Stephanie R. Wilson

Microbubble-enhanced US in Body Imaging: What Role?

Contrast agents for ultrasonography (US) comprise microscopic bubbles of gas in an encapsulating shell. They are unique in that they interact with the imaging process, oscillating in response to a low-intensity ultrasound field and disrupting in response to a high-intensity field. New contrast-specific imaging modes allow US to show exquisite vascularity and tissue perfusion in real time and with excellent spatial resolution. In Europe, Asia, and Canada, to name only the most obvious, characterization of focal liver masses is the first and best established use of contrast-enhanced (CE) US, allowing for the noninvasive diagnosis of commonly encountered liver masses with comparable accuracy to that of computed tomography and magnetic resonance studies. CE US is a preferred modality for the difficult task of diagnosis of liver nodules detected on surveillance scans in those at risk for hepatocellular carcinoma. Newer body applications include the guidance of ablative intervention, monitoring activity of bowel inflammation in Crohn disease, characterization of kidney masses, especially cystic renal cell carcinoma, diagnosis of prostate cancer, and monitoring the response of tumors to antivascular drug therapies. Microbubble contrast agents are easy to use and robust; their use poses no risk of nephrotoxicity and requires no ionizing radiation. CE US plays a vital and expanding role that improves management and patient care.

WFUMB Guidelines and Recommendations for Clinical Use of Ultrasound Elastography: Part 2: Breast

The World Federation for Ultrasound in Medicine and Biology (WFUMB) has produced these guidelines for the use of elastography techniques in liver disease. For each available technique, the reproducibility, results, and limitations are analyzed, and recommendations are given. Finally, recommendations based on the international literature and the findings of the WFUMB expert group are established as answers to common questions. The document has a clinical perspective and is aimed at assessing the usefulness of elastography in the management of liver diseases.

Guidelines and Good Clinical Practice Recommendations for Contrast Enhanced Ultrasound (CEUS) in the Liver – Update 2012

Initially, a set of guidelines for the use of ultrasound contrast agents was published in 2004 dealing only with liver applications. A second edition of the guidelines in 2008 reflected changes in the available contrast agents and updated the guidelines for the liver, as well as implementing some non-liver applications. Time has moved on, and the need for international guidelines on the use of CEUS in the liver has become apparent. The present document describes the third iteration of recommendations for the hepatic use of contrast enhanced ultrasound (CEUS) using contrast specific imaging techniques. This joint WFUMB-EFSUMB initiative has implicated experts from major leading ultrasound societies worldwide. These liver CEUS guidelines are simultaneously published in the official journals of both organizing federations (i.e., Ultrasound in Medicine and Biology for WFUMB and Ultraschall in der Medizin/European Journal of Ultrasound for EFSUMB). These guidelines and recommendations provide general advice on the use of all currently clinically available ultrasound contrast agents (UCA). They are intended to create standard protocols for the use and administration of UCA in liver applications on an international basis and improve the management of patients worldwide.

An algorithm for the diagnosis of focal liver masses using microbubble contrast-enhanced pulse-inversion sonography.

OBJECTIVE The objective of this study was to develop an algorithm for liver mass diagnosis using microbubble contrast-enhanced pulse-inversion sonography. SUBJECTS AND METHODS Ninety-six lesions in 92 patients were evaluated with DMP 115 (Definity)-enhanced pulse-inversion sonography, comprising 44 malignancies (29 hepatocellular carcinomas, 12 metastases, two peripheral cholangiocarcinomas, and one hepatic lymphoma) and 52 benign lesions (26 hemangiomas, 20 focal nodular hyperplasias, and six others). All had continuous low-mechanical-index imaging through the arterial and portal venous phase. A three-person blind review evaluated single images at baseline, early and peak arterial phases, and through the extended portal phases with a movie showing arterial phase wash-in. Reviewers assessed lesional vascularity and enhancement blindly but did not make a diagnosis. Combinations of answers were compared with independently determined final diagnoses to develop an algorithm for liver mass diagnosis. RESULTS Portal phase enhancement comprises the first step of the algorithm, with positive or sustained enhancement identifying 48 (92%) of 52 benign lesions and negative enhancement or washout present in 41 (93%) of 44 malignancies. Sustained portal phase enhancement with arterial phase peripheral nodularity and centripetal progression predicted 24 (92%) of 26 of the hemangiomas; diffuse arterial phase enhancement greater than the liver identified 19 (95%) of 20 of the focal nodular hyperplasias. With negative portal phase enhancement, arterial phase information was less effective at differentiating hepatocellular carcinoma (25 [86%] of 29 cases) from another hepatic malignancy (11 [73%] of 15 cases). CONCLUSION A simple diagnostic algorithm for interpretation of microbubble-enhanced sonography provides sensitive and accurate diagnosis of commonly encountered liver masses.

