shu-508 and Breast-Neoplasms

Sonography has become one of the most important imaging methods in breast diagnostics. Through the development of high-frequency transducers and the use of ultrasound contrast agents, the number of indications for sonography of the breast has continued to increase in recent years. Visualization of very small vessels under 100 µm enables sensitive detection and quantification of tissue perfusion. Thus, breast ultrasound can play an essential role in answering questions about certain pathologies. Further technical advances, such as automated breast ultrasound systems, provide an essential step for standardization of investigations. Targeted ultrasound is a new important development of this technique. Specific markers which are conjugated with the surface of contrast medium microspheres allow targeted molecular endothelial structures to be selectively visualized and quantified. These developments will strengthen the role of sonography in the future as a non-invasive and easy to use method.

Topics: Biomarkers, Tumor; Breast Neoplasms; Contrast Media; Diagnosis, Differential; Drug Delivery Systems; Female; Fibroblast Growth Factors; Humans; Image Enhancement; Image Processing, Computer-Assisted; Imaging, Three-Dimensional; Molecular Diagnostic Techniques; Neoadjuvant Therapy; Neovascularization, Pathologic; Phospholipids; Polysaccharides; Sulfur Hexafluoride; Ultrasonography, Mammary; Vascular Endothelial Growth Factor A

Topics: Blood Flow Velocity; Breast Neoplasms; Contrast Media; Female; Humans; Image Enhancement; Injections, Intravenous; Polysaccharides; Predictive Value of Tests; Ultrasonography, Doppler, Color; Ultrasonography, Mammary

The utility of ultrasound color Doppler flow mapping imaging for the differential diagnosis on the breast and thyroid tumors had already reported in 1991. Ultrasound contrast agent, SH/TA 508 (Levovist; Schering AG, Germany), had already finished clinical trials in Japan and reported the result phase II, III. On the breast and thyroid lesions, the utility of this contrast agent are safety and usefulness for the accurate diagnosis by the ultrasound color Doppler examination. Throughout of these clinical trials, a quit new ultrasound Doppler imaging methods had been developed, Harmonic Imaging and acoustic emission mode. As the result, ultrasound contrast agent is useful not only for the conventional color Doppler diagnosis but also for the developing of new diagnostic imaging methods.

Topics: Breast Neoplasms; Contrast Media; Female; Humans; Polysaccharides; Thyroid Neoplasms; Ultrasonography, Doppler, Color

Topics: Breast Neoplasms; Colorectal Neoplasms; Contrast Media; Humans; Liver Neoplasms; Lung Neoplasms; Polysaccharides; Ultrasonography

To evaluate the effects of a new microbubble contrast agent for ultrasound (US) on breast masses.. Thirty-four patients underwent color Doppler US before and after intravenous injection of a "contrast agent" containing microbubbles. The authors subjectively evaluated the increase in intensity of the Doppler signals, the changes in the vascular patterns, and the timing of the transit of the microbubble bolus. The diagnostic confidence was assessed before and after administration of contrast material.. After contrast material injection, there was greater and longer signal enhancement in the cancers than in the benign lesions. The cancers displayed characteristic vascular morphologic features, with more additional vessels visualized in relation to the lesion and a greater increase in vascular tortuousity. Shunts between vessels were demonstrated in all cancers but were not seen in any benign lesion. The diagnostic confidence increased with use of the contrast agent. The appearance at contrast-enhanced US led to a change in the US diagnosis in four patients. This increased both sensitivity and specificity to 100%.. Injection of a microbubble agent enabled accurate differentiation of benign masses from carcinomas.

Topics: Adult; Aged; Breast Diseases; Breast Neoplasms; Contrast Media; Diagnosis, Differential; Female; Humans; Injections, Intravenous; Middle Aged; Polysaccharides; ROC Curve; Sensitivity and Specificity; Ultrasonography, Doppler, Color; Ultrasonography, Mammary

The authors report their experience with color Doppler US of breast disease with a new parenteral contrast agent--i.e., SH U 508 A (Levovist)--in an international multicenter experimental trial. Over a 9-month period, 17 patients with 19 solid breast lesions were examined. A baseline color Doppler study was performed on every patient, together with a second exam after injecting the contrast agent into a peripheral vein to investigate possible changes in the depiction of tumor vessels, inside and around the lesions. The 19 nodules included 16 infiltrating ductal carcinomas, 2 fibroadenomas and 1 benign phylloid tumor. Levovist improved the depiction of tumor vessels in all cases and helped detect new vascular signals which had been missed on baseline images. The increase in color Doppler signal was graded as marked and mild: in 68.75% of ductal carcinomas and in the benign phylloid tumor signal increase was marked, while in 31.25% of carcinomas and in fibroadenomas signal increase was mild. All lesions exhibited vascular signals both inside and around the lesion; many afferent poles were also depicted. Our results demonstrate that conventional color Doppler semiology changes with the use of a contrast agent and pave the way for further studies on larger series of cases to assess new diagnostic criteria to differentiate breast lesions according to color Doppler signal patterns.

