Ultrasound Features of Rudimentary Horn Ectopic Pregnancies.

Rudimentary horn ectopic pregnancies are uncommonly encountered in women with müllerian duct anomalies. The clinical presentation of this entity is nonspecific, giving ultrasound a critical role in making the diagnosis. Timely diagnosis and management of rudimentary horn ectopic pregnancies are pivotal in reducing the high rates of uterine rupture and maternal mortality historically associated with this condition.

Clinical applications of sonoelastography.

INTRODUCTION: This review provides an overview of the current and potential clinical applications of sonoelastography, and describes the central principles that provide clinical applications. Areas covered: The clinical use of sonoelastography that is reviewed includes liver fibrosis, breast mass evaluation, thyroid nodule evaluation, detection and quantification of head/neck lymphedema. Other topics discussed include application for tendens, prostate, and salivary gland. A systematic literature search was done using PubMed database and the results were grouped according to the clinical applications. Expert commentary: This review highlights the clinical application of sonoelastography for breast, thyroid, and lymph nodes as well as the evaluation of lymphedema.

Preliminary evaluation of reliability and validity of head and neck external lymphedema and fibrosis assessment criteria.

PURPOSE: Measurement of head and neck external lymphedema and fibrosis (LEF) is challenging. To address this gap, we developed the Head and Neck External Lymphedema and Fibrosis (HN-LEF) Assessment Criteria. This article aimed to report preliminary data on reliability and validity of the HN-LEF Assessment Criteria. METHODS: Sixty head and neck cancer (HNC) patients who were ≥3-month post cancer therapy were recruited. Study measures included 1) demographic/medical data; 2) LEF physical examination completed independently by two staff members for interrater reliability (intrarater reliability completed by one of them); and 3) grayscale ultrasound examination of the head and neck skin. Reliability estimates used percent agreement and Kappa statistic. Validity was assessed via Spearman correlations of physical examination findings with ultrasound measurements. RESULTS: Fifty-one out of 60 HNC patients completed both physical examination and ultrasound assessments. Interrater reliability: 91.0% agreement (Kappa = 0.81, p < 0.001) on the presence of types of LEF; 84.9% agreement regarding the grade of LEF (Kappa = 0.70, p < 0.001) across all anatomic sites. Intrarater reliability: 96.1% agreement for type of LEF; and 91.4% agreement for grade across all sites. Ultrasound examination demonstrates characteristics and patterns for different types of LEF (particularly in the cheek, submental, and neck regions). CONCLUSIONS: The study provided initial reliability and validity data for a clinician-reported tool evaluating external LEF in the HNC population. These preliminary findings demonstrate that the tool had good reliability. Associations with the ultrasound examination results demonstrate that the tool validly captures soft tissue changes at select sites. Further validation of the tool is warranted.

Sonography of Responsive Versus Nonresponsive Ectopic Pregnancies.

This case series describes changes in size, vascularity, and cul-de-sac fluid in 30 patients with ectopic pregnancies who were treated with systemic methotrexate. Pretreatment and posttreatment transvaginal sonography of the ectopic pregnancies was performed with color Doppler imaging, and the images were assessed for changes in size, vascularity, and cul-de-sac free fluid. There was a trend for nonresponders to show increased vascularity on serial examinations, although this finding was also seen in a single responder. There was also a trend for nonresponders with increased vascularity to be associated with a greater increase in ß-human chorionic gonadotropin levels and responders with decreased vascularity to be associated with a greater decrease in ß-human chorionic gonadotropin levels.

Parametric mapping of contrasted ovarian transvaginal sonography.

