Real-time Phase-contrast Flow Research Articles

Assessment of Beat-To-Beat Variability in Left Atrial Hemodynamics Using Real Time Phase Contrast MRI in Patients With Atrial Fibrillation.

Hemodynamic assessment of left atrial (LA) flow using phase contrast MRI provides insight into thromboembolic risk in atrial fibrillation (AF). However, conventional flow imaging techniques are averaged over many heartbeats. To evaluate beat-to-beat variability and LA hemodynamics in patients with AF using real time phase contrast (RTPC) MRI. Prospective. Thirty-five patients with history of AF (68 ± 10 years, nine female), 10 healthy controls (57 ± 19 years, four female). 5T, 2D RTPC with through-plane velocity-encoded gradient echo sequence and 4D flow MRI with three-directional velocity-encoded gradient echo sequence. RTPC was continuously acquired for a mid-LA slice in all subjects. 4D flow data were interpolated at the RTPC location and normally projected for comparison with RTPC. RR intervals extracted from RTPC were used to calculate heart rate variability (HRV=interquartile range over median × 100%). Patients were classified into low (<9.7%) and high (>9.7%) HRV groups. LA peak/mean velocity and stasis (%velocities < 5.8cm/sec) were calculated from segmented 2D images. Variability in RTPC flow metrics was quantified by coefficient of variation (CV) over all cycles. Pearson's correlation coefficient (r), Bland-Altman analysis, Kruskal-Wallis test. A P value < 0.05 was considered statistically significant. RTPC and 4D flow measurements were strongly/significantly correlated for all hemodynamic parameters (R2 =0.75-0.83) in controls. Twenty-four patients had low HRV (mean=4 ± 2%) and 11 patients had high HRV (27 ± 9%). In patients, increased HRV was significantly correlated with CV of peak velocity (r=0.67), mean velocity (r=0.51), and stasis (r=0.41). A stepwise decrease in peak/mean velocity and increase in stasis was observed when comparing controls vs. low HRV vs. high HRV groups. Mean velocity and stasis differences were significant for control vs. high HRV groups. RTPC may be suitable for assessing the impact of HRV on hemodynamics and provide insight for AF management in highly arrhythmic patients. 1 TECHNICAL EFFICACY: Stage 2.

Deep breathing couples CSF and venous flow dynamics

Venous system pathologies have increasingly been linked to clinically relevant disorders of CSF circulation whereas the exact coupling mechanisms still remain unknown. In this work, flow dynamics of both systems were studied using real-time phase-contrast flow MRI in 16 healthy subjects during normal and forced breathing. Flow evaluations in the aqueduct, at cervical level C3 and lumbar level L3 for both the CSF and venous fluid systems reveal temporal modulations by forced respiration. During normal breathing cardiac-related flow modulations prevailed, while forced breathing shifted the dominant frequency of both CSF and venous flow spectra towards the respiratory component and prompted a correlation between CSF and venous flow in the large vessels. The average of flow magnitude of CSF was increased during forced breathing at all spinal and intracranial positions. Venous flow in the large vessels of the upper body decreased and in the lower body increased during forced breathing. Deep respiration couples interdependent venous and brain fluid flow—most likely mediated by intrathoracic and intraabdominal pressure changes. Further insights into the driving forces of CSF and venous circulation and their correlation will facilitate our understanding how the venous system links to intracranial pressure regulation and of related forms of hydrocephalus.

Spinal CSF flow in response to forced thoracic and abdominal respiration

BackgroundRespiration-induced pressure changes represent a powerful driving force of CSF dynamics as previously demonstrated using flow-sensitive real-time magnetic resonance imaging (MRI). The purpose of the present study was to elucidate the sensitivity of CSF flow along the spinal canal to forced thoracic versus abdominal respiration.MethodsEighteen subjects without known illness were studied using real-time phase-contrast flow MRI at 3 T in the aqueduct and along the spinal canal at levels C3, Th1, Th8 and L3. Subjects performed a protocol of forced breathing comprising four cycles of 2.5 s inspiration and 2.5 s expiration.ResultsThe quantitative results for spinal CSF flow rates and volumes confirm previous findings of an upward movement during forced inspiration and reversed downward flow during subsequent exhalation—for both breathing types. However, the effects were more pronounced for abdominal than for thoracic breathing, in particular at spinal levels Th8 and L3. In general, CSF net flow volumes were very similar for both breathing conditions pointing upwards in all locations.ConclusionsSpinal CSF dynamics are sensitive to varying respiratory performances. The different CSF flow volumes in response to deep thoracic versus abdominal breathing reflect instantaneous adjustments of intrathoracic and intraabdominal pressure, respectively. Real-time MRI access to CSF flow in response to defined respiration patterns will be of clinical importance for patients with disturbed CSF circulation like hydrocephalus, pseudotumor cerebri and others.

