Liver Cancer Vascularity Driven by Extracellular Matrix Stiffness: Implications for Imaging Research

Area of Science:

• Biomedical Engineering
• Radiology
• Oncology

Background:

• Extracellular matrix stiffness impedes drug delivery by disrupting tumor vasculature.
• Tumor stiffness influences vascular phenotypes, detectable via cross-sectional imaging.
• Contrast-enhanced imaging can reveal the relationship between liver tumor stiffness and vascularity.

Purpose of the Study:

• To correlate extracellular matrix stiffness with imaging features from dynamic contrast-enhanced computed tomography (DCE-CT) and ultrasound (DCE-US).
• To investigate two rat hepatocellular carcinoma models with varying stiffness and vascular characteristics.

Main Methods:

• Evaluated tumor stiffness using 2D shear wave elastography and atomic force microscopy.
• Assessed tumor perfusion with DCE-US and DCE-CT.
• Analyzed tumor necrosis and CD34+ blood vessel characteristics (percentage, distribution, thickness).

Main Results:

• Distinct stiffness signatures and vascular phenotypes were observed between the Buffalo-McA-RH7777 and SD-N1S1 models.
• SD-N1S1 tumors were stiffer with scant vasculature; Buffalo-McA-RH7777 tumors were softer with richer, peripherally distributed vasculature.
• Softer tumors (Buffalo-McA-RH7777) exhibited significantly greater contrast enhancement on DCE-US and DCE-CT.

Conclusions:

• Tumor stiffness signatures correlate with distinct vascular phenotypes.
• 2D shear wave elastography and DCE-US effectively characterized stromal patterns and perfusion parameters.
• Imaging revealed significantly greater contrast enhancement in softer tumors, suggesting implications for drug delivery.