# Synchrotron Radiation–Excited X-Ray Fluorescence (SR-XRF) Imaging for Human Hepatocellular Carcinoma Specimens

## TL;DR

This study explores how synchrotron X-ray imaging can reveal copper distribution in liver cancer, linking it to tumor characteristics and MRI signals.

## Contribution

The study introduces SR-XRF as a high-resolution, non-destructive method to map trace metals in hepatocellular carcinoma.

## Key findings

- Copper accumulation correlates with tumor differentiation and MRI signal intensity.
- SR-XRF provides detailed trace metal mapping with 1.0 µm spatial resolution.
- Higher copper tumor-to-liver ratios are observed in well-differentiated HCCs.

## Abstract

This study investigated the usefulness of SR-XRF to examine trace metal distribution in hepatocellular carcinoma by comparing the distribution of copper (Cu) and zinc in SR-XRF with histopathology and magnetic resonance imaging. SR-XRF provides important insights into the underlying pathophysiological processes of tumor formation and progression. The findings demonstrate a relationship between Cu accumulation and tumor differentiation and T1WI high signal intensity, which underscores the potential for the Cu tumor-to-liver ratio to serve as a marker of differentiation, contributing to diagnosis, prognosis estimation, and interpretation of stepwise tumor progression, ultimately bridging imaging, pathology, and elemental omics. This method integrates the requirements of “distribution” and “quantification” by allowing a non-destructive, multi-element, high-sensitivity mapping, which is difficult to achieve with conventional methods, thereby enabling evaluation of the boundary between the tumor and the surrounding liver, as well as tumor heterogeneity.

Background/Objectives: Trace metals, including copper (Cu) and zinc, are associated with the development and prognosis of hepatocellular carcinoma (HCC). However, their interference with magnetic resonance imaging (MRI) limits their use as potential biomarkers. This study investigated the usefulness of Synchrotron Radiation–excited X-ray Fluorescence (SR-XRF) imaging in studying the distribution of trace metals in HCC. Methods: This case–control study analyzed 33 specimens from 32 patients with HCC who underwent surgical resection (n = 29) or biopsy (n = 3) at Kobe University Hospital between December 1999 and November 2002. The findings of SR-XRF were compared with those of MRI and histopathology. Results: SR-XRF provided two-dimensional mapping of trace metal distribution with high spatial resolution (1.0 µm). The mean tumor-to-liver ratio (TLR) of Cu content was significantly higher in well-differentiated HCCs than in moderately and poorly differentiated HCCs (p < 0.05). Moreover, the mean TLRs of Cu content were significantly higher in high-intensity lesions than in iso- or low-intensity lesions on T1-weighted imaging (p < 0.05). Conclusions: This study supports previous evidence of the involvement of Cu in HCC development, suggesting its potential as a clinical biomarker for diagnosis and disease progression. Additionally, the results demonstrate that SR-XRF has potential for clinical application due to its ability to map trace metal distribution at high resolution. These findings suggest, rather than demonstrate, the association among Cu accumulation, tumor differentiation, and MRI signal characteristics.