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Biomedical subjects

Peter N Burns

Publications and source records attributed to Peter N Burns.

At least 19 recordsLinked to original sources

Focal liver masses: enhancement patterns on contrast-enhanced images--concordance of US scans with CT scans and MR images.

PURPOSE: To assess prospectively the concordance of enhancement patterns of focal liver masses on contrast material-enhanced ultrasonographic (US) scans with patterns on contrast-enhanced computed tomographic (CT) scans or magnetic resonance (MR) images. MATERIALS AND METHODS: This study was approved by the institutional review board; patients gave informed consent. Contrast-enhanced US and contrast-enhanced CT or MR imaging were performed in 135 patients (62 men, 73 women; mean age, 51 years) with 144 confirmed liver masses. Masses included 49 hepatocellular carcinomas, 13 metastases, 30 hemangiomas, 41 lesions of focal nodular hyperplasia, and 11 others. Randomized image sets from each modality were shown independently to three blinded readers, who answered identical questions about enhancement of the lesion and liver in the arterial and portal venous phases and changes with time. Concordance for modalities was calculated from answers of readers and consensus answers between readers, with 95% confidence intervals (CIs). The kappa values were calculated for interreader agreement. RESULTS: Features of arterial phase enhancement showed concordance of more than 76% for modalities. The highest concordance of 92% (132 of 144), with 95% CI of 86% and 95% (kappa>0.84), was for the presence of peripheral pools and centripetal progression. Concordance in the portal venous phase was lower, with agreement for predominant enhancement of the lesion in 61% (86 of 142), with 95% CI of 52% and 68% (kappa>0.83). Portal venous phase washout occurred in 75% (106 of 142), with 95% CI of 67% and 81% (kappa>0.81). The majority of discordances were for malignancies for which only US depicted no sustained enhancement in the portal venous phase. CONCLUSION: US shows high concordance with CT or MR imaging, especially for the arterial phase. Discordance in the portal venous phase may reflect the tendency of CT and MR contrast agents, unlike microbubbles, to diffuse into interstitium.

Adult↗

Investigating perfluorohexane particles with high-frequency ultrasound.

Submicron particles filled with liquid perfluorocarbon are currently being studied as a potential ultrasound-targeted contrast agent. The objective of this study was to evaluate the scattering properties of these particles. Sets of perfluorohexane-filled particles of different average sizes (300 nm to 1000 nm) were produced with a constant total volume fraction. The attenuation coefficient was measured in the 15- to 50-MHz frequency range and was found to increase smoothly with frequency and to be independent of the amplitude and bandwidth of the transmitted pulse. The values range from 0.31 to 0.64 dB/mm at 30 MHz for mean particle size ranging from 970 to 310 nm, respectively. The backscattering spectra of the particle solutions were measured and showed no sign of nonlinear scattering. The backscattering coefficient increased with the power 3.9 +/- 0.3 of the frequency. These results confirm that liquid perfluorocarbon droplets behave as linear Rayleigh scatterers.

Contrast Media↗

A model for reflectivity enhancement due to surface bound submicrometer particles.

Submicrometer particles filled with liquid perfluorocarbon have been shown to increase the ultrasound reflectivity of surfaces onto which they bind and, consequently, are seen as potential targeted contrast agents. The objective of this study is to explain the reflectivity enhancement as a result of the presence of randomly distributed particles on a surface. A model is presented where the diffraction-weighted scattering of all particles is summed over the exposed surface. Experiments were performed at frequencies ranging from 15 MHz to 60 MHz, with glass microbeads and perfluorohexane particles deposited on the surface of agar and Aqualene, a rubber closely matched to water, to confirm the validity of the model. Results showed that the model predicts the surface density and the frequency dependence of the reflectivity enhancement up to a density corresponding to twice the maximum packing of spheres on a surface (200% confluence fraction) for glass beads and a fifth (20% confluence fraction) for perfluorohexane particles. This suggests the possibility of predicting signal enhancement due to a bound contrast agent in simple geometries.

Contrast Media↗

An algorithm for the diagnosis of focal liver masses using microbubble contrast-enhanced pulse-inversion sonography.

