Clinical Ultrasound Imaging System Research Articles

Measurement of the Doppler Power of Flowing Blood Using Ultrasound Doppler Devices

Measurement of the Doppler power of signals backscattered from flowing blood (henceforth referred to as the Doppler power of flowing blood) and the echogenicity of flowing blood have been used widely to assess the degree of red blood cell (RBC) aggregation for more than 20 y. Many studies have used Doppler flowmeters based on an analogue circuit design to obtain the Doppler shifts in the signals backscattered from flowing blood; however, some recent studies have mentioned that the analogue Doppler flowmeter exhibits a frequency-response problem whereby the backscattered energy is lost at higher Doppler shift frequencies. Therefore, the measured Doppler power of flowing blood and evaluations of RBC aggregation obtained using an analogue Doppler device may be inaccurate. To overcome this problem, the present study implemented a field-programmable gate array-based digital pulsed-wave Doppler flowmeter to measure the Doppler power of flowing blood, in the aim of providing more accurate assessments of RBC aggregation. A clinical duplex ultrasound imaging system that can acquire pulsed-wave Doppler spectrograms is now available, but its usefulness for estimating the ultrasound scattering properties of blood is still in doubt. Therefore, the echogenicity and Doppler power of flowing blood under the same flow conditions were measured using a laboratory pulser–receiver system and a clinical ultrasound system, respectively, for comparisons. The experiments were carried out using porcine blood under steady laminar flow with both RBC suspensions and whole blood. The experimental results indicated that a clinical ultrasound system used to measure the Doppler spectrograms is not suitable for quantifying Doppler power. However, the Doppler power measured using a digital Doppler flowmeter can reveal the relationship between backscattering signals and the properties of blood cells because the effects of frequency response are eliminated. The measurements of the Doppler power and echogenicity of flowing blood were compared with those obtained in several previous studies.

Ultrasound-guided three-dimensional needle steering in biological tissue with curved surfaces

In this paper, we present a system capable of automatically steering a bevel-tipped flexible needle under ultrasound guidance toward a physical target while avoiding a physical obstacle embedded in gelatin phantoms and biological tissue with curved surfaces. An ultrasound pre-operative scan is performed for three-dimensional (3D) target localization and shape reconstruction. A controller based on implicit force control is developed to align the transducer with curved surfaces to assure the maximum contact area, and thus obtain an image of sufficient quality. We experimentally investigate the effect of needle insertion system parameters such as insertion speed, needle diameter and bevel angle on target motion to adjust the parameters that minimize the target motion during insertion. A fast sampling-based path planner is used to compute and periodically update a feasible path to the target that avoids obstacles. We present experimental results for target reconstruction and needle insertion procedures in gelatin-based phantoms and biological tissue. Mean targeting errors of 1.46±0.37mm, 1.29±0.29mm and 1.82±0.58mm are obtained for phantoms with inclined, curved and combined (inclined and curved) surfaces, respectively, for insertion distance of 86–103mm. The achieved targeting errors suggest that our approach is sufficient for targeting lesions of 3mm radius that can be detected using clinical ultrasound imaging systems.

Multimodal sentinel lymph node mapping with single-photon emission computed tomography (SPECT)/computed tomography (CT) and photoacoustic tomography

The identification of cancer cells in the lymph nodes surrounding a tumor is important in establishing a prognosis. Optical detection techniques such as fluorescence and photoacoustic tomography (PAT) have been reported in preclinical studies for noninvasive sentinel lymph node (SLN) mapping. A method for validation of these techniques is needed for clinical trials. We report the use of a multimodal optical-radionuclear contrast agent as a validation tool for PAT in a preclinical model. Methylene blue (MB) was radiolabeled with (125)I for multimodal SLN mapping and used in conjunction with MB to assess the feasibility of multimodal SLN mapping in a rat model by PAT and single-photon emission computed tomography (SPECT). MB provided sufficient contrast for identifying SLNs noninvasively with a PAT system adapted from a clinical ultrasound imaging system. The signal location was corroborated by SPECT using (125)I labeled MB. The translation of PAT into the clinic can be facilitated by a direct comparison with established imaging methods using a clinically relevant dual SPECT and photoacoustic imaging agent. The new high-resolution PAT is a promising technology for the sensitive and accurate SLN detection in cancer patients.

