Liver diseases are on the rise. Hepatocellular contrast agents have become a main asset for HCC screening, diagnosis and patient management, for evaluating metastatic disease and for differentiating focal nodular hyperplasia from adenomas.

Developments in Liver Imaging Over Time

Liver disease is on the rise, both hepatocellular carcinoma – especially due to alcoholic cirrhotic disease and viral hepatitis – and secondary disease, i.e., metastases. Both pose different challenges and require different imaging protocols. To gain insight into the latest liver imaging developments and understand their clinical implications, Bayer invited two renowned US liver experts for an interview session at RSNA.

Alexander C. Kagen, Mount Sinai Morningside Hospital, New York, USA, spotlighted three major developments in hepato-radiology:

1. Continuous scanner technology improvement in both CT and MRI,
2. Reporting standardization and education with LI-RADS,
3. Evolution of cirrhosis and its relation to viral hepatitis and the rise of fatty liver disease

For Rajan Gupta, Duke University, Durham, NC/USA, Primovist^®/Eovist^® is also a critical element in key areas, such as

1. Differentiating focal nodular hyperplasia against adenomas,
2. Evaluating metastatic disease, and
3. Figuring out whether “a lesion is real or not”. Due to the dual blood supply of the liver, multiple vascular phenomena may appear. However, if a lesion is hypervascular on the arterial phase, but shows low signal on the hepatobiliary phase, it is really a clinically relevant lesion.

In Kagen’s institution, the majority of HCC cases default to Primovist^®/Eovist^®, but radiologists also use it for HCC screening. As OATP-receptors are downregulated earlier than cancers become hypervascular, lesions can be detected earlier with hepatobiliary phase imaging.

However, there are some exceptions: Primovist^®/Eovist^® is not used in suspected or known hemangioma, recent local-regional therapy such as radiofrequency ablation or TACE, and in evaluating for initial treatment response. Patients with severe hepatic failure or severe renal failure do not receive Primovist^®/Eovist^®, since both conditions may impair Primovist^®/Eovist^® imaging performance.

Hepatobiliary Imaging for Metastatic Cancer

Imaging liver metastases is an entirely different routine. Gupta considers the hepatobiliary phase key to finding new and smaller metastases. In the hepatobiliary phase, all metastases will be hypointense – both hypervascular and hypovascular ones. 
“This knowledge is essential to choose the right treatment option”, he said.

Acute Transient Dyspnea

Acute transient dyspnea is a reported unwanted effect with Primovist^®/Eovist^®.
Gupta considers two preconditions necessary to deal with it: 1. understanding the concept of acute transient dyspnea and 2. knowing the ways to mitigate its impact. His institution manages this reaction very patient-oriented: “It really makes a big difference to let patients know that this condition exists – and that they should do their best to hold their breath”, he said.

He and his team run three arterial phases, which effectively mitigates the effects of acute transient dyspnea on a single arterial phase – as there are two additional phases to get the critical diagnostic information. Double arterial phases phase imaging also works.
Kagen mitigates this reaction by slowing down the injection rate to 1 mL per second and by lowering the resolution of image acquisition to e.g., an arterial phase matrix of 1.92 by 1.28 – therefore allowing for a double arterial phase. This translates into 8-10 seconds of breath hold for each phase of this acquisition.

Focus on Protocols

Kagen advises focusing on protocols. These are his recommendations:

1. Just adding the hepatobiliary phase to the usual liver MRI protocol will not work – because this means losing some of the unique benefits of Primovist^®/Eovist^®. The whole protocol should instead be adjusted for maximum value, especially since the hepatobiliary phase needs to be optimized with technical solutions and sequences.
2. Technologists should be engaged to look at the images during acquisition. “Your technologist can really pick up some issues you may find,” said Kagen.
3. The team needs to adapt the protocol to fit in the prescribed throughput time windows.
4. Focusing on the concept of multiple arterial phases helps, followed by portal-venous phases and venous phases, and then the hepatobiliary phase with similar imaging parameters, so image subtraction can be performed. The time between the venous phases and the hepatobiliary phases should be used for T2 and diffusion-weighted imaging.

Navigating the hepatobiliary phase is an option, if the patients cannot hold their breath – new scanners have this ability. This can be repeated as needed with multiple breath-holds. 
Gupta advised increasing the flip angle to 30°, if possible, and using 3D fat sat grading echo sequences. In addition, it is essential to acquire coronal and axial to ensure visualization of lesions under the diaphragm and below the heart.

Hepatobiliary Imaging and LI-RADS

Gupta and his team use LI-RADS, as it is highly effective in the accurate diagnosis and management of HCC, “It has really helped to homogenize the language we use – I think it is here to stay and it continues to be iterated”, he said.
For utilizing LI-RADS criteria with Primovist^®/Eovist^®, LI-RADS holds a section devoted to hepatobiliary contrast agents.
With Primovist^®/Eovist^®, washout is an essential concept. Wash-out can only be observed in the dynamic phases of contrast, specifically the arterial and portal-venous phases of imaging. However, it is critical to realize that washout cannot be used for the hepatobiliary phase. 
The heatobiliary phase has a major impact on determining the status of an arterially hyperenhancing lesion in cirrhotic patients; if there is no correlation on hepatobiliary phase imaging, it cannot be characterized as LI-RADS 5 and is likely not HCC.