Subtle Contrast
By Keith Loria
Radiology Today
Vol. 25 No. 5 P. 22

A Look at Best Practices for MR, CT, and Ultrasound Contrast Dose Safety

Best practices for contrast dose safety in MRI, CT, and ultrasound continue to focus on patient safety, minimizing risks, and maximizing the efficacy of imaging. Some significant trends that are taking shape involve AI and machine learning, which are optimizing contrast agent administration and enhancing image quality, implementing dose tracking and monitoring systems to keep track of patients’ cumulative exposure to contrast agents over time, and tailoring imaging protocols and contrast dosing to individual patient characteristics and needs.

Ari Jonisch, MD, president of Main Street Radiology and chief of service in the department of radiology at New York- Presbyterian/Queens, says maintaining patient safety during contrast imaging is always a top priority and involves several key steps. “Before administering contrast agents, clinicians should thoroughly screen patients for any allergies, underlying medical conditions, or risk factors that may increase the likelihood of adverse reactions,” he says. “Accurately calculate the appropriate dose of contrast agent based on factors such as patient weight, age, renal function, and the specific imaging protocol being used.”

It’s also important to continuously monitor patients during and after contrast administration for any signs of adverse reactions, such as allergic reactions, contrast-induced nephropathy, or extravasation. “Be prepared to intervene promptly in the event of an adverse reaction, with appropriate medications, equipment, and emergency protocols to manage any complications effectively,” Jonisch says. “We thoroughly train our personnel and employ cutting-edge technology to provide our patients with the safest possible experience.”

“We see drug safety as part of our strategy—to give the right patient the right dose at the right time in their care journey,” says Mark Hibberd, CMO of GE HealthCare’s pharmaceutical diagnostics business segment. “We provide product choice across major imaging modalities and support clinicians in delivering the lowest effective dose to meet diagnostic requirements.” The company’s global drug safety and pharmacovigilance team continuously monitors safety data received from all available sources and assesses the safety profile of its products. This helps ensure that the benefits of the contrast agents outweigh potential risks from adverse side effects.

The introduction of high-relaxivity gadolinium- based contrast agents (GBCAs) in the field of MRI contrast, such as gadopiclenol, which is sold under the brand names Elucirem (Guerbet) and VUEWAY (Bracco Diagnostics), have attracted attention, as they have been approved for use at half the gadolinium dose of traditional agents. “There are a number of factors that influence relaxivity such as structure, hydration number and molecular weight,” says Ahmed Abdelal, North American head of medical and regulatory affairs for Guerbet. “[Gadopiclenol] is designed with two water molecule exchange sites, which doubles the relaxivity, allowing the use of half the gadolinium dose compared with conventional GBCAs.”

Each GBCA is approved with specific indications for use, Abdelal says. For example, gadopiclenol injection is indicated in adult and pediatric patients aged 2 years and older for use with MRI to detect and visualize lesions with abnormal vascularity in the central nervous system (brain, spine, and associated tissues), and the body (head and neck, thorax, abdomen, pelvis, and musculoskeletal system).

“Gadolinium safety has been a concern in the past, and people are interested in reducing the amount injected into the body,” says Noelle M. Heber, senior director of MR and X-ray contrast media marketing for Bracco Diagnostics.

“Halving the dose should increase the safety profile,” says Anthony Pavone, lead MRI tech for the Northwell Health system in New York. “In addition, these higher relaxivity agents have higher kinetic stability. This should theoretically result in lower gadolinium deposition into various tissues, including the brain, skin, subcutaneous tissues, and muscles.” He adds that high-relaxivity agents allow the health care system’s imaging centers to administer half the gadolinium dose while maintaining the same diagnostic ability.

“MRI contrast agents are indispensable,” Abdelal says. “With innovation and commitment to the community, MRI contrast agents will continue to evolve to allow improvement in visualization and diagnosis, in addition to new MRI techniques and integration of AI.”

