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)     

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.     

High frequency nonlinear scattering from a micrometer to submicrometer sized lipid encapsulated contrast agent

An experimental lipid encapsulated contrast agent comprised substantially of micrometer to submicrometer diameter bubbles was evaluated for its capacity to produce nonlinear scattering in response to high transmit frequencies. Agent characterization experiments were conducted at transmit frequencies of 20 and 30 MHz with bandwidths of 5, 15 and 25% using a broadband focused PVDF transducer. The presence of subharmonic energy was observed for all bandwidths at a wide range of pressures (0.49 to 5.7 MPa and 0.45 to 4.5 MPa for the 20 and 30 MHz cases, respectively). Distinct ultraharmonics were observed only in the 5% bandwidth cases. Second harmonic energy was also present, but this was at least partly due to nonlinear propagation, as indicated by linear scatterer signals. Evidence of destruction was found only at higher peak negative pressures (e.g., >2 MPa for 30 MHz 5% bandwidth pulse). The results suggest that small lipid bubble formulations may be useful for the purposes of high frequency nonlinear contrast imaging.     

High-frequency subharmonic pulsed-wave Doppler and color flow imaging of microbubble contrast agents

A recent study has shown the feasibility of subharmonic (SH) flow imaging at a transmit frequency of 20 MHz. This paper builds on these results by examining the performance of SH flow imaging as a function of transmit pressure. Further, we also investigate the feasibility of SH pulsed-wave Doppler (PWD) imaging. In vitro flow experiments were performed with a 1-mm-diameter wall-less vessel cryogel phantom using the ultrasound contrast agent Definity and an imaging frequency of 20 MHz. The phantom results show that there is an identifiable pressure range where accurate flow velocity and power estimates can be made with SH imaging at 10 MHz (SH10), above which velocity estimates are biased by radiation force effects and unstable bubble behavior, and below which velocity and power estimates are degraded by poor SNR. In vivo validation of SH PWD was performed in an arteriole of a rabbit ear, and blood velocity estimates compared well with fundamental (F20) mode PWD. The ability to suppress tissue signals using SH signals may enable the use of higher frame rates and improve sensitivity to microvascular flow or slow velocities near large vessel walls by reducing or eliminating the need for clutter filters.     

Reduction of stent artifacts using high-frequency harmonic ultrasound imaging

Tissue harmonic imaging (THI) has been shown to improve medical ultrasound (US) image quality in the frequency range from 2 to 10 MHz and might, therefore, also be advantageous in high-frequency US applications, like US biomicroscopy and intravascular US (IVUS). In this study, we compared high-frequency THI (40 MHz) with fundamental imaging (20 and 40 MHz) with a distorting reflective metal stent in the near fields of both a spherically-focused US biomicroscopy transducer (aperture 8 mm, focal distance 13 mm) and an unfocused elliptical IVUS element. Hydrophone measurements of the harmonic beam (40 MHz) of both transducers showed relatively low signal strength in the near field compared with both (20 and 40 MHz) fundamental beams. For the focused transducer, THI suppressed the second stent echo up to 14 dB compared with fundamental imaging. No significant reduction in stent artifact imaging was observed for the unfocused IVUS element.     

Experimental characterization of fundamental and second harmonic beams for a high-frequency ultrasound transducer

In the diagnostic frequency range, nonlinear imaging has been shown to improve image contrast and decrease artefacts. The extension of these techniques to high-frequency imaging (>15 MHz) was investigated. The second harmonic beam at 40 MHz of a high-frequency focused transducer (aperture 6 mm, focal distance 10 mm, f-number 1.67) was measured experimentally in water, in transmission and pulse-echo, and compared with the fundamental beams at 20 MHz and 40 MHz. Measurements were performed at peak negative pressures of 0.8 to 4.7 MPa. Transmission measurements were performed with a custom hydrophone with a 25microm spot size to limit beam averaging. Over the range of peak negative pressures, the transmitted harmonic (40 MHz) beam had an average lateral beam width (-3 dB) of 77 microm and an average depth-of-field of 0.93 mm, whereas the fundamental beam had a corresponding beam width of 137 microm and a depth-of-field of 1.59 mm. The harmonic beam showed a 3-dB decrease in side lobe levels. Preliminary second harmonic images of mouse tissue in vitro are presented and compared to fundamental imaging at 20 and 40 MHz.     

