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Flemming Forsberg

Publications and source records attributed to Flemming Forsberg.

At least 19 recordsLinked to original sources
PubMed2006

The influence of acoustic transmit parameters on the destruction of contrast microbubbles in vitro.

In this study, the destruction of the contrast agent Sonazoid (GE Healthcare, Oslo, Norway) was measured in vitro as a function of centre frequency (2-3 MHz), acoustic amplitude (0.66-1.6 MPa), pulse length (2-16 cycles) and PRF (0.5-8.0 kHz). Up to 82% of microbubbles were destroyed after exposure to a single 1.6 MPa acoustic pulse (16 cycles, 2.5 MHz and PRF of 1.0 kHz), while at a low amplitude of 0.66 MPa, fractional destruction increased gradually from 0 to 40% after exposure to 9 (identical) pulses. Fractional destruction increased from approximately 8 to 66% as pulse length was changed from 2 to 16 cycles following exposure to a single 2.5 MHz, 1.3 MPa pulse. As the PRF was increased from 0.5 to 8.0 kHz, shorter exposure time intervals (from 4.8 to 1.2 ms) were needed to achieve the same fractional destruction of 80%. Conversely, as the transmit frequency was increased from 2 to 3 MHz the fractional destruction decreased (by more than half within the first 3 pulses). The influence of changes in acoustic pressure and duty cycle on the destruction of Sonazoid microbubbles was highly statistically significant (p < or = 0.01) with a threshold around 0.67 MPa for a duty cycle of 0.0064. In conclusion, the fractional destruction increases with the duty cycle and the acoustic pressure amplitude and decreases with ultrasonic transmit frequency. Better understanding of the influence of the ultrasound transmit parameters on the destruction of contrast microbubbles should help improve existing contrast-assisted imaging modalities and may help develop new techniques for better use of contrast agents.

Contrast Media↗
PubMed2006

Comparison of in vitro and in vivo acoustic response of a novel 50:50 PLGA contrast agent.

A comparison between in vitro and in vivo experiments conducted to investigate the acoustic properties of a novel, 1.2 microm diameter poly(lactic-co-glycolic acid) (50:50) (PLGA) ultrasound contrast agent, the development of which was described previously by us, is presented. A pulse-echo setup was used to determine enhancement in vitro. Additional in vitro studies further characterized the hollow microcapsules, including resonance frequency from attenuation measurements (from 2.25 to 15 MHz) and temperature effects (25 degrees C vs. 37 degrees C). In vivo, four rabbits received intravenous injections of the agent (dose range: 0.005-0.13 ml/kg). Quantitative in vivo dose-responses were calculated off-line using spectral power analysis of audio Doppler signals acquired from a custom-made 10 MHz cuff transducer placed around the surgically exposed distal aorta. This frequency was chosen since the very shallow scanning depths encountered in rabbits, in particular for the cuff transducer placed directly around the vessel, necessitates the use of high frequency imaging devices with sufficient spatial resolution to enable meaningful measurements. For qualitative assessments, two rabbits were imaged pre- and post-contrast administration (dose: 0.1 ml/kg) in power Doppler mode. Significant acoustic enhancements (up to 24 dB) were reported both in vitro and in vivo. Moreover, the rabbits did not show any adverse side effects from multiple injections (>20) of the agent. Measured in vitro resonance frequency between 3.09 and 3.49 MHz was lower than predicted for a similar sized free bubble, potentially due to capsule wall structure. Minimal loss of signal (approximately 4 dB) was observed at 25 degrees C over 20 min of insonation at 5 MHz but at 37 degrees C the signal dropped close to base line within the first 5 min. This temperature sensitivity could be due to loss of capsule integrity (and hence loss of gas). Potential causes include increased hydrolysis or polymer softening and increased water uptake by the shell at temperatures closer to the glass transition temperature (T(g)).

Acoustics↗
PubMed2006

Ultrasound guided site specific gene delivery system using adenoviral vectors and commercial ultrasound contrast agents.

