervenes in cellular metabolism, has been shown to reduce aortic growth rate in a mouse model of Marfan syndrome (MFS), a condition associated in humans with life-threatening aortic complications, often preceded by aortic dilatation. The primary objective of this study was to investigate the effects of resveratrol on aortic growth rate in patients with MFS . METHODS: In this investigator-initiated, single-arm open-label multicentre trial, we analysed resveratrol treatment in adults aged 18-50 years with MFS. The primary endpoint was the change in estimated annual aortic growth at five predefined levels in the thoracic aorta after 1 year of resveratrol treatment, evaluated using a linear mixed model. Aortic diameters were measured by cardiac MRI at three time points to analyse the annual aortic expansion rate before and after initiation of treatment. Additionally, annual aortic growth was compared with growth in a previously conducted losartan randomised clinical trial. RESULTS: 898 patients were screened of which 19% (168/898) patients met the inclusion criteria.36% (61/168) patients signed informed consent and 93% (57/61) aged 37±9 years, of which 28 males (49%) were included in the final analysis of the study. 46% (26/57) had undergone aortic root replacement prior to the study. Aortic root diameters remained stable after 1.2±0.3 years of resveratrol administration. A trend towards a decrease in estimated growth rate (mm/year) was observed in the aortic root (from 0.39±0.06 to -0.13±0.23, p=0.072), ascending aorta (from 0.40±0.05 to -0.01±0.18, p=0.072) and distal descending aorta (from 0.32±0.04 to 0.01±0.14, p=0.072). CONCLUSION: Resveratrol treatment for 1 year may stabilise the aortic growth rate in adult patients with MFS. However, a subsequent randomised clinical trial with a longer follow-up duration and a larger study cohort is needed to establish an actual long-term beneficial effect of this dietary supplement in patients with MFS. TRIAL REGISTRATION NUMBER: NL66127.018.18.

Optimizing pseudo-spiral sampling for abdominal DCE MRI using a digital anthropomorphic phantom.

PURPOSE: For reliable DCE MRI parameter estimation, k-space undersampling is essential to meet resolution, coverage, and signal-to-noise requirements. Pseudo-spiral (PS) sampling achieves this by sampling k-space on a Cartesian grid following a spiral trajectory. The goal was to optimize PS k-space sampling patterns for abdomin al DCE MRI. METHODS: The optimal PS k-space sampling pattern was determined using an anthropomorphic digital phantom. Contrast agent inflow was simulated in the liver, spleen, pancreas, and pancreatic ductal adenocarcinoma (PDAC). A total of 704 variable sampling and reconstruction approaches were created using three algorithms using different parametrizations to control sampling density, halfscan and compressed sensing regularization. The sampling patterns were evaluated based on image quality scores and the accuracy and precision of the DCE pharmacokinetic parameters. The best and worst strategies were assessed in vivo in five healthy volunteers without contrast agent administration. The best strategy was tested in a DCE scan of a PDAC patient. RESULTS: The best PS reconstruction was found to be PS-diffuse based, with quadratic distribution of readouts on a spiral, without random shuffling, halfscan factor of 0.8, and total variation regularization of 0.05 in the spatial and temporal domains. The best scoring strategy showed sharper images with less prominent artifacts in healthy volunteers compared to the worst strategy. Our suggested DCE sampling strategy also showed high quality DCE images in the PDAC patient. CONCLUSION: Using an anthropomorphic digital phantom, we identified an optimal PS sampling strategy for abdominal DCE MRI, and demonstrated feasibility in a PDAC patient.

Free-breathing motion corrected magnetic resonance elastography of the abdomen.