Carotid artery flow as determined by real-time phase-contrast flow MRI and neurovascular ultrasound: A comparative study of healthy subjects

BackgroundThe assessment of carotid artery flow by neurovascular ultrasound (nvUS) can be complemented by real-time phase-contrast (RT-PC) flow MRI which apart from quantitative flow parameters offers velocity distributions across the entire vessel lumen. Materials and methodsThe feasibility and diagnostic potential of RT-PC flow MRI was evaluated in 20 healthy volunteers in comparison to conventional nvUS. RT-PC flow MRI at 40 ms temporal resolution and 0.8 mm in-plane resolution resulted in velocity maps with low phase noise and high spatiotemporal accuracy by exploiting respective advances of a recent nonlinear inverse model-based reconstruction. Peak-systolic velocities (PSV), end-diastolic velocities (EDV), flow volumes and comprehensive velocity profiles were determined in the common, internal and external carotid artery on both sides. ResultsFlow characteristics such as pulsatility and individual abnormalities shown on nvUS could be reproduced and visualized in detail by RT-PC flow MRI. PSV to EDV differences revealed good agreement between both techniques, mean PSV and EDV were significantly lower and flow volumes were higher for MRI. ConclusionOur findings suggest that RT-PC flow MRI adds to clinical diagnostics, e.g. by alterations of dynamic velocity distributions in patients with carotid stenosis. Lower PSV and EDV values than for nvUS mainly reflect the longer MRI acquisition time which attenuates short peak velocities, while higher flow volumes benefit from a proper assessment of the true vessel lumen.

Respiration and the watershed of spinal CSF flow in humans

The dynamics of human CSF in brain and upper spinal canal are regulated by inspiration and connected to the venous system through associated pressure changes. Upward CSF flow into the head during inspiration counterbalances venous flow out of the brain. Here, we investigated CSF motion along the spinal canal by real-time phase-contrast flow MRI at high spatial and temporal resolution. Results reveal a watershed of spinal CSF dynamics which divides flow behavior at about the level of the heart. While forced inspiration prompts upward surge of CSF flow volumes in the entire spinal canal, ensuing expiration leads to pronounced downward CSF flow, but only in the lower canal. The resulting pattern of net flow volumes during forced respiration yields upward CSF motion in the upper and downward flow in the lower spinal canal. These observations most likely reflect closely coupled CSF and venous systems as both large caval veins and their anastomosing vertebral plexus react to respiration-induced pressure changes.

Abstract TP201: Carotid Artery Flow as Determined by Real-Time Phase-Contrast Flow Mri and Neurovascular Ultrasound: a Comparative Study of Healthy Subjects

Background: The assessment of carotid artery flow by neurovascular ultrasound (nvUS) may be complemented by real-time phase-contrast (RT-PC) flow MRI which apart from quantitative flow parameters offers velocity distributions across the entire vessel lumen. Methods: The feasibility and diagnostic potential of RT-PC flow MRI was evaluated in 20 healthy volunteers in comparison to conventional nvUS. RT-PC flow MRI at 40 ms temporal resolution and 0.8 mm in-plane resolution resulted in velocity maps with low phase noise and high spatiotemporal accuracy by exploiting respective advances of a recent nonlinear inverse model-based reconstruction. Peak-systolic velocities (PSV), end-diastolic velocities (EDV), flow volumes and comprehensive velocity profiles were determined in the common, internal and external carotid artery on both sides. Results: Characteristics in pulsatility and laminar flow, including individual flow abnormalities shown on nvUS, could be reproduced and visualized in detail by RT-PC flow MRI. Fig. 1 shows a representative color-coded duplex sonography with doppler spectrum (A), flow volume measurement by RT-PC flow MRI (B) and a three-dimensional representation of through-plane velocities at peak systole (C) and end diastole (D) in the internal carotid artery. PSV to EDV differences revealed good agreement between both techniques, mean PSV and EDV were significantly lower and flow volumes were higher for MRI. Conclusions: Our findings suggest that RT-PC flow MRI may add to clinical diagnostics, e.g. by alterations of dynamic velocity distributions in patients with carotid stenosis. Lower PSV and EDV values than for nvUS mainly reflect the longer MRI acquisition time which attenuates short peak velocities, while higher flow volumes benefit from a proper assessment of the true vessel lumen.

