Four-Dimensional Flow MR Imaging: Technique and Advances.

4D Flow MRI is an advanced imaging technique for comprehensive non-invasive assessment of the cardiovascular system. The capture of the blood velocity vector field throughout the cardiac cycle enables measures of flow, pulse wave velocity, kinetic energy, wall shear stress, and more. Advances in hardware, MRI data acquisition and reconstruction methodology allow for clinically feasible scan times. The availability of 4D Flow analysis packages allows for more widespread use in research and the clinic and will facilitate much needed multi-center, multi-vendor studies in order to establish consistency across scanner platforms and to enable larger scale studies to demonstrate clinical value.

Multimodality Deep Phenotyping Methods to Assess Mechanisms of Poor Right Ventricular-Pulmonary Artery Coupling.

Deep phenotyping of pulmonary hypertension (PH) with multimodal diagnostic exercise interventions can lead to early focused therapeutic interventions. Herein, we report methods to simultaneously assess pulmonary impedance, differential biventricular myocardial strain, and right ventricular:pulmonary arterial (RV:PA) uncoupling during exercise, which we pilot in subjects with suspected PH. As proof-of-concept, we show that four subjects with different diagnoses [pulmonary arterial hypertension (PAH); chronic thromboembolic disease (CTEPH); PH due to heart failure with preserved ejection fraction (PH-HFpEF); and noncardiac dyspnea (NCD)] have distinct patterns of response to exercise. RV:PA coupling assessment with exercise was highest-to-lowest in this order: PAH > CTEPH > PH-HFpEF > NCD. Input impedance (Z0) with exercise was highest in precapillary PH (PAH, CTEPH), followed by PH-HFpEF and NCD. Characteristic impedance (ZC) tended to decline with exercise, except for the PH-HFpEF subject (initial Zc increase at moderate workload with subsequent decrease at higher workload with augmentation in cardiac output). Differential myocardial strain was normal in PAH, CTEPH, and NCD subjects and lower in the PH-HFpEF subject in the interventricular septum. The combination of these metrics allowed novel insights into mechanisms of RV:PA uncoupling. For example, while the PH-HFpEF subject had hemodynamics comparable to the NCD subject at rest, with exercise coupling dropped precipitously, which can be attributed (by decreased myocardial strain of interventricular septum) to poor support from the left ventricle (LV). We conclude that this deep phenotyping approach may distinguish afterload sensitive vs. LV-dependent mechanisms of RV:PA uncoupling in PH, which may lead to novel therapeutically relevant insights.

Diffuse Myocardial Fibrosis at Cardiac MRI in Young Adults Born Prematurely: A Cross-sectional Cohort Study.

Purpose: To measure native T1 values, a marker of diffuse fibrosis, by using cardiac MRI (CMR) in young adults born prematurely. Materials and Methods: This secondary analysis of a prospective cohort study included young adults born moderately to extremely preterm and age-matched, term-born participants. CMR was performed with a 3.0-T imager that included cine imaging for the quantification of left ventricular (LV) and right ventricular (RV) volumes and function and native saturation recovery T1 mapping for the assessment of diffuse myocardial fibrosis. Values between preterm and term were compared by using the Student t test. Associations between T1 values and other variables were analyzed by using linear regression and multivariate regression. Results: Of the 50 young-adult participants, 32 were born preterm (mean age, 25.8 years ± 4.2 [SD]; 23 women) and 18 were born at term (mean age, 26.2 years ± 5.4; 10 women). Native T1 values were significantly higher in participants born preterm than in participants born at term (1477 msec ± 77 vs 1423 msec ± 71, respectively; unadjusted P = .0019). Native T1 values appeared to be positively associated with indexed LV end-diastolic and end-systolic volumes (ß = 2.1, standard error = 0.7 and ß = 3.8, standard error = 1.2, respectively), the RV end-diastolic volume index (ß = 1.3, standard error = 0.6), and the LV mass index (ß = 2.5, standard error = 0.9). Higher T1 values may be associated with reduced cardiac systolic strain measures and diastolic strain measures. Five-minute Apgar scores were inversely associated with native T1 values. Conclusion: Young adults born moderately to extremely preterm exhibited significantly higher native T1 values than age-matched, term-born young adults.Keywords: MRI, Cardiac, Heart, Left Ventricle, CardiomyopathiesClinical trial registration no. NCT03245723Published under a CC BY 4.0 license Supplemental material is available for this article.