Topics: Adult; Aged; Breast Neoplasms; Color; Contrast Media; Female; Humans; Italy; Middle Aged; Polysaccharides; Ultrasonography

This study was conducted to compare quantifiable measures of vascularity obtained from contrast-enhanced color flow images of breast lesions to pathologic vascularity measurements. Nineteen patients with solid breast masses received Levovist Injection (10 mL at 300 mg/mL; Berlex Laboratories, Montville, NJ, USA). Color flow images of the mass pre and post contrast were obtained using an HDI 3000 scanner (Philips Medical Systems, Bothell, WA, USA) optimized for clinical scanning on an individual basis. After surgical removal, specimens were sectioned in the same planes as the ultrasound images and stained with an endothelial cell marker (CD31). Microvessel area (MVA) and intratumoral microvessel density (MVD) were determined for vessels 10-19 microm, 20-29 microm, 30-39 microm, 40-49 microm and > or =50 microm in diameter using a microscope and image processing software. From the ultrasound images, the number of color pixels before and after contrast administration relative to the total area of the breast mass was calculated as a first-order measure of fractional tumor vascularity. Vascularity measures were compared using reverse stepwise multiple linear regression analysis. In total, 58 pathology slides (with 8,106 frames) and 185 ultrasound images were analyzed. There was a significant increase in flow visualization pre to post Levovist injection (p = 0.001), but no differences were found between the 11 benign and the eight malignant lesions (p > 0.35). Ultrasound vascularity measurements post contrast correlated significantly with pathology (0.15 < or = r2 < or = 0.46; p < 0.03). The 30-39 microm vessel range contributed most significantly to the MVD relationship (p < 0.001), whereas the MVA was mainly influenced by vessels 20-29 microm (p < 0.004). Precontrast ultrasound only correlated with pathology for relative MVA (r2 = 0.16; p = 0.01). In conclusion, contrast-enhanced color flow imaging provides a noninvasive measure of breast tumor neovascularity, corresponding mainly to vessels 20-39 microm in diameter, when used in a typical clinical setting.

Topics: Adult; Aged; Aged, 80 and over; Blood Flow Velocity; Breast Diseases; Breast Neoplasms; Contrast Media; Female; Humans; Image Enhancement; Linear Models; Microvessels; Middle Aged; Neovascularization, Pathologic; Pilot Projects; Polysaccharides; Sensitivity and Specificity; Ultrasonography, Doppler, Color; Ultrasonography, Mammary; Young Adult

To compare mammography with contrast-enhanced 2- and 3-dimensional power Doppler imaging for the diagnosis of breast cancer.. 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.. 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).. Contrast-enhanced 3-dimensional power Doppler imaging increases the ability to diagnose breast cancer relative to conventional 2- and 3-dimensional sonographic imaging.

Topics: Adult; Aged; Breast Neoplasms; Contrast Media; Female; Humans; Imaging, Three-Dimensional; Logistic Models; Mammography; Middle Aged; Polysaccharides; ROC Curve; Statistics, Nonparametric; Ultrasonography, Doppler; Ultrasonography, Mammary

To evaluate the efficacy of contrast-enhanced power Doppler sonography in the differential diagnosis of breast lesions after a mammography-gray scale sonography combination.. Sixty-eight patients with 69 breast masses underwent power Doppler sonography before and after intravenous injection of a contrast agent. The lesions were diagnosed as "highly suggestive of malignancy" (category 5; n = 32), "suspicious" (category 4; n = 21), and "probably benign" (category 3; n = 16) by mammography and gray scale sonography, modeled on the American College of Radiology Breast Imaging Reporting and Data System classification. Power Doppler findings did not affect patient treatment. The authors subjectively evaluated the estimated area of vascularity, degree of enhancement following contrast agent administration, morphologic features, and distribution of vessels within the lesions.. The final diagnoses were malignant in 28 lesions and benign in 41. Significant enhancement after contrast agent injection was detected in both the malignant and benign groups. Only 2 criteria, estimated area of vascularity and degree of enhancement following contrast agent administration, proved to be significant diagnostic determinants for contrast-enhanced power Doppler sonography (P < .001; interobserver agreements, 74.4 and 77.8, respectively). Contrast-enhanced power Doppler sonography provided a higher specificity, positive predictive value, and negative predictive value than power Doppler sonography but a lower sensitivity and negative predictive value than mammography-gray scale sonography. Only in the category 4 lesions could the combination of mammography-gray scale sonography and contrast-enhanced power Doppler sonography accomplish a higher specificity (71%) and positive predictive value (70%) than mammography-gray scale sonography (39% and 53%, respectively).. Power Doppler and contrast-enhanced power Doppler sonography cannot be recommended as confirmatory tests in Breast Imaging Reporting and Data System category 3 and category 5 lesions. Although contrast-enhanced power Doppler sonography may help reduce unnecessary biopsies in Breast Imaging Reporting and Data System category 4 lesions, recommendation of its use has many drawbacks, such as imperfectly established criteria, lack of absolute certainty, and high cost.