OBJECTIVE: The objective of this study was to develop an algorithm for liver mass diagnosis using microbubble contrast-enhanced pulse-inversion sonography. SUBJECTS AND METHODS: Ninety-six lesions in 92 patients were evaluated with DMP 115 (Definity)-enhanced pulse-inversion sonography, comprising 44 malignancies (29 hepatocellular carcinomas, 12 metastases, two peripheral cholangiocarcinomas, and one hepatic lymphoma) and 52 benign lesions (26 hemangiomas, 20 focal nodular hyperplasias, and six others). All had continuous low-mechanical-index imaging through the arterial and portal venous phase. A three-person blind review evaluated single images at baseline, early and peak arterial phases, and through the extended portal phases with a movie showing arterial phase wash-in. Reviewers assessed lesional vascularity and enhancement blindly but did not make a diagnosis. Combinations of answers were compared with independently determined final diagnoses to develop an algorithm for liver mass diagnosis. RESULTS: Portal phase enhancement comprises the first step of the algorithm, with positive or sustained enhancement identifying 48 (92%) of 52 benign lesions and negative enhancement or washout present in 41 (93%) of 44 malignancies. Sustained portal phase enhancement with arterial phase peripheral nodularity and centripetal progression predicted 24 (92%) of 26 of the hemangiomas; diffuse arterial phase enhancement greater than the liver identified 19 (95%) of 20 of the focal nodular hyperplasias. With negative portal phase enhancement, arterial phase information was less effective at differentiating hepatocellular carcinoma (25 [86%] of 29 cases) from another hepatic malignancy (11 [73%] of 15 cases). CONCLUSION: A simple diagnostic algorithm for interpretation of microbubble-enhanced sonography provides sensitive and accurate diagnosis of commonly encountered liver masses.

Adolescent↗

Microbubble contrast for radiological imaging: 1. Principles.

Microbubble contrast for ultrasound imaging in radiology has finally come of age, adding entirely new capabilities to real time imaging. Following a bolus injection into a peripheral vein of as little as 0.1mL of an aqueous suspension, contrast specific imaging modes show parenchymal and lesional perfusion in real time in the major organs of the abdomen and pelvis as well as breast, thyroid and prostate. These new imaging modes exploit the unique interaction between ultrasound and microbubbles, which gives rise to nonlinear echoes that are readily distinguishable from those of tissue. Furthermore, microbubbles can be deliberately disrupted by the ultrasound imaging field. The rate at which fresh bubbles then replenish the scanplane can be metered in subsequent images, offering a means to quantify both flowrate and relative vascular volume of the microvasculature in both organs and solid lesions.

Contrast Media↗

Microbubble contrast for radiological imaging: 2. Applications.

Conventional Doppler provides information on blood flow including both flow and direction and flow velocity. Information on the slowly flowing blood at the capillary level, however, has not previously been available on state of the art Doppler. Contrast enhanced ultrasound provides, for the first time, information on tissue perfusion such that CEUS may now play a role in liver mass characterization and the evaluation of masses in other solid viscera similar to the role of contrast enhanced CT and MR scan. Renal applications include similar mass characterization and evaluation of renal perfusion and the renal vasculature. Surveillance of aortic stent grafts, monitoring RFA, and evaluation of both prostate and breast masses are further areas of interest. Our experience with ultrasound contrast expands progressively, and essentially adds vascular information to any region when blood flow information is required. The addition of CEUS to clinical practice has significant impact on patient management. In patients with an incidental liver mass on sonography, for example, characterization at the time of tis detection reduces the time to diagnosis and decreases referrals to CT or MR scan. Ultrasound contrast agents are easy to use, have a very low incidence of adverse events, and are unaffected by renal function. As they add no radiation for their use, they are highly appropriate in pediatric and young adult patients. Ultrasound is enhanced by addition of contrast agents.

Contrast Media↗

Optimising phase and amplitude modulation schemes for imaging microbubble contrast agents at low acoustic power.

A series of in vitro experiments were performed to determine the efficacy of generalised phase- and amplitude-modulated sequences for low-power nonlinear microbubble contrast imaging. The microbubble agent Definity (Dupont, Boston, MA) was exposed to sequences in which the phase and amplitude were changed from one pulse to the next. Echoes from these pulses were combined to suppress or enhance particular linear or nonlinear components. The results show that established two-pulse pulse-inversion and amplitude-modulation approaches perform similarly, providing 14 +/- 1 dB of enhancement, compared with the echoes from the linear scatterer. A two-pulse combined phase and amplitude sequence achieved an additional 4 +/- 1 dB of enhancement. This improvement is due to improved preservation of second and third order harmonic signals, while maintaining the suppression of the linear signals. These results were obtained at low power, below the threshold of microbubble destruction, and are applicable to real-time perfusion imaging.