Fully automated intracardiac 4D flow MRI post-processing using deep learning for biventricular segmentation.

OBJECTIVES: 4D flow MRI allows for a comprehensive assessment of intracardiac blood flow, useful for assessing cardiovascular diseases, but post-processing requires time-consuming ventricular segmentation throughout the cardiac cycle and is prone to subjective errors. Here, we evaluate the use of automatic left and right ventricular (LV and RV) segmentation based on deep learning (DL) network that operates on short-axis cine bSSFP images. METHODS: A previously published DL network was fine-tuned via retraining on a local database of 106 subjects scanned at our institution. In 26 test subjects, the ventricles were segmented automatically by the network and manually by 3 human observers on bSSFP MRI. The bSSFP images were then registered to the corresponding 4D flow images to apply the segmentation to 4D flow velocity data. Dice coefficients and the relative deviation between measurements (automatic vs. manual and interobserver manual) of various hemodynamic parameters were assessed. RESULTS: The automated segmentation resulted in similar Dice scores (LV: 0.92, RV: 0.86) and lower relative deviations from manual segmentation in left ventricular (LV) average kinetic energy (KE) (8%) and RV KE (15%) than the Dice scores (LV: 0.91, RV: 0.87) and relative deviations between manual segmentation observers (LV KE: 11%, p = 0.01; RV KE: 19%, p = 0.03). CONCLUSIONS: The automated post-processing method using deep learning resulted in hemodynamic measurements that differ from a manual observer's measurements equally or less than the variation between manual observers. This approach can be used to decrease post-processing time on intraventricular 4D flow data and mitigate interobserver variability. KEY POINTS: • Our proposed method allows for fully automated post-processing of intraventricular 4D flow MRI data. • Our method resulted in hemodynamic measurements that matched those derived from manual segmentation equally as well as interobserver variability. • Our method can be used to greatly accelerate intraventricular 4D flow post-processing and improve interobserver repeatability.

Automatic measurement plane placement for 4D Flow MRI of the great vessels using deep learning.

PURPOSE: Despite the great potential and flexibility of 4D flow MRI for hemodynamic analysis, a major limitation is the need for time-consuming and user-dependent post-processing. We propose a fast four-step algorithm for rapid, robust, and repeatable flow measurements in the great vessels based on automatic placement of measurement planes and vessel segmentation. METHODS: Our algorithm works by (1) subsampling the 3D image into 3D patches, (2) predicting the probability of each patch containing individual vessels and location/orientation of the vessel within the patch via a convolutional neural network, (3) selecting the predicted planes with highest probabilities for each vessel, and (4) shifting the plane centers to the maximum velocity within each plane. The method was trained on 283 scans and evaluated on 40 unseen scans by comparing algorithm-derived processing times, plane locations, and flow measurements to those of two manual observers (graduate students) using t-tests, Pearson correlation, and Bland-Altman analysis. RESULTS: The average processing time for the algorithm (18 s) was shorter than observer 1 (362 s; P < 0.001) and observer 2 (317 s; P < 0.001). The distance between planes placed by the algorithm and those placed by manual observers was slightly greater (O1 vs. algorithm: 9.0 mm, O2 vs. algorithm: 10.3 mm) than the distance between planes placed by the two manual observers (8.3 mm). The correlation between flow values for planes placed by the algorithm and those placed by manual observers was slightly lower (O1 vs. algorithm: R = 0.68, O2 vs. algorithm: R = 0.72) than the flow correlation between the two manual observers (R = 0.81). CONCLUSION: Our method is a feasible and accurate approach for fast, reproducible, and automated flow measurement and visualization in 4D flow MRI of the great vessels, with similar variability compared to a manual annotator as the variability between two manual observers. This approach could be applied in other anatomical regions.

Exercise-induced irregular right heart flow dynamics in adolescents and young adults born preterm.

