Biomedical subjects

Flemming Forsberg

Publications and source records attributed to Flemming Forsberg.

At least 37 records · Page 2Linked to original sources

PubMed2005

Contrast-enhanced sonographic imaging of lymphatic channels and sentinel lymph nodes.

OBJECTIVE: The purpose of this study was to determine whether lymphatic channels (LCs) and sentinel lymph nodes (SLNs) could be detected on sonographic imaging after subcutaneous, submucosal, or parenchymal injections of a sonographic contrast agent (ie, lymphosonography) in a variety of anatomic locations in several animal models. METHODS: Eight swine, 7 canines, 4 rabbits, and a monkey were used for these evaluations. Gray scale pulse inversion harmonic imaging of the LCs and the SLNs was performed after subcutaneous (n = 58), submucosal (n = 14), or parenchymal (n = 8) injections of a tissue-specific sonographic contrast agent (Sonazoid; GE Healthcare, Oslo, Norway). In many instances, blue dye was injected into the same locations as Sonazoid, and surgical dissection of the SLNs and LCs was performed for comparison. Scanning electron microscopy (SEM) of contrast-enhanced and control lymph nodes from 2 rabbits was performed to determine the mechanism of contrast agent uptake and retention within SLNs. RESULTS: After subcutaneous, submucosal, or parenchymal contrast agent injections, gray scale pulse inversion harmonic imaging could be used to identify the number and location(s) of LCs and SLNs. After subcutaneous, submucosal, or parenchymal contrast agent injections, Sonazoid was confined to the SLNs (ie, contrast enhancement was not detected in the second-echelon nodes). There was good agreement between the results of lymphosonography and blue dye with surgical dissection in identifying the regional LCs and SLNs. Scanning electron microscopy identified vacuoles representing intact contrast microbubbles within contrast-enhanced SLN macrophages, which were not present in the control lymph nodes. CONCLUSIONS: Lymphosonography can be used to detect lymphatic drainage pathways and SLNs in a variety of animal models.

Abdomen↗

PubMed2004

Multi-frequency harmonic arrays: initial experience with a novel transducer concept for nonlinear contrast imaging.

Nonlinear contrast imaging modes such as second harmonic imaging (HI) and subharmonic imaging (SHI) are increasingly important for clinical applications. However, the performance of currently available transducers for HI and SHI is significantly constrained by their limited bandwidth. To bypass this constraint, a novel transducer concept termed multi-frequency harmonic transducer arrays (MFHA's) has been designed and a preliminary evaluation has been conducted. The MFHA may ultimately be used for broadband contrast enhanced HI and SHI with high dynamic range and consists of three multi-element piezo-composite sub-arrays (A-C) constructed so the center frequencies are 4f(A) = 2f(B) = f(C) (specifically 2.5/5.0/10.0 MHz and 1.75/3.5/7.0 MHz). In principle this enables SHI by transmitting on sub-array C receiving on B and, similarly, from B to A as well as HI by transmitting on A receiving on B and, likewise, from B to C. Initially transmit and receive pressure levels of the arrays were measured with the elements of each sub-array wired in parallel. Following contrast administration, preliminary in vitro HI and SHI signal-to-noise ratios of up to 40 dB were obtained. In conclusion, initial design and in vitro characterization of two MFHA's have been performed. They have an overall broad frequency bandwidth of at least two octaves. Due to the special design of the array assembly, the SNR for HI and SHI was comparable to that of regular B-mode and better than commercially available HI systems. However, further research on multi-element MFHA's is required before their potential for in vivo nonlinear contrast imaging can be assessed.

Acoustics↗

PubMed2004

Image enhancement by acoustic conditioning of ultrasound contrast agents.

A novel contrast imaging technique has been developed for use with microbubble contrast agents. It employs two acoustic fields: there is an excitation field for conditioning microbubbles and an imaging field for detecting microbubbles. The maximum increases (due to microbubble conditioning) in scattered first and second harmonic signals were 14.5 and 16 dB, respectively. This technique is unique for effectively enhancing the blood-to-tissue image contrast.

