Fluid- and Biomechanical Analysis of Ascending Thoracic Aorta Aneurysm with Concomitant Aortic Insufficiency.

We present a comprehensive and original framework for the biomechanical analysis of patients affected by ascending thoracic aorta aneurysm and aortic insufficiency. Our aim is to obtain crucial indications about the role played by deranged hemodynamics on the ATAAs risk of rupture. Computational fluid dynamics analysis was performed using patient-specific geometries and boundary conditions derived from 4D MRI. Blood flow helicity and wall shear stress descriptors were assessed. A bulge inflation test was carried out in vitro on the 4 ATAAs after surgical repair. The healthy volunteers showed no eccentric blood flow, a mean TAWSS of 1.5 ± 0.3 Pa and mean OSI of 0.325 ± 0.025. In 3 aneurismal patients, jet flow impingement on the aortic wall resulted in large TAWSS values and low OSI which were amplified by the AI degree. However, the tissue strength did not appear to be significantly reduced. The fourth patient, which showed the lowest TAWSS due to the absence of jet flow, had the smallest strength in vitro. Interestingly this patient presented a bovine arch abnormality. Jet flow impingement with high WSS values is frequent in ATAAs and our methodology seems to be appropriate for determining whether it may increase the risk of rupture or not.

Comprehensive 4-stage categorization of bicuspid aortic valve leaflet morphology by cardiac MRI in 386 patients.

Bicuspid aortic valve (BAV) disease is heterogeneous and related to valve dysfunction and aortopathy. Appropriate follow up and surveillance of patients with BAV may depend on correct phenotypic categorization. There are multiple classification schemes, however a need exists to comprehensively capture commissure fusion, leaflet asymmetry, and valve orifice orientation. Our aim was to develop a BAV classification scheme for use at MRI to ascertain the frequency of different phenotypes and the consistency of BAV classification. The BAV classification scheme builds on the Sievers surgical BAV classification, adding valve orifice orientation, partial leaflet fusion and leaflet asymmetry. A single observer successfully applied this classification to 386 of 398 Cardiac MRI studies. Repeatability of categorization was ascertained with intraobserver and interobserver kappa scores. Sensitivity and specificity of MRI findings was determined from operative reports, where available. Fusion of the right and left leaflets accounted for over half of all cases. Partial leaflet fusion was seen in 46% of patients. Good interobserver agreement was seen for orientation of the valve opening (κ = 0.90), type (κ = 0.72) and presence of partial fusion (κ = 0.83, p < 0.0001). Retrospective review of operative notes showed sensitivity and specificity for orientation (90, 93%) and for Sievers type (73, 87%). The proposed BAV classification schema was assessed by MRI for its reliability to classify valve morphology in addition to illustrating the wide heterogeneity of leaflet size, orifice orientation, and commissural fusion. The classification may be helpful in further understanding the relationship between valve morphology, flow derangement and aortopathy.

In Vivo Assessment of the Impact of Regional Intracranial Atherosclerotic Lesions on Brain Arterial 3D Hemodynamics.

BACKGROUND AND PURPOSE: Intracranial atherosclerosis induces hemodynamic disturbance, which is not well-characterized, particularly in cerebral flow redistribution. We aimed to characterize the impact of regional stenotic lesions on intracranial hemodynamics by using 4D flow MR imaging. MATERIALS AND METHODS: 4D flow MR imaging was performed in 22 symptomatic patients (mean age, 68.4 ± 14.2 years) with intracranial stenosis (ICA, n = 7; MCA, n = 9; basilar artery, n = 6) and 10 age-appropriate healthy volunteers (mean age, 60.7 ± 8.1 years). 3D blood flow patterns were visualized by using time-integrated pathlines. Blood flow and peak velocity asymmetry indices were compared between patients and healthy volunteers in 4 prespecified arteries: ICAs, MCAs, and anterior/posterior cerebral arteries. RESULTS: 3D blood flow pathlines demonstrated flow redistribution across cerebral arteries in patients with unilateral intracranial stenosis. For patients with ICA stenosis compared with healthy volunteers, significantly lower flow and peak velocities were identified in the ipsilateral ICA (P = .001 and P = .001) and MCA (P < .001 and P = .001), but higher flow, in the ipsilateral PCA (P < .001). For patients with MCA stenosis, significantly lower flow and peak velocities were observed in the ipsilateral ICA (P = .009 and P = .045) and MCA (P < .001 and P = .005), but significantly higher flow was found in the ipsilateral posterior cerebral artery (P = .014) and anterior cerebral artery (P = .006). The asymmetry indices were not significantly different between patients with basilar artery stenosis and the healthy volunteers. CONCLUSIONS: Regional intracranial atherosclerotic lesions not only alter distal arterial flow but also significantly affect ipsilateral collateral arterial hemodynamics.

