Nonlinear intravascular ultrasound contrast imaging

Nonlinear contrast agent imaging with intravascular ultrasound (IVUS) is investigated using a prototype IVUS system and an experimental small bubble contrast agent. The IVUS system employed a mechanically scanned single element transducer and was operated at a 20 MHz transmit frequency (F20) for second harmonic imaging (H40), and at a 40 MHz transmit frequency (F40) for subharmonic imaging (SH20). Characterization experiments were performed with agent and tissue phantom signals acquired during transducer rotation. The suppression of transmit frequency tissue signals was achieved using a combination of pulse-inversion and bandpass filtering. H40 was found to improve the contrast-to-tissue signal ratio (CTR) by up to 22 dB relative to F20, but suffered from tissue propagation harmonics at higher pressures (>0.3 MPa). SH20 was also shown to be possible at a range of pressures (approximately 0.25 to 1.8 MPa), with tissue signals suppressed to near the noise floor. Coronary phantom experiments demonstrated the detection of agent in 1 mm diameter vessels outside a larger 4 mm diameter vessel in which the IVUS catheter was situated. These results suggest the feasibility of harmonic IVUS contrast imaging, which may have applications in coronary lumen boundary detection and vasa vasorum imaging.     

Interframe clutter filtering for high frequency flow imaging

This study investigates 'interframe' clutter filtering with a high frequency (HF) flow imaging system with the objective of improving the performance of HF microvascular imaging at high frame rates. An interframe filter exploits the correlation of tissue signals on the time scale of the frame rate and is, therefore, insensitive to tissue spectral broadening induced by sweeping a single element transducer over a region of tissue. In vitro experiments were conducted in a tissue-mimicking flow phantom over a range of mean flow velocities (0.5 to 70.0 mm/s). Power Doppler (PD) imaging and color flow (CF) imaging were performed for both slow (0.25 fps) and fast (20 fps) scanning acquisitions. Flow data acquired at 20 fps and interframe filtered had similar velocity and mean Doppler power values as the 0.25 fps single-frame filtered data sets. In vivo validation experiments were conducted using a 500 microm blood vessel in a human finger and detected blood flow of 2 to 3 mm/s. Further in vivo experiments examining experimental murine tumors demonstrated the feasibility of performing HF PD and CF imaging at high frame rates using interframe filtering.     

运用彩色多普勒流速剖面图测定血流量的实验研究

运用实验血流模型，检测新近开发的彩色多普勒血流速度部面图（velocityprofile，VP）对血流量测定的准确性，并与脉冲型多普勒（PulsedwaveDoppler，PWD）测定法比较。结果显示在不同流速下两种方法的流量测值与实际流量间均有高度相关性，相关系数r分别为0．999（P＜0．001）和0．988（P<0．02）。但测得流量与实际流量之间的误差程度，VP法为-7.64～2．79％，PWD法为17.82～27.97％。表明VP法较PWD法更接近实际情况。     

Visualizing Angle-Independent Principal Strains in the Longitudinal View of the Carotid Artery: Phantom and In Vivo Evaluation

Non-invasive vascular elastography can evaluate the stiffness of the carotid artery by visualizing the vascular strain distribution. Axial strain estimates of the longitudinal cross section of the carotid artery are sensitive to the angle between the artery and the transducer. Anatomical variations in branching and arching of the carotid artery can affect the assessment of arterial stiffness. In this study, we hypothesized that principal strain elastograms computed using compounded plane wave imaging can reliably visualize the strain distribution in the carotid artery, independent of the transducer angle. We corroborated this hypothesis by conducting phantom and in vivo studies using a commercial ultrasound scanner (Sonix RP, Ultrasonix Medical Corp., Richmond, BC, Canada). The phantom studies were conducted using a homogeneous cryogel vessel phantom. The goal of the phantom study was to assess the feasibility of visualizing the radial deformation in the longitudinal plane of the vessel phantom, independent of the transducer angle (±30°, ±20°, ±10° and 0°). The in vivo studies were conducted on 20 healthy human volunteers in the age group 50–60 y. All echo imaging was performed at a transmit frequency of 5?MHz and sampling frequency of 40?MHz. The elastograms obtained from the phantom study revealed that for straight vessels, which had their lumen parallel to the transducer, principal strains were similar to axial strains. At non-parallel configurations (angles ±30°, ±20° and ±10°), the magnitudes of the mean principal strains were within 2.5% of the parallel configuration (0° angle) estimates and, thus, were observed to be relatively unaffected by change in angle. However, in comparison, the magnitude of the axial strain decreased with increase in angle because of coordinate dependency. Further, the pilot in vivo study indicated that the principal and axial strain elastograms were similar for subjects with relatively straight arteries. However, for arteries with arched geometry, axial strains were significantly lower (p?<0.01) than the corresponding principal vascular strains, which was consistent with the results obtained from the phantom study. In conclusion, the results of the phantom and in vivo studies revealed that principal strain elastograms computed using CPW imaging could reliably visualize angle-independent vascular strains in the longitudinal plane of the carotid artery.     

