Meghan L. Thorne

Clinical Doppler ultrasound for the assessment of plaque ulceration in the stenosed carotid bifurcation by detection of distal turbulence intensity: A matched model study

The assessment of flow disturbances due to carotid plaque ulceration may provide added diagnostic information to Doppler ultrasound (DUS) of the carotid stenosis, and indicate whether the associated hemodynamics are a potential thromboembolic source. We evaluated the effect of ulceration in a moderately stenosed carotid bifurcation on distal turbulence intensity (TI) measured using clinical DUS in matched anthropomorphic models. Several physiologically relevant ulcer geometries (hemispherical, mushroom-shaped, and ellipsoidal pointing distally and proximally) and sizes (2-mm, 3-mm and 4-mm diameter hemispheres) were investigated. An offline analysis was performed to determine several velocity-based parameters from ensemble-averaged spectral data, including TI. Significant elevations in TI were observed in the post-stenotic flow field of the stenosed carotid bifurcation by the inclusion of ulceration (P < 0.001) in a region two common carotid artery diameters distal to the site of ulceration during the systolic peak and the diastolic phase of the cardiac cycle. Both the size and shape of ulceration had a significant effect on TI in the distal region (P < 0.001). Due to the use of a clinical system, this method provides the means to evaluate for plaque ulcerations in patients with carotid atherosclerosis using DUS.

USE OF AN ULTRASOUND BLOOD-MIMICKING FLUID FOR DOPPLER INVESTIGATIONS OF TURBULENCE IN VITRO

Turbulence is an important factor in the assessment of stenotic disease and a possible causative mechanism for thromboembolism. Previous Doppler studies of turbulence have typically used whole-blood preparations or suspensions of erythrocytes. Recently, a water-glycerol based blood-mimicking fluid (BMF) has been developed for use in Doppler ultrasound studies. This fluid has desirable ultrasound properties but it has not previously been described during in vitro investigations of turbulence intensity. We report on investigations of grid-generated and constrained-jet turbulence in an in vitro test system. The BMF was found to generate significant levels of turbulence during steady flow at physiological flow rates, producing turbulent patterns in the distal region that were consistent with previous studies. Turbulence intensity increased significantly with flow rate (p < 0.005) for both the constrained jet and the constrained grid. Based on our observations, we conclude that a water-glycerol based BMF provides a suitable working fluid during in vitro investigations of turbulence using Doppler ultrasound.

Doppler Ultrasound Compatible Plastic Material for Use in Rigid Flow Models

A technique for the rapid but accurate fabrication of multiple flow phantoms with variations in vascular geometry would be desirable in the investigation of carotid atherosclerosis. This study demonstrates the feasibility and efficacy of implementing numerically controlled direct-machining of vascular geometries into Doppler ultrasound (DUS)-compatible plastic for the easy fabrication of DUS flow phantoms. Candidate plastics were tested for longitudinal speed of sound (SoS) and acoustic attenuation at the diagnostic frequency of 5 MHz. Teflon was found to have the most appropriate SoS (1376 +/- 40 m s(-1) compared with 1540 m s(-1) in soft tissue) and thus was selected to construct a carotid bifurcation flow model with moderate eccentric stenosis. The vessel geometry was machined directly into Teflon using a numerically controlled milling technique. Geometric accuracy of the phantom lumen was verified using nondestructive micro-computed tomography. Although Teflon displayed a higher attenuation coefficient than other tested materials, Doppler data acquired in the Teflon flow model indicated that sufficient signal power was delivered throughout the depth of the vessel and provided comparable velocity profiles to that obtained in the tissue-mimicking phantom. Our results indicate that Teflon provides the best combination of machinability and DUS compatibility, making it an appropriate choice for the fabrication of rigid DUS flow models using a direct-machining method.

In vivo Doppler Ultrasound Quantification of Turbulence Intensity Using A High-Pass Frequency Filter Method

The objective of this investigation was to implement a high-pass frequency filter method to analyze Doppler ultrasound velocity waveforms and quantify turbulence intensity (TI) in vivo. Doppler velocity data were analyzed using two techniques, based on either ensemble averaging or high-pass frequency domain filtering of the periodic waveforms. The accuracy and precision of TI measurements were determined with controlled in vitro experiments, using a pulsatile-flow model of a stenosed carotid bifurcation. The high-pass filter technique was also applied in vivo to determine whether this technique could successfully distinguish between pertinent hemodynamic sites within the carotid artery bifurcation. Twenty-five seconds of Doppler audio data were acquired at three sites (common carotid artery [CCA], internal carotid artery [ICA] stenosis and distal ICA) within 10 human carotid arteries, and repeated three times. Doppler velocity data were analyzed using a ninth-order high-pass Butterworth filter with a 12-Hz inflection point. TI measured within the CCA and distal ICA was found to be significantly different (p < 0.0001) for moderate to nearly occluded carotid artery classifications. Also, TI measured within the distal ICA increased with stenosis severity, with the ability to distinguish between each stenosis class (p < 0.05). This investigation demonstrated the ability to precisely quantify TI using a conventional Doppler ultrasound machine in human subjects, without interfering with normal clinical protocols.