Topics: Adult; Aged; Breast Neoplasms; Chi-Square Distribution; Contrast Media; Diagnosis, Differential; Female; Humans; Middle Aged; Polysaccharides; Predictive Value of Tests; Sensitivity and Specificity; Ultrasonography, Doppler; Ultrasonography, Mammary

The purpose of this article is to demonstrate the diagnostic impact of ultrasound in differentiating focal breast lesions with special regard on power Doppler and US contrast agents. The sonographic evaluation of breast lesions has become a standard procedure during the past 15 years. Especially the improvement of B-mode resolution and the use of high-frequency probes increased the diagnostic value of US. Assuming that the neoangiogenetic vascular architecture of solid breast lesions can be depicted reliably by color Doppler, many authors tried to differentiate between benignity and malignancy using Doppler criteria such as flow and morphologic aspects. Additionally, adjuvant techniques, such as harmonic imaging and new US contrast agents, are meant to be success-promising tools. Whereas the sensitivity and specificity of color Doppler have varied in different studies, prognostic prediction and treatment monitoring seem to be the future areas of application. To evaluate sufficiently flow signals of very small vessels with low flow velocity, the use of contrast-enhancing agents may be necessary. Nevertheless, an indispensable condition for successful Doppler-based assessment of the entity of breast lesions is the standardization of techniques, evaluation, analysis and weighting of the parameters.

Topics: Blood Flow Velocity; Breast Neoplasms; Contrast Media; Diagnosis, Differential; Female; Humans; Polysaccharides; Sensitivity and Specificity; Ultrasonography, Doppler, Color; Ultrasonography, Mammary

To evaluate the potential diagnostic value of quantification of contrast enhanced power Doppler sonography in breast lesions.. Before and after bolus application of 300 mg/ml of the contrast agent Levovist (Schering, Germany), 76 randomly selected equivocal breast lesions (37 benign, 39 malignant) underwent power Doppler sonography. The data were acquired with a 7.5 MHz linear array transducer (Sonoline Versa Pro and Sonoline Elegra Plus, Siemens, Germany). Following postprocessing digitalization, color pixel density (CPD) and dynamic contrast enhancement were calculated and compared using different regions of the tumor (entire lesion, center and periphery).. A measurable pixel signal prior to the application of the contrast agent was observed in 12 of 37 benign and in 18 of 39 malignant lesions (32.4 % and 46.2 %, respectively). After administration of the contrast agent, the lesions with measurable signal increased to 20 of 37 (54 %) and 25 of 39 (64.1 %), respectively. No statistically significant difference of dignity-related signal intensity could be verified before or after administration of the contrast agent. Maximum CPD and relative increase in pixel density after contrast medium was appreciably higher in the center of malignant lesions than in corresponding regions of benign lesions.. Quantification of color pixel density is rather nonspecific for the discrimination of equivocal breast lesions and not suitable for clinical routine. Signal detection and quantification of color coded pixels enable comparison of dynamic contrast enhancement.

Topics: Adult; Aged; Aged, 80 and over; Breast Diseases; Breast Neoplasms; Contrast Media; Diagnosis, Differential; Female; Humans; Image Processing, Computer-Assisted; Mathematical Computing; Middle Aged; Neovascularization, Pathologic; Polysaccharides; Prospective Studies; Regional Blood Flow; Sensitivity and Specificity; Ultrasonography, Doppler, Color; Ultrasonography, Mammary

Topics: Adult; Aged; Breast Neoplasms; Contrast Media; Diagnosis, Differential; Female; Humans; Imaging, Three-Dimensional; Microspheres; Middle Aged; Polysaccharides; ROC Curve; Ultrasonography, Doppler, Color