Contrast Media↗

High frequency nonlinear B-scan imaging of microbubble contrast agents.

It previously was shown that it is possible to produce nonlinear scattering from microbubble contrast agents using transmit frequencies in the 14-32 MHz range, suggesting the possibility of performing high-frequency, nonlinear microbubble imaging. In this study, we describe the development of nonlinear microbubble B-scan imaging instrumentation capable of operating at transmit center frequencies between 10 and 50 MHz. The system underwent validation experiments using transmit frequencies of 20 and 30 MHz. Agent characterization experiments demonstrate the presence of nonlinear scattering for the conditions used in this study. Using wall-less vessel phantoms, nonlinear B-scan imaging is performed using energy in one of the subharmonic, ultraharmonic, and second harmonic frequency regions for transmit frequencies of 20 and 30 MHz. Both subharmonic and ultraharmonic imaging modes achieved suppression of tissue signals to below the noise floor while achieving contrast to noise ratios of up to 26 and 17 dB, respectively. The performance of second harmonic imaging was compromised by nonlinear propagation and offered no significant contrast improvement over fundamental mode imaging. In vivo experiments using the subharmonic of a 20 MHz transmit pulse show the successful detection of microvessels in the rabbit ear and in the mouse heart. The results of this study demonstrate the feasibility of nonlinear microbubble imaging at high frequencies.

Animals↗

High-frequency, nonlinear flow imaging of microbubble contrast agents.

It has been shown that nonlinear scattering can be stimulated from microbubble contrast agents at high-transmit frequencies (14-32 MHz). This work was extended to demonstrate the feasibility of nonlinear contrast imaging through modifications of existing ultrasound biomicroscopy linear B-scan imaging instrumentation. In this study, we describe the development and evaluation of prototype coherent flow imaging instrumentation for nonlinear microbubble imaging using transmit frequencies from 10 to 50 MHz. Phantom validation experiments were conducted to demonstrate color and power flow imaging using nonlinear 10 MHz (subharmonic) scattering induced by a 20 MHz transmit frequency. In vivo flow imaging of a rabbit ear microvessel was successfully performed. This work indicates the feasibility of performing flow imaging at high frequencies using nonlinear scattering from microbubbles.

Animals↗

Investigation of the effects of microbubble shell disruption on population scattering and implications for modeling contrast agent behavior.

In a previous study, quantitative measurement of nonlinear scattering revealed some quantitative discrepancies with a model for ultrasound scattering by a population ensemble of microbubbles. This study is designed to investigate the effect of the shell on single-pulse scattering by a population of contrast microbubbles. Nonlinear scattering was measured shortly (15 micros) after exposure to a previous ultrasound pulse with variable intensity. The short time delay eliminated the influence of gas diffusion and focused the study on the consequence of ultrasound exposure. The results suggest that single-pulse scattering is dependent on the disruption properties of the bubble shell and confirm the significance of the shell properties.

Contrast Media↗

Transit time kinetics in ordered and disordered vascular trees.

Imaging modalities exploit tracer-dilution methods to measure bulk haemodynamic parameters such as blood flow and volume at the level of the microcirculation. Here, we ask the question of whether the kinetics of a tracer can reveal morphological information about the vessels through which the tracers flow. The goal is to relate the acquired time-intensity characteristic to details of the vascular structure that lies below the imaging resolution. Two fractal vascular models are developed that represent organized 'kidney-like' and disorganized 'tumour-like' structures. The models are generated using simple rules of branching and fractal geometry in two dimensions. Blood flow and tracer kinetics are simulated using fundamental laws of haemodynamics. The flow conditions are matched in the two models. The fractal box dimensions of the kidney (D(B) = 1.67 +/- 0.01) and the tumour (D(B) = 1.80 +/- 0.01) vasculatures fall in the range given in the literature (D(B) = 1.61 +/- 0.06 and D(B) = 1.84 +/- 0.04, respectively). The tracer kinetic curves of the kidney and the tumour vasculatures have the same initial slope and final asymptote, corresponding to the same flow rate and vascular volume, but have different forms. The difference in the two curves is related to the distribution function of transit times of the vascular models, and is a consequence of the randomness introduced in vessel diameter and length. In principle, the form of the tracer kinetic curve from a contrast imaging study may offer information relating not only to vascular volume and flow rate, but also to the organization of a microvascular network.