Background: Magnetic resonance elastography (MRE) is a non-invasive method to measure the viscoelastic properties of tissue and has been applied in multiple abdominal organs. However, abdominal MRE suffers from detrimental breathing motion causing misalignment of structures between repeated acquisitions for different MRE dimensions (e.g., motion encoding directions and wave phase offsets). This study investigated motion correction strategies to resolve all breathing motion on sagittal free-breathing MRE acquisitions in a phantom, in healthy volunteers and showed feasibility in patients. Methods: First, in silico experiments were performed on a static phantom dataset with simulated motion. Second, eight healthy volunteers underwent two sagittal MRE acquisitions in the pancreas and right kidney. The multi-frequency free-breathing spin-echo echo-planar-imaging (SE-EPI) MRE consisted of four frequencies (30, 40, 50, 60 Hz), eight wave-phase offsets, with 3 mm3 isotropic voxel size. Following data re-sorting in different number of motion states (4 till 12) based on respiratory waveform signal, three intensity-based registration methods (monomodal, multimodal, and phase correlation) and non-rigid local registration were compared. A ranking method was used to determine the best registration method, based on seven signal-to-noise and image quality measures. Repeatability was assessed for no motion correction (Original) and the best performing method (Best) using Bland-Altman analysis. Lastly, the best motion correction method was compared to no motion correction on patient MRE data [pancreatic ductal adenocarcinoma (PDAC, n=5) and metabolic dysfunction-associated steatotic liver disease (MASLD) (n=1)]. Results: In silico experiments showed a deviation of shear wave speed (SWS) with simulated motion to the ground truth, which was (partially) resolved using motion correction. In healthy volunteers ranking resulted in the best motion correction method of monomodal registration using nine motion states, while no motion correction was ranked last. Limits of agreement were (-0.18, 0.14), and (-0.25, 0.18) m/s for Best and Original, respectively. Using motion correction in patients resulted in a significant increase in SWS in the pancreas (Original: 1.39±0.10 and Best: 1.50±0.17 m/s). After motion correction PDAC had a mean SWS of 1.56±0.27 m/s (Original: 1.42±0.25 m/s). The fibrotic liver mean SWS was 2.07±0.20 m/s (Original: 2.12±0.18 m/s). Conclusions: Motion correction in sagittal free-breathing abdominal MRE results in improved data quality, inversion precision, repeatability, and is feasible in patients.

MR Elastography of the Pancreas: Bowel Preparation and Repeatability Assessment in Pancreatic Cancer Patients and Healthy Controls.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) stromal viscoelasticity can be measured using MR elastography (MRE). Bowel preparation regimens could affect MRE quality and knowledge on repeatability is crucial for clinical implementation. PURPOSE: To assess effects of four bowel preparation regimens on MRE quality and to evaluate repeatability and differentiate patients from healthy controls. STUDY TYPE: Prospective. POPULATION: 15 controls (41 ± 16 years; 47% female), 16 PDAC patients (one excluded, 66 ± 12 years; 40% female) with 15 age-/sex-matched controls (65 ± 11 years; 40% female). Final sample size was 25 controls and 15 PDAC. FIELD STRENGTH/SEQUENCE: 3-T, spin-echo echo-planar-imaging, turbo spin-echo, and fast field echo gradient-echo. ASSESSMENT: Four different regimens were used: fasting; scopolaminebutyl; drinking 0.5 L water; combination of 0.5 L water and scopolaminebutyl. MRE signal-to-noise ratio (SNR) was compared between all regimens. MRE repeatability (test-retest) and differences in shear wave speed (SWS) and phase angle (ϕ) were assessed in PDAC and controls. Regions-of-interest were defined for tumor, nontumorous (n = 8) tissue in PDAC, and whole pancreas in controls. Two radiologists delineated tumors twice for evaluation of intraobserver and interobserver variability. STATISTICAL TESTS: Repeated measures analysis of variance, coefficients of variation (CoVs), Bland-Altman analysis, (un)paired t-test, Mann-Whitney U-test, and Wilcoxon signed-rank test. P-value<0.05 was considered statistically significant. RESULTS: Preparation regimens did not significantly influence MRE-SNR. Therefore, the least burdensome preparation (fasting only) was continued. CoVs for tumor SWS were: intrasession (12.8%) and intersession (21.7%), and intraobserver (7.9%) and interobserver (10.3%) comparisons. For controls, CoVs were intrasession (4.6%) and intersession (6.4%). Average SWS for tumor, nontumor, and healthy tissue were: 1.74 ± 0.58, 1.38 ± 0.27, and 1.18 ± 0.16 m/sec (ϕ: 1.02 ± 0.17, 0.91 ± 0.07, and 0.85 ± 0.08 rad), respectively. Significant differences were found between all groups, except for ϕ between healthy-nontumor (P = 0.094). DATA CONCLUSION: The proposed bowel preparation regimens may not influence MRE quality. MRE may be able to differentiate between healthy tissue-tumor and tumor-nontumor. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.