Albumins↗

PubMed2004

Subharmonic signal generation from contrast agents in simulated neovessels.

Detection and measurement of blood flow in neovessels around a tumor can yield prognostic information about the tumor. Early detection and classification may help differentiate benign and malignant tumors; thus, improving patient management. This can be accomplished by injecting ultrasonic contrast agents and measuring the backscattered signals from them. Use of the subharmonic backscattered signals from these agents may be better than fundamental or second harmonic components because of the negligible subharmonics generated by the surrounding tissue. Preliminary results on the detection and measurement of subharmonic signal components up to 12 dB (at increasing pressures) from very small tubes (200 to 300 microm diameter) are reported, demonstrating the possibility and potential application of subharmonic imaging in detecting tumor angiogenesis.

Albumins↗

PubMed2004

Effect of shell type on the in vivo backscatter from polymer-encapsulated microbubbles.

This study compared in vivo enhancement from four different polymer-encapsulated ultrasound (US) contrast agents. The agents were produced with a rigid shell composed of the biodegradable block copolymer poly[D,L-lactide-co-glycolide] (PLGA) with the lactic and glycolic acid ratios 50:50, 75:25, 85:15 and 100:0 (i.e., increasingly hydrophobic shell compositions). Approximately the same bubble diameter (1.2 microm) and concentration (0.4 g/mL) were obtained for each agent. In four rabbits, audio Doppler signals were acquired from a 10 MHz cuff transducer placed around a surgically exposed vessel (contrast dose: 0.0125 to 0.15 mL/kg). In vivo dose responses were calculated off-line (in dB). Nine rabbit kidneys were imaged during contrast administration (0.1 mL/kg) in power Doppler and grey-scale pulse inversion harmonic (PIHI) modes using an HDI 5000 scanner (Philips Medical Systems, Bothell, WA). Time-intensity curves were produced and the time-to-peak, peak intensity, slope, area under the curve (AUC) and total duration of enhancement for each agent were compared. All agents produced marked Doppler enhancement with increasing duration from the 50:50 agent (48 +/- 10 s) to the 75:25 agent (166 +/- 46 s), the 85:15 agent (403 +/- 83 s) and with the 100:0 agent (603 +/- 93 s) lasting longest (p < 0.02). No other parameters changed significantly, except the AUC of the 85:15 agent, which was greater than that of the 50:50 agent (190.75 vs. 61.58; p = 0.02). The in vivo dose-response curves were similar for all agents, with mean enhancement up to 20.6 +/- 1.11 dB (p = 0.17). In conclusion, contrast duration increases by an order of magnitude as the lactic acid component in the polymer-encapsulated bubbles increases and the shell, thus, becomes increasingly hydrophobic.

Animals↗

PubMed2004

Breast tissue characterization using FARMA modeling of ultrasonic RF echo.

A number of empirical and analytical studies demonstrated that the ultrasound RF echo reflected from tissue exhibits 1/f characteristics. In this paper, we propose to model 1/f characteristics of the ultrasonic RF echo by a novel parsimonious model, namely the fractional differencing auto regressive moving average (FARMA) process, and evaluated diagnostic value of model parameters for breast cancer malignancy differentiation. FARMA model captures the fractal and long term correlated nature of the backscattered speckle texture and facilitates robust efficient estimation of fractal parameters. In our study, in addition to the computer generated FARMA model parameters, we included patient age and radiologist's prebiopsy level of suspicion (LOS) as potential indicators of malignant and benign masses. We evaluated the performance of the proposed set of features using various classifiers and training methods using 120 in vivo breast images. Our study shows that the area under the receiver operating characteristics (ROC) curve of FARMA model parameters alone is superior to the area under the ROC curve of the radiologist's prebiopsy LOS. The area under the ROC curve of the three sets of features yields a value of 0.87, with a confidence interval of [0.85, 0.89], at a significance level of 0.05. Our results suggest that the proposed method of ultrasound RF echo model leads to parameters that can differentiate breast tumors with a relatively high precision. This set of RF echo features can be incorporated into a comprehensive computer-aided diagnostic system to aid physicians in breast cancer diagnosis.