The purpose of this study was to assess the accuracy of parametric analysis of transvaginal contrast-enhanced ultrasound (TV-CEUS) for distinguishing benign versus malignant ovarian masses. A total of 48 ovarian masses (37 benign and 11 borderline/malignant) were examined with TV-CEUS (Definity; Lantheus, North Billerica, MA; Philips iU22; Philips Medical Systems, Bothell, WA). Parametric images were created offline with a quantification software (Bracco Suisse SA, Geneva, Switzerland) with map color scales adjusted such that abnormal hemodynamics were represented by the color red and the presence of any red color could be used to differentiate benign and malignant tumors. Using these map color scales, low values of the perfusion parameter were coded in blue, and intermediate values of the perfusion parameter were coded in yellow. Additionally, for each individual color (red, blue, or yellow), a darker shade of that color indicated a higher intensity value. Our study found that the parametric mapping method was considerably more sensitive than standard region of interest (ROI) analysis for the detection of malignant tumors but was also less specific than standard ROI analysis. Parametric mapping allows for stricter cutoff criteria, as hemodynamics are visualized on a finer scale than ROI analyses, and as such, parametric maps are a useful addition to TV-CEUS analysis by allowing ROIs to be limited to areas of the highest malignant potential.

Practical applications of 3D sonography in gynecologic imaging.

Volume imaging in the pelvis has been well demonstrated to be an extremely useful technique, largely based on its ability to reconstruct the coronal plane of the uterus that usually cannot be visualized using traditional 2-dimensional (2D) imaging. As a result, this technique is now a part of the standard pelvic ultrasound protocol in many institutions. A variety of valuable applications of 3D sonography in the pelvis are discussed in this article.

Two-/three-dimensional transperineal sonography of complicated tape and mesh implants.

Transperineal sonography (TPS) affords dynamic evaluation of suburethral slings using tensionless vaginal tape and mesh implants used to treat complications associated with surgical procedures of the pelvic floor. This review describes and illustrates the TPS findings in postoperative complications such as recurrent prolapse, cystocele, enterocele, and rectocele. The potential use of live 3-dimensional TPS to delineate the dynamics aspects of pelvic floor disorder is also mentioned.

Early detection of ovarian cancer with conventional and contrast-enhanced transvaginal sonography: recent advances and potential improvements.

Recently, there have been several major technical advances in the sonographic diagnosis of ovarian cancer in its early stages. These include improved assessment of tumor morphology with transvaginal sonography (TVS), and detection and characterization of tumor neovascularity with transvaginal color Doppler sonography (TV-CDS) and contrast-enhanced transvaginal sonography (CE-TVS). This paper will discuss and illustrate these improvements and describe how they enhance detection of early-stage ovarian cancer. Our initial experience with parametric mapping of CE-TVS will also be mentioned.

Molecular sonography with targeted microbubbles: current investigations and potential applications.

Sonography using targeted microbubbles affords a variety of diagnostic and potentially therapeutic clinical applications. It provides a whole new world of functional information at the cellular and molecular level. This information can then be used to diagnose and possibly prevent diseases at early stages as well as devise therapeutic strategies at the molecular level. It is also useful in monitoring tumor response to therapy and devising treatment timing and plans based on the molecular state of an individual's health. Moreover, targeted microbubble-enhanced sonography has several advantages over other imaging modalities, including widespread availability, low cost, fast acquisition times, and lack of radiation risk. These traits are likely to advance it as one of the imaging methods of choice in future clinical trials examining the impact of molecular imaging on treatment outcome. This review describes the fundamental concepts of targeted microbubble-enhanced sonography as well as its potential clinical applications.

Correlation of quantified contrast-enhanced sonography with in vivo tumor response.

OBJECTIVE: The purpose of our study was to establish in vivo criteria for monitoring tumor treatment response using 3-dimensional (3D) volumetric gray scale, power Doppler, and contrast-enhanced sonography. METHODS: Twelve mice were implanted with Lewis lung carcinoma cells on their hind limbs and categorized to 4 groups: control, chemotherapy, radiation therapy, and chemoradiation. A high-frequency ultrasound system with a 40-MHz probe was used to image the tumors. Follow-up contrast-enhanced sonography was performed on days 7 and 14 of treatment with two 50-microL boluses of a perflutren microbubble contrast agent injected into the tail vein. The following contrast-enhanced sonographic criteria were quantified: time to peak, peak intensity, alpha (microvessel cross-sectional area), and beta (microbubble velocity). Three-dimensional power Doppler images were also obtained after the acquisition of contrast data. On day 15, the tumors were excised for immunohistochemical analysis with CD31 fluorescent staining. RESULTS: The tumor size and 3D power Doppler vascular index showed no statistically significant correlation with microvascular density in all examined groups. Among all of the analyzed contrast-enhanced sonographic parameters, relative alpha showed the strongest correlation with the histologic microvessel density (Pearson r = 0.93; P < .01) and an independent association with the histologic data in a multiple regression model (beta = .93; R(2) = 0.86; P < .01). CONCLUSIONS: Of the various examined sonographic parameters, alpha has the strongest correlation with histologic microvessel density and may be the parameter of choice for the noninvasive monitoring of tumor angiogenic response in vivo.