To compare the ability of standard power Doppler and color harmonic imaging for visualising breast tumor vascularity using ultrasound probes of various frequencies, and to evaluate the influence on diagnostic accuracy using ultrasound contrast agent.. Twenty patients (x = 43.6 +/- 11.7 years) with suspected malignancy of the breast underwent power Doppler to evaluate vascularity and to offer a differential diagnosis of the lesion. Two criteria were used for differential diagnosis: The quantitative extent of vascularity ("percentage vessel area", PVA) and the qualitative assessment of vascular architecture. The following power Doppler modes were compared in every patient: Plain and enhanced (Levovist(R)) 9 MHz and 12 MHz standard power mode and enhanced 9 MHz color harmonic imaging-(CHI).. The PVA increased from a mean of 2.2 +/- 2.9 % (9 MHz standard plain) via 4.8 +/- 4.1 % (12 MHz standard plain), 9.7 +/- 15.3 % (9 MHz standard enhanced), 17.4 +/- 20.0 % (9 MHz CHI enhanced) up to 19.4 +/- 14.8 % (12 MHz standard enhanced). The perceptibility of the vascular structure was best using the enhanced 12 MHz standard power mode, immediately followed by the enhanced 9 MHz CHI mode. The improved detection of vascular signal did not translate into improved diagnostic accuracy. The highest diagnostic accuracy (95 %) was obtained using the enhanced 9 MHz CHI mode (criterion "PVA") and the enhanced 9 MHz standard power mode (criterion "vascular structure"), whereas the 12 MHz probes delivered insufficient diagnostic accuracy and very low specificity.. Best quantitative and qualitative visualisation of the tumor vascularity was achieved using the enhanced 12 MHz standard power mode. Nevertheless, the highest diagnostic accuracy was obtained using enhanced 9 MHz standard power Doppler and enhanced 9 MHz color harmonic imaging. The visualisation of tumor vascularity and, partially, the diagnostic accuracy are improved significantly by color harmonic imaging without changing the probe frequently.

Topics: Adult; Aged; Breast Neoplasms; Contrast Media; Diagnosis, Differential; Female; Humans; Image Enhancement; Male; Middle Aged; Neovascularization, Pathologic; Polysaccharides; Sensitivity and Specificity; Ultrasonography, Doppler, Color; Ultrasonography, Mammary

To evaluate the capability of contrast-enhanced wideband harmonic imaging (WHI) to detect liver metastases in comparison with fundamental B-mode US and postcontrast CT.. We studied 27 patients with hepatic metastases from different malignancies with conventional B-mode sonography, WHI 3 min after injection of contrast agent (Levovist(R) 2.5 g, 300 mg/ml) and postcontrast helical CT (HCT). The number and location of the lesions and the smallest lesion for each patient were noted by two different observers and compared.. Both readers recorded an increase in the number of lesions in harmonic mode compared with conventional B-mode in all 27 patients with hepatic metastases with a mean increase in both observers from 9.3 lesions with B-mode to 18.8 lesions with WHI. The smallest lesions were detected with WHI when compared with conventional US and HCT (2 mm with WHI, 5 mm with B-mode and 5 mm with CT). WHI detected more lesions than conventional US or HCT.. Contrast-enhanced WHI seems superior to conventional US and HCT for the detection of hepatic metastases, specially for those nodules under 1 cm of diameter.

Topics: Adult; Aged; Breast Neoplasms; Colonic Neoplasms; Contrast Media; Female; Humans; Image Enhancement; Liver Neoplasms; Male; Middle Aged; Polysaccharides; Sensitivity and Specificity; Tomography, Spiral Computed; Ultrasonography

MRI is the most reliable method to differentiate scar and recurrent carcinoma of the breast after surgical treatment. This study compares MRI and color-coded ultrasound with and without echo signal amplifier (ESA).. Forty-two patients with suspected recurrent tumors were enrolled in this prospective study, with 38 patients after breast conserving therapy and 4 after mastectomy. All patients had a clinical examination, mammography (n = 38), real time ultrasound (US), color-coded ultrasound without and with ESA (Levovist(R), Schering, Berlin), and dynamic MRI. The criteria used for duplex ultrasound were tumor vascularisation and flow pattern. The results were compared with histologic findings or the results of follow-up examinations for at least 12 months.. The detection of penetrating or central vessels proved to be an accurate sign of malignancy in duplex ultrasound. With the application of ESA, additional vessels were detected within the lesions, increasing the diagnostic accuracy (83 % with ESA versus 79 % without ESA). The sensitivity of color-coded ultrasound improved from 64 % to 86 % with echo signal amplifier. The specificity was 86 % without and 82 % with echo signal amplifier. MRI was found to have a sensitivity of 100 % and a specificity of 82 %. The same 5 lesions were false positive on MRI and color-coded US after Levovist(R). No lesion without signs of vascularity within or in its vicinity was malignant.. Color-coded ultrasound seems to be a promising method in the differentiation between scar and recurrence. Lesions with penetrating or central vessels have a high probability of being malignant, whereas lesions without any signs of vascularity inside or nearby have a high probability of being benign. Advantage of contrast-enhanced US is its ubiquitous availability.