Subharmonic contrast microbubble signals for noninvasive pressure estimation under static and dynamic flow conditions

Our group has proposed the concept of subharmonic aided pressure estimation (SHAPE) utilizing microbubble-based ultrasound contrast agent signals for the noninvasive estimation of hydrostatic blood pressures. An experimental system for in vitro SHAPE was constructed based on two single-element transducers assembled confocally at a 60 degree angle to each other. Changes in the first, second and subharmonic amplitudes of five different ultrasound contrast agents were measured in vitro at static hydrostatic pressures from 0-186 mmHg, acoustic pressures from 0.35-0.60 MPa peak-to-peak and frequencies of 2.5-6.6 MHz. The most sensitive agent and optimal parameters for SHAPE were determined using linear regression analysis and implemented on a Logiq 9 scanner (GE Healthcare, Milwaukee, WI). This implementation of SHAPE was then tested under dynamic-flow conditions and compared to pressure-catheter measurements. Over the pressure range studied, the first and second harmonic amplitudes reduced approximately 2 dB for all contrast agents. Over the same pressure range, the subharmonic amplitudes decreased by 9-14 dB and excellent linear regressions were achieved with the hydrostatic pressure variations (r = 0.98, p < 0.001). Optimal sensitivity was achieved at a transmit frequency of 2.5 MHz and acoustic pressure of 0.35 MPa using Sonazoid (GE Healthcare, Oslo, Norway). A Logiq 9 scanner was modified to implement SHAPE on a convex transducer with a frequency range from 1.5-4.5 MHz and acoustic pressures from 0-3.34 MPa. Results matched the pressure catheter (r2 = 0.87). In conclusion, subharmonic contrast signals are a good indicator of hydrostatic pressure. Out of the five ultrasound contrast agents tested, Sonazoid was the most sensitive for subharmonic pressure estimation. Real-time SHAPE has been implemented on a commercial scanner and offers the possibility of allowing pressures in the heart and elsewhere to be obtained noninvasively.     

Contrast harmonic transesophageal echocardiography: a feasibility study

Ultrasound (US) contrast agents serve as tracers for the noninvasive quantification of blood flow, and many of them are now approved for left ventricular opacification and for enhanced endocardial border delineation. The availability of more stable contrast bubbles has stimulated many new classes of imaging methods, such as harmonic imaging, which is already employed in commercial systems for transthoracic imaging. However, transesophageal echocardiography (TEE) still lacks appropriate technology, mainly transducer technology, to be able to take advantage of contrast harmonic benefits. We investigate, in this study, a new TEE transducer that has a frequency bandwidth wide enough to be able transmit at a lower fundamental frequency and to receive the second harmonic frequency. The transducer characteristics are measured, as well as the optimal transmit settings that allow the achievement of a high contrast-to-tissue ratio. The transducer has a center frequency of 3.5 MHz with a bandwidth ranging from 2.3 MHz to 3.9 MHz. For optimal harmonic imaging, transmit settings consisted of a transmit pulse at 2.5 MHz containing two periods. The transducer, using these settings, was then evaluated in patients to investigate myocardial contrast perfusion imaging using TEE in the operating theater.     

自然组织谐波成像与基波成像在心脏声学造影中的对比观察

组织谐波成像是新近开展的一种超声成像技术，其探头接受声波的频率是发射频率的两倍（分别为１．７５ＭＨｚ和３．５ＭＨｚ），我们将该技术应用于心脏声学造影检查，观察其对造影剂微气泡的显像效果，并与传统的基波成像技术相比较，发现前者右心显影更强，密度更高，散在造影剂微气泡颗粒更粗，更亮，并能清晰显示左心少量的穿肺的造影剂，这是传统方法难于探及的，但要达到心肌显影，还需改进造影剂的制备，开发出新的心肌声学造影剂。     

