Quantifying Liver Heterogeneity via R2*-MRI with Super-Paramagnetic Iron Oxide Nanoparticles (SPION) to Characterize Liver Function and Tumor

SIMPLE SUMMARY: Super-paramagnetic iron oxide nanoparticles (SPIONs) are phagocytized by the hepatic Kupffer cells (KC) in the liver and shorten MRI signals within the volume of functional liver parenchyma (FLP) where KCs are found. However, malignant tumors lacking KCs exhibit minimal signal change, resulting in increasing liver heterogeneity. This study investigates whether SPIONs improve liver heterogeneity on R2*-MRI to characterize FLP and non-FLP (i.e., tumor, hepatic vessels, liver fibrosis and scarring associated with hepatic cirrhosis, prior liver-directed therapies or hepatic resection). By using SPIONs, liver heterogeneity was improved across two MRI sessions with and without an intravenous SPION injection, and the volume of FLP was identified in our auto-contouring tool. This is a desirable technique for achieving more accurate characterizations of liver function and tumors during radiation treatment planning. ABSTRACT: The use of super-paramagnetic iron oxide nanoparticles (SPIONs) as an MRI contrast agent (SPION-CA) can safely label hepatic macrophages and be localized within hepatic parenchyma for T2*- and R2*-MRI of the liver. To date, no study has utilized the R2*-MRI with SPIONs for quantifying liver heterogeneity to characterize functional liver parenchyma (FLP) and hepatic tumors. This study investigates whether SPIONs enhance liver heterogeneity for an auto-contouring tool to identify the voxel-wise functional liver parenchyma volume (FLPV). This was the first study to directly evaluate the impact of SPIONs on the FLPV in R2*-MRI for 12 liver cancer patients. By using SPIONs, liver heterogeneity was improved across pre- and post-SPION MRI sessions. On average, 60% of the liver [range 40–78%] was identified as the FLPV in our auto-contouring tool with a pre-determined threshold of the mean R2* of the tumor and liver. This method performed well in 10 out of 12 liver cancer patients; the remaining 2 needed a longer echo time. These results demonstrate that our contouring tool with SPIONs can facilitate the heterogeneous R2* of the liver to automatically characterize FLP. This is a desirable technique for achieving more accurate FLPV contouring during liver radiation treatment planning.