Single Breath-Hold MR Elastography for Fast Biomechanical Probing of Pancreatic Stiffness.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) stromal disposition is thought to influence chemotherapy efficacy and increase tissue stiffness, which could be quantified noninvasively via MR elastography (MRE). Current methods cause position-based errors in pancreas location over time, hampering accuracy. It would be beneficial to have a single breath-hold acquisition. PURPOSE: To develop and test a single breath-hold three-dimensional MRE technique utilizing prospective undersampling and a compressed sensing reconstruction (CS-MRE). STUDY TYPE: Prospective. POPULATION: A total of 30 healthy volunteers (HV) (31 ± 9 years; 33% male) and five patients with PDAC (69 ± 5 years; 80% male). FIELD STRENGTH/SEQUENCE: 3-T, GRE Ristretto MRE. ASSESSMENT: First, optimization of multi breath-hold MRE was done in 10 HV using four combinations of vibration frequency, number of measured wave-phase offsets, and TE and looking at MRE quality measures in the pancreas head. Second, viscoelastic parameters delineated in the pancreas head or tumor of CS-MRE were compared against (I) 2D and (II) 3D four breath-hold acquisitions in HV (N = 20) and PDAC patients. Intrasession repeatability was assessed for CS-MRE in a subgroup of healthy volunteers (N = 15). STATISTICAL TESTS: Tests include repeated measures analysis of variance (ANOVA), Bland-Altman analysis, and coefficients of variation (CoVs). A P-value <.05 was considered statistically significant. RESULTS: Optimization of the four breath-hold acquisitions resulted in 40 Hz vibration frequency, five wave-phases, and echo time (TE) = 6.9 msec as the preferred method (4BH-MRE). CS-MRE quantitative results did not differ from 4BH-MRE. Shear wave speed (SWS) and phase angle differed significantly between HV and PDAC patients using 4BH-MRE or CS-MRE. The limits of agreement for SWS were [-0.09, 0.10] m/second and the within-subject CoV was 4.8% for CS-MRE. DATA CONCLUSION: CS-MRE might allow a single breath-hold MRE acquisition with comparable SWS and phase angle as 4BH-MRE, and it may still enable to differentiate between HV and PDAC. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 2.

Viscoelastic properties of small bowel mesentery at MR elastography in Crohn's disease: a prospective cross-sectional exploratory study.

BACKGROUND: Creeping fat is a pathological feature of small bowel Crohn's disease (CD), with literature suggesting that bowel resection with extended mesenteric resection is related to less postoperative recurrences. Conventional imaging is unable to accurately quantify the disease involvement (i.e., fibrosis) of creeping fat. Quantification of disease involvement could be useful in decision-making for additional extended mesenteric resection. We investigated the feasibility of magnetic resonance elastography (MRE) of the mesentery and if MRE is capable to detect fibrotic disease involvement of mesentery in active CD. METHODS: Multifrequency MRE yielded spatial stiffness (shear wave speed, SWS, |G*|) and fluidity maps (φ). Viscoelastic properties of seven CD patients' mesentery were compared to age- and sex-matched healthy volunteers (HV) (Mann-Whitney U-test). Within CD patients, the affected and "presumably" unaffected mesentery were compared (Wilcoxon-signed rank test). Repeatability was tested in 15 HVs (Bland-Altman analysis, coefficient of variation [CoV]). Spearman rank correlations were used to investigate the relation between microscopically scored amount of mesenteric fibrosis and viscoelastic parameters. RESULTS: SWS, |G*|, and φ of affected mesentery in CD were higher compared to HV (p = 0.017, p = 0.001, p = 0.017). Strong correlations were found between percentage of area of mesenteric fibrosis and SWS and |G*| (p < 0.010). No differences were found within CD between affected and presumably unaffected mesentery. Repeatability of SWS showed 95% limits of agreement of (-0.09, 0.13 m/s) and within-subject CoV of 5.3%. CONCLUSION: MRE may have the potential to measure fibrotic disease involvement of the mesentery in CD, possibly guiding clinical decision-making with respect to extended mesenteric resection. TRIAL REGISTRATION: Dutch trial register, NL9105 , registered 7 December 2020. RELEVANCE STATEMENT: MRE may have the potential to measure the amount of mesenteric fibrosis of the affected mesenteric fat in active Crohn's disease, giving more insight into disease progression and could potentially play a role in clinical decision-making for extended mesenteric resection. KEY POINTS: • MRE of the mesentery in patients with active CD is feasible. • Fluidity and stiffness of the mesentery increase in active CD, while stiffness correlates with the histopathological amount of mesenteric fibrosis. • MRE provides biomarkers to quantify mesenteric disease activity in active CD.

Fetal cardiovascular blood flow MRI: techniques and applications.

Fetal cardiac MRI is challenging due to fetal and maternal movements as well as the need for a reliable cardiac gating signal and high spatiotemporal resolution. Ongoing research and recent technical developments to address these challenges show the potential of MRI as an adjunct to ultrasound for the assessment of the fetal heart and great vessels. MRI measurements of blood flow have enabled the assessment of normal fetal circulation as well as conditions with disrupted circulations, such as congenital heart disease, along with associated organ underdevelopment and hemodynamic instability. This review provides details of the techniques used in fetal cardiovascular blood flow MRI, including single slice and volumetric imaging sequences, post-processing and analysis, along with a summary of applications in human studies and animal models.

