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.

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.

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.

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.

Three-dimensional volumetric sonography in gynecology: an overview of clinical applications.

Three-dimensional (3D) sonography can significantly improve on the diagnostic ability of two-dimensional sonography of the pelvic organs. 3D sonography has become a problem-solving technique in the evaluation of a variety of gynecologic disorders involving the uterus, adnexa, and pelvic floor. It allows an accurate depiction of the uterine cavity and outline of the uterus in the coronal plane. 3D sonography is less expensive than other modalities, is convenient, and does not have the risk of radiation or potential nephrotoxicity from contrast that other imaging modalities have. It is a cost-effective tool to assess the pelvic organs.

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.