Non-invasive measurement of local pulse pressure by pulse wave-based ultrasound manometry (PWUM)

Central blood pressure (CBP) has been established as a relevant indicator of cardiovascular disease. Despite its significance, CBP remains particularly challenging to measure in standard clinical practice. The objective of this study is to introduce pulse wave-based ultrasound manometry (PWUM) as a simple-to-use, non-invasive ultrasound-based method for quantitative measurement of the central pulse pressure. Arterial wall displacements are estimated using radiofrequency ultrasound signals acquired at high frame rates and the pulse pressure waveform is estimated using both the distension waveform and the local pulse wave velocity. The method was tested on the abdominal aorta of 11 healthy subjects (age 35.7±16 y.o.). PWUM pulse pressure measurements were compared to those obtained by radial applanation tonometry using a commercial system. The average intra-subject variability of the pulse pressure amplitude was found to be equal to 4.2 mmHg, demonstrating good reproducibility of the method. Excellent correlation was found between the waveforms obtained by PWUM and those obtained by tonometry in all subjects (0.94 < r < 0.98). A significant bias of 4.7 mmHg was found between PWUM and tonometry. PWUM is a highly translational method that can be easily integrated in clinical ultrasound imaging systems. It provides an estimate of the pulse pressure waveform at the imaged location, and may offer therefore the possibility to estimate the pulse pressure at different arterial sites. Future developments include the validation of the method against invasive estimates on patients, as well as its application to other large arteries.

Ultrasound Guidance for the Creation of a Small Animal Model of Aortic Injury

Purpose To develop a small animal model of controlled aortic intimal injury with ultrasound (US) imaging guidance. Materials and Methods Via carotid artery cutdown, a custom-made microcatheter/angled metal device system was advanced to damage the intima of the ascending aortas of 20 Sprague–Dawley rats and 10 JCR atherosclerotic rats. This minimally invasive endovascular procedure was monitored by a clinical US imaging system. Injured aortas were harvested for histologic confirmation via a grading system: grade I, intima injury; grade II, injury to media; and grade III, injury through the entire aortic wall. Neointimal reactions at the injury site were compared by calculating the ratio of intimal to medial thickness among different animal groups at various survival times (week 1, weeks 2–3, and weeks 4–7). Results Clear visualization of the architecture of the heart and great vessels and the exact location of the angled metal device by US imaging ensured consistent intimal damage of the aorta. Histopathologic analysis confirmed that most of the aortic injures were classified as grade I. There was no significant difference between the two rat groups. Analysis of pathophysiologic reactions at the injury sites revealed increased thickening of neointimal hyperplasia as animal survival times extended from week 1 to weeks 4–7 after the aortic interventions. Conclusions This study demonstrates the feasibility of clinical US imaging to precisely guide the creation of controlled aortic intimal injury in rats, which may become a useful tool to facilitate research involving the prevention and treatment of atherosclerotic cardiovascular disease.

A real-time device for converting Doppler ultrasound audio signals into fluid flow velocity

A Doppler signal converter has been developed to facilitate cardiovascular and exercise physiology research. This device directly converts audio signals from a clinical Doppler ultrasound imaging system into a real-time analog signal that accurately represents blood flow velocity and is easily recorded by any standard data acquisition system. This real-time flow velocity signal, when simultaneously recorded with other physiological signals of interest, permits the observation of transient flow response to experimental interventions in a manner not possible when using standard Doppler imaging devices. This converted flow velocity signal also permits a more robust and less subjective analysis of data in a fraction of the time required by previous analytic methods. This signal converter provides this capability inexpensively and requires no modification of either the imaging or data acquisition system.

An efficient sound speed estimation method to enhance image resolution in ultrasound imaging

Most of clinical ultrasound imaging systems use a pre-determined sound speed, mostly 1540 m/s, in transmit- and receive-beamforming while actual sound speed varies depending on tissue composition and temperature. Sound speed errors, particularly in receive-beamforming, lead to resolution degradation and sensitivity loss in ultrasound imaging. In this paper, we propose a sound speed estimation method in which an optimal sound speed, the speed that makes the echo signal delays at the transducer elements be best matched to the theoretical delays, is estimated by maximizing the beamformed echo signal amplitude with respect to the sound speed and the reflector displacement from the central axis of the ultrasound beam. Since the sound speed can be estimated from the echo signals on several scan lines, the proposed method does not require excessive computation. Experimental imaging studies of phantoms and porcine tissue with a 6 MHz 128-element linear probe and a 3 MHz 128-element convex probe have shown that spatial resolution, particularly in the lateral direction, can be improved by the proposed method.