Contrast-Enhanced Intravascular Ultrasound Pulse Sequences for Bandwidth-Limited Transducers

We demonstrate two methods for vasa vasorum imaging using contrast-enhanced intravascular ultrasound, which can be performed using commercial catheters. Plaque neovascularization was recognized as an independent marker of coronary artery plaque vulnerability. IVUS-based methods to image the microvessels available to date require high bandwidth (−6 dB relative frequency bandwidth >70%), which are not routinely available commercially. We explored the potential of ultraharmonic imaging and chirp reversal imaging for vasa vasorum imaging. In vitro recordings were performed on a tissue-mimicking phantom using a commercial ultrasound contrast agent and a transducer with a center frequency of 34 MHz and a −6 dB relative bandwidth of 56%. Acoustic peak pressures <500 kPa were used. A tissue-mimicking phantom with channels down to 200 μm in diameter was successfully imaged by the two contrast detection sequences while the smallest channel stayed invisible in conventional intravascular ultrasound images. Ultraharmonic imaging provided the best contrast agent detection.     

Nonlinear Emission from Individual Bound Microbubbles at High Frequencies

Targeted microbubbles detected with high-frequency ultrasound can establish the molecular expression of blood vessels with submillimeter resolution. To improve microbubble-specific imaging at high frequencies, the subharmonic and second harmonic signal from individual microbubbles were measured as a function of size and pressure. Single phospholipid-shell microbubbles (1.1 to 5.0 μm in diameter) bound to gelatin, co-aligned with an optical microscope and transducer, were insonated with 30 MHz Gaussian-enveloped pulses at pressures from 20 kPa to 1 MPa with –6 dB one-way bandwidths of 11%, 20% and 45%. A subharmonic signal (15 MHz) was detected above a pressure threshold of 110 kPa—independent of bandwidth. The signal peaked for microbubbles 1.60 μm in diameter subject to 20% and 11% bandwidth pulses, and 1.80 μm for 45% bandwidth pulses, for pressures up to 400 kPa, agreeing with the notion that microbubbles insonated at twice their resonant frequency preferentially emit a subharmonic component. For pressures between 400 kPa and 1 MPa, a broader range of microbubbles emitted a subharmonic signal, and microbubbles below 1.70 μm in diameter were disrupted. The second harmonic signal measured, within the limited experimental conditions, was consistent with nonlinear propagation. Further, the results shed light on the effect of the shell on the phase of the subharmonic signal with respect to the fundamental signal. (E-mail: michael.sprague@sri.utoronto.ca)     

Two dimensional arrays for real time 3D intravascular ultrasound

We have previously described 2D arrays operating at up to 10.0 MHz consisting of several thousand elements for transthoracic cardiac imaging and over a hundred elements for intracardiac imaging using 7 Fr to 12 Fr catheters. We have begun to explore forward viewing real time 3D phased array intravascular ultrasound, which may require imaging depths of a few centimeters to look down the axis of a vessel to view vulnerable atherosclerotic plaque. We used a noncoaxial based cable technology that allowed 100 signal wires to be placed inside a4.8 French IVUS lumen with an inner diameter of 1.3 mm. We pursued two different fabrication technologies for the building of the transducers. Each transducer was constructed in the forward viewing configuration to allow simultaneous real time B-scans, C-scans and volumetric rendering of vessels and vascular stents distal to the catheter tip. In order to obtain the desired penetration depth, each transducer was constructed to operate at 10.0 MHz. The first method included an ordered array of 11 x 11 = 121 elements. In order to conform to the round aperture of the IVUS lumen, the comers were cut off, resulting in a total of 97 signal channels. Real time images include a 4 mm diameter vessel in a tissue mimicking phantom, an expanded stent and a stent in an excised sheep aorta. The second method is based upon a laser dicing technique that cuts the individual elements in a random pattern. This resulted in 61 signal channels. Real time 3D images of the AIUM test object were made with this transducer.     