Advanced flow MRI: emerging techniques and applications.

Magnetic resonance imaging (MRI) techniques provide non-invasive and non-ionising methods for the highly accurate anatomical depiction of the heart and vessels throughout the cardiac cycle. In addition, the intrinsic sensitivity of MRI to motion offers the unique ability to acquire spatially registered blood flow simultaneously with the morphological data, within a single measurement. In clinical routine, flow MRI is typically accomplished using methods that resolve two spatial dimensions in individual planes and encode the time-resolved velocity in one principal direction, typically oriented perpendicular to the two-dimensional (2D) section. This review describes recently developed advanced MRI flow techniques, which allow for more comprehensive evaluation of blood flow characteristics, such as real-time flow imaging, 2D multiple-venc phase contrast MRI, four-dimensional (4D) flow MRI, quantification of complex haemodynamic properties, and highly accelerated flow imaging. Emerging techniques and novel applications are explored. In addition, applications of these new techniques for the improved evaluation of cardiovascular (aorta, pulmonary arteries, congenital heart disease, atrial fibrillation, coronary arteries) as well as cerebrovascular disease (intra-cranial arteries and veins) are presented.

Imaging of cardiovascular complications in patients with systemic lupus erythematosus.

In the long-term survival of patients with systemic lupus erythematosus (SLE), cardiovascular disease (CVD) is a leading cause of death. Recently, multimodality cardiovascular imaging methods have been adopted for the evaluation of cardiovascular risk, which has shown to be associated with both traditional cardiovascular risk factors and SLE-specific conditions. Quantitative imaging biomarkers, which can describe both morphological and functional abnormalities in the heart, are expected to provide new insights to stratify cardiovascular risks and to guide SLE management by assessing individual responses to therapies either protecting the cardiovascular system or suppressing the autoimmune reactions. In this review, we will discuss cutting-edge cardiovascular imaging techniques and potential clinical applications and limitations of those techniques for the evaluation of major SLE-related heart disorders.

Triapine-mediated ABCB1 induction via PKC induces widespread therapy unresponsiveness but is not underlying acquired triapine resistance.

Although triapine is promising for treatment of advanced leukemia, it failed against solid tumors due to widely unknown reasons. To address this issue, a new triapine-resistant cell line (SW480/tria) was generated by drug selection and investigated in this study. Notably, SW480/tria cells displayed broad cross-resistance against several known ABCB1 substrates due to high ABCB1 levels (induced by promoter hypomethylation). However, ABCB1 inhibition did not re-sensitize SW480/tria cells to triapine and subsequent analysis revealed that triapine is only a weak ABCB1 substrate without significant interaction with the ABCB1 transport function. Interestingly, in chemo-naive, parental SW480 cells short-time (24 h) treatment with triapine stimulated ABCB1 expression. These effects were based on activation of protein kinase C (PKC), a known response to cellular stress. In accordance, SW480/tria cells were characterized by elevated levels of PKC. Together, this led to the conclusion that increased ABCB1 expression is not the major mechanism of triapine resistance in SW480/tria cells. In contrast, increased ABCB1 expression was found to be a consequence of triapine stress-induced PKC activation. These data are especially of importance when considering the choice of chemotherapeutics for combination with triapine.

Evaluation of 4D vascular flow and tissue perfusion in cerebral arteriovenous malformations: influence of Spetzler-Martin grade, clinical presentation, and AVM risk factors.