In Vitro Doppler Ultrasound Investigation of Turbulence Intensity in Pulsatile Flow With Simulated Cardiac Variability

An in vitro investigation of turbulence intensity (TI) associated with a severe carotid stenosis in the presence of physiological cardiac variability is described. The objective of this investigation was to determine if fluctuations due to turbulence could be quantified with conventional Doppler ultrasound (DUS) in the presence of normal physiological cycle-to-cycle cardiac variability. An anthropomorphic model of a 70% stenosed carotid bifurcation was used in combination with a programmable flow pump to generate pulsatile flow with a mean flow rate of 6 mL/s. Utilizing the pump, we studied normal, nonrepetitive cycle-to-cycle cardiac variability (+/-3.9%) in flow, as well as waveform shapes with standard deviations equal to 0, 2 and 3 times the normal variation. Eighty cardiac cycles of Doppler data were acquired at two regions within the model, representing either laminar or turbulent flow; each measurement was repeated six times. Turbulence intensity values were found to be 11 times higher (p < 0.001), on average, in the turbulent region than in the laminar region, with a mean difference of 24 cm/s. Twenty cardiac cycles were required for confidence in TI values. In conclusion, these results indicate that it is possible to quantify TI in vitro, even in the presence of normal and exaggerated cycle-to-cycle cardiac variability.

Real-time virtual Doppler ultrasound

Doppler ultrasound (DUS) is widely used to diagnose and plan treatments for vascular diseases, but the relationship between complex blood flow dynamics and the observed DUS signal is not completely understood. In this paper, we demonstrate that Doppler ultrasound can be realistically simulated in a real-time manner via the coupling of a known, previously computed velocity field with a simple model of the ultrasound physics. In the present case a 3D computational fluid dynamics (CFD) model of physiologically pulsatile flow a stenosed carotid bifurcation was interrogated using a sample volume of known geometry and power distribution. Velocity vectors at points within the sample volume were interpolated using a fast geometric search algorithm and, using the specified US probe characteristics and orientation, converted into Doppler shifts for subsequent display as a Doppler spectrogram or color DUS image. The important effect of the intrinsic spectral broadening was simulated by convolving the velocity at each point within the sample volume by a triangle function whose width was proportional to velocity. A spherical sample volume with a Gaussian power distribution was found to be adequate for producing realistic Doppler spectrogram in regions of uniform, jet, and recirculation flow. Fewer than 1000 points seeded uniformly within a radius comprising more than 99% of the total power were required, allowing spectra to be generated from high resolution CFD data at 100Hz frame rates on an inexpensive desktop workstation.

Doppler ultrasound and numerical analysis for the assessment of hemodynamic disturbances in ulcerated carotid arteries

Carotid plaque ulcerations, or irregularities in plaque surface morphology, have been identified as an independent risk factor for ischemic stroke. Our previous studies using Doppler ultrasound (DUS) have indicated significant flow disturbances distal to ulceration in the atherosclerotic carotid bifurcation, as characterized by parameters such as turbulence intensity (TI). Additional tools are needed to understand the implications of such flow abnormalities on the risk of thrombogenesis and cerebral ischemic events. Numerical simulations using computational fluid dynamics (CFD) can supplement experimental DUS studies, providing higher resolution, time-resolved models of 3-D flow fields. CFD is also able to quantify hemodynamic factors that indicate thromboembolic or plaque rupture potential. We report a CFD analysis of an ellipsoidal ulcer model and a matched non-ulcerated model in a moderately stenosed carotid bifurcation, with the same vessel geometries and flow conditions used in our previous DUS studies. The CFD models used a spatial finite element discretization of over 160,000 quadratic tetrahedral elements to adequately resolve the flow field. Pulsatile flow simulations with boundary conditions and flowrate waveforms matching DUS experimental conditions were iterated for five cardiac cycles. Turbulence intensity was calculated for the CFD models and compared with DUS experimental results. The CFD models were able to capture differences in flow patterns between cardiac cycles. As observed in the empirical DUS results, the CFD ulcer model displayed higher levels of TI in the post-stenotic region than the CFD non-ulcerated model. The extent and magnitude of TI was comparable to the DUS results, after modeling for the effects of sample volume geometry and intrinsic spectral broadening, and by a high pass filter. Furthermore, the CFD results indicate that flow post-stenosis is likely transitional, with both disturbed and turbulent flow present. CFD facilitates the comparison of hemodynamic parameters between ulcer models and may help to demonstrate the risks of embolism or plaque rupture posed by ulcerated atherosclerotic plaques in the carotid bifurcation.

