No changes should be made to clinical guidelines on the use of ultrasound contrast agents in the wake of the U.S. Food and Drug Administration's (FDA) recent statement on adverse reactions to contrast, according to statements made by a group of medical societies.
The American Institute of Ultrasound in Medicine (AIUM), the American Society of Echocardiography (ASE), and the International Contrast Ultrasound Society (ICUS) have issued statements in response to the FDA following a warning the agency issued after 11 reported cases of anaphylaxis and two deaths in patients, reportedly in reaction to polyethylene glycol, an ingredient in the agents Definity and Lumason.
The societies wrote that such reactions are "extremely" rare and that the 13 cases identified by the FDA were drawn from historical data representing millions of doses of ultrasound contrast agents administered over more than a decade.
They also pointed out the clinical benefits of using contrast agents. These include helping detect heart disease, classifying the risk of heart attack or stroke, identifying abdominal tumors, and monitoring the effectiveness of cancer therapies in adults and children.
"The FDA alert does not contain any information that would justify changes in laboratory policy for patient monitoring or treatment algorithms for hypersensitivity reactions," the ASE said in its statement. "The use of these agents should continue in situations where they have been shown to be impactful."
Ultrasound contrast agents are radiation-free and enhance conventional ultrasound scans, often producing images with higher resolution than more expensive imaging options such as CT or MRI, which present their own risks, according to the ICUS.
The benefits of contrast-enhanced ultrasound (CEUS) include reducing downstream tests, which in turn can lower overall imaging costs, expedite the patient's diagnosis and treatment, and improve hospital workflows, according to the AIUM's response.
Polyethylene glycol is an inactive ingredient in contrast agents. It can also be found in "thousands" of enteral and parenteral drugs, including commonly used medications in cardiovascular medicine, according to the ASE's response, led by chairman Dr. Jonathan Lindner.
"It is also a component in COVID-19 journal preproof vaccines based on mRNA technology, and is present in many skin creams, cosmetics, and household products," Lindner and his team wrote.
The societies also pointed out that there was no apparent confirmation or data in the FDA's statement to show whether the 13 suspected reactions to polyethylene glycol were caused by other conditions or exposures.
Lindner and his team said that training sonographers, nurses, and physicians on hypersensitivity reactions is an established recommendation.
However, the societies also acknowledged that the FDA alert "enhanced" their understanding of the mechanism for reactions to contrast agents.
"Reactions to polyethylene glycol, although extremely rare, need to be considered alongside the clear benefits of CEUS," the AIUM said in a statement.
![Examples of ultrasound findings and techniques. (A) Images in a 39-year-old male patient with a mass in the left thigh. The mass is heterogeneous on the B-mode US image (compared with the patient in D) and showed increased microvascularity (superb microvascular imaging [SMI]) and shear-wave elastography (SWE) values. Undifferentiated pleomorphic sarcoma was diagnosed at biopsy (with pleomorphic rhabdomyosarcoma in surgical specimen). (B) Images in an 18-year-old male patient with a mass in the left leg. The mass is hypoechoic on the B-mode image, with no other findings suggestive of malignancy. The lesion is in contact with the cortex of the tibia, which is slightly irregular. CT revealed a doubtful anteromedial tibial erosion. The microvascular study demonstrated high vascularization, suggestive of malignancy. Periosteal Ewing sarcoma was diagnosed with both histologic and immunohistochemical confirmation. (C) Images in a 69-year-old female patient with a lump growing on the outside of the left leg. Multiple SWE examinations were performed (please note the high values obtained in the measurements, whereas the color map highlights the stiffness relative to adjacent tissues). SMI showed areas of increased vascularization to target for sampling. Undifferentiated spindle cell sarcoma was diagnosed at biopsy, with residual leiomyosarcoma in the surgical specimen after neoadjuvant therapy. (D) Images in a 56-year-old female patient with a mass in the right thigh. The mass is heterogeneous at both B-mode ultrasound (similar to patient A) and MRI (coronal T2-weighted spectral attenuated inversion recovery [SPAIR]; T1-weighted pre-contrast and postcontrast imaging), which even shows uptake after the administration of paramagnetic contrast material, which is traditionally suggestive of malignancy. Low values at SMI and elastography are suggestive of benignity. Spindle cell lipoma was diagnosed at biopsy, with atypical spindle cell lipomatous tumor in the surgical specimen.](https://img.auntminnie.com/mindful/smg/workspaces/default/uploads/2026/08/images-radiol250278fig2.APCFLSvX6p.jpg?auto=format%2Ccompress&fit=crop&h=100&q=70&w=100)
![Examples of ultrasound findings and techniques. (A) Images in a 39-year-old male patient with a mass in the left thigh. The mass is heterogeneous on the B-mode US image (compared with the patient in D) and showed increased microvascularity (superb microvascular imaging [SMI]) and shear-wave elastography (SWE) values. Undifferentiated pleomorphic sarcoma was diagnosed at biopsy (with pleomorphic rhabdomyosarcoma in surgical specimen). (B) Images in an 18-year-old male patient with a mass in the left leg. The mass is hypoechoic on the B-mode image, with no other findings suggestive of malignancy. The lesion is in contact with the cortex of the tibia, which is slightly irregular. CT revealed a doubtful anteromedial tibial erosion. The microvascular study demonstrated high vascularization, suggestive of malignancy. Periosteal Ewing sarcoma was diagnosed with both histologic and immunohistochemical confirmation. (C) Images in a 69-year-old female patient with a lump growing on the outside of the left leg. Multiple SWE examinations were performed (please note the high values obtained in the measurements, whereas the color map highlights the stiffness relative to adjacent tissues). SMI showed areas of increased vascularization to target for sampling. Undifferentiated spindle cell sarcoma was diagnosed at biopsy, with residual leiomyosarcoma in the surgical specimen after neoadjuvant therapy. (D) Images in a 56-year-old female patient with a mass in the right thigh. The mass is heterogeneous at both B-mode ultrasound (similar to patient A) and MRI (coronal T2-weighted spectral attenuated inversion recovery [SPAIR]; T1-weighted pre-contrast and postcontrast imaging), which even shows uptake after the administration of paramagnetic contrast material, which is traditionally suggestive of malignancy. Low values at SMI and elastography are suggestive of benignity. Spindle cell lipoma was diagnosed at biopsy, with atypical spindle cell lipomatous tumor in the surgical specimen.](https://img.auntminnie.com/mindful/smg/workspaces/default/uploads/2026/08/images-radiol250278fig2.APCFLSvX6p.jpg?auto=format%2Ccompress&dpr=2&fit=crop&h=167&q=70&w=250)