Adolescent↗

PubMed2004

Sentinel lymph nodes in a swine model with melanoma: contrast-enhanced lymphatic US.

PURPOSE: To determine if lymphatic channels and sentinel lymph nodes (SLNs) with and without metastases can be detected with lymphatic ultrasonography (US) after peritumoral injection of a US contrast agent and to determine if lymphatic US can be used to assess SLNs for the presence of metastatic infiltration. MATERIALS AND METHODS: Six swine with 17 melanomas were evaluated. Conventional gray-scale, color flow, and gray-scale phase-inversion harmonic US examinations were performed. A US contrast agent was administered in four sites around each melanoma (1-mL total dose). Lymphoscintigraphy was followed by injection of a blue dye and then dissection. SLNs identified at lymphatic US were characterized by two readers in consensus as normal or as having metastases; results were compared with histologic findings. Statistical analyses included the sign test and the kappa statistic. RESULTS: Lymphatic US depicted 28 SLNs, while lymphoscintigraphy depicted 27 "hot spots" suspected of representing SLNs (including two false-positive findings). Dissection after blue dye injection helped identify 31 SLNs. There were no false-positive US findings for SLN detection. Five of six nodes not seen with lymphoscintigraphy were detected with lymphatic US. The accuracy of SLN detection was 90% (28 of 31) for lymphatic US and 81% (25 of 31) for lymphoscintigraphy (P =.29). Lymphatic US correctly depicted metastases in 19 of 20 SLNs, and five of the eight normal SLNs were correctly characterized, with an accuracy of 86% (kappa = 0.62). CONCLUSION: Detection of SLNs with lymphatic US compared favorably with that at lymphoscintigraphy. Lymphatic US can depict metastases within the SLN, which was not possible with lymphoscintigraphy.

Animals↗

PubMed2004

Diagnosing breast lesions with contrast-enhanced 3-dimensional power Doppler imaging.

OBJECTIVE: To compare mammography with contrast-enhanced 2- and 3-dimensional power Doppler imaging for the diagnosis of breast cancer. METHODS: Fifty-five patients, who underwent breast biopsies with histopathologic assessment, participated in a study of mammography and contrast-enhanced sonography. Levovist (Berlex Laboratories, Montville, NJ) and Optison (Mallinckrodt, St Louis, MO) were administrated to 22 and 33 patients, respectively. Precontrast and postcontrast 2-dimensional power Doppler data of the lesion were obtained with an HDI 3000 system (Philips Medical Systems, Bothell, WA), and 3-dimensional data were acquired with an LIS 6000A system (Life Imaging Systems Inc, London, Ontario, Canada). Two independent and blinded readers assessed diagnosis. Receiver operating characteristic curves were computed individually and in combination for mammography and 2- and 3-dimensional sonography (before and after contrast). Histopathologic and imaging parameters were compared by Mann-Whitney statistics. RESULTS: Mammographic findings were available for 50 patients, biopsy for 54, and 2- and 3-dimensional sonographic images for 53 and 52, respectively. Of the 50 patients who had all 4 measures, 15 (30%) had malignancies. The areas under the receiver operating characteristic curve for the diagnosis of breast cancer were 0.51 for 2-dimensional contrast-enhanced imaging, 0.60 for 3-dimensional power Doppler imaging, and 0.76 for 3-dimensional contrast-enhanced imaging (P < .01). Mammography produced an area of 0.86, which increased when combined with 3-dimensional contrast-enhanced imaging to 0.90 and with all sonographic modalities to 0.96 (P < .001). The histopathologic diagnosis of benign or malignant correlated with the presence or absence of anastomoses and with the degree of vascularity assessed with contrast-enhanced 3-dimensional power Doppler imaging (P = .007 and .02). CONCLUSIONS: Contrast-enhanced 3-dimensional power Doppler imaging increases the ability to diagnose breast cancer relative to conventional 2- and 3-dimensional sonographic imaging.

Adult↗

PubMed2003

Classification of breast masses in ultrasonic B scans using Nakagami and K distributions.