7.5 MHz dual-layer transducer array for 3-D rectilinear imaging

The difficulties associated with fabrication and interconnection have limited the development of 2-D ultrasound transducer arrays with a large number ofelements (>5000). In previous work, we described a 5 MHz center frequency PZT-P[VDF-TrFE] dual-layer transducer that used two perpendicular 1-D arrays for 3-D rectilinear imaging. This design substantially reduces the channel count as well as fabrication complexity, which makes 3-D imaging more realizable. Higher frequencies (>5 MHz) are more commonly used in clinical applications or imaging targets near transducers, such as the breast, carotid and musculoskeletal tissue. In this paper, we present a 7.5 MHz dual-layer transducer array for 3-D rectilinear imaging. A modified acoustic stack model was designed and fabricated. PZT elements were sub-diced to eliminate lateral coupling. This sub-dicing process made the PZT into a 2-2 composite material, which could help improve transducer sensitivity and bandwidth. Full synthetic-aperture 3-D data sets were acquired by interfacing the transducer with a Verasonics data-acquisition system (VDAS). Offline 3-D beamforming was then performed to obtain volumes of a multiwire phantom and a cyst phantom. The generalized coherence factor (GCF) was applied to improve the contrast of cyst images. The measured -6 dB fractional bandwidth of the transducer was 71% with a center frequency of 7.5 MHz. The measured lateral beamwidths were 0.521 mm and 0.482 mm in azimuth and elevation, respectively, compared with a simulated beamwidth of 0.43 mm.     

Enhanced methods for visualizing myocardial perfusion with peripheral venous injection of Levovist®: Application of triggered harmonic imaging and triggered harmonic power Doppler imaging techniques

Objectives:The purpose of this study was to determine whether triggered harmonic imaging (THI) or triggered harmonic power Doppler imaging (THPDI) could obtain the myocardial contrast enhancement using peripheral venous injection of a first generation echocardiographic contrast agent, Levovist^®. Methods:In a phantom model, we examined the influence of an acoustic power, harmonic filters, transmitted frequencies and focus positions of transducer on Levovist^®. Then fundamental, harmonic or harmonic power Doppler imaging were performed with ECG-triggered imaging in eight closed-chest dogs using bolus injection of Levovist^®. Results:In a phantom model, the highest transmission power (Mechanical index 1.6), a medium harmonic filter and a focus position (6 cm) resulted in the best enhanced contrast in both THI and THPDI. Furthermore, higher pulse repetition frequency (5500 Hz) of harmonic power Doppler made clearer enhancement. In animal models, we could not observe the apparent myocardial contrast using triggered fundamental imaging, and the intensity of each region of interest (ROI) of myocardium had not changed significantly. However, homogeneous myocardial contrast could be obtained using THI, which was conditioned on the highest transmission power, a medium harmonic filter same as the phantom model, at a lower transmitted frequency (1.8 MHz) and a focus position, which were located in the middle portion of the left ventricle. The peak intensity of each ROI increased significantly in a gray level. Furthermore, THPDI caused emphasized myocardial contrast visually. Conclusions:These results indicate that THI and THPDI produce obvious MCE using peripheral venous injection of Levovist^®.     

In Vitro Superharmonic Contrast Imaging Using a Hybrid Dual-Frequency Probe

Superharmonic imaging is an ultrasound contrast imaging technique that differentiates microbubble echoes from tissue through detection of higher-order bubble harmonics in a broad frequency range well above the excitation frequency. Application of superharmonic imaging in three dimensions allows specific visualization of the tissue microvasculature with high resolution and contrast, a technique referred to as acoustic angiography. Because of the need to transmit and receive across a bandwidth that spans up to the fifth harmonic of the fundamental and higher, this imaging approach requires imaging probes comprising dedicated transducers for transmit and receive. In this work, we report on a new dual-frequency probe including two 1.7-MHz rectangular transducers positioned one on each side of a 20-MHz 256-element array. Finite element modeling-based design, fabrication processes and assembly of the transducer are described, as is integration with a high-frequency ultrasound imaging platform. Dual-frequency single-plane-wave imaging was performed with a microbubble contrast agent in flow phantoms and compared with conventional high-frequency B-mode imaging, and resolution and contrast-to-tissue ratio were quantified. This work represents an intermediate but informative step toward the development of dual-frequency imaging probes based on array technology, specifically designed for clinical applications of acoustic angiography.     