Detection of individual microbubbles of ultrasound contrast agents: imaging of free-floating and targeted bubbles.

During echo examinations with microbubble contrast, individual "dots" of ultrasound reflection can be visualized. To address the question whether these signals represent individual microbubbles, very dilute suspensions of ultrasound contrast agents or individual microbubbles attached to Petri dishes were prepared and studied by ultrasound imaging. Microbubble suspensions were diluted in saline and evaluated by a clinical ultrasound imaging system. Microbubble concentration was verified by Coulter counter. Single microbubble preparation on a Petri dish was established by streptavidin-biotin interaction under microscopy control and subjected to ultrasound imaging. Ultrasound of dilute microbubble dispersions demonstrated distinct white foci; concentration of these sites was consistent with signals from individual microbubbles as determined by Coulter. Individual microbubbles immobilized on polystyrene were also visualized by ultrasound. Ultrasound medical systems can resolve backscatter signals from individual microbubbles of ultrasound contrast, both in solution and in the targeted immobilized state, implying picogram sensitivity.

An in vitro study of a microbubble contrast agent using a clinical ultrasound imaging system

Optimal insonation settings for contrast imaging are yet to be specified, mainly due to the lack of good understanding of the behaviour of the microbubbles. A satisfactory model that explains the behaviour of individual contrast agent scatterers has not yet been reported in the literature. An in vitro system based on a commercial scanner (ATL HDI3000) has been developed to investigate the backscatter of such agents. Suspensions of Definity® were introduced in an anechoic tank. The frequency of transmitted ultrasound varied from 1 to 5 MHz, pulse period from 2 to 10 periods and peak negative acoustic pressure from 0.08 to 1.7 MPa. The backscatter at the fundamental and second harmonic frequency windows from the agent was normalized in terms of the corresponding components of backscatter from a blood mimicking fluid suspension. The agent provided a dominant resonance effect at 1.6 MHz transmit frequency. Second harmonic normalized backscatter averaged around 9 dB higher than the fundamental. The normalized fundamental backscatter intensity was linear with peak negative pressure. The second harmonic at resonance peaked at 0.5 MPa suggestive of bubble disruption above such pressure. The system proved capable of illustrating the ultrasonic behaviour of Definity® in vitro, and the investigation suggested particular insonation conditions for optimal image enhancement using Definity®.

Parametric analysis of carotid plaque using a clinical ultrasound imaging system

We evaluated quantitative ultrasonic methods for assessment of carotid plaque content. In vitro measurements of fixed, carotid plaque specimens obtained by surgical endarterectomy were performed using a clinical Philips HDI 5000 imaging system connected to a radiofrequency (RF) signal-acquisition system. We acquired RF signals and grey-scale images from carotid specimens ( n = 17) and a tissue-mimicking reference phantom. Imaged plaque sections were then classified according to histology. Parametric images were constructed from the integrated backscatter (IBS), and the midband, slope and intercept values of a straight-line fit to the apparent backscatter transfer function. Analysis was performed on 82 regions-of-interest (ROIs). The IBS values for collagen, lipid and hemorrhage plaques were 5.8 ± 5.4, 3.9 ± 3.7, 2.8 ± 2.2 dB, respectively. Midband and IBS parameter images exhibited good agreement in morphology with histology, whereas the slope and intercept parameter images were noisy. Mean IBS, midband, and grey-scale values of complex plaques were found to be statistically different ( p < 0.05) from lipid, hemorrhage and fibrolipid plaques. The bias and limits of agreement (1.3 ± 4.9 dB) between the grey-scale and IBS methods, however, indicated that the two methods were not interchangeable. Results indicate necessary improvements, such as reduction of large measurement variances and identification of robust parameters, that will permit multiparametric characterization of carotid plaque under in vivo conditions. (E-mail: krwaters@boulder.nist.gov)

A modified block matching method for real-time freehand strain imaging.