BACKGROUND AND PURPOSE: The role of intracranial hemodynamics in the pathophysiology and risk stratification of brain AVMs remains poorly understood. The purpose of this study was to assess the influence of Spetzler-Martin grade, clinical history, and risk factors on vascular flow and tissue perfusion in cerebral AVMs. MATERIALS AND METHODS: 4D flow and perfusion MR imaging was performed in 17 patients with AVMs. Peak velocity and blood flow were quantified in AVM feeding and contralateral arteries, draining veins, and the straight sinus. Regional perfusion ratios (CBF, CBV, and MTT) were calculated between affected and nonaffected hemispheres. RESULTS: Regarding flow parameters, high-grade AVMs (Spetzler-Martin grade of >2) demonstrated significantly increased peak velocity and blood flow in the major feeding arteries (P < .001 and P = .004) and straight sinus (P = .003 and P = .012) and increased venous draining flow (P = .001). The Spetzler-Martin grade significantly correlated with cumulative feeding artery flow (r = 0.85, P < .001) and draining vein flow (r = 0.80, P < .001). Regarding perfusion parameters, perinidal CBF and CBV ratios were significantly lower (P < .001) compared with the remote ratios and correlated negatively with cumulative feeding artery flow (r = -0.60, P = .014 and r = -0.55, P = .026) and draining vein flow (r = -0.60, P = .013 and r = -0.56, P = .025). Multiple regression analysis revealed no significant association of AVM flow or perfusion parameters with clinical presentation (rupture and seizure history) and AVM risk factors. CONCLUSIONS: Macrovascular flow was significantly associated with increasing Spetzler-Martin grade and correlated with perinidal microvascular perfusion in cerebral AVMs. Future longitudinal studies are needed to evaluate the potential of comprehensive cerebral flow and perfusion MR imaging for AVM risk stratification.

4D flow magnetic resonance imaging in bicuspid aortic valve disease demonstrates altered distribution of aortic blood flow helicity.

PURPOSE: Changes in aortic geometry or presence of aortic valve (AoV) disease can result in substantially altered aortic hemodynamics. Dilatation of the ascending aorta or AoV abnormalities can result in an increase in helical flow. METHODS: 4D flow magnetic resonance imaging was used to test the feasibility of quantitative helicity analysis using equidistantly distributed 2D planes along the entire aorta. The evaluation of the method included three parts: (1) the quantification of helicity in 12 healthy subjects, (2) an evaluation of observer variability and test-retest reliability, and (3) the quantification of helical flow in 16 patients with congenitally altered bicuspid AoVs. RESULTS: Helicity quantification in healthy subjects revealed consistent directions of flow rotation along the entire aorta with high clockwise helicity in the aortic arch and an opposite rotation sense in the ascending and descending aorta. The results demonstrated good scan-rescan and inter- and intraobserver agreement of the helicity parameters. Helicity quantification in patients revealed a significant increase in absolute peak relative helicity during systole and a considerably greater heterogeneous distribution of mean helicity in the aorta. CONCLUSION: The method has the potential to serve as a reference distribution for comparisons of helical flow between healthy subjects and patients or between different patient groups.

Wall shear stress distribution at the carotid bifurcation: influence of eversion carotid endarterectomy.

OBJECTIVES: To test the feasibility of four-dimensional (4D) flow MRI to quantify the systolic wall shear stress (WSSsystole) and oscillatory shear index (OSI) in high-grade internal carotid artery (ICA) stenosis before and after endarterectomy (CEA). METHODS: Twenty patients with ≥60 % ICA stenosis were prospectively and consequently included. Four-dimensional flow MRI was used to measure individual time-resolved 3D blood flow velocities. Segmental WSSsystole and OSI were derived at eight wall segments in analysis planes positioned along the ICA, common (CCA) and external carotid artery (ECA). RESULTS: Regional WSSsystole of all patients decreased after CEA (P < 0.05). Changes were most prominent at the ICA bulb but remained unchanged in the CCA and ECA. OSI was significantly lower after CEA in the lateral vessel walls (P < 0.05). For analysis planes at the stenosis in- and outlet, a reduction of mean WSSsystole by 32 % and 52 % (P < 0.001) and OSI distal to the stenosis (40 %, P = 0.01) was found after CEA. CONCLUSIONS: Our findings show the potential of in vivo 4D flow MRI to quantify haemodynamic changes in wall shear stress even in patients with complex flow conditions.