Classification of breast masses in greyscale ultrasound images is undertaken using a multiparameter approach. Five parameters reflecting the non-Rayleigh nature of the backscattered echo were used. These parameters, based mostly on the Nakagami and K distributions, were extracted from the envelope of the echoes at the site, boundary, spiculated region and shadow of the mass. They were combined to create a linear discriminant. The performance of this discriminant for the classification of breast masses was studied using a data set consisting of 70 benign and 29 malignant cases. The Az value for the discriminant was 0.96 +/- 0.02, showing great promise in the classification of masses into benign and malignant ones. The discriminant was combined with the level of suspicion values of the radiologist leading to an Az value of 0.97 +/- 0.014. The parameters used here can be calculated with minimal clinical intervention, so the method proposed here may therefore be easily implemented in an automated fashion. These results also support the recent reports suggesting that ultrasound may help as an adjunct to mammography in breast cancer diagnostics to enhance the classification of breast masses.

Adult↗

PubMed2003

Statistical modeling of atherosclerotic plaque in carotid B mode images--a feasibility study.

A feasibility study undertaken to model atherosclerotic plaque in carotid B-mode images is presented. The study is based on 33 regions-of-interest collected from arterial images obtained from four patients. A bimodal gamma distribution with five parameters is proposed to model the statistics of the pixels in the gray-level images. The parameters of the distribution are evaluated for regions containing plaque using curve-fitting techniques. This bimodal distribution appears to be a reasonable fit to the statistics of the pixels. This statistical model may aid in the objective classification of arterial plaque through the use of its parameters.

Algorithms↗

PubMed2003

ROC analysis of ultrasound tissue characterization classifiers for breast cancer diagnosis.

Breast cancer diagnosis through ultrasound tissue characterization was studied using receiver operating characteristic (ROC) analysis of combinations of acoustic features, patient age, and radiological findings. A feature fusion method was devised that operates even if only partial diagnostic data are available. The ROC methodology uses ordinal dominance theory and bootstrap resampling to evaluate A(z) and confidence intervals in simple as well as paired data analyses. The combined diagnostic feature had an A(z) of 0.96 with a confidence interval of at a significance level of 0.05. The combined features show statistically significant improvement over prebiopsy radiological findings. These results indicate that ultrasound tissue characterization, in combination with patient record and clinical findings, may greatly reduce the need to perform biopsies of benign breast lesions.

Age Factors↗

PubMed2003

Malignant and benign breast tissue classification performance using a scatterer structure preclassifier.

Benign and malignant breast tissue classification is examined for generalized-spectrum parameters computed from RF ultrasound data when a preclassification of subregions based on general scattering properties is performed. Results using a clinical database of 84 patients show statistically significant improvements (over 10% in receiver operation characteristic (ROC) areas) when only coherent scatterer subregions are used as compared to using all subregions within the region of interest.

Algorithms↗

PubMed2003

Computer-aided classification of breast masses in ultrasonic B-scans using a multiparameter approach.

Classification of breast masses in ultrasonic B-scan images is undertaken using a multiparameter approach. The parameters are generated on the basis of a non-Rayleigh statistic model of the backscattered envelope from the breast tissue. They can be computed automatically with minimal clinical intervention once the location of the mass is known. A new discriminant is developed that combines these parameters linearly. It is seen that this new discriminant performs classification of masses into benign or malignant better than the classification by any one of the individual parameters. The data set studied consisted of 99 cases (70 patients with benign masses and 29 patients with malignant masses). The areas under the receiver operating characteristic (ROC) curves (Az) and statistical attributes of the areas were studied to establish the enhancement in performance. The Az value after combining all the parameters was found to be 0.8701. Upon combining this parameter with the level of suspicion (LOS) scores of a radiologist, the performance is further enhanced with an area under the (empirical) ROC of 0.94 having an operating point at a sensitivity of 0.965 and specificity of 0.87. It is suggested that this automated approach may hold promise as a means of classifying breast masses.

