Transcervical sonography and human papillomavirus 16 E6 antibodies are sensitive for the detection of oropharyngeal cancer.

BACKGROUND: Human papillomavirus 16 (HPV-16) E6 seropositivity is a promising early marker of human papillomavirus-driven oropharyngeal cancer (HPV-OPC), yet more sensitive imaging modalities are needed before screening is considered. The objective of this study was to determine the sensitivity of transcervical sonography (TCS) for detecting clinically apparent HPV-OPC in comparison with computed tomography (CT) and positron emission tomography (PET)/CT. METHODS: Fifty-one patients with known or suspected HPV-OPC without prior treatment underwent oropharyngeal TCS and blood collection (for HPV multiplex serology testing). Eight standard sonographic images were collected; primary-site tumors were measured in 3 dimensions if identified. Each patient underwent a full diagnostic workup as part of standard clinical care. The pathologic details, HPV status, final staging, and imaging findings were abstracted from the medical record. The sensitivity of each imaging modality was compared with the final clinical diagnosis (the gold standard). RESULTS: Twenty-four base of tongue cancers (47%), 22 tonsillar cancers (43%), and 2 unknown primary cancers (4%) were diagnosed; 3 patients (6%) had no tumors. All p16-tested patients were positive (n = 47). Primary-site tumors were correctly identified in 90.2% (95% confidence interval [CI], 78.6%-96.7%) with TCS, in 69.4% (95% CI, 54.6%-81.7%) with CT, and in 83.3% (95% CI, 68.6%-93.0%) with PET/CT. TCS identified tumors in 10 of 14 cases missed by CT and recognized the absence of tumors in 3 cases for which CT or PET/CT was falsely positive. The smallest sonographically identified primary-site tumor was 0.5 cm in its greatest dimension; the average size was 2.3 cm. Among p16-positive patients, 76.1% (95% CI, 61.2%-87.4%) were seropositive for HPV-16 E6. CONCLUSIONS: TCS and HPV-16 E6 antibodies are sensitive for the diagnosis of HPV-OPC.

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.

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.

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.

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.

Contrast -Enhanced Ultrasound: State of the Art in North America.

The Society of Radiologists in Ultrasound convened a panel of specialists in contrast-enhanced ultrasound (CEUS) to produce a white paper on noncardiac CEUS in North America. The panel met in Chicago, Illinois, on October 24 and 25, 2017. The recommendations are based on analysis of current literature and common practice strategies and are thought to represent a reasonable approach to introduce the advantages of this safe and noninvasive technique for the benefit of our patients. Characterization of liver nodules, and pediatric vascular and intravesicular applications comprise the approved indications for CEUS in the United States. They, along with the very successful off-label use of CEUS for the kidney, are included in this publication.Other off-label uses are presented with emphasis on their value and literature support in the online version.

Contrast-enhanced Ultrasound-State of the Art in North America: Society of Radiologists in Ultrasound White Paper.

On October 24, 2017, in Chicago, the Society of Radiologists in Ultrasound convened a panel of specialists in contrast-enhanced ultrasound (CEUS) to arrive at a white paper regarding the use of CEUS in noncardiac applications in North America. Recommendations are based on analysis of the current literature and common practice strategies. They represent a reasonable approach to introduce the advantages of this safe and noninvasive technique for the benefit of our patients. Characterization of liver nodules with CEUS, as the approval indication worldwide, is the major focus of this endeavor. In addition, many off label uses are reviewed and literature supporting these indications provided.Key Points(1) Contrast-enhanced ultrasound (CEUS) allows cross-sectional imaging of the liver, kidneys and multiple other solid and hollow viscera, providing excellent characterization of identified focal mass lesions.(2) Performed with the injection of a microbubble contrast agent, CEUS provides a safe and readily available imaging technique which requires no ionizing radiation, making it appropriate for use in all ages, in those with renal insufficiency and when a portable examination is needed.(3) The CEUS can be considered in abdominal imaging whenever blood flow information is of value to diagnosis.(4) Dynamic real-time acquisition and the use of a purely intravascular contrast agent are the 2 most essential technical aspects of CEUS imaging which distinguish it from both computed tomography and magnetic resonance scan.

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.

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.

Color Doppler sonography in obstetrics and gynecology.