Intracranial 4D flow MRI: toward individualized assessment of arteriovenous malformation hemodynamics and treatment-induced changes.

BACKGROUND AND PURPOSE: Arteriovenous malformations are an important etiology of hemorrhagic stroke. However, current imaging modalities and risk do not provide insights into individual AVM hemodynamics and its role in pathophysiology. The aims of this study are to determine whether intracranial 4D flow MR imaging can provide insights into arteriovenous malformation hemodynamics independent of the Spetzler-Martin grade and to report the changes in flow observed during staged embolization. MATERIALS AND METHODS: Intracranial 3D blood flow was assessed in 20 patients with AVM (age = 39 ± 15 years, Spetzler-Martin grade ranging from 1-4) with the use of 4D flow MR imaging (temporal resolution = 45 ms, spatial resolution = [1.2-1.6mm](3)). AVM hemodynamics were visualized by means of time-integrated 3D pathlines depicting the AVM arterial feeding and venous draining patterns over the cardiac cycle. Analysis included the grading of feeding and draining velocities on a 3-point scale (0 = low <25 cm/s, 1 = medium <50 cm/s, 2 = high >50 cm/s). For 4 of 20 patients undergoing 4D flow MR imaging follow-up after staged embolization, peak velocities were quantified in arterial feeders, draining veins, the sagittal sinus, and contralateral arteries. RESULTS: In 50% of the cases with Spetzler-Martin grade >2, heterogeneous flow (velocity grade differences >1) was found across arteries and veins. Velocities in draining veins increased from Spetzler-Martin grade = 1 (grading = 0.5 ± 0.6) to Spetzler-Martin grade ≥3 (1.1 ± 0.6), whereas arterial velocities were similar (1.7 ± 0.6 versus 1.5 ± 0.6). In the postembolization subgroup of 4 patients, 4D flow MR imaging demonstrated successively more compact AVM and redistribution of velocities. Changes in arterial and venous velocities during treatment were highly different among individuals. CONCLUSIONS: Spetzler-Martin grade does not reflect differences in 3D AVM arterial and venous hemodynamics, and an individual assessment of AVM hemodynamics may be needed for improved lesion characterization. Four-dimensional flow MR imaging may have the potential to monitor and guide embolization treatment planning.

Comparison of blood flow velocity quantification by 4D flow MR imaging with ultrasound at the carotid bifurcation.

BACKGROUND AND PURPOSE: 4D flow MR imaging is an emerging technique that allows visualization and quantification of 3D blood flow in vivo. However, representative studies evaluating its accuracy are lacking. Therefore, we compared blood flow quantification by using 4D flow MR imaging with US within the carotid bifurcation. MATERIALS AND METHODS: Thirty-two healthy volunteers (age 25.3 ± 3.4 years) and 20 patients with ≥50% ICA stenosis (age 67.7 ± 7.4 years) were examined preoperatively and postoperatively by use of 4D flow MR imaging, with complete coverage of the left and right carotid bifurcation. Blood flow velocities were assessed with standardized 2D analysis planes distributed along the CCA and the ICA and were compared with US at baseline and postoperatively in patients. In addition, we tested reproducibility and interobserver agreement of 4D MR imaging in 10 volunteers. RESULTS: Overall, 101 CCAs and 79 ICAs were available for comparison. MR imaging underestimated (P < .05) systolic CCA and ICA blood flow velocity by 26% (0.79 ± 0.29 m/s vs 1.06 ± 0.31 m/s) and 19% (0.72 ± 0.21 m/s vs 0.89 ± 0.27 m/s) compared with US. Diastolic blood flow velocities were similar for MR imaging and US (differences, 9% and 3%, respectively; not significant). Reproducibility and interobserver agreement of 4D flow MR imaging was excellent. CONCLUSIONS: 4D flow MR imaging allowed for an accurate measurement of blood flow velocities in the carotid bifurcation of both volunteers and patients with only moderate underestimation compared with US. Thus, 4D flow MR imaging seems promising for a future combination with MRA to comprehensively assess ICA stenosis and related hemodynamic changes.

Hypertensive heart disease: MR tissue phase mapping reveals altered left ventricular rotation and regional myocardial long-axis velocities.

