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Biomedical subjects

F Forsberg

Publications and source records attributed to F Forsberg.

At least 19 recordsLinked to original sources

Breast tumor vascularity identified by contrast enhanced ultrasound and pathology: initial results.

Quantifiable measures of vascularity obtained from contrast enhanced color flow images were correlated with pathologic vascularity measurements in ten female patients with a solid breast mass. Each patient received Levovist Injection (Berlex Laboratories Inc., Montville, NJ). Color flow images pre- and post-contrast were obtained using an HDI 3000 unit (ATL, Bothell, WA) before removing the mass for pathologic vascularity assessments. Image-processing techniques were used to obtain both the ultrasound and pathologic vascularity measurements. Multiple linear regression found significant correlations for ultrasonic vascularity measurements post contrast and pathology (P = 0.02 and 0.06). No correlations were found between pre-contrast ultrasound and pathology. In conclusion, post-contrast ultrasonic flow measures provide a non-invasive measure of breast tumor neovascularity. However, the patient population is small, and until further patients are analyzed, these conclusions are preliminary.

Breast Neoplasms↗

Subharmonic imaging of contrast agents.

Ultrasound contrast agents promise to improve the sensitivity and specificity of diagnostic ultrasound imaging. It is of great importance to adapt ultrasound equipment for optimal use with contrast agents e.g., by exploiting the nonlinear properties of the contrast microbubbles. Harmonic imaging is one technique that has been extensively studied and is commercially available. However, harmonic imaging is associated with problems, due to second harmonic generation and accumulation within the tissue itself. Given the lack of subharmonic generation in tissue, one alternative is the creation of subharmonic images by transmitting at the fundamental frequency (fo) and receiving at the subharmonic (fo/2). Subharmonic imaging should have a much better lateral resolution and may be suitable for scanning deep-lying structures owing to the higher transmit frequency and the much smaller attenuation of scattered subharmonic signals. In this paper, we will review different aspects of subharmonic imaging including implementation, in-vitro gray-scale imaging and subharmonic aided pressure estimation.

Acoustics↗

Comparison of fundamental and wideband harmonic contrast imaging of liver tumors.

Wideband harmonic imaging (with phase inversion for improved tissue suppression) was compared to fundamental imaging in vivo. Four woodchucks with naturally occurring liver tumors were injected with Imagent (Alliance Pharmaceutical Corp., San Diego, CA). Randomized combinations of dose (0.05, 0.2 and 0.4 ml/kg) and acoustic output power (AO; 5, 25 and 63% or MI < or = 0.9) were imaged in gray scale using a Sonoline Elegra scanner (Siemens Medical Systems, Issaquah, WA). Tumor vascularity, conspicuity and contrast enhancement were rated by three independent observers. Imagent produced marked tumor enhancement and improved depiction of neovascularity at all dosages and AO settings in both modes. Tumor vascularity and enhancement correlated with mode, dose and AO (P < 0.002). Fundamental imaging produced more enhancement (P < 0.05), but tumor vascularity and conspicuity were best appreciated in harmonic mode (P < 0.05). Under the conditions studied here, the best approach was wideband harmonic imaging with 0.2 ml/kg of Imagent at an AO of 25%.

Analysis of Variance↗

Validation of volume measurements in esophageal pseudotumors using 3D endoluminal ultrasound.

The purpose of this study was to validate the accuracy and reliability of volume measurements using three-dimensional (3D) endoluminal ultrasound (ELUS) in canine pseudotumor esophageal specimens in vitro. Pseudotumors were created by injecting various volumes of US gel (0.1-1.0 ml) into canine esophageal specimens. A stepping-motor was used to pull either a 9, 12.5 or 20 MHz transducer through the lumen of the specimen at 1.5 mm/s. Images were downloaded to a LIFE computer system for 3D reconstruction. Volume measurements were made by two investigators and compared to spiral CT images. Averaging across all measurements, the average magnitude of error was 8.7% in individual US determinations and 11. 9% in CT measures. Volumes estimated from images spaced 0.5 and 1.0 mm apart, from images in the original and reconstructed planes, and from different scan frequencies, produced percentage errors that were not statistically significantly different from each other on ELUS. 3D ELUS can be used accurately and reproducibly to measure tumor volumes with a low mean percent in vitro.