Volumetric Fetal Flow Imaging With Magnetic Resonance Imaging.

Fetal development relies on a complex circulatory network. Accurate assessment of flow distribution is important for understanding pathologies and potential therapies. In this paper, we demonstrate a method for volumetric imaging of fetal flow with magnetic resonance imaging (MRI). Fetal MRI faces challenges: small vascular structures, unpredictable motion, and inadequate traditional cardiac gating methods. Here, orthogonal multislice stacks are acquired with accelerated multidimensional radial phase contrast (PC) MRI. Slices are reconstructed into flow sensitive time-series images with motion correction and image-based cardiac gating. They are then combined into a dynamic volume using slice-to-volume reconstruction (SVR) while resolving interslice spatiotemporal coregistration. Compared to prior methods, this approach achieves higher spatiotemporal resolution ( 1×1×1 mm3, ~30 ms) with reduced scan time - important features for the quantification of flow through small fetal structures. Validation is demonstrated in adults by comparing SVR with 4D radial PCMRI (flow bias and limits of agreement: -1.1 ml/s and [-11.8 9.6] ml/s). Feasibility is demonstrated in late gestation fetuses by comparing SVR with 2D Cartesian PCMRI (flow bias and limits of agreement: -0.9 ml/min/kg and [-39.7 37.8] ml/min/kg). With SVR, we demonstrate complex flow pathways (such as parallel flow streams in the proximal inferior vena cava, preferential shunting of blood from the ductus venosus into the left atrium, and blood from the brain leaving the heart through the main pulmonary artery) for the first time in human fetal circulation. This method allows for comprehensive evaluation of the fetal circulation and enables future studies of fetal physiology.

Clinical Feasibility of Structural and Functional MRI in Free-Breathing Neonates and Infants.

BACKGROUND: Evaluation of structural lung abnormalities with magnetic resonance imaging (MRI) has previously been shown to be predictive of clinical neonatal outcomes in preterm birth. MRI during free-breathing with phase-resolved functional lung (PREFUL) may allow for complimentary functional information without exogenous contrast. PURPOSE: To investigate the feasibility of structural and functional pulmonary MRI in a cohort of neonates and infants with no cardiorespiratory disease. Macrovascular pulmonary blood flows were also evaluated. STUDY TYPE: Prospective. POPULATION: Ten term infants with no clinically defined cardiorespiratory disease were imaged. Infants recruited from the general population and neonatal intensive care unit (NICU) were studied. FIELD STRENGTH/SEQUENCE: T1 -weighted VIBE, T2 -weighted BLADE uncorrected for motion. Ultrashort echo time (UTE) and 3D-flow data were acquired during free-breathing with self-navigation and retrospective reconstruction. Single slice 2D-gradient echo (GRE) images were acquired during free-breathing for PREFUL analysis. Imaging was performed at 3 T. ASSESSMENT: T1 , T2 , and UTE images were scored according to the modified Ochiai scheme by three pediatric body radiologists. Ventilation/perfusion-weighted maps were extracted from free-breathing GRE images using PREFUL analysis. Ventilation and perfusion defect percent (VDP, QDP) were calculated from the segmented ventilation and perfusion-weighted maps. Time-averaged cardiac blood velocities from three-dimensional-flow were evaluated in major pulmonary arteries and veins. STATISTICAL TEST: Intraclass correlation coefficient (ICC). RESULTS: The ICC of replicate structural scores was 0.81 (95% CI: 0.45-0.95) across three observers. Elevated Ochiai scores, VDP, and QDP were observed in two NICU participants. Excluding these participants, mean ± standard deviation structural scores were 1.2 ± 0.8, while VDP and QDP were 1.0% ± 1.1% and 0.4% ± 0.5%, respectively. Main pulmonary arterial blood flows normalized to body surface area were 3.15 ± 0.78 L/min/m2 . DATA CONCLUSION: Structural and functional pulmonary imaging is feasible using standard clinical MRI hardware (commercial whole-body 3 T scanner, table spine array, and flexible thoracic array) in free-breathing infants. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

Coronary Flow Assessment Using Accelerated 4D Flow MRI With Respiratory Motion Correction.