As a specialist in musculoskeletal radiology, Jonisch has witnessed firsthand the transformative impact of these agents. “They enhance the clarity and detail of MRI images, allowing for better visualization of tissues and abnormalities,” he says. “This improved imaging capability leads to more accurate diagnoses and better patient outcomes. High-relaxivity agents have elevated the standard of care in MRI contrast imaging, empowering radiologists like myself to provide even better health care solutions to our patients.”

However, Hibberd notes that at the FDA-approved dose for these highrelaxivity agents, there is no proven efficacy benefit over existing MR contrast agents. “Further research and clinical use are needed to establish the safety profile of high-relaxivity GBCAs,” he says. “Also, relaxivity isn’t the only consideration when selecting GBCAs. Professional societies advocate for a multifactorial assessment, considering factors such as allergic reaction risk, physicochemical properties, GBCA stability, patient age, and potential for repeated need for contrast-enhanced MRI.”

GE HealthCare offers a range of contrast agents, including the macrocyclic ionic agent Clariscan, the recently launched macrocyclic Pixxoscan, and the linear nonionic agent Omniscan, which is available in some markets. The company also has a first-of-its-kind manganesebased macrocyclic MRI contrast agent for general purpose imaging in clinical development.

“This could potentially offer a gadolinium-free alternative contrast agent for MRI and eliminate the risk of nephrogenic systemic fibrosis, potential risks from tissue gadolinium retention, and pollution of the environment by gadolinium in medical waste,” Hibberd says.

For MRI gadolinium contrast, Northwell Health only uses contrast agents that are macrocyclic, which means these agents have higher stability. “This translates to no or little risk for nephrogenic systemic fibrosis, which results in the deposition of fibrous material into the skin and subcutaneous tissues and the skeletal muscle,” Pavone says. “These agents have also been shown to have less gadolinium deposition into various organs.”

New CT scanners, postprocessing, and embedded AI technologies have allowed for the reduction of both radiation and contrast media doses in CT exams while maintaining or improving diagnostic image quality. “Recently, workflow improvements have been achieved with syringeless injectors, such as our CT Motion device, using multidose containers of [contrast media], as compared to single-use syringes,” Hibberd says. “Advancements in packaging have also reduced injuries (eg, from glass bottles), such as our polymer bottle packaging.”

Bracco has Isovue IBP (imaging bulk package), designed to increase safety and improve workflow while minimizing risk and maintaining compliance regarding the use of multidose contrast media for radiological procedures in the CT suite. “When it comes to CT, our focus is on iodine preservation,” Heber says. “Our IBP is a compliant multidose solution for iodinated contrast.”

According to Peter Seidensticker, MD, head of medical and clinical affairs CT/cardiovascular and digital radiology at Bayer, the company has been proactive in addressing safety concerns around contrast media. “When you look at the advances of the past year, many of these agents have been unchanged and are representing an inert type of molecule that is tough to beat, so there has not been much molecule innovation,” he said. “What we have seen relates to individualized dosing and to give as low as reasonably achievable, and what is to be achieved is diagnostic image quality.”

Bayer has been developing new injectors across all fields—such as its new Medrad Stellant FLEX Injection for CT—as well as new contrast media for MR, addressing the high-relaxtivity, low-dose class that is just recently entering the market.

One notable trend in CT Jonisch has noticed is the creation of lowerdose contrast protocols intended to reduce the quantity of contrast dye used while maintaining diagnostic image quality. “In addition, advances in imaging technology have made it possible to provide contrast material in a more focused and accurate manner, improving patient safety and lowering the possibility of negative reactions,” he says. “Radiologists are now more focused on providing customized patient care, adjusting contrast protocols according to patient characteristics including age, weight, and kidney function.”

Pavone says improvements in multislice CT scans with their larger detectors allow Northwell Health to reduce the amount of intravenous contrast needed while maintaining the same visual quality and diagnostic ability. “In addition, the introduction of dual-energy CT scans also allows lower contrast doses to be highlighted as effectively as a higher contrast dose on a traditional scanner,” he says.