Quantification of turbulence intensity in patients with symptomatic carotid atherosclerosis: a pilot study

The most widely performed test for patients suspected of having carotid atherosclerosis is Doppler ultrasound (DUS). Unfortunately, limitations in sensitivity and specificity prevent DUS from being the sole diagnostic tool. Novel DUS velocity-derived parameters, such as turbulence intensity (TI), may provide enhanced hemodynamic information within the carotid artery, increasing diagnostic accuracy. In this study, we evaluate a new technique for recording, storing and analyzing DUS in a clinical environment, and determine the correlation between TI and conventional DUS measurements. We have recruited 32 patients with a mean age of 69±11 yrs. An MP3 recorder was used to digitally record Doppler audio signals three times at three sites: the common carotid artery, peak stenosis and region of maximum turbulence. A Fourier-based technique was used to calculate TI, facilitating clinical application without additional ECGgating data. TI was calculated as the standard deviation of Fourier-filtered mean velocity data. We found that TI and clinical PSV were linearly dependent (P<0.001) within the region of maximum turbulence and the precision of all TI measurements was found to be 14%. We have demonstrated the ability to record Doppler waveform data during a conventional carotid exam, and apply off-line custom analysis to Doppler velocity data to produce measurements of TI.

Off-line recording and analysis of Doppler velocity waveform data

Doppler ultrasound velocity measurements are commonly used to diagnose atherosclerotic carotid artery disease. However, current Doppler techniques exhibit limitations with respect to sensitivity and specificity. We believe that advanced spectral analysis - including quantification of turbulence - could increase the diagnostic accuracy of duplex Doppler ultrasound. Routine application of advanced spectral analysis requires a practical technique to acquire and analyze the Doppler signal, which is compatible with clinical ultrasound machines. We describe the implementation of a technique for offline Doppler waveform analysis of carotid artery blood flow, using a portable MP3 recorder and custom analysis software. Forward and reverse audio signals were recorded with compression at 128 bps at prescribed points throughout the carotid bifurcation of human volunteers. Each data set was digitized at 44.1kHz and analyzed to produce velocity spectra at 12 ms intervals. From these instantaneous spectra, advanced Doppler indices of mean velocity and Fourier-based turbulence intensity (TI) were calculated. We found that MP3 compression had a negligible effect on the calculation of mean velocity data (0.17%) and TI (0.5%). We also found that Fourier-based TI was comparable to TI calculated by ensemble average. Finally, we were successful in applying this technique in vivo and demonstrated that long acquisitions and repeated measurements were possible in human volunteers. Our study demonstrates that it is feasible to acquire Doppler audio data using an MP3 recording device for off-line analysis, while only adding a short time to a conventional carotid exam.

Doppler ultrasound in vitro modeling of turbulence in carotid vascular disease

Turbulence is ubiquitous to many systems in nature, except the human vasculature. Development of turbulence in the human vasculature is an indication of abnormalities and disease. A severely stenosed vessel is one such example. In vitro modeling of common vascular diseases, such as a stenosis, is necessary to develop a better understanding of the fluid dynamics for a characteristic geometry. Doppler ultrasound (DUS) is the only available non-invasive technique for in vivo applications. Using Doppler velocity-derived data, turbulence intensity (TI) can be calculated. We investigate a realistic 70% stenosed bifurcation model in pulsatile flow and the performance of this model for turbulent flow. Blood-mimicking fluid (BMF) was pumped through the model using a flow simulator, which generated pulsatile flow with a mean flow rate of 6 ml/s. Twenty-five cycles of gated DUS data were acquired within regions of laminar and turbulent flow. The data was digitized at 44.1 kHz and analyzed at 79 time-points/cardiac cycle with a 1024-point FFT, producing a 1.33 cm/s velocity resolution. We found BMF to exhibit DUS characteristics similar to blood. We demonstrated the capabilities to generate velocities comparable to that found in the human carotid artery and calculated TI in the case of repetitive pulsatile flow.