Topics: Breast; Breast Neoplasms; Cicatrix; Contrast Media; Diagnosis, Differential; False Positive Reactions; Female; Follow-Up Studies; Humans; Magnetic Resonance Imaging; Mammography; Mastectomy, Modified Radical; Neoplasm Recurrence, Local; Polysaccharides; Prospective Studies; Sensitivity and Specificity; Time Factors; Ultrasonography, Doppler, Color; Ultrasonography, Mammary

To determine the scope of improving the distinction between a postoperative scar and the recurrence of a breast carcinoma through the use of the ultrasound echo enhancer Levovist?. In 23 patients with 26 lesions a colour-coded duplex sonography examination before and after administration of Levovist was performed. The parameters investigated were: degree of enhancement, number of tumour vessels and the pattern of vascular morphology and anatomy.. Recurrences (n = 15) demonstrated a greater number of vessels and a stronger enhancement after administration of Levovist. Individual vessels were also visible in scars (n = 11). Further evaluations with respect to the pattern of the tumour vascularization are therefore necessary with the exception of one false positive and one negative result a clear distinction was possible.. The administration of the ultrasound echo enhancer clearly improved the otherwise difficult distinction between a scar and a tumour recurrence through sonography and mammography. Further studies with larger number of patients are necessary to establish the value of the method.

Topics: Adult; Aged; Aged, 80 and over; Breast Neoplasms; Cicatrix; Contrast Media; Diagnosis, Differential; False Negative Reactions; False Positive Reactions; Female; Humans; Middle Aged; Neoplasm Recurrence, Local; Polysaccharides; Prospective Studies; Reproducibility of Results; Ultrasonography, Doppler, Color

We aimed to evaluate whether the histopathologic variability of fibroadenomas accounts for their varied appearance in contrast enhanced power Doppler (PD). Forty patients with fibroadenomas (aged 19 to 61 years) underwent power Doppler ultrasound (US) prior to and following IV bolus injection of a microbubble contrast agent. A 3-min computer-assisted assessment of the color pixel density (CPD) was used for objective evaluation of the increase in color Doppler signals. Enhancement characteristics were correlated to histopathologic features of microvessel density and epithelial hyperplasia, patient's age, tumor size, use of exogenous hormones and menopausal status. Epithelial hyperplasia was diagnosed in 19 patients. Compared to baseline values, patients with epithelial hyperplasia showed a significant increase in mean CPD following contrast media administration (p < 0.01). There was a significant correlation to patient's age (p < 0.0001) and tumor size (p < 0.0001), but not to the use of exogenous hormones and menopausal status. Microvessel counts did not show a significant correlation to CPD at baseline (p = 0.07) or with CPD on contrast enhanced PD (p = 0.13), or with patient age (p = 0.43) or tumor size (p = 0.34). Intratumoral epithelial hyperplasia, primarily occurring in young patients, may contribute to the differential diagnostic overlap in some fibroadenomas and thus limit the ability of PD to distinguish between benign and malignant masses on the basis of enhancement characteristics.

Topics: Adult; Breast Neoplasms; Contrast Media; Diagnosis, Differential; Female; Fibroadenoma; Humans; Image Processing, Computer-Assisted; Middle Aged; Polysaccharides; Ultrasonography, Doppler; Ultrasonography, Mammary

The aim of this study was to evaluate the accuracy of contrast-enhanced color Doppler ultrasound (CE-US) in comparison with contrast-enhanced MR imaging (CE-MRI) in the discrimination of hypervascularized breast tumors. An additional CE-US of the breast was preoperatively performed in 40 patients with a hypervascular breast lesion detected on CE-MRI. The presence of blood flow signals and the morphological characteristics of the vessels in the breast lesions were evaluated pre- and post-contrast administration, as well as the dynamic aspects of the Doppler signal, including time interval to maximum signal enhancement and persistence of the signal enhancement. Twenty-three carcinomas and 17 fibroadenomas were explored. Considering initial signal enhancement > 100% after the administration of contrast material as a criterion suggesting malignancy, CE-MRI showed a sensitivity of 100% and a specificity of 76.5% in the detection of malignant breast tumors. Color Doppler signals were consistently demonstrated in all carcinomas and in 68.7% of fibroadenomas after the administration of Levovist, with CE-US showing a sensitivity of 95.6% and a specificity of 5.9%. Neither the mean number of vessels per tumor, nor the location of vessels, the time to maximum increase of the Doppler signal or the persistence of signal enhancement showed significant differences between benign and malignant lesions. Additional CE-US does not increase the low specificity of MRI in patients with hypervascularized breast tumors.

Topics: Adult; Aged; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Intraductal, Noninfiltrating; Contrast Media; Diagnosis, Differential; Female; Fibroadenoma; Gadolinium DTPA; Humans; Image Enhancement; Magnetic Resonance Imaging; Middle Aged; Neovascularization, Pathologic; Polysaccharides; Predictive Value of Tests; Ultrasonography, Doppler, Color

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.