Animals↗

Destruction of contrast microbubbles and the association with inertial cavitation.

The destruction of insonified Sonazoid microbubbles and its association with inertial cavitation in vitro utilizing an active acoustic detector was investigated. The experimental observation indicated that contrast microbubbles could be damaged at moderate acoustic pressures of 0.6-1.6 MPa (0.4-1.0 in mechanical index, MI). A damaged bubble could be dissolved into the medium on the order of 1 ms, implying that the destruction at moderate pressures is a relatively slow (relative to inertial bubble collapse), nonviolent dissolution process following the disruption of encapsulating surface materials. Inertial cavitation events in the presence of contrast microbubbles were observed using multiple highly intense ultrasound (US) pulses (>1.6 MPa). This observation suggested that intense US might disintegrate contrast microbubbles, and fragments of disintegrated microbubbles could be activated by an upcoming highly intense imaging pulse. The above results imply that inertial cavitation is unlikely to take place in the presence of Sonazoid contrast microbubbles when exposed to diagnostic US with an MI <1.

Contrast Media↗

Use of the K-distribution for classification of breast masses.

The K-distribution had been introduced as a valid model to represent the statistics of the envelope of the backscattered echo from phantom and tissue. This paper investigates the efficacy of the parameters of this statistical model; namely, the effective number and the effective cross-section, to characterize breast lesions as benign or malignant. Based on the normalized values of the effective number and the effective scattering cross-section, images containing benign and malignant masses were classified for a data set from 52 patients having breast masses/lesions. The receiver operating characteristic (ROC) curves were then obtained to test the classification based on these two parameters. The results indicate that the parameters of the K-distribution may be useful in classification of the breast lesions as benign and malignant.

Breast Neoplasms↗

Ultrasonic characterization of the nonlinear properties of contrast microbubbles.

The nonlinear properties of microbubble contrast agents have been used to create contrast-specific imaging modalities such as harmonic imaging and subharmonic imaging. Thus, a better understanding of the nonlinear performance of contrast microbubbles may enhance the diagnostic capabilities of medical ultrasound (US) imaging. The first and second harmonic, the 1/2 order subharmonic and the 3/2 order ultraharmonic components in spectra of scattered signals from Optison microbubbles insonified at 2 and 4 MHz have been investigated using an in vitro laboratory pulse-echo system. The development of these signal components over time is quite different for 2-MHz insonification compared to 4-MHz insonification. Scattered subharmonic and ultraharmonic signals are much more time-dependent than first and second harmonic echoes. The dependence of the first and second harmonic, subharmonic and ultraharmonic components on acoustic pressure for 2-MHz insonification is similar to that for 4-MHz insonification. The first and second harmonic components increase linearly with acoustic pressure (in double logarithmic scales) and the subharmonic and ultraharmonic amplitudes undergo rapid growths in the intermediate acoustic pressure range and much slower increases at both lower and higher acoustic pressures.

Albumins↗

Enhanced detection of blood flow in the normal canine prostate using an ultrasound contrast agent.

RATIONALE AND OBJECTIVES: To evaluate the sonographic appearance of normal prostate vascularity in dogs before and after injection of a new ultrasound contrast agent, NC100100. METHODS: Thirty-five intravenous injections of NC100100, in doses ranging from 0.00625 to 0.05 microL microbubbles/kg, were administered to seven anesthetized mongrel male dogs. Transrectal color Doppler imaging and power Doppler imaging were used to perform the assessment. The visibility of the vascular pattern of the prostate was assessed, including dynamics of contrast inflow, blood flow symmetry, and duration times. RESULTS: Before contrast administration, the vascular pattern was poorly visualized in all cases. After contrast injection, the visibility of the vascular architecture improved significantly for both modalities. Independent of the imaging method used, higher doses tended to be more effective than lower doses. Contrast kinetics in the prostate vessels was demonstrated with a mean time from injection of the ultrasound contrast agent to enhancement of the Doppler signals in the subcapsular arteries (+/-1 SD) of 13+/-3 seconds, and the ultrasound contrast agent reached the central periurethral veins 3 to 6 seconds later. A spokelike radial pattern of internal prostatic vessels observed with enhanced ultrasound could also be seen on silicone microfil x-ray images. The Doppler enhancement persisted for a mean time ( +/-1 SD) of 904 seconds (approximately 15 minutes) +/- 225 seconds and tended to increase with increasing dose. CONCLUSIONS: NC100100 significantly improves the detection of blood flow in the normal canine prostate and allows more accurate depiction of the vascular architecture of the prostate.