Magnetic resonance imaging (MRI) can potentially be used for non-invasive screening of patients with stable angina pectoris to identify probable obstructive coronary artery disease. MRI-based coronary blood flow quantification has to date only been performed in a 2D fashion, limiting its clinical applicability. In this study, we propose a framework for coronary blood flow quantification using accelerated 4D flow MRI with respiratory motion correction and compressed sensing image reconstruction. We investigate its feasibility and repeatability in healthy subjects at rest. Fourteen healthy subjects received 8 times-accelerated 4D flow MRI covering the left coronary artery (LCA) with an isotropic spatial resolution of 1.0 mm3. Respiratory motion correction was performed based on 1) lung-liver navigator signal, 2) real-time monitoring of foot-head motion of the liver and LCA by a separate acquisition, and 3) rigid image registration to correct for anterior-posterior motion. Time-averaged diastolic LCA flow was determined, as well as time-averaged diastolic maximal velocity (VMAX) and diastolic peak velocity (VPEAK). 2D flow MRI scans of the LCA were acquired for reference. Scan-rescan repeatability and agreement between 4D flow MRI and 2D flow MRI were assessed in terms of concordance correlation coefficient (CCC) and coefficient of variation (CV). The protocol resulted in good visibility of the LCA in 11 out of 14 subjects (six female, five male, aged 28 ± 4 years). The other 3 subjects were excluded from analysis. Time-averaged diastolic LCA flow measured by 4D flow MRI was 1.30 ± 0.39 ml/s and demonstrated good scan-rescan repeatability (CCC/CV = 0.79/20.4%). Time-averaged diastolic VMAX (17.2 ± 3.0 cm/s) and diastolic VPEAK (24.4 ± 6.5 cm/s) demonstrated moderate repeatability (CCC/CV = 0.52/19.0% and 0.68/23.0%, respectively). 4D flow- and 2D flow-based diastolic LCA flow agreed well (CCC/CV = 0.75/20.1%). Agreement between 4D flow MRI and 2D flow MRI was moderate for both diastolic VMAX and VPEAK (CCC/CV = 0.68/20.3% and 0.53/27.0%, respectively). In conclusion, the proposed framework of accelerated 4D flow MRI equipped with respiratory motion correction and compressed sensing image reconstruction enables repeatable diastolic LCA flow quantification that agrees well with 2D flow MRI.

Open or closed: Changes in ductus arteriosus flow patterns at birth using 4D flow MRI in newborn piglets.

The ductus arteriosus (DA) functionally closes during the transition from fetal to postnatal life because of lung aeration and corresponding cardiovascular changes. The thorough and explicit measurement and visualization of the right and left heart output during this transition has not been previously accomplished. We combined 4D flow MRI (dynamic volumetric blood flow measurements) and T2 relaxometry (oxygen delivery quantification) in surgically instrumented newborn piglets to assess the DA. This was performed in Large White-Landrace-Duroc piglets (n = 34) spanning four age groups: term-9 days, term-3, term+1, and term+5. Subject's DA status was classified using 4D flow: closed DA, forward DA flow, reversed DA flow, and bidirectional DA flow. Over all states, vessel diameters and flows normalized to body weight increased with age (for example in the ascending aorta flow-term-9: 126.6 ± 45.4; term+5: 260.2 ± 80.0 ml/min per kg; p = 0.0005; ascending aorta diameter-term-9: 5.2 ± 0.8; term+5: 7.7 ± 0.4 mm; p = 0.0004). In subjects with reversed DA blood flow there was lower common carotid artery blood flow (forward: 37.5 ± 9.0; reversed: 20.0 ± 7.4 ml/min per kg; p = 0.032). Linear regression revealed that as net DA flow decreases, common carotid artery flow decreases (R2  = 0.32, p = 0.004), and left (R2  = 0.33, p = 0.003) and right (R2  = 0.34, p = 0.003) pulmonary artery flow increases. Bidirectional DA blood flow changed oxygen saturation as determined by MRI between the ascending and descending aorta (ascending aorta: 90.1% ± 8.4%; descending aorta: 75.6% ± 14.2%; p < 0.05). Expanded use of these techniques in preterm animal models will aid in providing new understandings of normal versus abnormal DA transition, as well as to test the effectiveness of related clinical interventions.

Fetal Flow Quantification in Great Vessels Using Motion-Corrected Radial Phase Contrast MRI: Comparison With Cartesian.

