In Vitro and Preliminary In Vivo Validation of Echo Particle Image Velocimetry in Carotid Vascular Imaging

Abstract

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. (E-mail: [email protected])

Introduction

Atherosclerosis, a systemic disease process in which fatty deposits, inflammation, cells, and scar tissue build up within the walls of arteries, is the underlying cause of the majority of clinical cardiovascular events (Cunningham and Gotlieb, 2005, Lloyd-Jones et al., 2009, Ohira et al., 2006). Locations of focal atherosclerotic lesions have been shown to correlate to locations of local blood flow disturbance and, more specifically, to locations of low or oscillatory fluid shear stress at the arterial wall (Carallo et al., 1999, Giddens et al., 1993, Gnasso et al., 1997, Ku and Giddens, 1983, Ku et al., 1985, Shaaban and Duerinckx, 2000, Stokholm et al., 2000, Zarins et al., 1983, Zarins et al., 2001). However, accurately and easily measuring wall shear stress (WSS) in vivo remains problematic.

WSS is typically obtained in vivo by measuring axial velocities close to the vessel lumen and computing the wall shear rate (WSR), after which WSS is obtained by assuming high shear conditions for blood flow and using the Newtonian value for blood viscosity. Although the assumption of Newtonian rheology can be problematic for a shear-thinning fluid such as blood, it has been commonly used for flow in large- and medium-sized blood vessels (pre-arteriolar) and is generally well accepted. Certainly, this approach is vastly superior to the current Doppler-based approach of simply measuring centerline velocity and assuming a parabolic velocity profile to calculate WSS (Gelfand et al., 2006, Gnasso et al., 1996, Nowak, 2002, Oshinski et al., 2006). In this regard, phase-contrast magnetic resonance imaging (PC-MRI) has shown promise because it provides WSR accurately (Cheng et al., 2002, Oyre et al., 1998, Taylor et al., 2002). However, PC-MRI is limited for routine WSR or WSS measurements because of relatively long data-collecting times (2∼5 min for each slice), poor temporal resolution (15∼30 ms), inherent cumbersomeness and high cost.

In recent years, many novel ultrasound-based techniques have emerged to overcome some of the typical Doppler limitations such as angle dependence. Vennemann et al. (2007) and Hoskins (2010) reviewed many of these methods. Since the time period covered by these reviews, there have been a few additional methods proposed. Hansen et al., 2009a, Hansen et al., 2009b and Udesen et al. (2008) proposed a method called plane wave excitation (PWE), which applies speckle-tracking algorithms (Crapper et al. 2000) to detect 2-D speckle displacements from two ultrasound images. The PWE method has been evaluated against PC-MRI in measuring volumetric flow rate in a human carotid artery showing a mean underestimation of the PWE of ∼9% for flow measurement. One of the big limitations of the PWE method is its degraded contrast of B-mode images compared with conventional B-mode imaging, which makes it difficult to get reliable velocity measurements. Thus, temporal averaging of 40 images was necessary to improve the quality of velocity mapping, which decreased the temporal resolution to approximately 10 ms. Beulen et al., 2010a, Beulen et al., 2010b proposed a technique termed ultrasonic perpendicular velocimetry (UPV), which applies cross correlation on raw radiofrequency (RF) data to detect velocity components perpendicular to the ultrasound beam. The in vitro validation on UPV against theoretical solutions and computational fluid dynamics (CFD) simulations in straight tube and curved vessels showed good accuracy of this technique. However, UPV uses a relatively large interrogation window size (∼4.4 mm) perpendicular to the beam direction, which limits its spatial resolution. Another limitation of UPV may be the low signal-to-noise ratio of speckles from red blood cells. The clinical feasibility of UPV remains unclear.

We have been working on the development and improvement of Echo particle image velocimetry (Echo PIV) over the last five years. Echo PIV enables the measurement of multidimensional and multicomponent velocity vectors in opaque flows (Edmond et al., 1995, Kim et al., 2004a, Kim et al., 2004b; Liu et al., 2008, Zhang et al., 2008, Zheng et al., 2006a). Advantages of this technique include ease of use, simple implementation using commercially available ultrasound imaging systems and probes, low cost, high temporal resolution (up to 0.7 ms in the current system) and good spatial resolution (up to 0.5 mm in the current system). Echo PIV has shown its capability in quantifying flow patterns in human left ventricles (Hong et al., 2007a, Hong et al., 2007b, Kheradvar et al., 2010, Sengupta et al., 2007); however, there is little or no validation on those measurements.

Certainly, validation of Echo PIV is essential before it is applied clinically. In validation studies using simple in vitro flow models, Echo PIV was shown to be accurate for velocity and WSR/WSS measurements (Kim et al. 2004a; Liu et al. 2008). Although the flow models used in these studies were nonphysiologic, results from these early validation studies provided confidence to begin considering Echo PIV for clinical measurements, specifically for measuring velocity vectors and WSR in blood vessels. The next step was assessing whether Echo PIV could in fact provide accurate results using more anatomically correct models and flow conditions. This paper presents the results of a study to further validate Echo PIV against the gold standard of optical PIV using an anatomically correct, elastic model of carotid bifurcation under pulsatile flow conditions. Before this study, some changes were performed to the Echo PIV technique, which are summarized here. First, the Echo PIV algorithm was improved to enhance its accuracy and reliability. A custom RF filtering technique was used to reduce the noise level of echo particle images, and advanced PIV algorithms, including adaptive window offset, subpixel interpolation and vector field filtering, were introduced. The details were discussed in another manuscript (Unpublished observations). Second, this study uses an anatomically correct carotid compliant model instead of the simplified and noncompliant flow models used in previous studies. The geometrical complexity of the model and its compliance led to the generation of complicated flow fields in the carotid model, particularly in the bifurcation area. Third, our previous studies on Echo PIV focused mainly on validations of this technique in either temporal or 2-D spatial domain. This study, for the first time, validated Echo PIV against Optical PIV in both temporal and 2-D spatial domains simultaneously. Fourth, the compliant model in this study provided the opportunity to develop and validate segmentation techniques for tracking artery wall motion (Zhang et al. 2009b). Fifth, the Echo PIV system used in this study was different from those in previous studies. Specifically, the system was improved to provide better control of data acquisition parameters and enhanced temporal resolution (up to 0.7 ms).

With the confidence from the in vitro validation study on the carotid artery model, we further explored the feasibility of Echo PIV in human subjects. We used Echo PIV to obtain detailed velocity vectors and flow rates from carotid artery in five normal human subjects, and compared these results with PC-MRI measurements in the same subjects. Good agreement was found between Echo PIV and PC-MRI measurements.