This review aims to provide the reader with an overview of the present and future clinical applications in color Doppler sonography for the evaluation of vascularity and blood flow within the uterus (both gravid and nongravid), ovaries, fetus and placenta. The clinical use of color Doppler sonography has been demonstrated within many organ systems. Color Doppler sonography has become an integral part of cardiovascular imaging. Significant improvements have recently occurred, improving the visualization and evaluation of intra-organ vascularity, resulting from enhancements in delineation of tissue detail through electronic compounding and harmonics, as well as enhancements in signal processing of frequency- and/or amplitude-based color Doppler sonography. Spatial representation of vascularity can be improved by utilizing 3D and 4D (live 3D) processing. Greater sensitivity of color Doppler sonography to macro- and microvascular flow has provided improved anatomic and physiologic assessment throughout pregnancy and for pelvic organs. The potential use of contrast enhancement is also mentioned as a means to further differentiate benign from malignant ovarian lesions. The rapid development of these new sonographic techniques will continue to enlarge the scope of clinical applications in a variety of obstetric and gynecologic disorders.

Sonography for deep venous thrombosis: current and future applications.

Deep venous thrombosis (DVT) is a one of the most common problems facing the clinician in medicine today. It is often asymptomatic and goes undiagnosed with potentially fatal consequences. Ultrasound has become the "gold standard" in the diagnosis of deep venous thrombosis and with proper attention to technique sensitivity of this test is approximately 97%. An understanding of anatomy, pathophysiology, and risk factors is important. Thrombus formation usually begins beneath a valve leaflet below the knee. Approximately 40% will resolve spontaneously, 40% will become organized, and 20% will propagate. Whether or not a calf vein thrombus is identified, a repeat examination in 7 to 10 days is recommended in patients with risk factors or when deep venous thrombosis is suspected. The three main risk factors for thrombus formation are age greater than 75 years, previous history of deep venous thrombosis, and underlying malignancy. Other diagnostic studies include the contrast venogram, CT or MRI venogram, Tc99m Apcitide study, and the laboratory test D-Dimer. The D-Dimer study is being used more frequently as a screening test with 99% sensitivity in detecting thrombus, whether deep venous thrombosis or pulmonary embolism. However, specificity is only approximately 50% with many conditions leading to false-positive exams. Therefore, a negative examination is useful in avoiding other diagnostic studies, but a positive one may be misleading. Conditions that can lead to a false-positive examination include, but are not limited to diabetes, pregnancy, liver disease, heart conditions, recent surgery, and some gastrointestinal diseases. Like the sonogram, two negative D-Dimer studies a week apart exclude the diagnosis of deep venous thrombosis. Compression sonography with color Doppler remains the best overall test for deep venous thrombosis. It is easy to perform, less expensive than most "high tech" studies, can be performed as a portable examination, and is highly reliable when done properly.

The sonographic diagnosis of adenomyosis.

Adenomyosis is a common but under-diagnosed gynecologic condition due to hypertrophied myometrial smooth muscle containing ectopic endometrial glands that is associated with pelvic pain, menorrhagia, and an enlarged uterus. This is an overview of the sonographic and magnetic resonance imaging features that have been developed in the diagnosis of adenomyosis emphasizing sonography as the initial study performed in the symptomatic patient. These features include myometrial heterogeneity, asymmetric thickening of myometrium, cysts, linear striations, and an ill-defined endometrium. Both magnetic resonance imaging and sonography can now diagnose adenomyosis with a high degree of accuracy so that treatment may be instituted specific to the disease process.

Sonographic depiction of changes of tumor vascularity in response to various therapies.

PURPOSE: To evaluate the diagnostic accuracy of power Doppler sonography for the depiction of changes in tumor vascularity with various therapeutic regimens. MATERIALS AND METHODS: Tumor cells were implanted subcutaneously in thirty-two mice and assigned to four treatment groups: control, radiation therapy, antiangiogenesis therapy (VEGF [vascular endothelial growth factor] receptor antagonist, SU11248), or combined antiangiogenesis and radiation therapy. Twenty of these mice were scanned with power Doppler sonography at two time points over the course of treatment, and power-weighted pixel densities were assessed. The other twelve mice each underwent subcutaneous placement of a dorsal skin-fold window over the tumor site, allowing for daily angiogenesis assessment of vascular length density. All tumor specimens had correlative histologic analyses performed, including immunohistochemical stains for microvasculature. RESULTS: Sonographic measurements revealed significant longitudinal differences in tumor vascularity among the four treatment groups: control mice receiving no treatment demonstrated a doubling in intra-tumor color pixel density (P < 0.02); those receiving radiation alone increased by 68% (P < 0.04); those receiving oral therapy alone increased by 44% (P = 0.016); and those receiving combination therapy decreased by 38% (P < 0.02). Tumor vascularity independently measured in the twelve mice with the skin-fold windows revealed a similar response to each type of treatment. Post-mortem tumor histology was consistent with both sonographic and skin-fold window measurements. CONCLUSION: Power Doppler sonography was accurate and reliable in measuring tumor vascularity changes in this model. These results were independently confirmed by a quantitative method relying on direct visualization of the microvasculature. Because it is rapid and non-invasive, sonographic quantification is beneficial in assessing the anti-angiogenic effects of various treatment strategies for cancer.

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.