New frontiers for ovarian cancer risk evaluation: proteomics and contrast-enhanced ultrasound.

OBJECTIVE: The grim ovarian cancer statistics are attributed to the fact that most women typically present with widespread disease at the time of initial diagnosis. Our current diagnostic tools, such as pelvic examination and standard ultrasound, are inadequate to detect early-stage epithelial ovarian cancer. In recent years there has been an explosion of important advances in biomedical engineering, proteomic technologies, and computational analyses that has led to the identification of hundreds of previously unknown proteins unique to the pathophysiology of ovarian cancer, some of which are currently under clinical validation. At present, no one biomarker exists with 100% specificity and sensitivity for the accurate detection of early-stage epithelial ovarian cancer. CONCLUSION: As the search for a panel of biomarkers detecting cancer, let alone early-stage disease, progresses, diagnostic imaging will continue to play a critical role to confirm or refute these biomarker assays. Interestingly, recent studies using contrast-enhanced ultrasound have shown potential as an early-detection tool by detecting the aberrant vascularity required for tumor growth before the development of a mass. Thus, we propose that the use of proteomic-based biomarker discovery and contrast-enhanced ultrasound may serve as a promising combination to help accurately identify early-stage epithelial ovarian cancer to improve women's health care.

Advances in sonographic detection of ovarian cancer: depiction of tumor neovascularity with microbubbles.

OBJECTIVE: The purpose of this article is to discuss and illustrate the use of contrast-enhanced transvaginal sonography for the early detection of ovarian cancer and suggest how this technique may best be used to distinguish benign from malignant ovarian masses. CONCLUSION: Microbubble-enhanced transvaginal sonography can enhance the evaluation of ovarian masses by early detection of tumor microvascularity.

Sonographic assessment of tumor response: from in vivo models to clinical applications.

The advent of antiangiogenic drugs in cancer therapy necessitates an imaging modality that can longitudinally assess posttreatment changes in tumor vasculature. In this regard, microbubble contrast-enhanced ultrasonography (CEUS) offers several advantages over conventional imaging modalities. The small size of microbubbles (approximately 2-3 mum) permits their retention in the intravascular compartment and travel through the tortuous tumor vasculature. Mathematical models applied to signal intensity versus time depicting the kinetics of microbubble flow through the tumor are used to characterize tumor vascular density, blood flow velocity, and perfusion. In vivo studies using CEUS have demonstrated its comparability to dynamic contrast-enhanced magnetic resonance imaging and fluorodeoxyglucose positron emission tomography in distinguishing between diseased or malignant tissue and normal tissue. Moreover, CEUS has great potential for other novel clinical applications such as improved cancer diagnosis, enhanced medication delivery, and early antiangiogenic cancer treatment response evaluation. This review discusses the principles and potential clinical applications of CEUS in determining tumor response and its promising role in enhancing medication delivery in certain tumors.

Diagnostic parameters to differentiate benign from malignant ovarian masses with contrast-enhanced transvaginal sonography.

