Alternative Reference Regions for PET When Liver Has Diffuse Metastases
When diffuse liver metastases preclude using the liver as a reference region on PET imaging, use the spleen as the primary alternative reference organ, or alternatively the blood pool (descending aorta or mediastinal blood pool) for standardized uptake value (SUV) normalization.
Primary Alternative: Spleen
The spleen serves as the most reliable alternative reference organ when the liver is diffusely involved with metastatic disease, as it maintains relatively stable FDG uptake in most clinical scenarios and is not commonly affected by metastatic disease from most primary tumors 1.
The spleen provides consistent physiologic FDG uptake that can be used for background normalization and lesion-to-background ratio calculations when hepatic parenchyma is compromised 1.
Secondary Alternative: Blood Pool
The descending aorta or mediastinal blood pool can serve as alternative reference regions when both liver and spleen are unsuitable, though this approach has higher variability due to cardiac output fluctuations 1.
Blood pool measurements are particularly useful for calculating target-to-background ratios in scenarios where solid organ reference regions are unavailable or unreliable 1.
Clinical Context and Limitations
The liver normally serves as the reference region because it demonstrates relatively homogeneous physiologic FDG activity, with accuracy for detecting metastases reported at 92-100% when the parenchyma is normal 1.
When diffuse hepatic metastases are present, the heterogeneous FDG activity throughout the liver parenchyma makes it unsuitable as a reference standard for SUV calculations or visual interpretation 1.
For PSMA PET imaging specifically in prostate cancer patients, approximately 22.3% of liver metastases may be PSMA-negative and show SUV values lower than normal liver tissue, further complicating reference region selection 2.
Practical Implementation
Document which reference region is used in the imaging report, as this affects SUV calculations and serial comparison of disease burden 1.
When using alternative reference regions, maintain consistency across serial scans for the same patient to enable accurate assessment of treatment response 1.
Consider that false-positive FDG uptake can occur in the spleen due to infectious or inflammatory causes, though this is less common than in lymph nodes 1.