Spatial distribution of fractionally administered holmium microspheres in non-tumorous human liver tissue: how livers survive transarterial radioembolisation.

Abstract

Background: Relatively high mean absorbed doses to the non-tumorous liver tissue (NTLT) are generally well tolerated in transarterial radioembolisation (TARE), potentially due to a heterogeneous dose distribution. This study investigates the macroscopic and microscopic distribution of fractionally administered TARE holmium microspheres in NTLT using an experimental setup of ex vivo perfused human donor livers under magnetic resonance imaging (MRI), and validates these findings through a comparison with MRI data from TARE-treated patients.

Results: MRI-based dose maps of the TARE-treated ex vivo livers and patients revealed a heterogeneous dose distribution pattern throughout the NTLT (heterogeneity index (HI) range 2.96-10.11). Microscopic analysis confirmed this, as a wide variation in the percentage of tissue within 2.1 mm of microspheres (5.4%-84.3%) was observed. Microspheres administered in consecutive fractions decreased the heterogeneity, which was observed macroscopically by a decreased HI, and microscopically by the formation of new microsphere clusters. However, this HI decrease appeared finite, and new clusters formed near existing clusters, maintaining the overall distribution pattern.

Conclusions: TARE induces a heterogeneous dose distribution pattern in human NTLT. This heterogeneous dose distribution pattern persists across additional microsphere fractions, leaving parts of the NTLT unexposed to lethal doses of ionising radiation. Combined with the regenerative capacity of the liver, this may explain why relatively high mean absorbed doses to the NTLT are generally well tolerated in TARE.

Registration: For validation purposes, clinical data from patients who participated in a previous study (ClinicalTrials.gov, identifier NCT04269499, registered on February 13, 2020) was analysed in the current study.