Animals↗

Initial experience with contrast-enhanced sonography of the prostate.

OBJECTIVE: We investigated the usefulness of contrast-enhanced sonography to depict vascularity in the prostate and improve the detection of prostatic cancer. SUBJECTS AND METHODS: Twenty-six patients with an elevated prostate-specific antigen level (> or = 4 ng/ml) or an abnormal digital rectal examination were enrolled in a phase II study of an i.v. injected sonographic contrast agent. Continuous gray-scale, intermittent gray-scale, phase inversion gray-scale, and power Doppler sonography of the prostate were performed. Sonographic findings were correlated with sextant biopsy results. RESULTS: After the administration of contrast material, gray-scale and Doppler images revealed visible enhancement (p < 0.05). Using intermittent imaging, we found focal enhancement in two isoechoic tumors that were not visible on baseline images. No definite focal area of enhancement was identified in any patient without cancer. Contrast-enhanced images revealed transient hemorrhage in the biopsy tracts of three patients. CONCLUSION: Enhancement of the prostate can be seen on gray-scale and Doppler sonographic images after the administration of an i.v. contrast agent. Contrast-enhanced intermittent sonography of the prostate may be useful for the selective enhancement of malignant prostatic tissue.

Adult↗

Gray scale second harmonic imaging of acoustic emission signals improves detection of liver tumors in rabbits.

This study evaluates a new reticuloendothelium specific sonographic contrast agent NC100100 (Sonazoid) for detection of liver VX-2 tumors in rabbits. Gray scale imaging of five groups of three rabbits, with hepatic VX-2 tumors implanted 7, 10, 12, 14, and 18 days previously, was performed prior to injection of Sonazoid (dosages, 0.01-0.5 ml/kg). Sonazoid produces induced acoustic emission after uptake in the liver. Therefore, harmonic gray scale images were obtained immediately after injection as well as delayed (by up to 2(1/2) h). Five rabbits (one from each group) also had angiography performed, while all animals were evaluated by pathologic examination. Non-contrast enhanced sonography detected 17 of 61 tumors (29%), as well as three false-positives, while the addition of Sonazoid detected 57 tumors (93%) and one false-positive (P<0.001). Acoustic emission made 2 x 2 mm tumors (invisible in conventional B-mode sonography) clearly perceivable in harmonic gray scale. In the subgroup that received angiography, 12 of 36 tumors (33%) were detected with conventional sonography compared to 22 tumors (61%) seen with angiography (P = 0.002). After injection of Sonazoid the ultrasonographic detection rate increased to 97% (35 of 36 tumors), which was a significant improvement over angiography (P = 0.00024). Improved detection of hepatic VX-2 tumors with second harmonic gray scale imaging of Sonazoid is possible because of this agent's acoustic emission capabilities.

Animals↗

Shear rate estimation using a clinical ultrasound scanner.