Contrast-Enhanced Ultrasound: What Is the Evidence and What Are the Obstacles?

OBJECTIVE Although ultrasound contrast agents (UCAs) are popular and widely used in Europe and Asia, the U.S. Food and Drug Administration (FDA) has not approved a microbubble agent for radiology imaging in the United States. Herein, we discuss the evidence for and the obstacles to using UCAs for contrast-enhanced ultrasound (CEUS). CONCLUSION Despite the obstacles to the use of UCAs for CEUS including regulatory and practice patterns, the evidence indicates that radiologists and patients will be missing an effectual imaging option if we do not encourage the use of CEUS and strongly support the approval of UCAs by the FDA. The evidence outweighs the obstacles: CEUS is cost-effective; can be performed at the bedside; uses no ionizing radiation; has no nephrotoxicity; and, most importantly, can provide accurate diagnostic information comparable to CT and MRI.

Elastography Assessment of Liver Fibrosis: Society of Radiologists in Ultrasound Consensus Conference Statement

The Society of Radiologists in Ultrasound convened a panel of specialists from radiology, hepatology, pathology, and basic science and physics to arrive at a consensus regarding the use of elastography in the assessment of liver fibrosis in chronic liver disease. The panel met in Denver, Colo, on October 21-22, 2014, and drafted this consensus statement. The recommendations in this statement are based on analysis of current literature and common practice strategies and are thought to represent a reasonable approach to the noninvasive assessment of diffuse liver fibrosis.

Focal Nodular Hyperplasia and Hepatic Adenoma: Differentiation with Low-Mechanical-Index Contrast-Enhanced Sonography

OBJECTIVE The purpose of our study was to determine the differentiating features of focal nodular hyperplasia (FNH) and hepatic adenoma on contrast-enhanced sonography. MATERIALS AND METHODS Sixty-two patients who underwent contrast-enhanced sonography and were confirmed to have FNH (n = 43) or hepatic adenoma (n = 19) were assessed retrospectively for arterial phase enhancement, filling direction, stellate arteries, and portal phase enhancement. An algorithm was applied to these interpreted features to determine the contrast-enhanced sonography diagnosis. RESULTS All lesions were hypervascular in the arterial phase. Centrifugal filling was more common in FNH (39 and 32 of 43, 91% and 74% [reader 1 and reader 2]) than in adenoma (3 and 3 of 19, 16%). Centripetal or mixed filling was more common in adenoma (16 and 16 of 19, 84%) than in FNH (4 and 11 of 43, 9% and 26%) (p < 0.001, kappa = 0.61). Stellate arteries characterized FNH (29 and 26 of 43, 67% and 60%) but not adenoma (3 and 2 of 19, 16% and 11%) (p < 0.001, kappa = 0.36). Sustained portal phase enhancement was more common in FNH (37 and 39 of 43, 86% and 91%) than in adenoma (9 and 12 of 19, 47% and 63%) (p < 0.02, kappa = 0.79). The sensitivity, specificity, positive predictive value, and negative predictive value of sonography for diagnosing FNH were 95% and 86%, 74% and 79%, 89% and 90%, and 88% and 71%, (reader 1 and reader 2, respectively). CONCLUSION FNH is predicted on the basis of arterial phase centrifugal filling and stellate vascularity on contrast-enhanced sonography. Adenoma is less reliably predicted on the basis of centripetal or mixed filling without stellate vascularity. Sustained portal phase enhancement is more common in FNH than in adenoma but contributes less to the differentiation of these lesions.