An eigenvalue approach for the automatic scaling of unknowns in model-based reconstructions: Application to real-time phase-contrast flow MRI.

The purpose of this work is to develop an automatic method for the scaling of unknowns in model-based nonlinear inverse reconstructions and to evaluate its application to real-time phase-contrast (RT-PC) flow magnetic resonance imaging (MRI). Model-based MRI reconstructions of parametric maps which describe a physical or physiological function require the solution of a nonlinear inverse problem, because the list of unknowns in the extended MRI signal equation comprises multiple functional parameters and all coil sensitivity profiles. Iterative solutions therefore rely on an appropriate scaling of unknowns to numerically balance partial derivatives and regularization terms. The scaling of unknowns emerges as a self-adjoint and positive-definite matrix which is expressible by its maximal eigenvalue and solved by power iterations. The proposed method is applied to RT-PC flow MRI based on highly undersampled acquisitions. Experimental validations include numerical phantoms providing ground truth and a wide range of human studies in the ascending aorta, carotid arteries, deep veins during muscular exercise and cerebrospinal fluid during deep respiration. For RT-PC flow MRI, model-based reconstructions with automatic scaling not only offer velocity maps with high spatiotemporal acuity and much reduced phase noise, but also ensure fast convergence as well as accurate and precise velocities for all conditions tested, i.e. for different velocity ranges, vessel sizes and the simultaneous presence of signals with velocity aliasing. In summary, the proposed automatic scaling of unknowns in model-based MRI reconstructions yields quantitatively reliable velocities for RT-PC flow MRI in various experimental scenarios.

4D real-time phase-contrast flow MRI with sparse sampling.

Conventional phase-contrast (PC) MRI relies on electrocardiogram (ECG)-synchronized cine acquisition and respiration control. It often results in relatively low data acquisition efficiency, and is unable to assess blood flow variabilities. Real-time imaging is a promising technique to overcome these limitations; however, it results in a challenging image reconstruction problem with highly-undersampled (k; t)-space data. This paper presents a novel model-based imaging method, which integrates low-rank modeling with parallel imaging, to enable 4D real-time PC MRI without ECG gating and respiration control. The proposed method achieves an isotropic spatial resolution of 2.4 mm and temporal resolution of 35.2 ms, with three directional flow encodings. Moreover, it is able to resolve beat-by-beat flow variations, which cannot be achieved by the conventional cine-based approach. The proposed method was evaluated with in vivo experiments with one healthy subject and one arrhythmic patient. For the first time, we demonstrate the feasibility of 4D real-time PC MRI.

Real-time phase-contrast flow cardiovascular magnetic resonance with low-rank modeling and parallel imaging

BackgroundConventional phase-contrast cardiovascular magnetic resonance (PC-CMR) employs cine-based acquisitions to assess blood flow condition, in which electro-cardiogram (ECG) gating and respiration control are generally required. This often results in lower acquisition efficiency, and limited utility in the presence of cardiovascular pathology (e.g., cardiac arrhythmia). Real-time PC-CMR, without ECG gating and respiration control, is a promising alternative that could overcome limitations of the conventional approach. But real-time PC-CMR involves image reconstruction from highly undersampled (k, t)-space data, which is very challenging. In this study, we present a novel model-based imaging method to enable high-resolution real-time PC-CMR with sparse sampling.MethodsThe proposed method captures spatiotemporal correlation among flow-compensated and flow-encoded image sequences with a novel low-rank model. The image reconstruction problem is then formulated as a low-rank matrix recovery problem. With proper temporal subspace modeling, it results in a convex optimization formulation. We further integrate this formulation with the SENSE-based parallel imaging model to handle multichannel acquisitions. The performance of the proposed method was systematically evaluated in 2D real-time PC-CMR with flow phantom experiments and in vivo experiments (with healthy subjects). Additionally, we performed a feasibility study of the proposed method on patients with cardiac arrhythmia.ResultsThe proposed method achieves a spatial resolution of 1.8 mm and a temporal resolution of 18 ms for 2D real-time PC-CMR with one directional flow encoding. For the flow phantom experiments, both regular and irregular flow patterns were accurately captured. For the in vivo experiments with healthy subjects, flow dynamics obtained from the proposed method correlated well with those from the cine-based acquisitions. For the experiments with the arrhythmic patients, the proposed method demonstrated excellent capability of resolving the beat-by-beat flow variations, which cannot be obtained from the conventional cine-based method.ConclusionThe proposed method enables high-resolution real-time PC-CMR at 2D without ECG gating and respiration control. It accurately resolves beat-by-beat flow variations, which holds great promise for studying patients with irregular heartbeats.