Helise Coopersmith, MD, who specializes in diagnostic and musculoskeletal radiology, is vice chair of quality for the imaging service line at Northwell Health and vice chair of radiology at Northwell Health’s North Shore University Hospital. She says that for iodinated CT contrast, the best practice is screening for patients who have acute kidney injury, severe chronic kidney disease, or a known contrast allergy. “For pediatric patients under the age of 3, there is particular concern for a hypoactive thyroid gland,” she says. “For these patients, we advocate for a follow-up thyroid evaluation two to three weeks after contrast administration, which is done with lab testing.”

Contrast-enhanced ultrasound is routinely used worldwide to detect heart disease and pathology in organs such as the liver, breast, kidney, and prostate. In combination with ultrasound’s portability, availability, low cost, and radiation-free imaging capabilities, microbubbles render contrast-enhanced ultrasound as an essential imaging modality within the clinicians’ armamentarium of diagnostic tools.

“Microbubbles generally have low rates of adverse reactions in patients when compared with iodinated [contrast media],” Hibberd says. “However, in recent years, the FDA required additional product labeling around the potential for hypersensitivity reactions in patients with allergy to polyethylene glycol (PEG) as a constituent found within two lipid-shelled microbubbles approved in the USA.”

GE HealthCare’s FDA-approved microbubble for cardiac imaging, Optison (perflutren protein-type A microspheres), is the only PEG-free ultrasound enhancing agent available in the United States today. “Our other, lipid-based microbubble, Sonazoid, approved for liver imaging in Norway and Asian markets, is also PEG-free,” Hibberd says. “Hence, the current AI developments in ultrasound are not focused on dose reduction, but rather more on improving the diagnostic confidence and workflow.”

Coopersmith says ultrasound contrast agents are relatively newer products, but they can help highlight solid organ lesions, look for endovascular stent graft leaks, identify fallopian tube patency on hysterosonography, and target lesions for biopsies during interventional procedures that may be less visible without contrast. “The concerns for these agents are cardiac issues and seizures,” she says. “The main benefit of ultrasound contrast over MRI and CT contrast is we don’t need to worry about patients that may be renally compromised or concerns around allergies or anaphylaxis. Our radiology department has been using these agents for several years and has not had any issues.”

Evolving Technology
As the technology of modalities and contrast agents develops, less contrast dose will likely be needed to produce the same image quality, and contrast agents will most likely have a higher safety profile, according to most industry insiders. “The most recent large trials regarding CT contrast have shown that the nephrotoxic effects of the iodinated contrast may be less than previously thought and possibly nonexistent,” Coopersmith says. “In addition, the safety steps we have already taken with gadolinium contrast, including limiting use to the most stable agents, keeping the dose as low as possible, and having heightened awareness around patients with severe kidney disease, have already resulted in no new cases of nephrogenic systemic fibrosis in the United States in more than a decade.”

As companies continue working to improve contrast dose safety, expect more development and deployment of software to assess and screen patients for their risk of contrast media-associated adverse outcomes, support safer contrast media dosing practices, and increase AI-powered patient selection for diagnostic procedures and utilization of advanced screening technology. “Imaging protocols will evolve, reducing [contrast media] doses to the minimum needed for diagnostic performance,” Hibberd says. “Advances in the image analysis, interpretation, and diagnostic capabilities of [contrast media]- enhanced scans will all play a key role in the evolution of modern precision care medicine.”

As someone deeply invested in advancing radiology practices, Jonisch anticipates several improvements in contrast dose safety in the future, including the potential discovery of safer and more effective contrast agents, utilization of AI-driven algorithms to predict and prevent adverse reactions, and more innovation, collaboration, and a commitment to patient safety. “I expect contrast dose safety in radiology to continue improving, ultimately benefiting patients and health care providers alike,” he says, citing several trends that will positively impact the field.

Jonisch anticipates “advances in MRI, which can occasionally replace contrast-enhanced CT scans, and better CT scanner technology, which will allow for lower radiation doses while obtaining decent images.” He also expects “AI-powered image reconstruction algorithms, which can provide diagnostic-quality images from low-dose CT scans.”

Keith Loria is a freelance writer based in Oakton, Virginia. He is a frequent contributor to Radiology Today.