OBJECTIVES: The aim of this study was the evaluation of left ventricular (LV) segmental 3D velocities in patients with hypertensive heart disease using magnetic resonance (MR) tissue phase mapping (TPM). METHODS: LV radial, long-axis and rotational myocardial velocities were assessed by TPM in patients with LV hypertrophy and preserved EF (n = 18, age = 53 ± 12 years) and volunteers (n = 20, age = 51 ± 4 years). Systolic and diastolic peak and time-to-peak velocities were mapped onto a 16-segment LV model. 3D myocardial motion was displayed on an extended visualisation model. Correlation coefficients were calculated to investigate differences in regional dynamics. RESULTS: Patients revealed diastolic dysfunction as expressed by decreased peak long-axis velocities in all (except apical) segments (basal, P ≤ 0.01; two midventricular segments, P = 0.02, P = 0.03). During systole, hypertrophy was associated with heterogeneous behaviour for long-axis velocities including an increase in anteroseptal apical and midventricular regions (P = 0.001), a reduction in mid-inferior segments (P = 0.03) and enhanced septal velocities (P < 0.05). Segmental correlation analysis revealed altered dynamics of LV base rotation and increased dyssynchrony of lateral long-axis motion. CONCLUSIONS: Patients with hypertensive heart disease demonstrated alterations in systolic long-axis motion, basal rotation and dyssynchrony. Longitudinal studies are needed to investigate the value of regional wall motion abnormalities regarding disease progression and outcome.

Assessment of aortic stenosis severity by cardiovascular magnetic resonance / Evaluación de la severidad de la estenosis aórtica usando resonancia magnética cardiovascular

Cardiovascular magnetic resonance (CMR) has become a valuable tool to corroborate aortic stenosis (AS) severity when echocardiography assessment is discordant. Moreover, CMR can provide useful complementary information about AS severity and hemodynamic markers. In particular, the use of advanced 4D flow CMR allows a comprehensive assessment of complex flow alterations produced by AS. This review provides an overview of the added value obtained by standard 2D flow and advanced 4D flow quantification for AS severity assessment and discusses the advantages and disadvantages of current clinical metrics. This includes an introduction of promising new hemodynamic markers, and discusses how these novel makers may identify potential complications and disease progression in patients with AS.

La imagenología de resonancia magnética cardiovascular (RMC) se ha establecido como una importante herramienta para corroborar la severidad de la estenosis aórtica (EA) cuando el examen por ecocardiografía es contradictorio. Además, la RMC puede proveer importante información complementaria con respecto a la severidad de la EA y diversos indicadores hemodinámicos. En particular, el uso de técnicas avanzadas de flujo en 4D por RMC permite una extensiva evaluación de las complejas alteraciones de flujo provocadas por la presencia de la EA. Este artículo de revisión describe de manera detallada el valor agregado obtenido en la práctica clínica con el uso de las técnicas de medición de flujo bidimensionales, así como las técnicas avanzadas de flujo en 4D para la cuantificación y evaluación de la severidad de la EA. De igual modo, se discuten las ventajas y desventajas de los parámetros clínicos comúnmente utilizados para la estratificación de la severidad de la EA. Además, incluye una introducción a nuevos y prometedores índices hemodinámicos, discute su utilidad para la identificación de potenciales complicaciones y de progresión de la EA in vivo.

Closed circuit MR compatible pulsatile pump system using a ventricular assist device and pressure control unit.

The aim of this study was to evaluate the performance of a closed circuit MR compatible pneumatically driven pump system using a ventricular assist device as pulsatile flow pump for in vitro 3D flow simulation. Additionally, a pressure control unit was integrated into the flow circuit. The performance of the pump system and its test-retest reliability was evaluated using a stenosis phantom (60% lumen narrowing). Bland-Altman analysis revealed a good test-retest reliability (mean differences = -0.016 m/s, limits of agreement = ±0.047 m/s) for in vitro flow measurements. Furthermore, a rapid prototyping in vitro model of a normal thoracic aorta was integrated into the flow circuit for a direct comparison of flow characteristics with in vivo data in the same subject. The pneumatically driven ventricular assist device was attached to the ascending aorta of the in vitro model to simulate the beating left ventricle. In the descending part of the healthy aorta a flexible stenosis was integrated to model an aortic coarctation. In vivo and in vitro comparison showed significant (P = 0.002) correlations (r = 0.9) of mean velocities. The simulation of increasing coarctation grade led to expected changes in the flow patterns such as jet flow in the post-stenotic region and increased velocities.