Wall shear stress is a factor in the development of atherogenesis, thrombus formation, and embolization, but its existence is very difficult to determine with ultrasonography. Instead, we estimated shear rates using a clinical ultrasound scanner and compared results from vessels with and without stenoses. Velocity profiles were obtained from color M-mode images on a P700 scanner. Maximum shear rates were calculated off-line as the maximum velocity gradients. In vitro, studies were performed on a flow phantom with a vessel containing a 50% stenosis. Shear rates within the stenosis were significantly higher than those obtained outside the stenosis (P < 0.00001) and varied more than the peak velocities. In vivo, the internal carotid artery of 10 volunteers and 13 patients (with stenoses) was studied. The mean shear rate was 414 s(-1) +/- 154.5 s(-1) in normal vessels and 687 s(-1) +/- 263.5 s(-1) in stenotic vessels (P = 0.00017). In conclusion, shear rate estimates can be obtained with a clinical ultrasound scanner from color M-mode images. Shear rates estimated in vessels with stenoses are significantly higher than those obtained in normal vessels in vitro as well as in vivo.

Blood Flow Velocity↗

Pressure dependence of subharmonic signals from contrast microbubbles.

Noninvasive pressure estimation in heart cavities and in major vessels would provide clinicians with a valuable tool for assessing patients with heart and vascular diseases. Some microbubble-based ultrasound contrast agents are particularly well suited for pressure measurements because their substantial compressibility enables microbubbles to vary significantly in size in response to changes in pressure. Pressure changes should then affect reflectivity of microbubbles after intravenous injection of a contrast agent. This has been demonstrated with a galactose-based contrast agent using 2.0-MHz ultrasound tone bursts. Preliminary results indicate that, over the pressure range of 0-186 mmHg, the subharmonic amplitude of scattered signals decreases by as much as 10 dB under optimal acoustic settings and the first and second harmonic amplitudes decrease by less than 3 dB. An excellent correlation between the subharmonic amplitude and the hydrostatic pressure suggests that the subharmonic signal may be utilized for noninvasive detection of pressure changes.

Contrast Media↗

Effect of filling gases on the backscatter from contrast microbubbles: theory and in vivo measurements.

Two surfactant-based contrast agents, ST44 and ST68, were produced according to US Patent # 5,352,436 and filled with either air, C4F10 (perfluorobutane) or SF6 (sulfur hexaflouride). Ten rabbits received i.v. injections of each agent/gas combination with 5 repetitions of each dose (range: 0.005-0.13 mL/kg). A custom-made 10-MHz cuff transducer was placed around the surgically exposed distal aorta and audio Doppler signals were acquired in vivo. Quantitative in vivo dose responses were calculated off-line using spectral power analysis and compared to a theoretical model of microbubble dissolution and enhancement. For qualitative comparisons, 10 rabbits were imaged pre- and postcontrast administration (dose: 0.1 mL/kg) in gray-scale and colour. All agent/gas combinations produced marked Doppler enhancement with air bubbles enhancing least of all (p < 0.0001) and ST68-SF6 best of all (maximum: 27.6 +/- 2.04 dB; p < 0.012). There were no significant differences between other agent/gas combinations (0.30 < p < 0.70). Theoretical enhancement was within 1 order of magnitude of the experimental observations (i.e., deviations of up to 10 dB). The duration of contrast enhancement was 1-2 min for air-filled bubbles, 3-5 min for SF6-filled bubbles and more than 7 min for C4F10-filled bubbles. In conclusion, ST68-SF6 microbubbles produced most in vivo enhancement of the agent/gas combinations studied. Theory matched the measurements within an order of magnitude.

Animals↗

Tissue-specific US contrast agent for evaluation of hepatic and splenic parenchyma.

PURPOSE: To evaluate the recently developed ultrasonographic (US) contrast agent SHU 563A, which is specifically taken up by the reticuloendothelial system (RES). MATERIALS AND METHODS: Color Doppler imaging (CDI) was performed in a gel phantom, with SHU 563A microbubbles in stationary suspension. CDI was performed in vivo in five woodchucks with natural hepatomas and in 12 rabbits before and after intravenous bolus injections of SHU 563A (0.16-0.48 mL/kg). After a 15-135-minute delay, the liver and spleen were scanned again, and the image findings were compared with pathologic analysis results. RESULTS: Phantom CDI demonstrated a random mosaic color pattern in spite of the lack of flow. This phenomenon, which is associated with bubble rupture, is termed induced acoustic emission. In vivo, delayed imaging demonstrated acoustic emission signals in normal parenchyma, whereas no mosaic color was seen in regions lacking reticuloendothelial cells (e.g., tumors). Four of 12 VX-2 tumors detected with pathologic analysis were detected with US alone; the remaining eight tumors were detected by using US with contrast agent (100%, P = .0078). Nine of 20 hepatomas were detected at baseline US, whereas 17 were detected after administration of SHU 563A (P = .0215). Acoustic emission enabled detection of hepatic tumors as small as 3 mm in diameter. CONCLUSION: CDI with SHU 563A demonstrates a random mosaic color pattern, even without flow. The characteristic appearance of acoustic emission signals provides a distinctive method of visualizing normal hepatic tissues and substantially improves the detectability of hepatic tumors.