Algorithms↗

Improved detection of hepatic metastases with pulse-inversion US during the liver-specific phase of SHU 508A: multicenter study.

PURPOSE: To compare conventional B-mode ultrasonography (US) alone with the combination of conventional B-mode US and contrast material-enhanced (SHU 508A) late-phase pulse-inversion US for the detection of hepatic metastases by using dual-phase spiral computed tomography (CT) as the standard of reference. MATERIALS AND METHODS: One hundred twenty-three patients underwent conventional US, US in the liver-specific phase of SHU 508A, and single-section spiral CT. US and CT images were assessed by blinded readers. Differences in sensitivity, specificity, and the number and smallest size of metastases at conventional and contrast-enhanced US were compared by using CT as the standard of reference. Lesion conspicuity was assessed objectively (quantitatively) and subjectively by one reader before and after contrast material administration. RESULTS: In 45 of 80 (56%) patients with metastases, more metastases were seen at contrast-enhanced US than at conventional US. In three of these patients, conventional US images appeared normal. The addition of contrast-enhanced US improved sensitivity for the detection of individual metastases from 71% to 87% (P <.001). On a patient basis, sensitivity improved from 94% to 98% (P =.44), and specificity improved from 60% to 88% (P <.01). Contrast enhancement improved the subjective conspicuity of metastases in 66 of 75 (88%) patients and the objective contrast by a mean of 10.8 dB (P <.001). Contrast-enhanced US showed more metastases than did CT in seven patients, and CT showed more than did contrast-enhanced US in one of 22 patients in whom an independent reference (magnetic resonance imaging, intraoperative US, or pathologic findings) was available. CONCLUSION: Contrast-enhanced US improved sensitivity and specificity in the detection of hepatic metastases.

Adolescent↗

High-frequency 3-D color-flow imaging of the microcirculation.

High-frequency (> 20 MHz) ultrasound (US) flow imaging has the potential to be an important tool for assessing microvascular blood flow in superficial tissues noninvasively. In this paper, we describe the development and evaluation of a 3-D US flow imaging system capable of operating at center frequencies in the 20- to 50-MHz range. Flow images are made for tissue volumes of sizes up to 10 mm laterally and 5 mm in depth, permitting a range of scientific and clinical applications. To acquire data sets in a reasonable time, the 2-D sections were derived from data collected with a transducer that was scanning continuously in a direction perpendicular to the beam axis. Due to spectral broadening effects induced by scanning tissue, significant tradeoffs must be made between frame rate, lateral resolution and the minimum detectable blood velocity. 3-D flow images were reconstructed with flow data acquired from a series of adjacent planes. The system was evaluated at a center frequency of 50 MHz, using two PVDF transducers with lateral resolutions of 43 microm and 65 microm and axial resolutions of 66 microm to 72 microm, respectively. Velocity ranges were from below 1 mm/s to 25 mm/s. In vivo validation experiments using the mouse ear demonstrated the ability to follow branching patterns of closely spaced microvessels from 30 microm to 100 microm in diameter. Experiments conducted on mouse tumors successfully imaged microvessel morphology in the tumor microcirculation.

Animals↗

High-frequency Doppler ultrasound monitors the effects of antivascular therapy on tumor blood flow.

The effect of antivascular therapy on blood flow in superficial tumors was monitored using novel high frequency Doppler (HFD) ultrasound techniques. Human melanoma cells (MeWo) were injected orthotopically into the skin of athymic nude mice. Volumetric HFD imaging of established melanomas detected a significant reduction in blood flow 4 h after injection of the tumor vascular targeting agent ZD6126 followed by a recovery of flow by 24 h after injection. Measurements of tumor perfusion in situ by Hoechst 33342 staining correlated with the ultrasound results. This study demonstrates the feasibility of HFD as a noninvasive, quantitative tool for following longitudinally the effects of antivascular therapy on blood flow in superficial tumors.

Angiogenesis Inhibitors↗

Instrumentation for contrast echocardiography.