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.     

Flow index evaluation of 3-D volume flow images: an in vivo and in vitro study

Three-dimensional (3-D) ultrasound imaging has improved evaluation of organ circulation and might contribute new information on maternal and fetal blood supply. Flow index (FI) of 3-D color images has been proposed as a measure of perfusion. The aim of this study was to evaluate whether the 3-D FI is a parameter of volume flow and flow velocity in a human vessel and in a flow phantom. A 1-cm-long strip of the uterine artery was recorded in 3-D power Doppler (3D-PD) mode in a cross-sectional study of 170 normal singleton pregnancies between 26 and 42 weeks' gestation. A fixed ultrasound system installation was used during the examination. The VOCAL software integrated in the ultrasound unit calculated vessel volume and FI. Reproducibility of the measurements was tested. The method was also tested on a commercially available flow phantom. Reproducibility measurements gave satisfactory results, both in terms of inter- and intraobserver variation. Unexpectedly, in normal pregnancy, the uterine artery FI decreased slightly with gestation. Uterine artery vessel volume increased, however, with gestational age. A poor correlation was found between the FI and both flow velocity and volume flow in the flow phantom. In conclusion, 3D-PD imaging can give impressive anatomical pictures of organ vascular tree. However, the new FI is poorly related to flow velocity or volume of flow.     

Relative Blood Flow Changes Measured Using Calibrated Frequency-Weighted Doppler Power at Different Hematocrit Levels

In theory, the power of a trans-cranial Doppler signal may be used to measure changes in blood flow and vessel diameter in addition to velocity. In this study, a flow index (FI) of relative changes in blood flow was derived from frequency-weighted Doppler power signals. The FI, plotted against velocity, was calibrated to the zero intercept with absent flow to reduce the effects of non-uniform vessel insonation. An area index was also calculated. FIs were compared with actual flow in four silicone tubes of different diameter at increasing flow rates and increasing hematocrit (Hct) in a closed-loop phantom model. FI values were strongly correlated with actual flow, at constant Hct, but varied substantially with changes in Hct. Percentage changes in area indexes, relative to the 4-mm tube, were strongly correlated with tube cross-sectional area. The implications of these results for in vivo use are discussed.     

Design and characterisation of a wall motion phantom

Arterial wall motion is an essential feature of a healthy cardiovascular system and it is known that wall motion is affected by age and disease. In recent years, methods have been developed for measurement of wall motion with the intention of providing diagnostically useful information. An issue with all of these techniques is the accuracy and variability of both wall motion and derived quantities such as elasticity, which requires the development of suitable test tools. In this paper, a vessel wall phantom is described for use in ultrasound studies of wall motion. The vessel was made from polyvinyl alcohol (PVA) subjected to a freeze-thaw process to form a cryogel (PVA-C). The elastic modulus, acoustic velocity and attenuation coefficient varied from 57 kPa, 1543 m s(-1) and 0.18 dB cm(-1) MHz(-1) for one freeze-thaw cycle to 330 kPa, 1583 m s(-1) and 0.42 dB cm(-1) MHz(-1) for 10 freeze-thaw cycles. Wall motion was effected by the use of pulsatile flow produced from a gear pump. The use of a downstream flow resistor removed gross distortions in the wall motion waveform, possibly by removal of reflected pressure waves. However, a low amplitude 20 Hz oscillation remained, which is unphysiologic and thought to be caused by the vibration of the distended PVA-C vessel.     