BACKGROUND: Preterm birth has been linked to an elevated risk of heart failure and cardiopulmonary disease later in life. With improved neonatal care and survival, most infants born preterm are now reaching adulthood. In this study, we used 4D flow cardiovascular magnetic resonance (CMR) coupled with an exercise challenge to assess the impact of preterm birth on right heart flow dynamics in otherwise healthy adolescents and young adults who were born preterm. METHODS: Eleven young adults and 17 adolescents born preterm (< 32 weeks of gestation and < 1500 g birth weight) were compared to 11 young adult and 18 adolescent age-matched controls born at term. Stroke volume, cardiac output, and flow in the main pulmonary artery were quantified with 4D flow CMR. Kinetic energy and vorticity were measured in the right ventricle. All parameters were measured at rest and during exercise at a power corresponding to 70% VO2max for each subject. Multivariate linear regression was used to perform age-adjusted term-preterm comparisons. RESULTS: With exercise, stroke volume increased 10 ± 21% in term controls and decreased 4 ± 18% in preterm born subjects (p = 0.007). This resulted in significantly reduced capacity to increase cardiac output in response to exercise stress for the preterm group (58 ± 26% increase in controls, 36 ± 27% increase in preterm, p = 0.004). Elevated kinetic energy (KEterm = 71 ± 22 nJ, KEpreterm = 87 ± 38 nJ, p = 0.03) and vorticity (ωterm = 79 ± 16 s-1, ωpreterm = 94 ± 32 s-1, p = 0.01) during diastole in the right ventricle (RV) suggested altered RV flow dynamics in the preterm subjects. Streamline visualizations showed altered structure to the diastolic filling vortices in those born preterm. CONCLUSIONS: For the participants examined here, preterm birth appeared to result in altered right-heart flow dynamics as early as adolescence, especially during diastole. Future studies should evaluate whether the altered dynamics identified here evolves into cardiopulmonary disease later in life. Trial registration None.

Altered Right Ventricular Filling at Four-dimensional Flow MRI in Young Adults Born Prematurely.

PURPOSE: To use four-dimensional (4D) flow MRI to measure intraventricular flow in young adults who were born prematurely to investigate mechanisms that may account for increased heart failure risk in this population. MATERIALS AND METHODS: In this secondary analysis of a prospective study, a total of 56 young adults participated in an observational cardiac 4D flow MRI study from 2016 to 2020. There were 35 participants who had been born moderately to extremely prematurely (birth weight <1500 g or gestational age ≤32 weeks; 23 women; mean age, 26 years ± 4) and 21 term-born participants (11 women; mean age, 25 years ± 3). Participants underwent cardiac MRI, including cine cardiac structure and function assessment, as well as 4D flow MRI. In each ventricle, normalized kinetic energy (KE/end diastolic volume) and flow through the atrioventricular valve were computed and compared between term-born and preterm participants at systolic and diastolic (early diastolic filling rate [E wave] and late diastolic filling [atrial contraction] rate [A wave]) time points by using Wilcoxon rank-sum tests. RESULTS: Preterm-born participants had lower right ventricular (RV) E wave/A wave (E/A) KE ratios (2.4 ± 1.7 vs 3.5 ± 1.4; P <.01) and lower E/A peak filling rate ratios (computed from RV volume-time curves; 2.3 ± 1.3 vs 3.5 ± 2.5; P = .03). Additionally, viscous energy dissipation was increased during systole (5.7 µW/mL ± 3.0 vs 4.2 µW/mL ± 1.6; P = .03), increased during late diastole (3.9 µW/mL ± 4.0 vs 2.2 µW/mL ± 1.6; P = .03), and summed over the cardiac cycle (2.4 µJ/mL ± 1.0 vs 1.9 µJ/mL ± 0.6; P = .02) in preterm relative to term participants. CONCLUSION: These results suggest that RV diastolic filling is altered in young adults who were born moderately to severely prematurely.Supplemental material is available for this article. Keywords: Adults, Cardiac, Comparative Studies, MR-Imaging, Right Ventricle © RSNA, 2021.

Exaggerated Cardiac Contractile Response to Hypoxia in Adults Born Preterm.