Model-based reconstruction for real-time phase-contrast flow MRI: Improved spatiotemporal accuracy.

To develop a model-based reconstruction technique for real-time phase-contrast flow MRI with improved spatiotemporal accuracy in comparison to methods using phase differences of two separately reconstructed images with differential flow encodings. The proposed method jointly computes a common image, a phase-contrast map, and a set of coil sensitivities from every pair of flow-compensated and flow-encoded datasets obtained by highly undersampled radial FLASH. Real-time acquisitions with five and seven radial spokes per image resulted in 25.6 and 35.7 ms measuring time per phase-contrast map, respectively. The signal model for phase-contrast flow MRI requires the solution of a nonlinear inverse problem, which is accomplished by an iteratively regularized Gauss-Newton method. Aspects of regularization and scaling are discussed. The model-based reconstruction was validated for a numerical and experimental flow phantom and applied to real-time phase-contrast MRI of the human aorta for 10 healthy subjects and 2 patients. Under all conditions, and compared with a previously developed real-time flow MRI method, the proposed method yields quantitatively accurate phase-contrast maps (i.e., flow velocities) with improved spatial acuity, reduced phase noise and reduced streaking artifacts. This novel model-based reconstruction technique may become a new tool for clinical flow MRI in real time. Magn Reson Med 77:1082-1093, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Advances in real-time phase-contrast flow MRI using asymmetric radial gradient echoes.

To provide multidimensional velocity compensation for real-time phase-contrast flow MRI. The proposed method introduces asymmetric gradient echoes for highly undersampled radial FLASH MRI with phase-sensitive image reconstruction by regularized nonlinear inversion (NLINV). Using an adapted gradient delay correction the resulting image quality was analyzed by simulations and experimentally validated at 3 Tesla. For real-time flow MRI the reduced gradient-echo timing allowed for the incorporation of velocity-compensating waveforms for all imaging gradients at even shorter repetition times. The results reveal a usable degree of 20% asymmetry. Real-time flow MRI with full velocity compensation eliminated signal void in a flow phantom, confirmed flow parameters in healthy subjects and demonstrated signal recovery and phase conservation in a patient with aortic valve insufficiency and stenosis. Exemplary protocols at 1.4-1.5 mm resolution and 6 mm slice thickness achieved total acquisition times of 33.3-35.7 ms for two images (7 spokes each) with and without flow-encoding gradient. Asymmetric gradient echoes were successfully implemented for highly undersampled radial trajectories. The resulting temporal gain offers full velocity compensation for real-time phase-contrast flow MRI which minimizes false-positive contributions from complex flow and further enhances the temporal resolution compared with acquisitions with symmetric echoes.

Validation of segmented and real-time EPI phase contrast flow quantification against segmented gradient echo sequences

Background MR based Flow Quantification is an established method for measuring cardio-pulmonary haemodynamics, but is challenging to perform in situations where it may be advantageous to asses real-world physiological behavior, for example in exercise. The availability of a new real time flow quantification sequence presents the opportunity to measure velocity and flow without these challenges. This study is a preliminary validation of the method as a precursor to use of the sequence in subjects undergoing assessment of induced haemodynamic change by exercise and preload alteration. Methods

Spatiotemporal phase unwrapping for real-time phase-contrast flow MRI.

