Hepatobiliary and pancreatic imaging

Sequences

Our hepatobiliary/pancreatic protocol consists of a noncontrast-enhanced whole-body PET/MRI acquisition and a dedicated contrast-enhanced upper abdominal PET/MRI acquisition. The incubation time for either FDG or SSTR agonists ranges between 45 and 60 min.

The whole-body noncontrast-enhanced PET/MRI is acquired from the mid-thighs to the base of the neck and consists of a two-point Dixon sequence for attenuation correction, an axial T2-weighted half-Fourier acquisition single-shot turbo spin-echo (HASTE/SSFSE), and an axial simultaneous multislice (SMS) diffusion-weighted imaging (DWI) sequence. SMS-DWI, when compared to standard single-shot echo-planar imaging (SSEPI) DWI, decreases acquisition time by roughly 50% while maintaining or even improving sensitivity, according to our initial unpublished data.

The dedicated upper abdominal protocol includes the following sequences: precontrast coronal T2-weighted HASTE, axial T2-weighted fat-suppressed fast spin-echo (FSE), axial T1-weighted Dixon, and finally dynamic contrasted-enhanced (CE) sequences. Most commonly, extracellular gadolinium-based contrasts are used. Alternatively, hepatocyte-specific contrast agents, such as gadoxetate, may be used for the detection and assessment of focal liver lesions. Magnetic resonance cholangiopancreatography (MRCP) sequences may be added in the case of biliary or pancreatic cancers. The entire examination lasts 45–60 min.

Radiopharmaceuticals

FDG is the workhorse radiopharmaceutical in most hepatobiliary and pancreatic imaging. When using FDG, we recommend ≥6 h fasting before PET/MRI scanning to ensure adequate glucose/insulin homeostasis, with a target blood glucose level of less than 200 mg/dL ( ). In patients with diabetes or poorly controlled blood glucose levels, due to severe pancreatic pathologies or post pancreatectomy, short-acting insulin may be administered to bring the blood glucose level to a more acceptable value before injecting FDG ( ; ). Ideally, the interval between insulin injection and FDG administration should be at least 1 h ( ). In insulin-dependent diabetic patients, we recommend fasting for ≥4 h.

While higher blood glucose levels may not significantly impact the physiologic FDG uptake in organs other than the brain ( ; ), tumor uptake may be altered, thus rendering semiquantitative parameters such as the standardized uptake value (SUV) both unreliable and unreproducible. A possible workaround in these instances is a correction of SUV to the blood glucose level ( ).

FAPI is a very promising radiopharmaceutical to assess cholangiocarcinomas and hepatocellular carcinomas (HCC), with reported sensitivities of 85.7%–100% in mixed cholangiocarcinoma/HCCs populations. Moreover, in primary hepatic malignancies, the reported tumor to background ratio is way higher with FAPI (15.18) than with FDG (2.08) ( ; ; ; ).

In well-differentiated neuroendocrine tumors, SSTR agonists radiopharmaceuticals are used, such as ⁶⁸ Ga-DOTATOC or ⁶⁸ Ga-DOTATATE ( ; ). On the other hand, in the case of poorly differentiated neuroendocrine tumors, with low expression of SSRT but high mitotic activity and sheer glycolytic metabolism, FDG is a more ideal option.

For HCC, ¹⁸ F or ¹¹ C-Coline, and ⁶⁸ Ga-PSMA are options, potentially better than FDG ( ; ). ⁶⁸ Ga-PSMA PET, predominantly used in prostate cancer imaging, is also taken up by benign entities and other malignancies, including HCC, as it binds to neovasculature ( ; ; ; ). ¹¹ C-labeled acetate ( ¹¹ C-ACT) and ¹⁸ F-Fluorocholine (CHOL) have also been used to evaluate HCC.