Individuals born prematurely have smaller hearts, cardiac limitations to exercise, and increased overall cardiometabolic risk. The cardiac effects of acute hypoxia exposure as another physiologic stressor remain under explored. The purpose of this study was to determine the effects of hypoxia on ventricular function in adults born preterm. Adults born moderately to extremely preterm (≤32 weeks gestation or <1500 g, N = 32) and born at term (N = 18) underwent cardiac magnetic resonance imaging under normoxic (21% O2) and hypoxic (12% O2) conditions to assess cardiovascular function. In normoxia, cardiac function parameters were similar between groups. During hypoxia, the right ventricular (RV) contractile response was significantly greater in participants born premature, demonstrated by greater increases in RV ejection fraction (EF) (p = 0.002), ventricular-vascular coupling (VVC) (p = 0.004), and strain (p < 0.0001) measures compared to term-born participants, respectively. Left ventricular contractile reserve was similar to term-born participants. Adults born preterm exhibit an exaggerated contractile response to acute hypoxia, particularly in the RV. This suggests that adults born preterm may have contractile reserve, despite the lack of volume reserve identified in previous exercise studies. However, this exaggerated and hyper-adapted response may also increase their risk for late RV failure.

Sildenafil administration improves right ventricular function on 4D flow MRI in young adults born premature.

Extreme preterm birth conveys an elevated risk of heart failure by young adulthood. Smaller biventricular chamber size, diastolic dysfunction, and pulmonary hypertension may contribute to reduced ventricular-vascular coupling. However, how hemodynamic manipulations may affect right ventricular (RV) function and coupling remains unknown. As a pilot study, 4D flow MRI was used to assess the effect of afterload reduction and heart rate reduction on cardiac hemodynamics and function. Young adults born premature were administered sildenafil (a pulmonary vasodilator) and metoprolol (a ß blocker) on separate days, and MRI with 4D flow completed before and after each drug administration. Endpoints include cardiac index (CI), direct flow fractions, and ventricular kinetic energy including E/A wave kinetic energy ratio. Sildenafil resulted in a median CI increase of 0.24 L/min/m2 (P = 0.02), mediated through both an increase in heart rate (HR) and stroke volume. Although RV ejection fraction improved only modestly, there was a significant increase (4% of end diastolic volume) in RV direct flow fraction (P = 0.04), consistent with hemodynamic improvement. Metoprolol administration resulted in a 5-beats/min median decrease in HR (P = 0.01), a 0.37 L/min/m2 median decrease in CI (P = 0.04), and a reduction in time-averaged kinetic energy (KE) in both ventricles (P < 0.01), despite increased RV diastolic E/A KE ratio (P = 0.04). Despite reduced right atrial workload, metoprolol significantly depressed overall cardiac systolic function. Sildenafil, however, increased CI and improved RV function, as quantified by the direct flow fraction. The preterm heart appears dependent on HR but sensitive to RV afterload manipulations.NEW & NOTEWORTHY We assessed the effect of right ventricular afterload reduction with sildenafil and heart rate reduction with metoprolol on cardiac hemodynamics and function in young adults born premature using 4D flow MRI. Metoprolol depressed cardiac function, whereas sildenafil improved cardiac function including right ventricular direct flow fraction by 4D flow, consistent with hemodynamic improvement. This suggests that the preterm heart is dependent on heart rate and sensitive to right ventricular afterload changes.

Dynamic FDG PET Imaging to Probe for Cardiac Metabolic Remodeling in Adults Born Premature.

Individuals born very premature have an increased cardiometabolic and heart failure risk. While the structural differences of the preterm heart are now well-described, metabolic insights into the physiologic mechanisms underpinning this risk are needed. Here, we used dynamic fluorodeoxyglucose (FDG) positron emission tomography/magnetic resonance imaging (PET-MRI) in young adults born term and preterm during normoxic (N = 28 preterm; 18 term) and hypoxic exposure (12% O2; N = 26 preterm; 17 term) to measure the myocardial metabolic rate of glucose (MMRglc) in young adults born term (N = 18) and preterm (N = 32), hypothesizing that young adults born preterm would have higher rates of MMRglc under normoxic conditions and a reduced ability to augment glucose metabolism under hypoxic conditions. MMRglc was calculated from the myocardial and blood pool time-activity curves by fitting the measured activities to the 3-compartment model of FDG kinetics. MMRglc was similar at rest between term and preterm subjects, and decreased during hypoxia exposure in both groups (p = 0.02 for MMRglc hypoxia effect). There were no differences observed between groups in the metabolic response to hypoxia, either globally (serum glucose and lactate measures) or within the myocardium. Thus, we did not find evidence of altered myocardial metabolism in the otherwise healthy preterm-born adult. However, whether subtle changes in myocardial metabolism may preceed or predict heart failure in this population remains to be determined.

