Luciano Mazzaro

IN VITRO AND PRELIMINARY IN VIVO VALIDATION OF ECHO PARTICLE IMAGE VELOCIMETRY IN CAROTID VASCULAR IMAGING

Noninvasive, easy-to-use and accurate measurements of wall shear stress (WSS) in human blood vessels have always been challenging in clinical applications. Echo particle image velocimetry (Echo PIV) has shown promise for clinical measurements of local hemodynamics and wall shear rate. Thus far, however, the method has only been validated under simple flow conditions. In this study, we validated Echo PIV under in vitro and in vivo conditions. For in vitro validation, we used an anatomically correct, compliant carotid bifurcation flow phantom with pulsatile flow conditions, using optical particle image velocimetry (optical PIV) as the reference standard. For in vivo validation, we compared Echo PIV-derived 2-D velocity fields obtained at the carotid bifurcation in five normal subjects against phase-contrast magnetic resonance imaging (PC-MRI)-derived velocity measurements obtained at the same locations. For both studies, time-dependent, 2-D, two-component velocity vectors; peak/centerline velocity, flow rate and wall shear rate (WSR) waveforms at the common carotid artery (CCA), carotid bifurcation and distal internal carotid artery (ICA) were examined. Linear regression, correlation analysis and Bland-Altman analysis were used to quantify the agreement of different waveforms measured by the two techniques. In vitro results showed that Echo PIV produced good images of time-dependent velocity vector maps over the cardiac cycle with excellent temporal (up to 0.7 ms) and spatial (∼0.5 mm) resolutions and quality, comparable with optical PIV results. Further, good agreement was found between Echo PIV and optical PIV results for velocity and WSR measurements. In vivo results also showed good agreement between Echo PIV velocities and phase contrast MRI velocities. We conclude that Echo PIV provides accurate velocity vector and WSR measurements in the carotid bifurcation and has significant potential as a clinical tool for cardiovascular hemodynamics evaluation.

Aortic Input Impedance Increases With Age in Healthy Men and Women

Aortic input impedance represents the hydraulic load presented by the systemic circulation to the left ventricle of the heart and is increased in patients with cardiovascular disease. Aging is a strong independent risk factor for cardiovascular disease and could exert this effect partly through an increase in modulus of aortic input impedance. We used a novel noninvasive technique to determine aortic input impedance in 71 healthy men and women aged 20 to 69 years. We found that the aortic input impedance spectrum was shifted rightward with advancing age, characterized by a 37% increase in the frequency of the minimum modulus between the third and seventh decade (P<0.0001). The frequency of the minimum modulus correlated with age in all subjects (r=0.48; P<0.0001), in men (r=0.43; P<0.005), and in women (r=0.53; P=0.001). Although several physical characteristics were associated with the frequency of the minimum modulus (bivariate correlation), a regression model that included age and these physical characteristics showed that age was the only independent predictor of the frequency of the minimum modulus. We conclude that aortic input impedance increases with advancing age in healthy men and women. This increase in aortic input impedance may be an important mechanism by which age increases the risk of cardiovascular disease in humans.

Cellular, pharmacological, and biophysical evaluation of explanted lungs from a patient with sickle cell disease and severe pulmonary arterial hypertension.

Pulmonary hypertension is recognized as a leading cause of morbidity and mortality in patients with sickle cell disease (SCD). We now report benchtop phenotyping from the explanted lungs of the first successful lung transplant in SCD. Pulmonary artery smooth muscle cells (PASMCs) cultured from the explanted lungs were analyzed for proliferate capacity, superoxide (O2•–) production, and changes in key pulmonary arterial hypertension (PAH)–associated molecules and compared with non-PAH PASMCs. Upregulation of several pathologic processes persisted in culture in SCD lung PASMCs in spite of cell passage. SCD lung PASMCs showed growth factor– and serum-independent proliferation, upregulation of matrix genes, and increased O2•– production compared with control cells. Histologic analysis of SCD-associated PAH arteries demonstrated increased and ectopically located extracellular matrix deposition and degradation of elastin fibers. Biomechanical analysis of these vessels confirmed increased arterial stiffening and loss of elasticity. Functional analysis of distal fifth-order pulmonary arteries from these lungs demonstrated increased vasoconstriction to an α1-adrenergic receptor agonist and concurrent loss of both endothelial-dependent and endothelial-independent vasodilation compared with normal pulmonary arteries. This is the first study to evaluate the molecular, cellular, functional, and mechanical changes in end-stage SCD-associated PAH.

