Association between diffusion-weighted imaging and tumor matrix in liver cancer: a cross-sectional study.

Background: Imaging modalities can reflect the underlying histopathology of tumors. However, the precise interactions between histopathological microstructure and the resulting imaging phenotype remain elusive. Predicting histopathological features, including the extracellular matrix, in a non-invasive manner could improve clinical care of liver tumors. The present study used cross-sectional guided biopsy specimens to utilize accurate spatial biopsy localization to correlate magnetic resonance imaging (MRI) derived the apparent diffusion coefficient (ADC) values with collagen IV expression in various liver cancers. Methods: A total of 127 patients (n=68 female; 45.6%) with a mean age of 65.3±12.3 years were included in the analysis. Inclusion criteria were an available cross-sectional biopsy, available biopsy specimens and a pre-interventional MRI with diffusion-weighed imaging (DWI) sequence. The tumors included 45 patients (35.4%) with hepatocellular carcinoma (HCC), 26 patients (20.5%) with cholangiocellular carcinoma and 56 patients (44.1%) with liver metastases of various primary tumors. Prebioptic liver MRI with diffusion-weighted imaging was used to correlate ADC values with collagen IV expression obtained from liver biopsy. The ADC values were measured in a co-registered way with cross-sectional biopsy imaging to ensure the spatial concordance between imaging and histopathology. The stained area and signal intensity of the immunohistochemical staining were examined. Results: The mean average stained area of collagen IV was 32.6%±27.4% and the mean staining intensity was 2.03±1.01. HCC showed statistically less stained area compared to the other tumor types (analysis of variance P<0.0001). In the overall patient sample, there was no correlation between ADCmean and average stained area (r=0.05, P=0.55) and staining intensity (r=-0.04, P=0.60). In a subgroup analysis of HCC patients, there was a significant correlation between ADCmin and the staining intensity (r=-0.33, P=0.02). Conclusions: ADC values are not associated with collagen IV expression in liver tumors. The complex extracellular matrix is not reflected by the DWI signal, which can be discussed as mainly be influenced by the cellularity of the tumors. Further research is needed to investigate the complex interactions between histopathology and the resulting imaging phenotype of MRI for clinical care.