Pulsatile flow phantom for ultrasound image-guided HIFU treatment of vascular injuries

A pulsatile flow phantom was developed for studies of ultrasound image-guided high intensity focused ultrasound (HIFU) application in transcutaneous hemostasis of injured blood vessels. The flow phantom consisted of a pulsatile pump system with instrumented excised porcine carotid artery, which was imbedded in a transparent agarose gel to model structural configuration of in vivo tissues. Heparinized porcine blood was circulated through the phantom. The artery was injured using an 18-gauge needle to model a penetrating injury in human peripheral vasculature. A HIFU transducer with the diameter of 7 cm, focal length of 6.3 cm and frequency of 3.4 MHz was used to seal the puncture. Ultrasound imaging was used to localize and target the puncture site and to monitor the HIFU treatment. Triphasic blood flows present in the human arteries were reproduced, with flow rates of 50 to 500 mL/min, pulse rates of 62 to 138 beats/min and peak pressures of 100 to 250 mm Hg. The penetrating injury of an artery was mimicked successfully in the flow phantom setting and was easily visualized both optically through the transparent gel and with power Doppler ultrasound imaging. Hemostasis was achieved in 55 +/- 31 s (n = 9) of HIFU application. Histologic observations showed that a HIFU-sealed puncture was filled with clotted blood and covered with a fibrin cap. The pulsatile flow phantom provides a controlled and repeatable environment for studies of transcutaneous image-guided HIFU application in hemostasis of a variety of blood vessel injuries.     

A Method for Differentiating Targeted Microbubbles in Real Time Using Subharmonic Micro-Ultrasound and Interframe Filtering

This study introduces a new method for differentiating targeted microbubbles in the presence of flowing microbubbles and tissue using micro-ultrasound. The method relies on subharmonic (SH) imaging for segmenting microbubble signals from tissue signals, and low-pass interframe filtering for segmenting bound targeted microbubbles from flowing microbubbles. The method is evaluated with 30 frames per second SH B-mode imaging in vitro, using a wall-less vessel flow phantom. The SH B-mode cineloops were postprocessed using an interframe moving average filter to segment the regions of bound microbubbles on the inner surface of the vessel phantom. The bound bubbles were then disrupted with sufficiently high ultrasound pressures, so that the dynamic process of targeted microbubble binding under flowing conditions could be observed. These preliminary results show that the proposed method is a feasible solution to the challenge of differentiating targeted microbubbles in the presence of tissue and freely flowing microbubbles at high frequencies, which in turn should improve the specificity of targeted microbubble detection. (E-mail: aneedles@visualsonics.com)     

Subharmonic contrast intravascular ultrasound for vasa vasorum imaging

The feasibility of subharmonic contrast intravascular ultrasound (IVUS) imaging was investigated using a prototype nonlinear IVUS system and the commercial contrast agent Definity™. The system employed a mechanically scanned commercial catheter with a custom transducer element fabricated to have sensitivity at both 15 and 30 MHz. Experiments were conducted at a fundamental frequency of 30 MHz (F30; 25% bandwidth), with on-axis pressures ranging from 0.12 to 0.79 MPa, as measured with a needle hydrophone. In vitro characterization experiments demonstrated the detection of 15 MHz subharmonic signals (SH15) when pressure levels reached 360 kPa. The formation of SH15 images was shown, with tissue signals suppressed to near the noise floor and contrast to tissue ratios were improved by up to 30 dB relative to F30. In vivo experiments were performed using the atherosclerotic rabbit aorta model. Following the bolus injection of contrast agent upstream of the imaging catheter, agent was detected within the aorta, vena cava and within the perivascular space. These results provide a first in vivo demonstration of subharmonic contrast IVUS and suggest its potential as a new technique for imaging vasa vasorum. (E-mail: goertz@sri.utoronto.ca)     

Measurement of coronary flow using high-frequency intravascular ultrasound imaging and pulsed Doppler velocimetry: in vitro feasibility studies.

The recent development of intravascular ultrasound imaging offers the potential to measure blood flow as the product of vessel cross-sectional area and mean velocity derived from pulsed Doppler velocimetry. To determine the feasibility of this approach for measuring coronary artery flow, we constructed a flow model of the coronary circulation that allowed flow to be varied by adjusting downstream resistance and aortic driving pressure. Assessment of intracoronary flow velocity was accomplished using a commercially available end-mounted pulsed Doppler catheter. Cross-sectional area of the coronary artery was measured using a 20 MHz mechanical imaging transducer mounted on a 4.8 F catheter. The product of mean velocity and cross-sectional area was compared with coronary flow measured by timed collection in a graduated cylinder by linear regression analysis. Excellent correlations were obtained between coronary flow calculated by the ultrasound method and measured coronary flow at both ostial (r = 0.99, standard error of the estimate [SEE] = 13.9 ml/min) and distal (r = 0.98, SEE = 23.0 ml/min) vessel locations under steady flow conditions. During pulsatile flow, calculated and measured coronary flow also correlated well for ostial (r = 0.98, SEE = 12.7 ml/min) and downstream (r = 0.99, SEE = 9.3 ml/min) locations. That the SEE was lower for pulsatile as compared with steady flow may be explained by the blunting of the flow profile across the vessel lumen by the acceleration phase of pulsatile flow. These data establish the feasibility of measuring coronary artery blood flow using intravascular ultrasound imaging and pulsed Doppler techniques.     