Evaluation of segmentation algorithms for vessel wall detection in echo particle image velocimetry

Recent in-vitro and in-vivo validation studies confirmed the accuracy of echo particle image velocimetry (echo PIV), a simple non-invasive means of measuring multi-component blood velocity vectors. Echo PIV should also be useful for direct measurement of wall shear stress (WSS) in clinical studies. However, calculation of WSS requires accurate delineation of vessel walls in ultrasound images, which may be problematic when conventional segmentation techniques are used. In this paper, we proposed two methods for segmenting contrast enhanced B-mode images. The first is based on the intensity profile of ultrasound images, termed intensity-based edge detection (IBED) and the second based on the movement of microbubbles, termed movement-based quadratic difference (MBQD). The parameters related with the two methods were optimized over large sets of microbubble images acquired from human carotid vessels using an echo PIV system (Illumasonix LLC, Boulder, CO). A validation study on the two algorithms was carried out against manual delineations on both common carotid artery (CCA) and carotid bifurcation images, with 20 frames for each group. The inter-observer variability of three manual delineations, in pixels (about 80 µm/pixel), was 0.9±0.4, 1.3±0.6, 1.3±0.6 on CCA images, and 2.5±1.0, 3.9±1.1, 2.3±1.1 on bifurcation images. The absolute difference (mean±SD) between each computer-generated contour and the ground truths, taken as the average of three manual delineations, were 1.3±0.8, 3.8±0.8, 5.3±0.5 on CCA images, and 2.3±0.9, 4.6±1.3, 6.3±0.6 on bifurcation images, for the MBQD, IBED and active contour methods, respectively. The MBQD method shows comparable performance with manual delineations on particle images even with poor intima-media layer quality.

Noninvasive wall shear stress measurements in human carotid artery using echo particle image velocimetry: Initial clinical studies

Wall shear stress (WSS) has been shown to be important to endothelial cell function and gene expression. Previous studies have shown that fluid dynamics might be closely related to the initialization of atherosclerotic plaques which preferentially originate in areas of disturbed flow in human vessels, where WSS is low or oscillatory. We recently developed a novel ultrasound-based technique, termed echo particle image velocimetry (echo PIV), by which the multi-component hemodynamic information in human cardiovascular system could be assessed. In this paper, we show that echo PIV was successfully employed to measure hemodynamic information in the right common carotid artery (rCCA) of ten healthy volunteers and that the values show good agreement with phase-contrast magnetic resonance imaging (PC-MRI) measurements with mean absolute differences (mean±SD) of 10.0%±9.8%, 10.1%±8.8% and 17.0%±15.3% for velocity, flow rate and WSS, respectively. In particular, the mean WSS (dynes/cm^2) in rCCA of ten volunteers was found to be 9.2±2.0 by echo PIV, and 8.0±1.4 by PC-MRI, both in agreement with published data. We further showed that calculating WSS by either peak/mean velocity or flow rate together with arterial diameter was invalid for in-vivo measurements due to invalidity of assuming parabolic velocity profile in carotid artery. We found that the peak velocity across radial direction in rCCA was about 1.6 times of the mean velocity, not 2 times as it should be in parabolic distribution. In conclusion, echo PIV demonstrated several advantages over traditional techniques in terms of both temporal and spatial resolution when measuring WSS in human vessels.

Systematic validation of the echo particle image velocimetry technique using a patient specific carotid bifurcation model

Full field opaque flow measurement technique has significant applications in evaluating details of cardiovascular hemodyamics non-invasively. Echo Particle Image Velocimetry (Echo PIV) is a simple-to-use method that has shown promising results in our previous in vitro studies on measurements of blood flow characteristics. So far, however, no systematic validation of Echo PIV in a realistic vascular anatomy against reference-standard methods has been done. In this paper, a patient-specific carotid bifurcation model was created using biplane angiography data from an adult human male. The model reproduced vascular geometry accurately, while allowing for both Optical PIV and Echo PIV to be performed on the same flow field. A pulsatile pump and a compliance chamber were used to produce physiologically realistic flow conditions with a peak velocity around 70 cm/s, heart rate of 75 beats/min, mean Reynolds number of 1484, and a Womersley number of 16.1. The Echo PIV measurements were validated by Optical PIV technique, a gold standard for velocity field measurement, in terms of velocity, flow rate and wall shear rate profiles at a few different positions in carotid artery. Results show that the Echo PIV measurements agreed well with Optical PIV results, with a mean error 7.7% +/- 3.5% for velocity profiles, and a mean error 9.2% +/- 5.7% for wall shear rate profiles.