Animals↗

Subharmonic imaging with microbubble contrast agents: initial results.

The subharmonic emission from insonified contrast microbubbles was used to create a new imaging modality called Subharmonic Imaging. The subharmonic response of contrast microbubbles to ultrasound pulses was first investigated for determining adequate acoustic transmit parameters. Subharmonic A-lines and gray scale images were then obtained using a laboratory pulse-echo system in vitro and a modified ultrasound scanner in vivo. Excellent suppression of all backscattered signals other than from contrast microbubbles was achieved for subharmonic A-lines in vitro while further optimization is required for in vivo gray scale subharmonic images.

Animals↗

Clinical applications of ultrasound contrast agents.

Within the last decade safe and practical ultrasound contrast agents have been introduced. Most of these are based on gas-filled microbubbles, which markedly enhance Doppler signals and, in some cases, also gray-scale images. The clinical improvements expected from ultrasound contrast is reviewed. Tissue-specific contrast agents constitute another area of potential clinical significance. One particular agent is taken up by the reticulo-endothelial system and produces so-called acoustic emission signals when imaged. An introduction to the unique clinical applications of acoustic emission is given. Harmonic imaging is a new contrast-specific imaging modality, which utilizes the nonlinear properties of some agents in an attempt to alleviate current limitations of ultrasound contrast studies. Examples of harmonic images are presented.

Acoustics↗

Comparisons of the Rayleigh and K-distribution models using in vivo breast and liver tissue.

There is a strong interest in finding out which statistical model is the most appropriate for describing the envelope of the backscattered ultrasonic echoes from different types of tissues. The Rayleigh model is commonly employed, but this requires conditions, such as the presence of large number of randomly located scatterers with fairly uniform cross-sections, that are not always met. However, our research indicates that a model based on the K-distribution may provide a better fit to empirical data over a range of scattering conditions than the standard Rayleigh model. In this study, we looked at the K-distribution as a descriptor of the backscattered envelope of the breast and liver tissues (in vivo). By examining data from various tissue regions, a goodness-of-fit test (a least squares error method) was used to determine whether a Rayleigh or K-distribution model is more appropriate. From a large group of patients and volunteer scans (a total of 72 subjects), the fit between the K-distribution and the data is shown to have a much smaller error than the Rayleigh model.

Adult↗

Using phase information in ultrasonic backscatter for in vivo liver analysis.

In recent studies, it has been shown that information about scatterer spacing can be obtained from analyzing the phase of the ultrasound echo from various media. Such information proves to be useful when examining the ultrasonic backscatter from well-organized tissue, such as the liver. By quantifying the deviations in scatterer spacing and/or varying degrees of regularity, conclusions may be drawn about the underlying pathology of the tissue. This paper examines the physical basis of how the scatterer locations affect the phase of the data. Computer simulations were performed that mimic various scattering conditions and that display the effects of differing degrees of regularity, as well as increases in a diffuse random background scattering component. Results of studies on a phantom are also included to investigate and display the phase response under well-controlled scattering conditions. Finally, in vivo data taken from liver scans were analyzed. In this work, it was shown that the phase of the backscattered signal holds valuable information regarding the pathological state of liver tissue. It is suggested that this simple examination of the phase can be refined into a technique to be used as a method to consistently detect the onset of pathological change.

Algorithms↗