4D-MR flow analysis in patients after repair for tetralogy of Fallot.

OBJECTIVES: Comprehensive analysis of haemodynamics by 3D flow visualisation and retrospective flow quantification in patients after repair of tetralogy of Fallot (TOF). METHODS: Time-resolved flow-sensitive 4D MRI (spatial resolution ~ 2.5 mm, temporal resolution = 38.4 ms) was acquired in ten patients after repair of TOF and in four healthy controls. Data analysis included the evaluation of haemodynamics in the aorta, the pulmonary trunk (TP) and left (lPA) and right (rPA) pulmonary arteries by 3D blood flow visualisation using particle traces, and quantitative measurements of flow velocity. RESULTS: 3D visualisation of whole heart haemodynamics provided a comprehensive overview on flow pattern changes in TOF patients, mainly alterations in flow velocity, retrograde flow and pathological vortices. There was consistently higher blood flow in the rPA of the patients (rPA/lPA flow ratio: 2.6 ± 2.5 vs. 1.1 ± 0.1 in controls). Systolic peak velocity in the TP was higher in patients (1.9 m/s ± 0.7 m/s) than controls (0.9 m/s ± 0.1 m/s). CONCLUSIONS: 4D flow-sensitive MRI permits the comprehensive evaluation of blood flow characteristics in patients after repair of TOF. Altered flow patterns for different surgical techniques in the small patient cohort may indicate its value for patient monitoring and potentially identifying optimal surgical strategies.

Magnetic resonance tissue phase mapping: analysis of age-related and pathologically altered left ventricular radial and long-axis dyssynchrony.

PURPOSE: To employ magnetic resonance tissue phase mapping (TPM) for the assessment of age-related left ventricular (LV) synchrony of radial and long-axis motion in healthy volunteers and in hypertensive heart disease, dilated cardiomyopathy (DCM), and left bundle branch block (LBBB). MATERIALS AND METHODS: TPM (spatial/temporal resolution = 1.3 × 2.6 mm(2)/13.8 msec) was employed to measure radial and long-axis myocardial velocities in 58 healthy volunteers of three age groups and 37 patients (hypertensive, n = 18; DCM, n = 12; DCM and LBBB n = 7). Regional times-to-peak velocities (TTP) in systole and diastole were derived for all LV segments. Four measures of dyssynchrony were defined as the standard deviation of systolic and diastolic TTP for radial and long-axis motion. RESULTS: Systolic radial and diastolic long-axis dyssynchrony was increased (P < 0.01) in all patient groups compared to controls. Multiple regressions revealed a significant relationship of dyssynchrony with LV ejection fraction and mass for systolic radial (P < 0.001 resp. P = 0.02), diastolic radial (P < 0.001 resp. P < 0.05), and long-axis (P < 0.001 resp. P = 0.001) motion. Diastolic dyssynchrony correlated with the LV remodeling index (P < 0.05) and increased with age (P < 0.03). Systolic long-axis dyssynchrony was not influenced by disease or LV function. CONCLUSION: Radial systolic and long-axis diastolic dyssynchrony were the most sensitive markers for altered dyssynchrony in hypertensive heart disease or DCM. Future studies are needed to evaluate the diagnostic value of TPM-derived dyssynchrony parameters.

Iatrogenic neonatal type B aortic dissection: comprehensive MRI-based diagnosis and follow-up.

Neonatal aortic dissection is rare and most frequently iatrogenic. Decision making and appropriate imaging are highly challenging for pediatric cardiologists and radiologists. We present MRI and echocardiographic findings in the follow-up at 6 months of age of a boy with a conservatively treated iatrogenic neonatal aortic dissection (type B). To evaluate the morphology of the aortic arch and descending aorta, we carried out multidirectional time-resolved three-dimensional flow-analysis and contrast-enhanced MR angiography (CE-MRA). The MRI and Doppler echocardiographic results were closely comparable. Three-dimensional visualization helped assess details of blood flow acceleration and alteration caused by the dissection, and played a key role in our deciding not to treat surgically.