A phantom study comparing radial trajectories for accelerated cardiac 4D flow MRI against a particle imaging velocimetry reference.

PURPOSE: Radial sampling is one method to accelerate 4D flow MRI acquisition, making feasible dual-velocity encoding (Venc) assessment of slow flow in the left ventricle (LV). Here, two radial trajectories are compared in vitro for this application: 3D radial (phase-contrast vastly undersampled isotropic projection, PC-VIPR) versus stack of stars (phase-contrast stack of stars, PC-SOS), with benchtop particle imaging velocimetry (PIV) serving as a reference standard. METHODS: The study contained three steps: (1) Construction of an MRI- and PIV-compatible LV model from a healthy adult's CT images. (2) In vitro PIV using a pulsatile flow pump. (3) In vitro dual-Venc 4D flow MRI using PC-VIPR and PC-SOS (two repeat experiments). Each MR image set was retrospectively undersampled to five effective scan durations and compared with the PIV reference. The root-mean-square velocity vector difference (RMSE) between MRI and PIV images was compared, along with kinetic energy (KE) and wall shear stress (WSS). RESULTS: RMSE increased as scan time decreased for both MR acquisitions. RMSE was 3% lower in PC-SOS images than PC-VIPR images in 30-min scans (3.8 vs. 3.9 cm/s) but 98% higher in 2.5-min scans (9.5 vs. 4.8 cm/s). PIV intrasession repeatability showed a RMSE of 4.4 cm/s, reflecting beat-to-beat flow variation, while MRI had intersession RMSEs of 3.8/3.5 cm/s for VIPR/SOS, respectively. Speed, KE, and WSS were overestimated voxel-wise in 30-min MRI scans relative to PIV by 0.4/0.3 cm/s, 0.2/0.1 µJ/mL, and 36/43 mPa, respectively, for VIPR/SOS. CONCLUSIONS: PIV is feasible for application-specific 4D flow MRI protocol optimization. PC-VIPR is better-suited to dual-Venc LV imaging with short scan times.

Feasibility of Cardiovascular Four-dimensional Flow MRI during Exercise in Healthy Participants.

PURPOSE: To explore the feasibility of using four-dimensional (4D) flow MRI to quantify blood flow and kinetic energy (KE) in the heart during strenuous exercise. MATERIALS AND METHODS: For this prospective study, cardiac 4D flow MRI was performed in 11 healthy young adult participants (eight men, three women; mean age, 26 years ± 1 [standard deviation]) at rest and during exercise with an MRI-compatible exercise stepper between March 2016 and July 2017. Flow was measured in the ascending aorta (AAo) and main pulmonary artery (MPA). KE was quantified in the left and right ventricle. Significant changes in flow and KE during exercise were identified by using t tests. Repeatability was assessed with inter- and intraobserver comparisons and an analysis of internal flow consistency. RESULTS: Nine participants successfully completed both rest and exercise imaging. Internal flow consistency analysis in systemic and pulmonary circulation showed average relative differences of 10% at rest and 16% during exercise. For flow measurements in the AAo and MPA, relative differences between observers never exceeded 6% in any vessel and showed excellent correlation, even during exercise. Relative differences were increased for KE, typically on the order of 30%, with poor interobserver correlation between measurements. CONCLUSION: Four-dimensional flow MRI can quantify increases in flow in the AAo and MPA during strenuous exercise and is highly repeatable. KE had reduced repeatability because of suboptimal segmentation methods and requires further development before clinical implementation. Supplemental material is available for this article. © RSNA, 2020See also the commentary by Markl and Lee in this issue.

Reduced regional flow in the left ventricle after anterior acute myocardial infarction: a case control study using 4D flow MRI.