Fluorescein isothiocynate-dextran uptake by chinese hamster ovary cells in a 1.5 MHz ultrasonic standing wave in the presence of contrast agent

Uptake of fluorescein isothiocynate-dextran (FITC-dextran) by Chinese hamster ovary cells was studied after exposure to ultrasonic standing wave (USW) in presence of Optison, an ultrasound contrast agent. Confluent Chinese hamster ovary cells were harvested and suspended in phosphate-buffered saline + 0.1% bovine serum albumin containing FITC-dextran (10, 40, and 500 kDa) at 10 microM final concentration. The suspension was seeded with contrast agent (75 microL/mL) and exposed to a 1.5 MHz USW system at acoustic pressures ranging from 0.98 to 4.2 MPa. Macromolecular uptake was assessed by fluorescent microscopy and quantified by flow cytometry 10 min after exposure. FITC-dextran positive cells, as assessed by flow cytometry, were 1 +/- 0.05% and 2.58 +/- 0.27% for acoustic pressures of 1.96 and 4.2 MPa, respectively (p = 0.006). Fluorescent microscopy indicated a degree of macromolecular loading at 0.98 MPa with 46% of peripherally FITC-dextran- and/or propidium iodide-stained cells coincident with the appearance of significant frequency (f0/2 and 2 f0) emission signals. At higher pressures, high macromolecular loading with 6% peripherally stained cells at 1.96 MPa was associated with lower order emission signals and white noise. The study conclusively demonstrates macromolecular loading in an USW, a significantly higher macromolecular loading at higher pressures and indicates potential of emission signals for a feedback loop to control the acoustic power outputs and fine-tune the biologic effects associated with sonoporation.     

Effects of transmit focusing on finite amplitude distortion based second harmonic generation

Generation of the second harmonic signal was studied for finite amplitude distortion based harmonic imaging. Acoustic field amplitudes along the range axis of a fixed focus transducer were measured using a PVDF needle hydrophone. Results indicated that on-axis amplitudes strongly depended on the f-number at both the fundamental and the second harmonic frequencies. Differences of the on-axis amplitudes between the two frequencies were also investigated. To explore the possibility of increasing harmonic generation by extending the depth of focus, a two-focus transducer was employed. Hydrophone measurements, pulse-echo imaging and simulations were performed. Although the increase in harmonic generation depended on specific imaging parameters, the effectiveness of improving the harmonic signal-to-noise ratio (SNR) by increasing the depth of field was clearly demonstrated. Degradation in contrast resolution associated with the two-focus transducer was also evaluated. It was found that the contrast resolution was still significantly better than that of the fundamental image at the same frequency. Results of the study using the two-focus transducers can be generalized to imaging systems with full dynamic transmit focusing capabilities. In other words, it is expected that dynamic transmit focusing can improve the SNR of finite amplitude distortion based second harmonic imaging while improving the contrast resolution over fundamental imaging.     

Assessment of the Superharmonic Response of Microbubble Contrast Agents for Acoustic Angiography as a Function of Microbubble Parameters

Acoustic angiography is a superharmonic contrast-enhanced ultrasound imaging technique that enables 3-D high-resolution microvascular visualization. This technique utilizes a dual-frequency imaging strategy, transmitting at a low frequency and receiving at a higher frequency, to detect high-frequency contrast agent signatures and separate them from tissue background. Prior studies have illustrated differences in microbubble scatter dependent on microbubble size and composition; however, most previously reported data have utilized a relatively narrow frequency bandwidth centered around the excitation frequency. To date, a comprehensive study of isolated microbubble superharmonic responses with a broadband dual-frequency system has not been performed. Here, the superharmonic signal production of 14 contrast agents with various gas cores, shell compositions, and bubble diameters at mechanical indices of 0.2 to 1.2 was evaluated using a transmit 4 MHz, receive 25 MHz configuration. Results indicate that perfluorocarbon cores or lipid shells with 18- or 20-carbon acyl chains produce more superharmonic signal than sulfur hexafluoride cores or lipid shells with 16-carbon acyl chains, respectively. As microbubble diameter increases from 1 to 4 µm, superharmonic generation decreases. In a comparison of two clinical agents, Definity and Optison, and one preclinical agent, Micromarker, Optison produced the least superharmonic signal. Overall, this work suggests that microbubbles around 1 μm in diameter with perfluorocarbon cores and longer-chained lipid shells perform best for superharmonic imaging at 4 MHz. Studies have found that microbubble superharmonic response follows trends different from those described in prior studies using a narrower frequency bandwidth centered around the excitation frequency. Future work will apply these results in vivo to optimize the sensitivity of acoustic angiography.     