A number of new imaging methods have been developed specifically for use with ultrasound contrast agents. These methods rely on the peculiar behavior of microbubbles in an ultrasound field. At low incident acoustic pressures (reflected by the mechanical index, MI) microbubbles emit harmonics. These can be detected using harmonic or pulse inversion imaging. At higher MI, bubbles are disrupted, emitting a strong, nonlinear echo. Harmonic power Doppler methods are able to detect this echo, offering the most sensitive method for the detection of microbubble at the perfusion level. Although the first images of myocardial perfusion were made using this disruption method, it requires intermittent imaging with interframe intervals of up to 6 heart beats. Pulse inversion Doppler imaging is a newer method that is able to detect the nonlinear component of bubble echoes at a very low MI, thereby making possible real-time myocardial perfusion imaging. An understanding of the behavior of bubbles during an imaging examination is an essential prerequisite to its success in clinical practice.

Contrast Media↗

Focal hepatic masses: enhancement patterns with SH U 508A and pulse-inversion US.

PURPOSE: To evaluate the role of SH U 508A-enhanced ultrasonography (US) in the differentiation of focal hepatic masses. MATERIALS AND METHODS: Contrast material-enhanced pulse inversion US was performed on 58 unknown hepatic lesions: 23 hepatocellular carcinomas, 10 focal nodular hyperplasias, 16 hemangiomas, and nine metastases. Selected images were sequentially reviewed by readers blinded to the final diagnosis. On a baseline image, they determined lesion echogenicity, and on a vascular image, the presence or absence of distinct vascularity. On an arterial phase interval-delay flash image and a postvascular image, they assessed enhancement of the lesion and liver. Responses were compared with confirmed diagnoses. RESULTS: Focal nodular hyperplasia was characterized by detectable vascularity and positive enhancement on interval-delay and postvascular scans (sensitivity, 83% [eight of 10 lesions]; specificity, 98% [40 of 41 lesions]). Hepatocellular carcinoma also showed detectable vascularity and positive enhancement on interval-delay images but no postvascular enhancement (sensitivity, 68% [14 of 20 lesions]; specificity, 74% [23 of 31 lesions]). Vascular imaging with SH U 508A did not contribute to the diagnosis of metastasis or hemangioma. However, no or weak enhancement during the arterial phase flash without postvascular enhancement produced a sensitivity of 83% (seven of eight lesions) and sensitivity of 77% (33 of 43 lesions) for metastasis. Peripheral nodular enhancement on arterial phase flash images was highly specific (98% [37 of 38 lesions]) but not sensitive (44% [six of 13 lesions]) for hemangioma. CONCLUSION: SH U 508A-enhanced pulse-inversion interval-delay flash and postvascular phase imaging are helpful in differential diagnosis of focal hepatic lesions.

Adult↗

Echogenic ovarian foci without shadowing: are they caused by psammomatous calcifications?

PURPOSE: To determine and report the spectrum of ultrasonographic appearances of echogenic ovarian foci (EOF) without shadowing in otherwise normal ovaries and the histopathologic and physical characteristics of these foci. MATERIALS AND METHODS: The appearances of foci on transvaginal pelvic sonograms obtained in 189 patients with EOF were prospectively analyzed. The foci were classified according to bilaterality, size, number (<5, 5-10, or >10), and location (peripheral, central, or diffuse). At histopathologic analysis, resected normal ovaries, seven with and 10 without echogenic foci, in a water bath were scanned. The foci were then localized for histopathologic correlation. To assess the physical properties of the foci, tissue-mimicking water- and glycerol-based phantoms, with voids of different diameters, in a water bath were scanned with 8- and 70-MHz transducers. RESULTS: At appearance analysis, EOF (mean diameter, 1.8 mm +/- 0.6 [SD]) were detected unilaterally in 103 (54.5%) of 189 patients. EOF were distributed peripherally in 183 (66.5%), centrally in 15 (5.5%), and diffusely in 77 (28.0%) of 275 ovaries. There were fewer than five foci in 123 (44.7%), five to 10 foci in 91 (33.1%), and more than 10 foci in 61 (22.2%) of 275 ovaries. At histopathologic analysis of the seven ovaries with EOF, the foci had tiny cysts with no evidence of calcifications. A single cyst cluster was identified in two of 10 ovaries that did not have echogenic foci. At physical property analysis, single echogenic foci were associated with specular reflection from the walls of unresolved cysts that were comparable in size to the ultrasound wavelength (about 0.50 mm). CONCLUSION: EOF without shadowing are caused by a specular reflection from the walls of tiny unresolved benign cysts rather than by psammomatous calcifications.

Adult↗