BACKGROUND: Phase contrast MRI in the great vessels is a potential clinical tool for managing fetal pathologies. One challenge is the uncontrollable fetal motion, potentially corrupting flow quantifications. PURPOSE: To demonstrate improvements in fetal blood flow quantification in great vessels using retrospectively motion-corrected golden-angle radial phase contrast MRI relative to Cartesian phase contrast MRI. STUDY TYPE: Method comparison. PHANTOM/SUBJECTS: Computer simulation. Seventeen pregnant volunteers. FIELD STRENGTH/SEQUENCE: 1.5T and 3T. Cartesian and golden-angle radial phase contrast MRI. ASSESSMENT: Through computer simulations, radial (with and without retrospective motion correction) and Cartesian phase contrast MRI were compared using flow deviations. in vivo Cartesian and radial phase contrast MRI measurements and reconstruction qualities were compared in pregnancies. Cartesian data were reconstructed into gated reconstructions (CINEs) after cardiac gating with metric optimized gating (MOG). For radial data, real-time reconstructions were performed for motion correction and MOG followed by CINE reconstructions. STATISTICAL TESTS: Wilcoxon signed-rank test. Linear regression. Bland-Altman plots. Student's t-test. RESULTS: Simulations showed significant improvements (P < 0.05) in flow accuracy and reconstruction quality with motion correction ([mean/peak] flow errors with ±5 mm motion corruption: Cartesian [35 ± 1/115 ± 7] mL/s, motion uncorrected radial [25 ± 1/75 ± 2] mL/s and motion-corrected radial [1.0 ± 0.5/-5 ± 1] mL/s). in vivo Cartesian reconstructions without motion correction had lower quality than the motion-corrected radial reconstructions (P < 0.05). Across all fetal mean flow measurements, the bias [limits of agreement] between the two measurements were -0.2 [-76, 75] mL/min/kg, while the linear regression coefficients were (Mradial = 0.81 × MCartesian + 29.8 [mL/min/kg], r2 = 0.67). The corresponding measures for the peak fetal flows were -23 [-214, 167] mL/min/kg and (Pradial = 0.95 × PCartesian -1.2 [mL/min/kg], r2 = 0.80). Cartesian reconstructions of low quality showed significantly higher estimated mean and peak (P < 0.05) flows than the corresponding radial reconstructions. DATA CONCLUSION: Simulations showed that radial phase contrast MRI with motion compensation improved flow accuracy. For fetal measurements, motion-corrected radial reconstructions showed better image quality than, and different flow values from, Cartesian reconstructions. Level of Evidence 1. Technical Efficacy Stage 1. J. MAGN. RESON. IMAGING 2021;53:540-551.

Seeing the fetus from a DOHaD perspective: discussion paper from the advanced imaging techniques of DOHaD applications workshop held at the 2019 DOHaD World Congress.

Advanced imaging techniques are enhancing research capacity focussed on the developmental origins of adult health and disease (DOHaD) hypothesis, and consequently increasing awareness of future health risks across various subareas of DOHaD research themes. Understanding how these advanced imaging techniques in animal models and human population studies can be both additively and synergistically used alongside traditional techniques in DOHaD-focussed laboratories is therefore of great interest. Global experts in advanced imaging techniques congregated at the advanced imaging workshop at the 2019 DOHaD World Congress in Melbourne, Australia. This review summarizes the presentations of new imaging modalities and novel applications to DOHaD research and discussions had by DOHaD researchers that are currently utilizing advanced imaging techniques including MRI, hyperpolarized MRI, ultrasound, and synchrotron-based techniques to aid their DOHaD research focus.

Umbilical vein infusion of prostaglandin I2 increases ductus venosus shunting of oxygen-rich blood but does not increase cerebral oxygen delivery in the fetal sheep.

KEY POINTS: The ductus venosus (DV) is a dynamic fetal shunt that allows substrate-rich blood from the umbilical vein to bypass the hepatic circulation. In vitro studies suggest a direct role of prostaglandin I2 (PGI2 ) in the regulation of DV tone; however, the extent of this regulation has not been determined in utero. 4D flow and T2 oximetry magnetic resonance imaging can be combined to determine blood flow and oxygen delivery within the fetal circulation. PGI2 increases DV shunting of substrate-rich blood but this does not increase cerebral oxygen delivery. ABSTRACT: During fetal development, the maintenance of adequate oxygen and nutrient supply to vital organs is regulated through specialized fetal shunts. One of these shunts, the ductus venosus (DV), allows oxygen-rich blood to preferentially stream from the placenta toward the heart and brain. Herein, we combine magnetic resonance imaging (MRI) techniques that measure blood flow (4D flow) and oxygen saturation (T2 oximetry) in the fetal circuit to determine whether umbilical vein infusion of prostaglandin I2 (PGI2 , regulator of DV tone ex utero) directly dilates the DV and thus increases the preferential streaming of oxygen-rich blood toward the brain. At 114-115 days gestational age (dGA; term = 150 days), fetal sheep (n = 6) underwent surgery to implant vascular catheters in the fetal femoral artery, femoral vein, amniotic cavity and umbilical vein. Fetal MRI scans were performed at 119-124 dGA. 4D flow and T2 oximetry were performed to measure blood flow and oxygen saturation across the fetal circulation in both a basal state and whilst the fetus was receiving a continuous infusion of PGI2 . The proportion of oxygenated blood that passed through the DV from the umbilical vein was increased by PGI2 . Cerebral oxygen delivery was unchanged in the PGI2 state. This may be a result of decreased flow from the right to left side of the heart as blood flow through the foramen ovale was decreased by PGI2 . We have shown that although PGI2 acts on the DV to increase the proportion of oxygen-rich blood that bypasses the liver, this does not increase cerebral oxygen delivery in the fetal sheep.