We have evaluated if ultrasound imaging (US) and various commercially available contrast microbubbles can serve as a non-invasive systemically administered delivery vehicle for site-specific adenoviral-mediated gene transfer in vitro and in vivo. The contrast agents were tested for their ability to enclose and to protect an adenoviral vector carrying the GFP marker gene (Ad-GFP) into the microbubbles. We have also evaluated the ability of the innate immune system to inactivate free adenoviruses as well as unenclosed viruses adsorbed on the surface of the contrast agents and in turn the ability of the microbubbles to enclose and to protect the viral vectors from such agents. In vitro as well as in vivo, innate components of the immune system were able to serve as inactivating agents to clear free viral particles and unenclosed adenoviruses adsorbed on the microbubbles' surface. Systemic delivery of Ad-GFP enclosed into microbubbles in the tail vein of nude mice resulted in specific targeting of the GFP transgene. Both fluorescence microscopy and GFP immunohistochemistry demonstrated US guided specific transduction in the targeted cells only, with no uptake in either heart, lungs or liver using complement-pretreated Ad-GFP microbubbles. This approach enhances target specificity of US microbubble destruction as a delivery vehicle for viral-mediated gene transfer.

Adenoviridae↗
PubMed2006

Validating volume flow measurements from a novel semiautomated four-dimensional Doppler ultrasound scanner.

RATIONALE AND OBJECTIVES: Accurate measurement of blood volume flow (in ml/min) is an important clinical goal. This project compared in vitro and in vivo volume flow measurements obtained with a novel, real-time three-dimensional (i.e., four-dimensional) ultrasound scanner (Encore PV; Vuesonix Sensors, Wayne, PA) with those from an invasive transit time flowmeter. MATERIALS AND METHODS: A flow pump was used to generate pulsatile flow rates from 60 to 600 ml/min. The Encore detected absolute blood velocity vectors within a volume. The scanner determined the centerline of the vessel and volume flow was then automatically calculated. Results were compared with those of an invasive technique for volumetric blood flow measurements utilizing a transit-time flowmeter (TS420; Transonic Systems Inc., Ithaca, NY). In vivo, 10 second datasets of the volume flow in the distal aorta of six rabbits were obtained simultaneously with the Encore PV and the flowmeter. Data were compared using linear regression and Bland-Altman analysis (due to the lack of independence). RESULTS: In vitro, Encore and flowmeter measurements both matched the flow pump (r2 > 0.99; P < .0001) with mean errors of -11.8% and -0.3%, respectively. Marked underestimation of the true flow rates was encountered with the Encore at the lowest pump setting. In vivo mean volume flows between 10.6 and 79.3 ml/min were measured. Mean and maximum volume flows obtained with the two techniques correlated significantly (P < .0001) with r2 values of 0.86 and 0.62, respectively. The corresponding root-mean-square errors were 6.9% for mean flow and 61.2% for maximum volume flow measurements. CONCLUSION: A new semiautomated four-dimensional Doppler device has been tested in vitro and in vivo. Mean volume flow measurements with this unit are comparable to those of an invasive flowmeter.

Blood Flow Velocity↗
PubMed2006

Contrast enhanced ultrasound for radio frequency ablation of canine prostates: initial results.

PURPOSE: We determined the feasibility of contrast enhanced ultrasound for radio frequency ablation of the entire prostate as a method of minimally invasive treatment for prostate cancer in a canine model. MATERIALS AND METHODS: Approval of the Institutional Animal Use and Care committee was obtained. Initially 5 dogs (group 1) were tested using variable power (5 to 30 W), time (4 to 12 minutes), bolus (0.01 to 0.04 ml/kg) and infusion (3 to 11 ml per minute at 0.015 microl/kg) injections of an ultrasound contrast agent with conventional grayscale power Doppler and pulse inversion harmonic imaging to establish optimal parameters. Subsequently 4 dogs (group 2) underwent entire prostate ablation using parameters based on group 1. The size of the thermal lesions and residual viable tissue was measured with ImageJ software (National Institutes of Health, Bethesda, Maryland) on ultrasound and pathological study. Linear regression and Student's t test were used for statistical analysis. RESULTS: A bolus of 0.04 ml/kg, an infusion of 11 ml per minute at 0.015 microl/kg and the contrast enhanced pulse inversion harmonic imaging mode were ranked best for guiding ablation. Thermal lesion volume was proportional to ablation power and time. There was no significant difference in measured thermal lesion size in group 1 between ultrasound and pathological findings (mean +/- SD 1.51 +/- 0.74 and 1.46 +/- 0.74 cm3, p = 0.56) or in residual viable tissue in group 2 (0.43 +/- 0.043 and 0.41 +/- 0.291 cm3, p = 0.21). The average volume of prostate ablation achieved in group 2 was 96.3%. CONCLUSIONS: Contrast enhanced pulse inversion harmonic imaging is able to guide, monitor and control radio frequency ablation of the entire prostate.