To develop and evaluate a practical phase unwrapping method for real-time phase-contrast flow MRI using temporal and spatial continuity. Real-time phase-contrast MRI of through-plane flow was performed using highly undersampled radial FLASH with phase-sensitive reconstructions by regularized nonlinear inversion. Experiments involved flow in a phantom and the human aorta (10 healthy subjects) with and without phase wrapping for velocity encodings of 100 cm·s(-1) and 200 cm·s(-1) . Phase unwrapping was performed for each individual cardiac cycle and restricted to a region of interest automatically propagated to all time frames. The algorithm exploited temporal continuity in forward and backward direction for all pixels with a "continuous" representation of blood throughout the entire cardiac cycle (inner vessel lumen). Phase inconsistencies were corrected by a comparison with values from direct spatial neighbors. The latter approach was also applied to pixels exhibiting a discontinuous signal intensity time course due to movement-induced spatial displacements (peripheral vessel zone). Phantom and human flow MRI data were successfully unwrapped. When halving the velocity encoding, the velocity-to-noise ratio (VNR) increased by a factor of two. The proposed phase unwrapping method for real-time flow MRI allows for measurements with reduced velocity encoding and increased VNR.

Real-time phase-contrast flow MRI of the ascending aorta and superior vena cava as a function of intrathoracic pressure (Valsalva manoeuvre)

Real-time phase-contrast flow MRI at high spatiotemporal resolution was applied to simultaneously evaluate haemodynamic functions in the ascending aorta (AA) and superior vena cava (SVC) during elevated intrathoracic pressure (Valsalva manoeuvre). Real-time phase-contrast flow MRI at 3 T was based on highly undersampled radial gradient-echo acquisitions and phase-sensitive image reconstructions by regularized non-linear inversion. Dynamic alterations of flow parameters were obtained for 19 subjects at 40-ms temporal resolution, 1.33-mm in-plane resolution and 6-mm section thickness. Real-time measurements were performed during normal breathing (10 s), increased intrathoracic pressure (10 s) and recovery (20 s). Real-time measurements were technically successful in all volunteers. During the Valsalva manoeuvre (late strain) and relative to values during normal breathing, the mean peak flow velocity and flow volume decreased significantly in both vessels (p < 0.001) followed by a return to normal parameters within the first 10 s of recovery in the AA. By contrast, flow in the SVC presented with a brief (1-2 heartbeats) but strong overshoot of both the peak velocity and blood volume immediately after pressure release followed by rapid normalization. Real-time phase-contrast flow MRI may assess cardiac haemodynamics non-invasively, in multiple vessels, across the entire luminal area and at high temporal and spatial resolution. Future clinical applications of this technique promise new insights into haemodynamic alterations associated with pre-clinical congestive heart failure or diastolic dysfunction, especially in cases where echocardiography is technically compromised.

Real-time phase-contrast flow MRI of haemodynamic changes in the ascending aorta and superior vena cava during Mueller manoeuvre

To evaluate the potential of real-time phase-contrast flow magnetic resonance imaging (MRI) at 40 ms resolution for the simultaneous determination of blood flow in the ascending aorta (AA) and superior vena cava (SVC) in response to reduced intrathoracic pressure (Mueller manoeuvre). Through-plane flow was assessed in 20 healthy young subjects using real-time phase-contrast MRI based on highly undersampled radial fast low-angle shot (FLASH) with image reconstruction by regularized non-linear inversion. Haemodynamic alterations (three repetitions per subject = 60 events) were evaluated during normal breathing (10 s), inhalation with nearly closed epiglottis (10 s), and recovery (20 s). Relative to normal breathing and despite interindividual differences, reduced intrathoracic pressure by at least 30 mmHg significantly decreased the initial peak mean velocity (averaged across the lumen) in the AA by -24 ± 9% and increased the velocity in the SVC by +28 ± 25% (p < 0.0001, n = 23 successful events). Respective changes in flow volume per heartbeat were -25 ± 9% in the AA and +49 ± 44% in the SVC (p < 0.0001, n = 23). Flow parameters returned to baseline during sustained pressure reduction, while the heart rate was elevated by 10% (p < 0.0001) after the start (n = 24) and end (n = 17) of the manoeuvre. Real-time flow MRI during low intrathoracic pressure non-invasively revealed quantitative haemodynamic adjustments in both the AA and SVC.