OBJECTIVE: The aim of this study was to evaluate diagnostic parameters to differentiate between benign versus malignant ovarian masses using contrast-enhanced transvaginal sonography (TVS). METHODS: Thirty-three consecutive patients with 36 morphologically abnormal ovarian masses (solid or cystic with papillary excrescences, focally thickened walls, or irregular solid areas) smaller than 10 cm received a microbubble contrast agent intravenously while undergoing pulse inversion harmonic TVS. The following parameters were assessed: presence of contrast enhancement, time to peak enhancement, peak contrast enhancement, half wash-out time, and area under the enhancement curve (AUC). Tumor histologic analysis was used to distinguish benign from malignant ovarian tumors. RESULTS: Twenty-six benign masses and 10 malignancies were studied. Of all examined criteria, an AUC of greater than 787 seconds(-1) was the most accurate diagnostic criterion for ovarian cancer, with 100.0% sensitivity and 96.2% specificity. Additionally, peak contrast enhancement of greater than 17.2 dB (90.0% sensitivity and 98.3% specificity) and half wash-out time of greater than 41.0 seconds (100.0% sensitivity and 92.3% specificity) proved to be useful. CONCLUSIONS: Our data suggest that the AUC, peak enhancement, and half wash-out time had the greatest diagnostic accuracy for contrast-enhanced TVS in differentiation between benign and malignant ovarian masses.

Contrast-enhanced transvaginal sonography of benign versus malignant ovarian masses: preliminary findings.

OBJECTIVE: The aim of this prospective study was to evaluate differences in contrast enhancement and contrast enhancement kinetics in benign versus malignant ovarian masses with pulse inversion harmonic transvaginal sonography. METHODS: Seventeen consecutive patients with 23 morphologically abnormal ovarian masses (solid or cystic with papillary excrescences, focally thickened walls, or irregular solid areas) smaller than 10 cm received a microbubble contrast agent intravenously while undergoing pulse inversion harmonic transvaginal sonography. The following parameters were assessed in all tumors: detectable contrast enhancement, time to peak enhancement (wash-in), peak contrast enhancement, half wash-out time, and area under the enhancement curve. Tumor histologic analysis was used to distinguish benign from malignant ovarian tumors. RESULTS: Fourteen benign masses and 9 malignancies were studied. There was a statistically significant difference in the peak enhancement (mean +/- SD, 23.3 +/- 2.8 versus 12.3 +/- 3.9 dB; P < .01), half wash-out time (139.9 +/- 43.6 versus 46.3 +/- 19.7 seconds; P < .01), and area under the enhancement curve (2012.9 +/- 532.9 versus 523.9 +/- 318 seconds(-1); P < .01) in malignant masses compared with benign disease. There was no statistically significant difference in the time to peak enhancement (26.1 +/- 6.3 versus 24.9 +/- 7.6 seconds; P = .07). CONCLUSIONS: Overall, our data showed a significant difference in the contrast enhancement kinetic parameters between benign and malignant ovarian masses.

Relationship between retention of a vascular endothelial growth factor receptor 2 (VEGFR2)-targeted ultrasonographic contrast agent and the level of VEGFR2 expression in an in vivo breast cancer model.

OBJECTIVE: The aim of this study was to characterize the relationship between retention of a vascular endothelial growth factor receptor 2 (VEGFR2)-targeted ultrasonographic contrast agent (UCA) and VEGFR2 expression in tumor vasculature of breast cancer. METHODS: 67NR breast cancer tumors implanted in mice were evaluated in vivo with both VEGFR2-targeted and nontargeted UCAs, and a high-frequency ultrasound system. A bolus of the UCA was injected and allowed to circulate for 4 minutes to allow binding of targeted microbubbles. After that, 2 sets of images before and after a high-power ultrasonic destruction sequence were acquired. The average video intensity of predestruction and postdestruction images was measured and used as a relative measure of retention of the UCA in the tumor. Levels of VEGFR2 expression and tumor vascular density were quantified by immunohistochemical staining and compared with retention of the VEGFR2-targeted UCA. RESULTS: Retention of VEGFR2-targeted microbubbles in tumors was significantly higher than retention of nontargeted microbubbles (mean +/- SD, 47.75+/-9.85 versus 18.5+/-5.46 dB; P< .001). Retention of the VEGFR2-targeted UCA was found to correlate with the level of VEGFR2 expression in the studied tumors (r(2)=0.41). In contrast, retention of the nontargeted UCA was not correlated with the level of VEGFR2 expression (r(2)=0.08). Furthermore, retention of the VEGFR2-targeted UCA was not correlated with the level of tumor vascularity. CONCLUSIONS: The magnitude of the molecular ultrasonographic signal from a VEGFR2-targeted UCA retained by tissue correlates with VEGFR2 expression. These results validate the use of molecular ultrasonography for in vivo detection and quantification of VEGFR2 expression in this breast cancer model.