Processing of subharmonic signals from ultrasound contrast agents to determine ambient pressures

Subharmonic-aided pressure estimation (SHAPE) is a technique that utilizes the subharmonic emissions, occurring at half the insonation frequency, from ultrasound contrast agents to estimate ambient pressures. The purpose of this work was to compare the performance of different processing techniques for the raw radiofrequency (rf) data acquired for SHAPE. A closed loop flow system was implemented circulating reconstituted Sonazoid (GE Healthcare, Oslo, Norway; 0.2 ml for 750 ml diluent) and the beam-formed unprocessed rf data were obtained from a 4 mm diameter lumen of a Doppler flow phantom (ATS Laboratories, Inc., Bridgeport, CT) using a SonixRP scanner (Ultrasonix, Richmond, BC, Canada). The transmit frequency and incident acoustic pressures were set to 2.5 MHz and 0.22 MPa, respectively, in order to elicit Sonazoid subharmonic emissions that are ambient-pressure sensitive. The time-varying ambient pressures within the flow phantom were recorded by a Millar pressure catheter. Four techniques for extracting the subharmonic amplitude from the rf data were tested along with two noise filtering techniques to process this data. Five filter orders were tested for the noise removing filters. The performance was evaluated based on the least root-mean-square errors reported after linear least-square regression analyses of the subharmonic data and the pressure catheter data and compared using a repeated ANOVA. When the subharmonic amplitudes were extracted as the mean value within a 0.2 MHz bandwidth about 1.25 MHz and when the resulting temporally-varying subharmonic signal was median filtered with an order of 500, the filtered subharmonic signal significantly predicted the ambient pressures (r2 = 0.90; p < 0.001) with the least error. The resulting root mean square and mean absolute errors were 8.16 +/- 0.26 mmHg and 6.70 +/- 0.17 mmHg, respectively. Thus, median processing the subharmonic data extracted as the mean value within a 0.2 MHz bandwidth about the theoretical subharmonic frequency turned out to be the best technique to process acoustic data for SHAPE. The implementation of this technique on ultrasound scanners may permit real-time SHAPE applications.     

Imaging of pulmonary vascular disease by intravascular ultrasound

To assess the ability of intravascular ultrasound (IVUS) to image changes in the pulmonary arterial wall associated with pulmonary hypertension (PHT), 10 subjects requiring diagnostic right and left heart catheterization were studied. In addition to measurements of pulmonary artery pressure and pulmonary vascular resistance and pulmonary angiography, when indicated, all underwent simultaneous IVUS imaging in the pulmonary arterial system using a 20 MHz ultrasound transducer mounted on a 2 mm diameter catheter. Four patients had normal pulmonary artery pressures and 6 had varying degrees of PHT. Satisfactory ultrasound images were obtained in 9 out of the 10 patients. In those with normal pulmonary artery pressures ultrasound showed a thin vessel wall with no destinction between separate layers. In patients with systemic PHT, a threelayered vessel wall was apparent and areas compatible with intimai proliferation were seen. In a patient with pulmonary embolic disease areas consistent with mural thrombus were detected at sites of luminal narrowing on the pulmonary angiogram. IVUS is capable of imaging some of the morphological changes in the wall of the pulmonary artery known to occur in longstanding PHT and may therefore become a useful adjunct to haemodynamic measurements and pulmonary angiography for thein vivo assessement of pulmonary vascular disease.