Topics: Breast Neoplasms; Contrast Media; Female; Humans; Image Processing, Computer-Assisted; Linear Models; Polysaccharides; Ultrasonography, Doppler, Color

To evaluate the benefit of echo-contrast-enhanced Doppler sonography in the differentiation of benign vs. malignant breast lesions after surgical removal of a malignant breast mass.. Thirty-eight patients referred for biopsy of a palpable, suspicious scar lesion 1-15 years (mean 3.3 years) after surgery for breast cancer were examined. During baseline ultrasound examination a subjective scoring system of the vascularity, the number, the regularity of vessels' course and their Doppler parameters were assessed. After injection of an ultrasound contrast agent (Levovist) the same scoring system was applied to the parameters together with enhancement kinetics, enhancement intensity and enhancement pattern. Any increase in the scoring level of two or more characteristics (vascularity, number of vessels, intensity of enhancement in the tumor or regularity score of vessels in the lesion) was defined as suspicious for malignancy. A marked increase of enhancement in the immediate tumor periphery was also regarded as suspicious for malignancy. The sonographic results were assessed prospectively and correlated with the histology of the lesion.. Of the 38 patients with a clinically-suspicious scar lesion, there were 28 true scars and 10 malignant scar lesions. All scar lesions showed no or slight vascularity on baseline sonography. After Echocontrast-enhancement a significant increase in tumor vascularity and the number of tumor vessels could be demonstrated in all 10 malignant lesions but in only one of the 28 benign scars.. Scars pose inherent technical problems for optimal mammography. Sonographic evaluation of the vascularity of the lesion with contrast enhancing agents showed improved diagnostic accuracy in the hands of an experienced examiner.

Topics: Adult; Aged; Aged, 80 and over; Blood Flow Velocity; Blood Vessels; Breast Neoplasms; Cicatrix; Contrast Media; Diagnosis, Differential; Female; Humans; Middle Aged; Neoplasm Recurrence, Local; Polysaccharides; Sensitivity and Specificity; Ultrasonography, Doppler, Color; Ultrasonography, Mammary

We investigated improving the evaluation of benignity in breast lesions using Doppler sonography with galactose palmitic acid-coated microbubbles.. In 77 patients with 84 breast tumors scheduled for surgical tumor removal, color-coded duplex sonography was performed before and after administration of Levovist. Of the 77 patients, 25 with 28 lesions had been treated for prior breast carcinoma. The parameters investigated were the following: degree of enhancement, number of tumor vessels, time to maximum enhancement, and the pattern of vascular morphology and course.. Findings in malignant tumors (n = 53) showed a greater number of vessels and a faster stronger enhancement after Levovist administration, whereas a definite partial overlap with results from benign tumors (n = 31) was found. The best distinction was produced by vascular morphology and course, with a sensitivity of 90% and a specificity of 81 %. In 23 of the 25 patients who previously underwent surgery, a clear distinction was possible between a postoperative scar (n = 11) and a tumor recurrence (n = 17).. Although administration of the contrast agent clearly improved evaluation of benign features on Doppler sonography, absolute certainty cannot be achieved. The feasibility of making an otherwise difficult distinction between a scar and tumor recurrence on sonography and mammography appears to be promising, but further studies are necessary.

Topics: Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Contrast Media; Female; Humans; Middle Aged; Neoplasm Recurrence, Local; Polysaccharides; Prospective Studies; Sensitivity and Specificity; Ultrasonography, Doppler, Color; Ultrasonography, Mammary

We describe three cases where biopsies from various tumors were guided by contrast enhancement of tumor perfusion. After i.v. administration of Levovist (Schering AG, Berlin, Germany), the tumors showed both hyper- and hypovascular areas. Biopsies from the latter showed marked necrosis or fibrosis. This may cause biopsies not being conclusive. To ensure fully diagnostic biopsies from irregular tumors we propose the biopsy to be performed from the most vascular part demonstrated by contrast enhancement.

Topics: Abdominal Neoplasms; Biopsy; Breast Neoplasms; Carcinoma, Renal Cell; Contrast Media; Female; Humans; Liver Neoplasms; Middle Aged; Neurofibrosarcoma; Polysaccharides; Ultrasonography, Interventional