Technique for comprehensive fetal hepatic blood flow assessment in sheep using 4D flow MRI.

KEY POINTS: The comprehensive visualization and quantification of in vivo fetal hepatic haemodynamics, particularly the shunting of ductus venosus blood, has been elusive and is not yet fully understood. We introduce the combination of chronically instrumented fetal sheep and 4D flow MRI of the whole fetal liver, which allows retrospective blood flow measurement in all visible vessels as well as qualitative assessment. The applicability and usefulness of this technique is exhibited in normally grown fetal Merino sheep in mid- and late-gestation with detailed dynamic distribution of hepatic blood flow presented. The feasibility of this approach in clinical pathology is demonstrated in two growth-restricted fetuses at mid-gestation. Further exemplification of blood flow quantification is performed over major hepatic vessels. ABSTRACT: Although the fetal vasculature has been demarcated and well understood for several decades, the corresponding haemodynamics permitting oxygen- and nutrient-rich blood delivery to the fetal organs has been comparatively difficult to study. We married two well-established methods: 4D flow MRI, a volumetric and dynamic blood-flow measurement technique, and chronically instrumented sheep to broadly assess fetal hepatic circulation. We performed this technique in mid- and late-gestation fetal Merino sheep under normoxemic conditions and major hepatic vasculature was segmented to quantify blood flow and related parameters. Dynamic blood flow was visualized, exhibiting an acceleration of umbilical vein blood through the ductus venosus as well as spiralling into the inferior vena cava where its stream remained separate from that of the hepatic veins and lower body. Ductus venosus changes from mid- to late-gestation included larger diameter (mid: 5.8 ± 0.9 vs. late: 7.1 ± 1.1 mm; P = 0.003) and cross-sectional area (mid: 27.1 ± 8.6 vs. late: 40.4 ± 11.8 mm2 ; P = 0.003), and lower velocity averaged over the cardiac cycle (mid: 15.7 ± 5.4 vs. late: 9.8 ± 7.0 cm s-1 ; P = 0.020). This resulted in higher magnitude blood flow (indexed to umbilical vein input) at mid-gestation in the ductus venosus (mid: 0.73 ± 0.21; late: 0.46 ± 0.21; P = 0.008). The visualization and quantification results support the further use of this technique to better understand regional blood flow changes during normal or abnormal fetal growth, as well as to observe acute haemodynamic responses to physiological challenges or drug interventions.

Simulation of semilunar valve function: computer-aided design, 3D printing and flow assessment with MR.

BACKGROUND: The structure of the valve leaflets and sinuses are crucial in supporting the proper function of the semilunar valve and ensuring leaflet durability. Therefore, an enhanced understanding of the structural characteristics of the semilunar valves is fundamental to the evaluation and staging of semilunar valve pathology, as well as the development of prosthetic or bioprosthetic valves. This paper illustrates the process of combining computer-aided design (CAD), 3D printing and flow assessment with 4-dimensional flow magnetic resonance imaging (MRI) to provide detailed assessment of the structural and hemodynamic characteristics of the normal semilunar valve. METHODS: Previously published geometric data on the aortic valve was used to model the 'normal' tricuspid aortic valve with a CAD software package and 3D printed. An MRI compatible flow pump with the capacity to mimic physiological flows was connected to the phantom. A peak flow rate of 100 mL/s and heart rate of 60 beats per minute were used. MRI measurements included cine imaging, 2D and 4D phase-contrast imaging to assess valve motion, flow velocity and complex flow patterns. RESULTS: Cine MRI data showed normal valve function and competency throughout the cardiac cycle in the 3D-printed phantom. Quantitative analysis of 4D Flow data showed net flow through 2D planes proximal and distal to the valve were very consistent (26.03 mL/s and 26.09 mL/s, respectively). Measurements of net flow value agreed closely with the flow waveform provided to the pump (27.74 mL/s), confirming 4D flow acquisition in relation to the pump output. Peak flow values proximal and distal to the valve were 78.4 mL/s and 63.3 mL/s, respectively. Particle traces of flow from 4D-phase contrast MRI data demonstrated flow through the valve into the ascending aorta and vortices within the aortic sinuses, which are expected during ventricular diastole. CONCLUSION: In this proof of concept study, we have demonstrated the ability to generate physiological 3D-printed aortic valve phantoms and evaluate their function with cine- and 4D Flow MRI. This technology can work synergistically with promising tissue engineering research to develop optimal aortic valve replacements, which closely reproduces the complex function of the normal aortic valve.