Real-time cardiac phase contrast MRI blood flow including Valsalva and Mueller maneuver. Initial experiences

Background A high resolution real-time phase-contrast MRI flow technique was used to measure flow dynamics in the ascending aorta as well as superior vena cava. MRI technique based on undersampled radial fast low-angle shot acquisitions with phase-sensitive image reconstructions by regularized nonlinear inversion. Normal flow values as well as flow measurements during physiologic stress tests like Valsalva (increased intrathoracic pressure) and Mueller (decreased intrathoracic pressure, reverse of Valsalva maneuver) were obtained in healthy volunteers.

Simultaneous Right and Left Heart Real-Time, Free-Breathing CMR Flow Quantification Identifies Constrictive Physiology

The purpose of this study was to evaluate the ability of a novel cardiac magnetic resonance (CMR) real-time phase contrast (RT-PC) flow measurement technique to reveal the discordant respirophasic changes in mitral and tricuspid valve in flow indicative of the abnormal hemodynamics seen in constrictive pericarditis (CP). Definitive diagnosis of CP requires identification of constrictive hemodynamics with or without pericardial thickening. CMR to date has primarily provided morphological assessment of the pericardium. Sixteen patients (age 57 ± 13 years) undergoing CMR to assess known or suspected CP and 10 controls underwent RT-PC that acquired simultaneous mitral valve and tricuspid valve inflow velocities over 10 s of unrestricted breathing. The diagnosis of CP was confirmed via clinical history, diagnostic imaging, cardiac catheterization, intraoperative findings, and histopathology. Ten patients had CP, all with increased pericardial thickness (6.2 ± 1.0 mm). RT-PC imaging demonstrated discordant respirophasic changes in atrioventricular valve inflow velocities in all CP patients, with mean ± SD mitral valve and tricuspid valve inflow velocity variation of 46 ± 20% and 60 ± 15%, respectively, compared with 16 ± 8% and 24 ± 11% in patients without CP (p < 0.004 vs. patients with CP for both) and 17 ± 5% and 31 ± 13% in controls (p < 0.001 vs. patients with CP for both). There was no difference in atrioventricular valve inflow velocity variation between patients without CP compared with controls (p > 0.3 for both). Respiratory variation exceeding 25% across the mitral valve yielded a sensitivity of 100%, a specificity of 100%, and an area under the receiver-operating characteristic curve of 1.0 to detect CP physiology. Using a cutoff of 45%, variation of transtricuspid valve velocity had a sensitivity of 90%, a specificity of 88%, and an area under the receiver-operating characteristic curve of 0.98. Accentuated and discordant respirophasic changes in mitral valve and tricuspid valve inflow velocities characteristic of CP can be identified noninvasively with RT-PC CMR. When incorporated into existing CMR protocols for imaging pericardial morphology, RT-PC CMR provides important hemodynamic evidence with which to make a definite diagnosis of CP.

Pectus Excavatum With Compression of the Inferior Vena Cava

Pectus excavatum (PE) is a common disorder of the chest wall that affects 1 in 500 of the general population. Affected individuals have cosmetic and, less commonly, cardiopulmonary consequences that typically present during the adolescent years. The latter is appreciated only in those with severe phenotypes, especially if associated with a “straight back” that further limits the anterior-posterior thoracic dimensions. Although the cardiopulmonary complications of PE have been well described, we describe a unique presentation of a patient who had experienced years of intractable syncope before receiving corrective surgery for severe PE. The role of cardiovascular magnetic resonance imaging (CMR) in her diagnosis and subsequent treatment is also highlighted. A 22-year-old woman presented with a long-standing history of recurrent syncope, beginning in early adolescence. These episodes typically occurred after prolonged periods of standing or walking, beginning with a prodrome of diaphoresis and blurred vision and culminating in loss of consciousness. She described self-taught maneuvers that reduced these symptoms, including twisting her torso to the side and performing rapid, shallow breathing. In spite of these maneuvers, she continued to be limited by frequent syncope and ultimately stopped attending school at 16 years of age. On examination, she had a marked pectus deformity with a straight back appearance. Her heart sounds were normal, with a Grade II out of VI systolic ejection murmur at the left sternal border. There was no jugular venous distention and no peripheral edema. Following indentification of the chest wall deformity further questioning revealed that both her brother and paternal uncle had severe PE, suggesting an autosomal dominant inheritance …