Animals↗
PubMed2006

Surfactant-stabilized contrast agent on the nanoscale for diagnostic ultrasound imaging.

Ultrasound contrast agents (CA) are generally micron-sized stabilized gas bubbles, injected IV. However, to penetrate beyond the vasculature and accumulate in targets such as tumors, CA must be an order of magnitude smaller. We describe a method of achieving nanometer-sized, surfactant-stabilized CA by differential centrifugation. High g force was shown to destroy bubble integrity. Optimal conditions (300 rpm for 3 min) produced an agent with a mean diameter of 450 nm, which gave 25.5 dB enhancement in vitro at a dose of 10 microL/mL, with a 13 min half-life. In vivo, the CA produced excellent power Doppler and grey-scale pulse inversion harmonic images at low acoustic power when administered. In vivo dose-response curves obtained in three rabbits showed enhancement between 20 and 25 dB for dosages above 0.025 mL/kg. These results encourage further investigation of the possible diagnostic and therapeutic benefits of using nanoparticles as CA, including passive targeting and accumulation in tumors.

Animals↗
PubMed2006

Detection of breast lesion regions in ultrasound images using wavelets and order statistics.

Accurate detection and segmentation of suspicious regions within the complex and irregular tissues of the breast, as depicted with ultrasonic B scans, typically require human analysis and decision making. Tissue characterization methods for classifying suspicious regions often depend on identifying and then accurately segmenting these regions. Motivated by an ultimate goal to automate this critical identification and segmentation step for tissue characterization problems, this work examines ultrasonic signal characteristics between various regions of breast tissue broadly classified as normal tissue and breast lesions. This paper introduces a nonparametric model based on order statistics (OS) estimated from multiresolution (MR) decompositions of energy-normalized subregions. Experimental results demonstrate the classification performance of the OS-based features extracted from the tumor and normal tissue regions in multiple scans from 84 patients, which resulted in a total of 204 tumor regions (from 43 malignant and 161 benign) and 816 normal tissue regions. Performance results indicate that OS-based features achieved an area under the receiver-operator characteristic curve of 91% in the discrimination between breast lesions and surrounding normal tissues.

Algorithms↗
PubMed2006

In vivo perfusion estimation using subharmonic contrast microbubble signals.

OBJECTIVE: The purpose of this study was to quantify perfusion in vivo using contrast-enhanced subharmonic imaging (SHI). METHODS: A modified LOGIQ 9 scanner (GE Healthcare, Milwaukee, WI) operating in gray scale SHI mode was used to measure SHI time-intensity curves in vivo. Four dogs received intravenous contrast bolus injections (dose, 0.1 mL/kg), and renal SHI was performed. After 3 contrast agent injections, a microvascular staining technique based on stable (nonradioactive) isotope-labeled microspheres (BioPhysics Assay Laboratory Inc, Worcester, MA) was used to quantify the degree of perfusion in 8 sections of each kidney. Low perfusion states were induced by ligating surgically exposed segmental renal arteries followed by contrast agent injections and microvascular staining. Digital clips were transferred to a personal computer, and SHI time-intensity curves were acquired in each section using Image-Pro Plus software (Media Cybernetics, Silver Spring, MD). Subharmonic fractional blood volumes were calculated, and the perfusion was estimated from the initial slope of the fractional blood volume uptake averaged over 3 injections. Subharmonic perfusion data were compared with the gold standard (ie, the microspheres) using linear regression analysis. RESULTS: In vivo gray scale SHI clearly showed flow and, thus, perfusion in the kidneys with almost complete suppression of tissue signals. In total, 270 SHI time-intensity curves were acquired, which reduced to 94 perfusion estimates after averaging. Subharmonic perfusion estimates correlated significantly with microsphere results (r = 0.57; P < .0001). The best SHI perfusion estimates occurred for high perfusion states in the anterior of the kidneys (r = 0.73; P = .0001). The corresponding root mean square error was 2.4%. CONCLUSIONS: Subharmonic perfusion estimates have been obtained in vivo. The perfusion estimates were in reasonable to good agreement with a microvascular staining technique.

Albumins↗
PubMed2005

Analysis of a hybrid spectral strain estimation technique in elastography.