Algorithms↗

PubMed2003

Power Doppler assessment of vascular changes during fracture treatment with low-intensity ultrasound.

OBJECTIVE: To study the use of power Doppler sonography for assessing changes in vascularity during treatment of fracture sites with low-intensity ultrasound. METHODS: In 6 dogs (3 pairs), subcutaneous dissection of the midshaft of the ulna allowed symmetrical osteotomies to be made with a reciprocation saw. Three dogs were treated and 3 were used as controls. The fracture site was subjected to 1.5-MHz low-intensity ultrasound (30 mW/cm2) for 20 minutes daily from a therapeutic ultrasonic device. Gray scale sonography was performed to evaluate the fracture site. Power Doppler sonography was used to assess flow patterns at the fracture site and surrounding soft tissue. A sonographic contrast agent was administered intravenously. The dose was 0.2 mL/kg. RESULTS: Power Doppler sonography showed an increase in flow around the fracture site in the treated dogs compared with that in control dogs. Color pixel values on day 7 were 3-fold higher in treated legs than control legs and on day 11 were 33% higher in treated legs than control legs. Enhancement after contrast agent administration was consistently higher in treated legs than control legs. CONCLUSIONS: Power Doppler sonography showed increased vascularity around the fracture sites in treated dogs with and without contrast agent administration.

Animals↗

PubMed2002

Comparing contrast-enhanced ultrasound to immunohistochemical markers of angiogenesis in a human melanoma xenograft model: preliminary results.

This study compared contrast-enhanced ultrasound (US) measures of tumor neovascularity with molecular markers of angiogenesis in a human melanoma xenograft model. A total of 14 mice were implanted with a human melanoma cell line (WM-9) in the thigh. After 2 to 3 weeks, a tumor, approximately 12 mm in diameter, developed. The US contrast agent Optison (Mallinckrodt, St. Louis, MO) was injected in a tail vein (dose: 0.4 to 0.6 mL/kg). Power Doppler and pulse-inversion harmonic imaging (HI) were performed with an Elegra scanner (Siemens Medical Systems, Issaquah, WA) and a 7.5 MHz linear array. Frame-rates of 30 Hz and 0.5 Hz (intermittent imaging) were used for pulse-inversion HI. After surgical removal, specimens were sectioned in the same planes as the US images. Immunohistochemical stains for endothelial cells (CD31), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and cyclooxygenase-2 (COX-2) were performed. Two observers graded the stains (for intensity and percent area), and two other observers graded the US imaging modes (for fractional tumor neovascularity) on the same scale from 0 to 3. Of the 14 mice, 4 failed for technical reasons (i.e., n = 10). Linear regressions indicated statistically significant correlations between percent area stained with COX-2 and power Doppler (r = -0.789; p < 0.01), as well as intermittent pulse-inversion HI (r = -0.795; p < 0.05). There was a trend toward significance between percent area stained with VEGF and intermittent pulse-inversion HI (r = -0.720; 0.05 < p < 0.10). No other comparisons were significant. In conclusion, contrast-enhanced US measures of tumor neovascularity in a human melanoma xenograft model appear to provide a noninvasive marker of angiogenesis corresponding to expression of COX-2. However, the sample size of this study is small and, until further studies have been conducted, these conclusions are preliminary.

Albumins↗

PubMed2002

Hepatic tumor detection: MR imaging and conventional US versus pulse-inversion harmonic US of NC100100 during its reticuloendothelial system-specific phase.