Hepatocellular carcinoma

HCC is the most common primary liver cancer and the third cause of cancer-related deaths worldwide ( ; ; ) HCC is increasing in incidence, with risk factors including cirrhosis and chronic viral hepatitis ( ; ). Early imaging diagnosis of HCC is critical, as there is curative potential with surgical resection or liver transplantation in early-stage tumors.

Current standard of care imaging

When evaluating hepatic lesions, MRI has high accuracy in the identification and characterization of HCC and better delineates intrahepatic lesions when compared to CT or PET/CT, commonly obviating the need for tissue confirmation. FDG-PET alone is not typically used in the evaluation of HCC, due to its low overall sensitivity of approximately 64% ( ; ). This is in part explained by the stronger enzymatic activity of well-differentiated HCC, resulting in less FDG uptake, compared to possibly high and heterogeneous uptake of background liver.

However, since tissue sampling is uncommonly needed for diagnosis, the biological behavior of these tumors is often unknown; this is a potential area where FDG-PET may provide additional information. While well-differentiated HCC demonstrates less FDG uptake, poorly differentiated HCC has weaker enzymatic activity ( ), which leads to increased FDG uptake in up to 40% of cases Fig. 11.1 .

Therefore, it may be possible to predict the degree of differentiation of HCC based on its FDG uptake, providing insight into tumor biology and prognosis. Poorly differentiated HCC also tends to recur and metastasize, making whole-body imaging with FDG-PET more useful ( ), as FDG-PET has a high sensitivity for detecting distant extrahepatic metastases ( ; ). FDG-PET/CT can also differentiate neoplastic from bland portal venous thrombosis, which can also affect prognosis, therapeutic approach, and eligibility for liver transplantation ( Fig. 11.2 ). Therefore, FDG-PET can be considered for initial HCC staging of candidates for hepatic resection (HR) or transplantation ( ).

In terms of prognostic implication, FDG uptake can also predict therapeutic response and provide information about the risk of recurrence after surgery or transplant ( ; ). Moreover, the tumor-to-liver FDG uptake ratio can predict microvascular invasion ( ). Hypermetabolism on PET has been related to early recurrence of HCC after orthotopic liver transplant, and, when combined with elevated alpha-fetoprotein levels, can provide even greater predictive value.

Regarding post-treatment evaluation, FDG-PET has been used to evaluate early response after transarterial chemoembolization (TACE), by quantifying differences in SUV of the HCC before and after TACE ( ; ; ). Other studies demonstrated increased sensitivity of PET/CT over CT or MRI alone for detecting recurrence after radiofrequency ablation ( ).

In recent studies, ⁶⁸ Ga-PSMA PET has demonstrated high sensitivity in detecting primary HCC (97%, comparable to CT) and distant metastases (100%, outperforming CT) ( ). PSMA-PET led to management changes in 33% of the patients. A separate study showed PSMA uptake in all 15 patients with HCC, without significant differences in SUV measurements or tumor-to-liver ratios between untreated and previously treated patients ( ). Moreover, in the setting of HCC, PSMA-PET detects more lesions than FDG-PET/CT ( ). Unlike CT and MRI, PSMA-PET allows for adequate evaluation even if the background parenchyma has architectural and anatomic abnormalities ( ).

¹¹ C- and ¹⁸ F-Fluorocholine (CHOL) are other promising radiopharmaceuticals for the evaluation of HCC, with improved tumor-to-background contrast ( ) and high sensitivity for intrahepatic HCC (89%) and extrahepatic metastases (100%) ( ; ; ; ).

FAPI is an extremely appealing radiopharmaceutical for evaluating HCC; according to preliminary studies, its uptake is inversely correlated to HCC grading and directly correlated to HCC size. FAPI tends to outperform FDG in local and whole body staging. Reported sensitivities for detecting intrahepatic HCC with FAPI and FDG were 68.8% versus 18.8% in tumors <2 cm, 100% versus 81.8% in tumors 2–5 cm, and 100% for both in HCC >5 cm ( ).