Conventional spectral elastographic techniques estimate strain using cross-correlation methods. Despite promising results, decorrelation effects compromise the accuracy of these techniques and, subsequently, the tissue strain estimates. Since tissue compression in the time-domain corresponds to upscaling in the frequency-domain, decorrelation effects become more pronounced as tissue strains increase and are a fundamental concern in spectral cross-correlation elastography. In this paper, a two-stage hybrid spectral elastographic technique is introduced. For the first stage, an approximated spectral scaling factor (i.e. initial strain estimate) is employed to compensate for bandwidth broadening (due to tissue compression) between pre- and post-compression power spectra pairs. The second stage then estimates any residual strain information using spectral cross-correlation methods due to improper scaling factor selection in the first stage. This novel hybrid spectral elastographic technique was compared to both conventional spectral and adaptive temporal elastographic methods in simulation and experimentation. In addition to demonstrating enhancement in performance over the conventional spectral elastographic technique, the hybrid spectral-based method introduced in this paper is shown to outperform the adaptive temporal-based elastographic approach.

Algorithms↗
PubMed2005

Comparison of shift estimation strategies in spectral elastography.

This paper compares the performance of various spectral shift estimators for use in spectral elastography, namely, the normalized cross-correlation (NCC), sum squared difference (SSD) and sum absolute difference (SAD). Simulation and experimental results demonstrate that the spectral SSD-based elastographic method exhibits no marked difference in performance compared to the more computationally costly NCC-based approach, which has conventionally been the preferred estimator in spectral elastography. The spectral SAD-based strain estimator, despite being computationally less burdening, failed to exhibit performance comparable to that of the NCC- and SSD-based techniques. Furthermore, though spectral subsample estimation techniques using a cosine-fit interpolation method outperformed that of the parabolic-fit method in terms of both reduced bias errors and standard deviations, the latter was analyzed in this study due to computational simplicity. The role of spectral density was evaluated without and with parabolic-based subsample interpolation. Based on minimizing computational complexity, it is concluded that a (low density) spectral SSD strain estimator coupled with parabolic-based subsample estimation is the preferred choice for spectral elastography.

Bias↗
PubMed2005

In vivo elastographic investigation of ethanol-induced hepatic lesions.

Ethanol-induced hepatic lesions were investigated in swine for in vivo use as a strain imaging animal model. Lesions (n = 25) were induced by injecting ethanol (doses 0.33 to 2.0 mL) directly into the surgically exposed liver at depths of 12, 15 or 25 mm. Lesions were imaged with a modified HDI 1000 scanner (Philips Medical Systems, Bothell, WA, USA). The elastograms (n = 91) characterized lesions as being areas harder than the surrounding soft hepatic tissue. Elastographic lesion sizes and the corresponding injected ethanol dose used to induce the lesions were shown to be statistically significant (r(2) = 0.22; p = 0.029) using a linear regression analysis. Additionally, lesion depth was shown to be statistically insignificant (r(2) < 0.12; p > 0.10) when regressed against elastographic lesion size. An analysis of elastographic and gross pathology lesion sizes indicated no correlation (r(2) < 0.01; p = 0.973). Subsequently, lesion types were sorted by size and regression lines were computed from quasilinear regions of the corresponding run charts. Trend lines indicate a four-to-three size relationship between the selected elastographic and pathology lesion sizes. Comparison of elastogram lesion sizes from two independent observers using a paired t-test resulted in no statistically significant difference (p = 0.14). In conclusion, ethanol-induced hepatic lesions in swine is a suitable animal model for evaluation of strain-based imaging systems, due to the ease of generation and repeatability.

Animals↗
PubMed2005

Investigation of parametric spectral estimation techniques for elasticity imaging.

Several autoregressive (AR) and autoregressive moving average (ARMA) parametric spectral estimators were evaluated for use in tissue strain estimation. Using both 1-D simulations and in vitro phantom experiments, the performance of these parametric spectral strain estimators were compared against both a nonparametric discrete Fourier transform (DFT) spectral strain estimator and a coherent elastographic technique. Parametric spectral estimator model orders were selected based on a modified strain filter approach. This technique illustrated the trade-offs between different signal-processing parameters and a strain estimator performance measure, namely the area under the strain filter (using applied strain dynamic range of 0.1 to 50%). The Yule-Walker AR spectral strain estimator outperformed all other parametric methods evaluated, but failed to outperform the DFT-based approach. Furthermore, both these spectral strain-estimation techniques exhibit an elastographic signal-to-noise ratio (SNR(e)) and strain estimation dynamic range not achievable using conventional elastography without global stretching.

Algorithms↗
PubMed2005

In vivo pressure estimation using subharmonic contrast microbubble signals: proof of concept.