To define the technique for contrast-enhanced power Doppler US studies of breast lesions and to identify possible clinical applications.. We studied 51 breast lesions detected at mammography and confirmed at cytology and/or surgical biopsy; 15 were benign lesions and 36 carcinomas, namely 14 T1ab, 29 T1c and 8 T2. We found 14 masses with regular margins, 28 with irregular margins, 1 asymmetric density, 2 architectural distortions and 6 clustered calcifications. US studies were performed with an AU5 Harmonic unit (Esaote Biomedica, Genoa, Italy) equipped with a software for online image storage, analysis and automatic quantification of US signal intensity changes after contrast agent injection, namely wash-in and wash-out contrast enhancement curves. The echocontrast agent Levovist (Schering AG, Berlin, Germany), 4.0 g preparation, was administered by i.v. injection (cubital vein) in two times at a concentration of 400 mg/mL. The first 4 mL of Levovist suspension were injected as a bolus at approximately .5 mL/s to evaluate lesion vascularization and choose the best scanning plane for wash-in and wash-out quantification. The remaining 6 mL of Levovist suspension were injected at approximately 1.0 mL/s and dedicated to wash-in and wash-out recording.. The region of interest could not be identified in 2 of 6 calcifications. After Levovist administration, signal enhancement was seen in 36 lesions. Nonsignificant curves were obtained in 7 fibroadenomas, 1 fibrocystic mastopathy and 5 carcinomas. Pathology diagnosed an in situ component around the lesion core (true positives) in 12 carcinomas with perilesional vessels and also 3 more carcinomas with perilesional foci in situ missed at contrast-enhanced US (false negatives). The wash-in/wash-out curves of 30 carcinomas differed from those of the 6 fibroadenomas, in that the former had faster wash-in and an earlier enhancement peak, as well as longer enhancement than the latter. Moreover, fibroadenoma curves are regularly increasing, with moderate variations. As for wash-out, carcinomas exhibited three main patterns, namely a monophasic, a polyphasic and a plateau pattern.. The pattern of enhancement curves in fibroadenomas is related to straight and regular vessels, while arteriovenous shunts in carcinomas cause early signal intensity peaks. Wash-out is longer in carcinomas than in fibroadenomas because the former present anarchic and tortuous vessels with slow flows.. Levovist enhanced US is a complementary test to study known breast lesions which permits the differential diagnosis of carcinomas and fibroadenomas. Our results justify a larger clinical trial to assess the role of this technique for diagnosis, prognosis and staging purposes.

Topics: Adult; Aged; Aged, 80 and over; Breast Neoplasms; Contrast Media; Female; Humans; Middle Aged; Polysaccharides; Ultrasonography, Doppler, Color

At the women's hospital of the University of Erlangen we performed a prospective clinical study to evaluate the use of color Doppler imaging supported by the new echo contrast agent Levovist in comparison to clinical examination, B-mode sonography, mammography, and MRI. In 40 patients the sensitivity and specificity of each method was estimated in predicting the dignity of palpable or mammographically detectable tumors of the breast. Prior to and after administration of Levovist we recorded the number of vessels, the PI, RI, SD-ratio, and maximum flow velocity after correction of the angle. Color Doppler imaging of the tumor and the surrounding tissue was documented on video tape for five minutes after the administration of Levovist. We measured the time until an increase and decrease in color signal was detectable. The following sensitivities/specificities were found: clinical examination 57.1% (12/21)/73.7% (14/19), B-mode sonography 100% (21/21)/84.2% (16/19), mammography 100% (21/21)/89.5% (17/19) and MRI 92.3% (14/15)/78.6% (15/18). Without the contrast agent color Doppler imaging could not differentiate between malignant and benign lesions. There was no significant difference in the perfusion of benign and malignant tumors. However, after the administration of Levovist, there appeared to be a significant difference for SD-ratio. With a cut-off-level of 3.5 we found a sensitivity/specificity of 85% (17/ 20)/78.6% (11/14) for the Doppler method. There was a weak correlation between the time of appearance of the augmented Signal in color Doppler and the velocity of enhancement of the contrast agent in MRI (n = 24, r = 0.47, p = 0.02). Only with the use of a contrast agent was color Doppler ultrasound able to support the other methods in pre-operative differentiation of benign and malignant lesions in the breast.

Topics: Adult; Aged; Aged, 80 and over; Breast Diseases; Breast Neoplasms; Contrast Media; Diagnosis, Differential; Female; Humans; Middle Aged; Polysaccharides; Radiography; Ultrasonography, Doppler, Color

Prospective comparison of plain and signal-enhanced frequency and amplitude-modulated colour Doppler ultrasound of intramammary tumours to evaluate new criteria for diagnostic analysis.. Frequency and amplitude-modulated colour Doppler examination with qualitative and quantitative analysis of 80 potentially malignant intramammary lesions were performed before and after application of d-galactose.. Signal-enhanced sonography revealed a typical vessel morphology of primary and recurrent breast cancer facilitating differential diagnosis. In 18 (frequency modulated US) or 16 (amplitude modulated US) of 51 carcinomas, the typical malignant vascularisation structure was sufficiently visible only after application of the signal enhancing agent. In 50% of the fibroadenomas, Doppler analysis of the vessels was possible only after application of d-galactose.. The application of d-galactose provides additional criteria for the differential diagnosis of breast lesions due to improved visualisation of the vascularisation structure.

