R N Rankin’s research while affiliated with Western University and other places

Objectives: To determine the interrelationship of stenosis grade and ulceration with distal turbulence intensity (TI) in the carotid bifurcation measured using conventional clinical Doppler ultrasound (DUS) in vitro, in order to establish the feasibility of TI as a diagnostic parameter for plaque ulceration. Methods: DUS TI was evaluated in a matched set of ulcerated and smooth-walled carotid bifurcation phantoms with various stenosis severities (30, 50, 60 and 70 %), where the ulcerated models incorporated a type 3 ulceration. Results: Post-stenotic TI was significantly elevated owing to ulceration in the mild and moderate stenoses (P < 0.001). TI increased with stenosis severity in both the ulcerated and non-ulcerated series, with a statistically significant effect of increasing stenosis severity (P < 0.001). Whereas TI in the mild and non-ulcerated moderate stenoses was less than 20.4 ± 1.3 cm s(-1), TI in the ulcerated moderate and severe models was higher than 25.6 ± 1.3 cm s(-1), indicating a potential diagnostic threshold. Conclusion: We report a two-curve relationship of stenosis grade and ulceration to distal TI measured using clinical DUS in vitro. Clinical DUS measurement of distal TI may be a diagnostic approach to detecting ulceration in the mild and moderately stenosed carotid artery. Key points: • Patients with carotid artery plaque ulcerations are at higher risk of stroke. • Clinical Doppler ultrasound is routinely used to detect carotid artery stenosis. • Doppler ultrasound turbulence intensity can detect ulceration in realistic flow models. • Turbulence intensity also increases with stenosis severity independent of ulceration. • Doppler ultrasound should help in assessing both stenosis severity and ulceration.

Hemodynamics play a significant role in stroke risk, where thrombus formation may be accelerated in regions of slow or recirculating flow, high shear and increased turbulence. An in vitro investigation was performed with pulsed Doppler ultrasound (DUS) using the complete spectral data to investigate the three-dimensional (3-D) distribution of advanced parameters that may have potential for making a more specific in vivo diagnosis of carotid disease and stroke risk. The effect of stenosis symmetry and the potential of DUS spectral parameters for visualizing regions of recirculation or turbulence were explored. DUS was used to map pulsatile flow in four model geometries representing two different plaque symmetries (eccentricity) and two stenosis severities (mild, severe). Qualitative comparisons were made with flow patterns visualized using digital particle imaging. Color-encoded maps of DUS spectral parameters (mean velocity, spectral-broadening index and turbulence intensity) clearly distinguished regions of slow or recirculating flow and disturbed or turbulent flow. Distinctly different flow patterns resulted from stenoses of equal severity but different eccentricity. Noticeable differences were seen in both the size and location of recirculation zones and in the paths of high-velocity jets. Highly elevated levels of turbulence intensity were seen distal to severe stenosis. Results demonstrated the importance of plaque shape, which is typically not considered in standard diagnosis, in addition to stenosis severity. (E-mail: [email protected] /* */).

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.

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

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.

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

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. (E-mail: [email protected] /* */).

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. (E-mail: [email protected] /* */).

For years, the reference standard in the evaluation of living donor vascular anatomy has been selective renal angiography (SRA). Because of the potential morbidity associated with SRA, we prospectively evaluated magnetic resonance angiography (MRA) in the assessment of renal donors. All patients had SRA and 53 renal units were prospectively evaluated by MRA. We used SRA supplemented by findings at donor nephrectomy (DN) as our standard. We defined a positive test as the detection of any abnormality in the number of renal arteries. Selective renal angiography yielded a sensitivity of 86%, specificity of 95%, positive predictive value (PPV) of 75%, and negative predictive value (NPV) of 97% compared with findings at DN. MRA had a sensitivity of 64%, 88% specificity, 58% PPV, and 90% NPV. MRA correctly identified only 7 of 11 renal units with accessory arteries. MRA also incorrectly identified 5 accessory arteries not present on SRA or DN. Two patients diagnosed with fibromuscular dysplasia by SRA were missed using MRA. We have shown that MRA is not capable of replacing SRA as the reference standard in renal donor imaging.