Changes in ambient pressure affects the reflectivity of ultrasound contrast microbubbles leading to an excellent correlation between subharmonic signals and hydrostatic pressure. The aortas of two dogs were scanned with an experimental pulse-echo system to validate in vivo pressure estimation based on subharmonic microbubble signals. Results matched well with instantaneous pressure measurements (from 20-60 mmHg) obtained simultaneously with a pressure catheter (root mean square errors <27%).

Algorithms↗
PubMed2005

Characterization of ultrasound contrast microbubbles using in vitro experiments and viscous and viscoelastic interface models for encapsulation.

Zero-thickness interface models are developed to describe the encapsulation of microbubble contrast agents. Two different rheological models of the interface, Newtonian (viscous) and viscoelastic, with rheological parameters such as surface tension, surface dilatational viscosity, and surface dilatational elasticity are presented to characterize the encapsulation. The models are applied to characterize a widely used microbubble based ultrasound contrast agent. Attenuation of ultrasound passing through a solution of contrast agent is measured. The model parameters for the contrast agent are determined by matching the linearized model dynamics with measured attenuation data. The models are investigated for its ability to match with other experiments. Specifically, model predictions are compared with scattered fundamental and subharmonic responses. Experiments and model prediction results are discussed along with those obtained using an existing model [Church, J. Acoust. Soc. Am. 97, 1510 (1995) and Hoff et al., J. Acoust. Soc. Am. 107, 2272 (2000)] of contrast agents.

Capsules↗
PubMed2005

Real-time excitation-enhanced ultrasound contrast imaging.

A new nonlinear contrast specific imaging modality, excitation-enhanced imaging (EEI) has been implemented on commercially-available scanners for real-time imaging. This novel technique employs two acoustic fields: a low-frequency, high-intensity ultrasound field (the excitation field) to actively condition contrast microbubbles, and a second lower-intensity regular imaging field applied shortly afterwards to detect enhanced contrast scattering. A Logiq 9 scanner (GE Healthcare, Milwaukee, WI) with a 3.5C curved linear array and an AN2300 digital ultrasound engine (Analogic Corporation, Peabody, MA) with a P4-2 phased array transducer (Philips Medical Systems, Bothell, WA) were modified to perform EEI on a vector-by-vector basis in fundamental and pulse inversion harmonic grayscale modes. Ultrasound contrast microbubbles within an 8 mm vessel embedded in a tissue-mimicking flow phantom (ATS Laboratories, Bridgeport, CT) were imaged in vitro. While video intensities of scattered signals from the surrounding tissue were unchanged, video intensities of echoes from contrast bubbles within the vessel were markedly enhanced. The maximum enhancement achieved was 10.4 dB in harmonic mode (mean enhancement: 6.3 dB; p = 0.0007). In conclusion, EEI may improve the sensitivity of ultrasound contrast imaging, but further work is required to assess the in vivo potential of this new technique.

Albumins↗
PubMed2005

On the usefulness of the mechanical index displayed on clinical ultrasound scanners for predicting contrast microbubble destruction.

OBJECTIVE: The purpose of this study was to evaluate the mechanical index (MI) displayed on clinical ultrasound scanners as a predictor of exposure conditions related to the destruction of sonographic microbubble contrast agents. METHODS: Sonazoid (GE Healthcare, Oslo, Norway) and Optison (GE Healthcare, Princeton, NJ) microbubbles were injected into a tissue-mimicking flow phantom. Gray scale imaging was performed with 4 different scanners and 3 different transducers (3.5 MHz curved linear, 2.5 MHz convex, and 7.5 MHz linear array), and the MI displayed by the scanner was varied from 0.2 to 1.5 by changing the system output power. All other scanning parameters were kept constant. Downstream changes in echogenicity were monitored with a PowerVision 7000 scanner (Toshiba America Medical Systems, Tustin, CA) as an indirect measure of bubble destruction. Video intensity changes within the flow tube were determined as a function of MI for the different scanner/transducer combinations, and the best linear fit was determined. RESULTS: At a displayed MI of 0.7, different scanner/transducer combinations exhibited a range in video intensity from +16% to -3% of baseline for Sonazoid and from +8% to -71% for Optison. At an MI of 0.3, reductions in video intensity of up to 32% were produced. These results indicate a wide range in bubble destruction at identical MI values. Likewise, regression analysis found no linear fits for all scanner/transducer combinations (r2 < 0.046). CONCLUSIONS: The MI displayed on clinical ultrasound scanners does not predict the degree of microbubble destruction and should not be used by itself to define exposure conditions for destruction of microbubble contrast agents.

Acoustics↗