Topics: Adult; Aged; Breast Neoplasms; Carcinoma; Contrast Media; Diagnosis, Differential; Evaluation Studies as Topic; Female; Fibroadenoma; Humans; Middle Aged; Polysaccharides; Prospective Studies; Ultrasonography, Doppler, Color

Findings in previous investigations have indicated that contrast-enhanced colour Doppler can be used to improve the demonstration of characteristic features of neovascularization in malignancies. However, the quantification of the increase in colour Doppler signals after Levovist in the cited study relied only on descriptive criteria defined by the investigator, resulting in a subjective scoring system. A computer-assisted method for quantitative analysis of colour pixel density is a novel approach for objective assessment of colour Doppler signal after contrast media administration. After microbubble contrast medium injection in 47 patients, carcinomas and benign lesions behaved differently regarding degree, onset and duration of Doppler enhancement. However, the high interindividual variability and the temporal variations of the Doppler signal still limit the value of these criteria for prospective diagnosis. Rapid image-acquisition techniques are needed in order to apply the necessary mathematical processing before the contrast kinetics can be used for diagnostic purposes.

Topics: Adult; Aged; Blood Flow Velocity; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Contrast Media; Diagnosis, Computer-Assisted; Female; Fibroadenoma; Fibrocystic Breast Disease; Humans; Image Processing, Computer-Assisted; Middle Aged; Neovascularization, Pathologic; Polysaccharides; Sensitivity and Specificity; Ultrasonography, Doppler, Color; Ultrasonography, Mammary

To evaluate objectively the effects of a microbubble contrast agent on the color Doppler ultrasound (US) examination of breast lesions.. Forty-seven patients aged 23-71 years underwent color Doppler US before and after intravenous injection of a microbubble contrast agent. A 3-minute computer-assisted assessment of the color pixel density (CPD) was used to evaluate objectively the increase in the number of color Doppler US signals, the transit time of the microbubble bolus, and the potential additional differential diagnostic information.. Peak CPD at contrast agent-enhanced color Doppler US was 14.3% +/- 8.1 (mean +/- 1 standard deviation) for carcinomas and 9.3% +/- 4.9 for benign lesions (P = .04). The time to peak enhancement was shorter in carcinomas (38 seconds +/- 20) than in benign tumors (71 seconds +/- 48, P = .02). Final CPD was close or equal to baseline values. With the median of 13% for peak CPD as a threshold, the sensitivity for this parameter was 55%, the specificity was 79%, and the accuracy was 62% (P = .04). For a median time to peak of 50 seconds, the sensitivity was 84%, the specificity was 57%, and the accuracy was 76%.. After microbubble contrast agent injection, carcinomas and benign lesions behave differently in degree, onset, and duration of Doppler US enhancement. High interindividual variability and temporal variations in the Doppler US signal still limit the value of these criteria for prospective diagnosis.

Topics: Adult; Aged; Blood Flow Velocity; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Contrast Media; Female; Fibroadenoma; Fibrocystic Breast Disease; Humans; Image Processing, Computer-Assisted; Middle Aged; Polysaccharides; Sensitivity and Specificity; Ultrasonography, Doppler, Color

Topics: Breast Neoplasms; Contrast Media; Diagnosis, Differential; Humans; Polysaccharides; Ultrasonography

The objectives of the present study were to investigate the utility of an ultrasound echo enhancer in the evaluation of the dignity of breast tumors and to identify the best examination parameters.. 68 breast tumors in 61 female patients who were referred for operative tumor removal were examined by color-coded duplex sonography before and after administration of Levovist. The investigated parameters were: a) the degree of enhancement, b) the number of tumor vessels, c) the time to maximum enhancement, and d) the morphological pattern and course of vessels.. With regard to parameters A, B, and C there were in part pronounced overlaps between malignant (n = 44) and benign (n = 24) lesions. The best differentiation was found for parameter D with a sensitivity of 95% and a specificity of 83%. In all previously operated patients a distinction between a postoperative scar (n = 8) and a tumor recurrence (n = 13) was possible.. The use of Levovist leads to a clear improvement in the evaluation of dignity by duplex sonography. On the basis of our preliminary results, the characteristic pattern of vascular morphology and course is the best examination parameter. In particular, the otherwise difficult distinction between scar and recurrence appears to be an interesting application.

Topics: Adult; Aged; Aged, 80 and over; Blood Flow Velocity; Breast Neoplasms; Contrast Media; Female; Humans; Middle Aged; Neovascularization, Pathologic; Polysaccharides; Sensitivity and Specificity; Ultrasonography, Doppler, Color; Ultrasonography, Mammary