Improved objective selection of power Doppler wall-filter cut-off velocity for accurate vascular quantification

The wall-filter selection curve method is proposed to objectively identify a cut-off velocity that minimizes artifacts in power Doppler images. A selection curve, which is constructed by plotting the color pixel density (CPD) as a function of the cut-off velocity, exhibits characteristic intervals hypothesized to include the optimum cut-off velocity. This article presents an improved implementation of the method that automatically detects characteristic intervals in a selection curve and selects an operating point cut-off velocity along a characteristic interval. The method is applied to subregions within the Doppler image to adapt the cut-off velocity to local variations in vascularity. The method's performance is evaluated in 30-MHz power Doppler images of a four-vessel flow phantom. At high (>5 mm/s) flow velocities, qualitative improvements in vessel delineation are achieved and the CPD in the resulting images is accurate to within 3% of the vascular volume fraction of the phantom.     

A thin-walled carotid vessel phantom for Doppler ultrasound flow studies

A technique is discussed for producing a robust ultrasound (US)-compatible flow phantom that consists of a thin-walled silicone-elastomer vessel with a lumen of arbitrary geometry, embedded in an agar-based tissue-mimicking material (TMM). The TMM has an acoustic attenuation of 0.56 dB cm(-1) MHz(-1) at 5 MHz, with nearly linear frequency-dependence and acoustic velocity of 1539 +/- 4 m s(-1). The vessel-mimicking material (VMM) has an acoustic attenuation of 3.5 dB cm(-1) MHz(-1) with linear frequency-dependence and an acoustic velocity of 1020 +/- 20 m s(-1). Scattering particles, which are added to the VMM to increase echogenicity and add speckle texture, lead to higher attenuation, depending on particle concentration and frequency. The VMM is stable over time, with a Young's elastic modulus of 1.3 to 1.7 MPa for strains of up to 10%, which mimics human arteries under typical physiological conditions. The phantom is sealed to prevent TMM exposure to air or water, to avoid changes to the acoustic velocity.     

Evaluation of breast tumors with color Doppler imaging: A comparison with image-directed Doppler ultrasound

Doppler ultrasound is an adjunct to other imaging modalities in differentiating benign from malignant breast tumors. Two groups of patients with breast nodules were examined using a 10/4.5 MHz (imaging frequency/pulsed Doppler frequency) image-directed Doppler probe and a 7.0/5.0 MHz color Doppler imaging probe, separately. Whenever flow signals were detected within or at the margin of the breast nodule, the lesion was considered to be malignant. In detecting malignant breast tumors, the sensitivity was 77.3% and 94.5%, specificity 83.3% and 40.1%, accuracy 81% and 63.4% for image directed Doppler and color Doppler imaging, respectively. We found color Doppler to be easier and more efficient in detecting the flow signals of neovascularity in breast tumor. Color Doppler exhibits a higher sensitivity in detecting the malignant breast tumors. However, more false-positive diagnoses were made. Color Doppler ultrasound also expedited the examination, and the whole procedure could be shortened from 35 minutes to 8 minutes compared with our previous examination performed by image-directed Doppler ultrasound. Due to its higher sensitivity and saving in examination time, we use color Doppler imaging as a routine procedure when solid lesions are observed in x-ray mammography or sonography, as a supplement to the diagnosis of breast tumors. © 1995 John Wiley & Sons, Inc.     

Harmonic intravascular ultrasound imaging with a dual-frequency catheter

Recent studies have shown the feasibility of tissue and contrast harmonic imaging with a prototype nonlinear intravascular ultrasound (IVUS) system using a conventional single-element rotating IVUS catheter. In this study, a dual-frequency transducer element was mounted in an IVUS catheter and its second harmonic imaging performance was investigated and compared with that of a conventional IVUS catheter. Hydrophone measurements showed a transmit efficiency improvement of >6 dB for the dual-frequency catheter at 20 MHz. In vitro phantom experiments showed a signal-to noise ratio improvement of >5 dB in second harmonic mode at 40 MHz (H40) with the dual-frequency catheter, when using equal transmit voltage for both catheters. Finally, in vivo experiments were conducted and showed image improvement in H40 acquisitions with respect to the conventional IVUS catheter.     

