The ultrasound community is taking another run at removing the "black box" warning required by the U.S. Food and Drug Administration (FDA) for ultrasound contrast agents. Several societies have asked the FDA to remove the warning from the labeling of ultrasound contrast agents.
The International Contrast Ultrasound Society (ICUS) has filed a citizen petition with the FDA for removing the black box warning, which was first mandated by the FDA in 2007. The warning was implemented after the FDA received reports of 11 deaths that occurred between 2001 and 2007 that at the time were believed to have been related to ultrasound contrast administration.
But since then, a number of clinical studies have been published demonstrating the good safety profile of the agents. Black box warnings are typically reserved for products with the highest level of safety risk, a profile that does not fit ultrasound contrast, proponents of the technology maintain.
Indeed, the citizen petition filed by ICUS references an extensive body of favorable safety that wasn't available when the FDA first mandated the black box warnings in 2007, according to the society. Other societies supporting the petition include the American Institute of Ultrasound in Medicine, the World Federation of Ultrasound in Medicine and Biology, the Society of Radiologists in Ultrasound, the Society of Diagnostic Medical Sonography, the Society for Pediatric Radiology, the American Society of Echocardiography, and the Liver Imaging Reporting and Data System (LI-RADS) contrast-enhanced ultrasound working group. ICUS said that other individual physicians have also submitted letters in support of the petition.
ICUS had previously petitioned the FDA for the removal of the black box warnings in September 2018. Three ultrasound contrast agents -- Definity (Lantheus Medical Imaging), Lumason (Bracco Diagnostics), and Optison (GE Healthcare) -- are currently approved for use in the U.S.
The ICUS petition pointed out that the FDA has downgraded package insert contradictions three times since 2007 and removed a 30-minute monitoring requirement for patients with pulmonary hypertension or unstable cardiopulmonary conditions. The FDA has also recently approved new ultrasound contrast indications for adults and children, ICUS said.
![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)