In Vivo Validation of Echo Partical Image Velocimetry (Echo PIV) in Human Carotid Arteries Using Phase-Contrast MRI

Accurate non-invasive measurements of dynamic wall shear stresses (WSS) in the cardiovascular system should allow clinicians to evaluate the progression of atherosclerosis, estimate vulnerability of plaques, and assess hemodynamic changes in the proximity of implants such as vascular grafts and stents that may contribute to restenosis. Although computational methods have been used to obtain blood flow characteristics from patients, these methods are difficult to apply in routine fashion, are prone to errors due to incorrect application of boundary conditions and are time and resource intensive. Ultrasound Doppler methods [1] allow simple measurement of blood flow velocities but are not acceptable for shear measurements because they do not provide multiple-component velocity vectors, are prone to angulation error and have relatively poor spatial resolution. Phase contrast magnetic resonance imaging (PC-MRI) velocimetry [2] does provide good spatial resolution and multiple-component velocity vectors in vivo and is considered the gold-standard. However, PC-MRI is expensive, time consuming and possesses relatively poor temporal resolution.Copyright

Measurement of Wall Shear Stress Exerted by Flowing Blood in the Human Carotid Artery: Ultrasound Doppler Velocimetry and Echo Particle Image Velocimetry

Vascular endothelial cells lining the arteries are sensitive to wall shear stress (WSS) exerted by flowing blood. An important component of the pathophysiology of vascular diseases, WSS is commonly estimated by centerline ultrasound Doppler velocimetry (UDV). However, the accuracy of this method is uncertain. We have previously validated the use of a novel, ultrasound-based, particle image velocimetry technique (echo PIV) to compute 2-D velocity vector fields, which can easily be converted into WSS data. We compared WSS data derived from UDV and echo PIV in the common carotid artery of 27 healthy participants. Compared with echo PIV, time-averaged WSS was lower using UDV (28 ± 35%). Echo PIV revealed that this was due to considerable spatiotemporal variation in the flow velocity profile, contrary to the assumption that flow is steady and the velocity profile is parabolic throughout the cardiac cycle. The largest WSS underestimation by UDV was found during peak systole (118 ± 16%) and the smallest during mid-diastole (4.3± 46%). The UDV method underestimated WSS for the accelerating and decelerating systolic measurements (68 ± 30% and 24 ± 51%), whereas WSS was overestimated for end-diastolic measurements (-44 ± 55%). Our data indicate that UDV estimates of WSS provided limited and largely inaccurate information about WSS and that the complex spatiotemporal flow patterns do not fit well with traditional assumptions about blood flow in arteries. Echo PIV-derived WSS provides detailed information about this important but poorly understood stimulus that influences vascular endothelial pathophysiology.

Validation of a Second-Generation Echo PIV System in Patient-Specific Carotid Artery Models: In Vitro Studies Using Pulsatile Flow

Echo Particle Image Velocimetry (Echo PIV), a novel opaque flow velocimetry technique developed in our laboratory, has been shown to be an effective 2-D flow measurement velocimetry method in prior studies for both steady and pulsatile flow conditions [1,2]. However, certain limitations remained in the first-generation system. These include inconsistent spatial resolution caused by the phased array transducer, and the relatively low frame rate (i.e., lower temporal resolution) [2]. To overcome these limitations, we developed a second-generation Echo PIV system with a custom-designed linear array transducer (5–14MHz, center frequency 10MHz) and customized post-processing of backscatter data. In vascular applications, the new system can provide frame rates up to 1428 fps (temporal resolution of 0.7 ms). The transducer has a consistent axial resolution of 150um, which brings a maximal velocity field resolution around 500um in axial direction. An ECG module was also integrated to enable the capture of ensemble data over the cardiac cycle.Copyright