On the design of a capillary flow phantom for the evaluation of ultrasound contrast agents at very low flow velocities

Recently, a new imaging technology has become available that allows the evaluation of tissue perfusion using echo-contrast agents in real-time imaging: power pulse inversion imaging (PPI). Although numerous in vitro phantoms have been designed for different imaging modalities in ultrasound (US), there is a need for a phantom that mimics microcirculation and allows, in particular, the assessment of contrast replenishment kinetics following US-induced destruction of microbubbles using the new method. We, therefore, designed a new capillary flow phantom that takes the requirements of the new US imaging techniques and the physical properties of microbubbles into account and serves flow velocities in the range of microcirculation (1 to 10 mm/s). PPI studies were performed in the newly designed phantom. The contrast agent used was AF0150. We studied homogeneity of contrast distribution within the capillary phantom, constancy of contrast infusion, the dose-effect relationship and, finally, the feasibility of flow assessment using the method of contrast replenishment following US-induced microbubble destruction in a flow velocity range of 2.1 to 9.45 mm/s. Analysis of the replenishment kinetics was performed using the mathematical model f(t) = A(1 - e(-beta t)), with A representing the blood volume and beta the microbubble velocity. The new capillary phantom allowed homogeneous contrast opacification within the perfused capillaries independently of the flow. Constancy of signal intensity was achieved over a time period of almost 2 h, indicating constant contrast delivery. A strong linear correlation between the PPI signal and the contrast dose was found (r = 0.998). Analysis of the replenishment parameters revealed a strong linear relationship between parameter beta and flow (r = 0.994) as well as A * beta and flow (r = 0.984) in the observed flow range. The newly designed perfusion phantom for the evaluation of echo-contrast replenishment kinetics fulfills, at very low flow velocities, important prerequisites such as constancy of contrast delivery, homogeneity of contrast signals, linear dose-effect relation and minimal attenuation. Thus, the new phantom allows standardized analysis of contrast replenishment kinetics using real-time perfusion imaging techniques at flow velocities comparable to those of the microcirculation.     

A Method to Validate Quantitative High-Frequency Power Doppler Ultrasound With Fluorescence in Vivo Video Microscopy

Flow quantification with high-frequency (>20 MHz) power Doppler ultrasound can be performed objectively using the wall-filter selection curve (WFSC) method to select the cutoff velocity that yields a best-estimate color pixel density (CPD). An in vivo video microscopy system (IVVM) is combined with high-frequency power Doppler ultrasound to provide a method for validation of CPD measurements based on WFSCs in mouse testicular vessels. The ultrasound and IVVM systems are instrumented so that the mouse remains on the same imaging platform when switching between the two modalities. In vivo video microscopy provides gold-standard measurements of vascular diameter to validate power Doppler CPD estimates. Measurements in four image planes from three mice exhibit wide variation in the optimal cutoff velocity and indicate that a predetermined cutoff velocity setting can introduce significant errors in studies intended to quantify vascularity. Consistent with previously published flow-phantom data, in vivo WFSCs exhibited three characteristic regions and detectable plateaus. Selection of a cutoff velocity at the right end of the plateau yielded a CPD close to the gold-standard vascular volume fraction estimated using IVVM. An investigator can implement the WFSC method to help adapt cutoff velocity to current blood flow conditions and thereby improve the accuracy of power Doppler for quantitative microvascular imaging.     

A Rotating Cylinder Phantom for Flow and Tissue Color Doppler Testing

Ultrasound Doppler using two-dimensional (2D) techniques is commonly used to study blood flow and myocardial tissue motion. This use includes measurement of velocity and time intervals, often in relation to the electrocardiogram (ECG) signal. 2D Doppler is frequently considered a real-time technique but in reality the acquisition time can be as long as 200 ms per image. We have developed a test-phantom using a rotating cylinder to simulate blood flow and tissue motion in a whole sector or space angle to evaluate velocity and timing characteristics. The phantom can produce constant velocities for velocity testing, as well as accelerating movement for testing the timing characteristics of ultrasound systems. Our investigation shows that the cylinder phantom is especially suitable for timing measurements in 2D Doppler imaging and that time delays between the Doppler signals and the ECG signal exist in the tested ultrasound system. (E-mail: andrew.walker@ltv.se)