Emerging applications of contrast-enhanced ultrasound in pediatric imaging

March 19, 2019
By Ryne A. Didier and Anush Sridharan

Pediatric imaging comes with unique challenges, including unpredictable patient cooperation, varying child size and wide breadth of pathology.

As parents continue to rightfully advocate for their child, concerns regarding invasive procedures, radiation exposure and sedation risks often arise in conversations with clinicians and radiologists. Therefore, being able to obtain diagnostic information using noninvasive technologies with minimal risks is an important and appealing area of shared interest for researchers, clinicians and families.

Ultrasonography (or ultrasound), which uses high-frequency sound waves transmitted through the body to generate images, offers a noninvasive, radiation-free and cost-effective imaging modality. By providing dynamic, real-time visualization of the internal organs and structures, ultrasound (US) affords additional benefits when compared to other diagnostic imaging modalities. However, limitations of US include operator dependence and challenges associated with the patient’s body habitus and scanning characteristics. Furthermore, US employs the Doppler principle to specifically study vascular structures and perfusion defects, but this technique is most sensitive in organs with relatively high blood flow and larger vessels. The discovery and development of US contrast agents has paved the way to overcome some of these limitations and augment diagnostic examinations.

Commonly used US contrast agents consist of gas-filled microbubbles encapsulated by a lipid shell. Their size, typically 1 to 8 microns in diameter, makes them purely intravascular agents that do not diffuse into the interstitial or intracellular space. Contrast-enhanced US (CEUS) relies on the physical interactions between the transmitted US waves and these microbubbles to provide optimal visualization. Administration of the contrast agent can be into the patient’s veins (intravascular) or into a specific cavity (intraluminal/intracavitary). Visualization of the contrast agent is short-lived, on the order of minutes, due to damage by shear forces and instability of the lipid shell. The gas released when the microbubble is destroyed is ultimately expelled by the patient’s lungs. The US contrast agents currently available for medical use in the U.S. have excellent safety profiles and do not cause renal toxicity, which is in contradistinction to the iodine- or gadolinium-based media used in computed tomography (CT) and magnetic resonance (MR) imaging. Advancements in US system software now allow excellent spatial and temporal resolution for real-time CEUS evaluation. These advantages are attractive to pediatric imagers and CEUS has emerged as an incredibly valuable imaging technique.

Initially championed in European countries, CEUS has been widely utilized in adult echocardiography and additional uses are gaining traction in the U.S. In addition, recent expansion of the Food and Drug Administration’s approval for a specific US contrast agent in the pediatric population has encouraged further exploration into the applications of this imaging technique. Intravesicular administration, where the contrast agent is directly introduced into the patient’s bladder via catheter, has been used in US voiding cystourethrogram examinations to allow visualization of urologic anatomy and detection of vesicoureteral reflux in children. The use of CEUS obviates the need for radiation exposure, which is required with the traditional imaging examination in this situation (fluoroscopic vesicoureterography). CEUS has also been used following intravenous administration for a wide variety of indications including characterization of indeterminate liver lesions, evaluation of solid organ injury following blunt abdominal trauma and hypoxic-ischemic brain injury.

Despite the multitude of medical indications for which CEUS has been explored, these should be considered the “tip of the iceberg” for future imaging applications. CEUS plays an important role at our institution in troubleshooting challenging cases, particularly where there is a strong desire to avoid sedation or radiation exposure to the child. One common example is with oncology patients in whom staging and recurrent follow-up examinations require CT or MR, and any abnormalities identified on these imaging studies necessitate accurate characterization to exclude recurrence or metastasis. At our institution, we frequently employ CEUS to better delineate complex cystic lesions of the kidney and indeterminate lesions of the liver to determine the need for biopsy or resection. This imaging technology has also been used by interventional radiologists to identify solid components of tumors as targets for image-guided biopsy, ensure adequate placement of drainage catheters and continuity of abscess cavities, depict vascular anatomy and confirm correct placement of tubes and lines of the gastrointestinal tract or vascular system. Where traditional imaging modalities may be inadequate in determining the diagnosis or be limited in their ability to sufficiently depict abnormalities, CEUS can be considered.

In addition to the diagnostic benefits of CEUS, novel scientific advancements in image processing methods now allow production of quantifiable metrics which can complement and enhance diagnostic information while also providing functional data. These metrics, such as time-to-peak, wash-in-slope, peak intensity and wash-out-slope, have the benefit of assessing more than just “where” there is blood flow, but also “how much” and “how quickly.” These quantification methods, while still in their infancy, have the ability to transform US into an important modality for functional imaging.

Future applications of CEUS are extensive and include quantification of blood flow and perfusion to organs of interest, including kidneys, bowel and the brain. In this capacity, CEUS can provide functional data in addition to detailed diagnostic information. Contrast capabilities are available on most commercially available US systems with continued expansion of available technology to multiple transducers. In this environment, technologic advancements directly intersect with pediatric imaging and offer innovative benefits to this special patient population. Ultimately, these developments have spawned widespread interest in educational opportunities, thus, prompting the creation of the Center for Pediatric Contrast Ultrasound at the Children’s Hospital of Philadelphia. This center was founded to educate sonographers and physicians in the benefits and applications of CEUS specifically in pediatric imaging in an effort to encourage and promote knowledge and encourage advancement of this imaging technology.

CEUS offers many benefits to pediatric imagers, referring clinicians and families in the imaging evaluation of children. Continued advancements in the existing technology ensure that this modality will thrive in our healthcare environment by providing extensive diagnostic and potentially functional information that ultimately improves care for our young patients.

About the Authors: Dr. Ryne Didier is a board-certified pediatric radiologist at the Children’s Hospital of Philadelphia. Her clinical work focuses on fetal and neonatal imaging at the Center for Fetal Diagnosis and Therapy. Her research interests include the applications of novel technologies to improve diagnostic and functional imaging in infants and children. Dr. Anush Sridharan is a postdoctoral fellow in the Department of Radiology at the Children’s Hospital of Philadelphia. His research focuses primarily on the development of applications for contrast-enhanced ultrasound in pediatrics. He is also involved in the development of novel image analysis techniques for diagnostic ultrasound and MR imaging.