BACKGROUND: Acute myocardial infarction (AMI) alters left ventricular (LV) hemodynamics, resulting in decreased global LV ejection fraction and global LV kinetic energy. We hypothesize that anterior AMI effects localized alterations in LV flow and developed a regional approach to analyze these local changes with 4D flow MRI. METHODS: 4D flow cardiac magnetic resonance (CMR) data was compared between 12 anterior AMI patients (11 males; 66 ± 12yo; prospectively acquired in 2016-2017) and 19 healthy volunteers (10 males; 40 ± 16yo; retrospective from 2010 to 2011 study). The LV cavity was contoured on short axis cine steady-state free procession CMR and partitioned into three regions: base, mid-ventricle, and apex. 4D flow data was registered to the short axis segmentation. Peak systolic and diastolic through-plane flows were compared region-by-region between groups using linear models of flow with age, sex, and heart rate as covariates. RESULTS: Peak systolic flow was reduced in anterior AMI subjects compared to controls in the LV mid-ventricle (fitted reduction = 3.9 L/min; P = 0.01) and apex (fitted reduction = 1.4 L/min; P = 0.02). Peak diastolic flow was also lower in anterior AMI subjects compared to controls in the apex (fitted reduction = 2.4 L/min; P = 0.01). CONCLUSIONS: A regional method to analyze 4D LV flow data was applied in anterior AMI patients and controls. Anterior AMI patients had reduced regional flow relative to controls.

Uteroplacental and Fetal 4D Flow MRI in the Pregnant Rhesus Macaque.

BACKGROUND: Pregnancy complications are often associated with poor uteroplacental vascular adaptation and standard diagnostics are unable to reliably quantify flow in all uteroplacental vessels and have poor sensitivity early in gestation. PURPOSE: To investigate the feasibility of using 4D flow MRI to assess total uteroplacental blood flow in pregnant rhesus macaques as a precursor to human studies. STUDY TYPE: Retrospective feasibility study. ANIMAL MODEL: Fifteen healthy, pregnant rhesus macaques ranging from the 1st trimester to 3rd trimester of gestation. FIELD STRENGTH/SEQUENCE: Abdominal 4D flow MRI was performed on a 3.0T scanner with a radially undersampled phase contrast (PC) sequence. Reference ferumoxytol-enhanced angiograms were acquired with a 3D ultrashort echo time sequence with a center-out radial trajectory. ASSESSMENT: Repeatability of flow measurements was assessed with scans performed same-day and on consecutive days in the uterine arteries and ovarian veins. In-flow was compared against out-flow in the uterus, umbilical cord, and fetal heart with a conservation of mass analysis. Conspicuity of uteroplacental vessels was qualitatively compared between PC angiograms derived from 4D flow data and ferumoxytol-enhanced angiograms. STATISTICAL TESTS: Bland-Altman analysis was used to quantify same-day and consecutive-day repeatability. RESULTS: Same-day flow measurements showed an average difference between scans of 13% in both the uterine arteries and ovarian veins, while consecutive-day measurements showed average differences of 22% and 24%, respectively. Comparisons of in-flow and out-flow showed average differences of 15% in the uterus, 8% in fetal heart, and 15% in the umbilical cord. PC angiograms showed similar depiction of main uteroplacental vessels as high-resolution, ferumoxytol-enhanced angiograms. DATA CONCLUSION: 4D flow MRI could be used in the rhesus macaque for repeatable flow measurements in the uteroplacental and fetal vasculature, setting the stage for future human studies. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:534-545.

Perceived success and failure of intrathecal infusion pump implantation in chronic pain patients.

Objectives. Over the past few years, there has been an increased reliance on the intrathecal delivery of drugs for patients suffering from intractable pain. We sought to demonstrate the effectiveness of the intrathecal pain pump by examining self-reported pre- and postimplantation pain levels. Methods. Eighty-four patients who had elected to implant a Medtronic SynchroMed 1 or 2 system in order to control their pain were asked to complete a survey. The survey consisted of pain ratings before implantation, pain ratings postimplantation, medications used before and after implantation, and patient satisfaction with the procedure. Results. Perceived success rate for implantation is 68%, when measured by the ability to reduce reliance on oral medication. When measured by willingness to undergo the procedure again, the success rate is 86%. Conclusions. Overall, the implantation of an intrathecal pain pump is an effective way for most people to manage their intractable pain and reduce reliance on oral medications.