Understanding Fetal Hemodynamics Using Cardiovascular Magnetic Resonance Imaging.

Human fetal circulatory physiology has been investigated extensively using grey-scale ultrasound, which provides excellent visualization of cardiac anatomy and function, while velocity profiles in the heart and vessels can be interrogated using Doppler. Measures of cerebral and placental vascular resistance, as well as indirect measures of intracardiac pressure obtained from the velocity waveform in the ductus venosus are routinely used to guide the management of fetal cardiovascular and placental disease. However, the characterization of some key elements of cardiovascular physiology such as vessel blood flow and the oxygen content of blood in the arteries and veins, as well as fetal oxygen delivery and consumption are not readily measured using ultrasound. To study these parameters, we have historically relied on data obtained using invasive measurements made in animal models, which are not equivalent to the human in every respect. Over recent years, a number of technical advances have been made that have allowed us to examine the human fetal circulatory system using cardiovascular magnetic resonance (CMR). The combination of vessel blood flow measurements made using cine phase contrast magnetic resonance imaging and vessel blood oxygen saturation and hematocrit measurements made using T1 and T2 mapping have enabled us to emulate those classic fetal sheep experiments defining the distribution of blood flow and oxygen transport across the fetal circulation in the human fetus. In addition, we have applied these techniques to study the relationship between abnormal fetal cardiovascular physiology and fetal development in the setting of congenital heart disease and placental insufficiency. CMR has become an important diagnostic tool in the assessment of cardiovascular physiology in the setting of postnatal cardiovascular disease, and is now being applied to the fetus to enhance our understanding of normal and abnormal fetal circulatory physiology and its impact on fetal well-being.

Motion robust respiratory-resolved 3D radial flow MRI and its application in neonatal congenital heart disease.

PURPOSE: To test and implement a motion-robust and respiratory-resolved 3D Radial Flow framework that addresses the need for rapid, high resolution imaging in neonatal patients with congenital heart disease. METHODS: A 4-point velocity encoding and 3D radial trajectory with double-golden angle ordering was combined with bulk motion correction (from projection center of mass) and respiration phase detection (from principal component analysis of heartbeat-averaged data) to create motion-robust 3D velocity cardiac time-averaged data. This framework was tested in a whole-chest digital phantom with simulated bulk and realistic physiological motion. In vivo imaging was performed in 20 congenital heart disease infants under feed-and-sleep with submillimeter isotropic resolution in ~3 min. Flows were validated against clinical 2D PCMRI and whole-heart visualizations of blood flow were performed. RESULTS: The proposed framework resolved all simulated digital phantom motion states (mean ± standard error: rotation - azimuthal = 0.29 ± 0.02°; translation - Ty = 1.29 ± 0.12 mm, Tz = -0.27 ± 0.13 mm; rotation+translation - polar = 0.49 ± 0.16°, Tx = -2.47 ± 0.51 mm, Tz = 5.78 ± 1.33 mm). Measured timing errors of peak expiration across all signal-to-noise ratio values were 22% of the true respiratory period (range = [404-489 ± 298-334] ms). For in vivo imaging, motion correction improved 3D Radial Flow measurements (no correction: R2 = 0.62, root mean square error = 0.80 L/min/m2 , Bland-Altman bias [limits of agreement] = -0.21 [-1.40, 0.94] L/min/m2 ; motion corrected, expiration: R2 = 0.90, root mean square error = 0.46 L/min/m2 , bias [limits of agreement] = 0.06 [-0.49, 0.62] L/min/m2 ). Respiratory-resolved 3D velocity visualizations were achieved in various neonatal pathologies pre- and postsurgical correction. CONCLUSION: 3D cardiac flow may be visualized and accurately quantified in neonatal subjects using the proposed framework. This technique may enable more comprehensive hemodynamic studies in small infants.

Intracardiac 4D Flow MRI in Congenital Heart Disease: Recommendations on Behalf of the ISMRM Flow & Motion Study Group.

LEVEL OF EVIDENCE: 5 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2019;50:677-681.