Gd-BOPTA offers both imaging properties of conventional extracellular MR agents as well as an uptake by hepatocytes with a biliary excretion of 5%. Due to this pharmacodynamic, the MRI protocole includes an arterial phase (30-35 sec), a portal phase (60-70 sec), a delayed phase (2-3 min) and a hepatobiliary phase (90-120 min).
It is used to characterise lesions that contain bile ducts (dysplastic nodules in cirrhotic patients and focal nodular hyperplasia in non-cirrhotic patients) from lesions like hepatocellular carcinoma (HCC), adenoma and metastasis. In addition, its biliary excretion can be useful in the imaging of the biliary tract, with the advantages of a better spatial resolution in comparison with the classical MRI Cholangiography.
Focal Nodular Hyperplasia
Represents a hyperplastic growth of normal hepatocytes with a malformed biliary draining system, around a central fibrous scar with a dystrophic arterial vessel. It appears iso- or hypointense on T1-WI, and iso- or slightly hyperintense on T2-WI. In approximately 50%-84% of cases, the central scar can be seen with low signal intensity on T1-WI and moderate high signal on T2-WI. On postcontrast images, FNHs show typical enhancement pattern: early arterial homogeneous enhancement (Fig. 2), which becomes isointense to the background liver on portal venous phase, and late enhancement of the central scar (Fig. 3). No washout is seen with FNH. Histologically, focal nodular hyperplasia consists of functional hepatocytes associated with abnormal blind-ending biliary ductules, which do not communicate with larger bile ducts. Hence, biliary excretion is slow compared with that of normal liver. In addition, the density of hepatocytes is increased in focal nodular hyperplasia compared with that of normal liver. At imaging with hepatobiliary-specific agents in the delayed phase, focal nodular hyperplasia becomes iso- to hyperintense because of retained contrast agent and the high density of hepatocytes (Fig. 4).
Adenomas
Unlike FNH, adenomas are considered true neoplasms, being histologically characterized by a proliferation of pleomorphic hepatocytes without normal lobular architecture, devoid of bile ducts.
The largest ones tend to present signal heterogeneity, with mild to moderate hypersignal on T2-weighted (Fig. 5), hyposignal on T1-weighted sequences, homogeneous or heterogeneous arterial contrast-enhancement (Fig. 6), late washout (Fig. 7), and possible development of a capsule (distinct characteristics depending upon the type of adenoma - inflammatory, beta catenin mutated or TCF1/HNF1alpha mutated). At the hepatobiliary phase, they appear hypointense to the surrounding parenchyma (Fig. 8) This is due to the smaller expression of OATP1 as well as their lack of biliary ducts which results in a deficiency in bilirubin and hepatobiliary contrast excretion.
Being able to differentiate between FNH and adenoma, especially when multiple and coexisting in the liver parenchyma is extremely important in order to limit the number of biopsies and to guide the surgical treatment, given adenoma’s risk of haemorrhage and malignant degeneration.
Hepatocellular Carcinoma
HCC is a malignant neoplasm with hepatocellular origin that has been proved to develop by a multistep carcinogenesis from a low grade dysplastic nodule to an overt HCC, in a progressive dedifferentiation and neoangiogenesis phenomena.
Classic MRI findings of HCC include slightly low signal intensity on T1-WI, tissular high signal intensity on T2-WI, increased heterogeneous arterial enhancement (Fig. 9), and washout with fibrous tumor capsule enhancement on the delayed phase (Fig. 10).
During the carcinogenesis process, there is a progressive decrease in the expression of the OATP 8 in the hepatocytes [3], which results in a non-uptake by malignant liver nodules that appear hypointense at the hepatobiliary phase. As such, hepatobiliary contrast uptake by HCC depends on its differentiation stage. Well-differentiated HCCs contain functioning hepatocytes and might show hepatobiliary contrast uptake. On the other hand, poorly-differentiated or undifferentiated hepatocarcinomas do not contain functioning hepatocytes and do not show hepatobiliary contrast uptake, remaining hypointense in relation to the surrounding parenchyma (Fig. 11).
Dysplastic nodules
As opposed to HCC, regenerative and low-grade dysplastic nodules show iso-enhancement to the surrounding liver parenchyma by presenting a preferentially portal vascularisation. High-grade dysplastic nodules classically present an iso to high signal on T1-WI (Fig. 12) and iso signal intensity on T2-WI. As they begin to lose portal vascularisation and start gaining abnormal arterial supplies, they may show intense early enhancement (Fig. 13) and fade to isointensity, but do not show washout (Fig. 14).
Regenerative and both low-grade and high-grade dysplastic nodules are composed of functioning hepatocytes, so they all present the same hepatobiliary contrast uptake as the surrounding parenchyma (Fig. 15).
Patients with the diagnosis of high-grade dysplastic nodules are at higher risk of developing HCC and should have closer follow-up MRI.
Metastasis
On MRI, hepatic metastases have variable appearances depending on the primary tumor.
As metastatic tumors do not contain functioning hepatocytes or biliary ducts, they do not show contrast uptake during the hepatobiliary phase, resulting in a high contrast between enhancing liver tissue and metastases (Fig. 16).
Hepatobiliary contrast increases MRI’s sensitivity to detect liver hypo- and hyper vascular metastasis (Fig. 17), particularly the small-sized ones.