PURPOSE: To compare conventional ultrasonography (US) and magnetic resonance (MR) imaging with contrast agent-enhanced US for detection of VX-2 liver tumors in rabbits. MATERIALS AND METHODS: Conventional gray-scale liver US was performed in 65 rabbits, 38 of which had VX-2 hepatic tumor implants. Twenty minutes after contrast agent injection, gray-scale pulse-inversion harmonic US images of the liver-specific phase were obtained. Following sacrifice of the animals, T1- and T2-weighted MR imaging was performed at 4-mm intervals. Pathologic analysis was performed as the reference standard. The capability of each imaging modality to correctly depict tumor presence or absence and the number of tumors was compared. RESULTS: Conventional US correctly depicted the presence or absence of tumors in 54 rabbits, for an accuracy of 83%, sensitivity of 71%, and specificity of 100%. With contrast-enhanced US, accuracy increased to 92% (60 correct cases); sensitivity, to 87%; and specificity, to 100%. MR imaging facilitated 56 correct diagnoses, for an accuracy of 86%, sensitivity of 82%, and specificity of 93%. There was a marginally significant difference between US with and US without contrast agent (P =.07) but not between MR imaging and contrast-enhanced US (P > or = .34). When the numbers of correctly detected tumors were compared, contrast-enhanced US performed significantly better than MR imaging (P =.02) and conventional US (P =.04). CONCLUSION: There was no significant difference between contrast-enhanced US and MR imaging in the detection of hepatic tumors, whereas contrast-enhanced US had the highest accuracy (92%) of the three modalities studied.

Animals↗

PubMed2002

High-frequency Doppler US of the prostate: effect of patient position.

PURPOSE: To evaluate cancer detection with directed biopsy of the prostate on the basis of high-frequency Doppler ultrasonographic (US) findings, and to determine the effect of patient position on the observed flow pattern. MATERIALS AND METHODS: Thirty-two patients were evaluated in the left lateral decubitus position with gray-scale, color Doppler, and power Doppler transrectal US. Up to four directed biopsy specimens were obtained on the basis of gray-scale and Doppler US findings, and modified sextant biopsy followed. Analysis of variance and the Wilcoxon signed rank test were used to evaluate the distribution of Doppler signals within the prostate. Three healthy volunteers with no known prostate disease were also examined in supine and both decubitus positions. RESULTS: In the patient group, both color and power Doppler US demonstrated increased flow on the left side of the prostate, with greater flow toward the base of the gland (P <.002). Consequently, 62 of 90 directed-biopsy cores were obtained in the left base and mid-gland. The positive biopsy rate for directed biopsy was not significantly different from that of sextant biopsy (P =.4). Seven patients had cancer that was identified with sextant biopsy, but only four cancers were identified with directed biopsy. Each of the three healthy volunteers demonstrated increased Doppler flow on the dependent side when the subject was in the lateral decubitus position. CONCLUSION: The positive yield of directed biopsy was similar to the yield of sextant biopsy. On the basis of observations made in healthy volunteers, the authors conclude that flow asymmetry in patients who underwent biopsy may have been related to patient position.

Adult↗

PubMed2002

Contrast-enhanced two- and three-dimensional sonography for evaluation of intra-abdominal hemorrhage.

OBJECTIVE: To determine whether a contrast agent enhances sonographic detection of bleeding sites in the abdomen and whether contrast-enhanced three-dimensional sonography provides additional information compared with contrast-enhanced two-dimensional sonography. METHODS: Bleeding sites were created within the livers (n = 3), spleens (n = 5), and kidneys (n = 3) of 3 dogs. A sonographic contrast agent with vascular and parenchymal enhancement capabilities was administered intravenously at a dose of 0.02 mL/kg. Before and after each contrast agent injection, the bleeding sites were imaged with two- and three-dimensional sonography in gray scale harmonic imaging and color flow modes. Sonographic findings were compared with gross pathologic findings. RESULTS: Noncontrast-enhanced sonography was not able to show the specific location of the active bleeding in any of the organs evaluated. The contrast agent enhanced the sonographic detection of blood flow in normal vessels and extravasated blood from damaged vessels or organs in all cases. Intrasplenic and intrahepatic hematomas were better identified on delayed imaging sequences because there was marked enhancement of the normal parenchyma, whereas the hematomas remained unenhanced. Reconstructed three-dimensional sonography showed spatial relationships of the bleeding sites and surrounding structures. Gross pathologic findings were consistent with the contrast-enhanced sonographic results. CONCLUSIONS: Contrast-enhanced sonography improves the detection and evaluation of abdominal bleeding sites. Contrast-enhanced three-dimensional sonography appears to provide additional information when compared with two-dimensional sonography.

Animals↗