This manuscript reports a technical innovation that has been developed for real-time, freehand strain imaging. This work is based on a well-known block-matching algorithm with two significant modifications. First, since displacements are estimated row-by-row, displacement estimates from the previous row are used to predict the displacement estimates in the current row, thereby drastically reducing the search-region size and increasing computational efficiency. Second, a displacement error detection and correction method is developed to overcome the local tracking errors that may be more severe with freehand scanning and thereby improve the robustness of the algorithm. This algorithm has been implemented on a clinical ultrasound imaging system, and with real-time imaging feedback, long sequences of high quality strain images are observed using freehand compression. Displacement estimation errors with this method are experimentally measured and compared with results from simulation. We report only a specific implementation, with no comparison to other displacement estimators in the literature and no optimization of this specific technique. Images of tissue-mimicking phantoms with small spherical targets are used to test the ability to detect small lesions using the strain imaging technique. In vivo strain images of breast and thyroid are also shown.

A new technique for real-time freehand ultrasonic elasticity imaging

A method for high-speed, freehand ultrasonic elasticity imaging will be described. The method is based on a modified block matching technique. The modification serves two purposes. First, in order to achieve real-time performance a forward prediction mechanism is used to reduce the computational load that a conventional block matching technique requires. Second, in order to accommodate the waveform decorrelation associated with freehand scanning a statistical error detection and correction method was developed. This prevents the displacement estimation errors from propagating to affect a larger area. This new algorithm has been implemented on a Siemens Elegra (a high-end clinical ultrasound imaging system). The initial tests show that the new system can perform B-mode and strain display task at real-time frame rates. The strain images have low noise and excellent contrast. Some results obtained with this system will also be presented. [Support by USAMRAA DAMD17-00-1-0596, NSF BES-9708221, and Siemens Medical Systems is gratefully acknowledged.]

Statistics of the log-compressed echo envelope

Log compression of A lines to produce B-scan images in clinical ultrasound imaging systems is a standard procedure to control the dynamic range of the images. The statistics of such compressed images in terms of underlying scatterer statistics have not been derived. The statistics are analyzed for partially formed speckle using a general K distribution model of envelope statistics to derive the density function for the log-compressed envelope. This density function is used to elucidate the relation between the moments of the compressed envelope, the compression parameters, and the statistics of the scatterers. The analysis shows that the mean of the log-compressed envelope is an increasing function of both the backscattered energy and the effective scatterer density. The variance of the log-compressed envelope is a decreasing function of the effective scatterer density and is independent of the backscattered energy.

Cavitation from diagnostic ultrasound

The possibility of cavitation as a consequence of short‐pulse diagnostic ultrasound was predicted theoretically in 1982 by Apfel [R. E. Apfel, Br. J. Cancer 45 (Suppl. V), 140–146 (1982)] and Flynn [H. G. Flynn, J. Acoust. Soc. Am. 72, 1926–1932 (1982)]. Experiments were performed in ultraclean water to test this hypothesis under conditions comparable to those found in clinical ultrasound examinations. The development of an ultrasensitive acoustic backscattering technique that utilizes 30‐MHz pulsed ultrasound has made it possible to detect the presence of transient cavitation due to microsecond‐length pulses [R. A. Roy et al., J. Acoust. Soc. Am. 87, 2451–2458 (1990)]. This “active cavitation detector” has been employed in an in vitro study to probe the potential of cavitation production by a clinical ultrasound imaging system, specifically, an HP 77020A. Two calibrated, phased‐array HP imaging transducers with and 5.0‐MHz operating frequencies were driven in M‐mode (single cycle) and Doppler mode (4 cycles) by the HP imaging system. Hydrophobic polystyrene spheres with an average diameter of 0.245 μm served as potential cavitation nuclei. Cavitation was detected in the water at 2.5 MHz in both M‐mode and Doppler mode at a peak negative acoustic pressure of 1.1 MPa or greater. Insonfication at 5.0 MHz in either mode did not produce a detectable amount of cavitation, even with peak negative pressures as high as 1.2 MPa. [Work supported by the National Institutes of Health, Grant No. 5‐RO1‐CA‐39374‐05.]