Enhancement Patterns of Focal Liver Masses: Discordance Between Contrast-Enhanced Sonography and Contrast-Enhanced CT and MRI

OBJECTIVE The purpose of this study was to investigate the origin of the infrequent discordance between the contrast enhancement patterns of liver lesions on sonography and those on CT and MRI. Forty-four discordant cases were reviewed retrospectively. CONCLUSION Four categories of discordance were identified, one of which is unexplained. Contrast agent diffusion caused portal venous phase discordance in malignant tumors (n = 6) whereby CT and MRI contrast material diffused through the vascular endothelium into the tumor interstitium, concealing washout. Sonographic microbubbles were purely intravascular and showed washout. Arterial phase timing discordance occurred in metastatic lesions (n = 10) with hypervascularity and rapid washout on contrast-enhanced sonography. CT arterial imaging performed later showed hypovascularity. Rapidly enhancing hemangiomas (n = 7) exhibited hypervascularity on CT when contrast-enhanced sonography also showed peripheral nodules and fast centripetal progression. Discordance caused by fat in lesions (n = 4) or liver (n = 10) reflected the inherent echogenicity of fat on sonography compared with its low attenuation on CT and low signal intensity on MRI. Infrequent cases of discordance remain unexplained. Recognition of the cause of the infrequent disagreement in enhancement patterns on contrast-enhanced sonography with those on CT and MRI improves diagnostic interpretation.

Hypervascular Liver Masses on Contrast-Enhanced Ultrasound: The Importance of Washout

OBJECTIVE The objective of our study was to determine the role of negative enhancement (washout), its presence and timing, in the differential diagnosis of hypervascular liver masses on contrast-enhanced ultrasound. MATERIALS AND METHODS One-hundred forty-six hypervascular liver lesions (mean size, 3.9 cm; range, 1.0-17.0 cm) were evaluated with contrast-enhanced ultrasound over a 6-month period. Seventy-four were benign (29 hemangiomas, 31 focal nodular hyperplasia [FNH] lesions, seven adenomas, five inflammatory lesions, two other) and 72, malignant (41 hepatocellular carcinomas [HCCs], 25 metastases, six other). Two independent reviewers retrospectively recorded the presence and timing of washout in the portal venous phase, observing until 4 minutes after injection, of a contrast agent (perflutren microspheres). Diagnoses were confirmed by histopathology (n = 68) or clinicoradiologic follow-up (n = 78). Timing of washout was compared between types of lesion using Fishers exact test. RESULTS Washout occurred in both benign (27/74, 36%) and malignant (70/72, 97%) lesions but was more frequently seen in malignancy (p < 0.001) (kappa = 0.91). Metastases showed more rapid washout than HCCs (p < 0.001): 20 of 25 metastases showed washout by 30 seconds after injection and 23 of 41 HCCs, later than 75 seconds. All malignant lesions without washout were HCCs (2/41). Among the benign lesions, all five inflammatory lesions showed rapid washout before 75 seconds and six of seven adenomas showed washout, mostly later than 75 seconds (5/6). Washout also occurred in hemangiomas (6/29) and FNH lesions (9/31), mostly later than 75 seconds after injection (12/15). CONCLUSION Hypervascular malignant lesions show washout except infrequent cases of HCC. Rapid washout characterizes metastases, whereas HCCs show variable, often slow, washout. However, washout is not unique to malignancy and may be seen in benign lesions.

Real-Time Temporal Maximum-Intensity-Projection Imaging of Hepatic Lesions with Contrast-Enhanced Sonography

OBJECTIVE We sought to perform a preliminary evaluation of temporal maximum intensity projection (MIP) of focal hepatic masses in selected patients. The technique processes real-time contrast-enhanced sonography images by integrating the path of moving bubbles to depict vascular morphology. Following a high-intensity ultrasound pulse that disrupts bubbles within the scan plane, MIP images the trajectories of fresh bubbles replenishing the plane and revealing their course. CONCLUSION Vascular morphology is depicted at a level or detail not seen before with sonography. High-frame-rate sequences of less than one second uniquely show arterial structure in liver lesions.