Molecular imaging of vascular endothelial growth factor receptor 2 expression using targeted contrast-enhanced high-frequency ultrasonography.

OBJECTIVE: The aim of our study was to investigate the use of targeted contrast-enhanced high-frequency ultrasonography for molecular imaging of vascular endothelial growth factor receptor 2 (VEGFR2) expression on tumor vascular endothelium in murine models of breast cancer. METHODS: Highly invasive metastatic (4T1) and nonmetatstatic (67NR) breast cancer cells were implanted in athymic nude mice. Tumors were examined in vivo with targeted contrast-enhanced high-frequency ultrasonography using a scanner with a 40-MHz probe. Randomized boluses of ultrasound contrast agents (UCAs) conjugated with an anti-VEGFR2 monoclonal antibody or an isotype control antibody (immunoglobulin G) were injected into the animals. Sonograms were analyzed by calculation of the normalized video intensity amplitudes caused by backscatter of the bound UCA. After ultrasonography, the tumor samples were harvested for analysis of VEGFR2 expression by immunoblotting and immunocytochemistry. RESULTS: The mean video intensity amplitude caused by backscatter of the retained VEGFR2-targeted UCA was significantly higher than that of the control UCA (mean +/- SD: 4T1 tumors, 15 +/- 3.5 versus 7 +/- 1.6 dB; P < .01; 67NR tumors, 50 +/- 12.3 versus 12 +/- 2.6 dB; P < .01). There was a significant difference in VEGFR2-targeted UCA retention between 4T1 and 67NR tumors (normalized video intensity amplitudes, 15 +/- 3.5 and 50 +/- 12.3 dB, respectively; P < .001), and this correlated well with relative VEGFR2 expression in the two tumor types. CONCLUSIONS: Targeted contrast-enhanced high-frequency ultrasonography may enable in vivo molecular imaging of VEGFR2 expression on the tumor vascular endothelium and may be used for noninvasive longitudinal evaluation of tumor angiogenesis in preclinical studies.

Ovarian volume measurements in mice with high-resolution ultrasonography.

OBJECTIVE: The aim of our study was to evaluate the intraobserver and interobserver variability of ovarian volume measurements in mice with high-resolution 2-dimensional ultrasonography (2DUS) and 3-dimensional ultrasonography (3DUS). METHODS: Ovaries of 10 nude mice were visualized with a small-animal ultrasound scanner and a 40-MHz probe. For each ovary, volume was measured 3 times by 2 independent readers using both 2DUS and 3DUS methods. The 2DUS method used a biplane ellipsoid model. The 3DUS method estimated the volume by integrating 10 to 12 parallel image planes of the ovary after semiautomated outlining of the boundaries. For each type of measurement, intraobserver and interobserver standard error of measurement (SEM) values and minimal detectable volume changes were calculated by analysis of variance. RESULTS: Two-dimensional ultrasonography showed much poorer reproducibility, with higher absolute intraobserver and interobserver SEM values (0.50 and 0.61 mm3, respectively) than 3DUS (0.20 and 0.35 mm3; P < .01). Relative intraobserver and interobserver SEM values were also much higher for 2DUS (12.20% and 14.88%) than for 3DUS (5.12% and 8.97%; P < .01). The minimal volume changes that could be detected with a 95% confidence level in successive measurements by the same (or different) observers were 33.90% (41.22%) for 2DUS and 14.10% (24.87%) for 3DUS. CONCLUSIONS: High-resolution 3DUS can provide a reliable tool for noninvasive, longitudinal ovarian volume measurements in mice.