MRI-Based Interstitial Fluid Velocity Analysis for Drug Delivery Efficiency Evaluation in Tumor

Area of Science:

• Biomedical Engineering
• Medical Imaging
• Oncology

Background:

• Tumor interstitial fluid (TIF) dynamics are crucial for microenvironment regulation and drug delivery.
• Conventional phase contrast MRI (PC-MRI) lacks sensitivity for slow interstitial flow.
• Previously developed vertical plane echo PC-MRI enhances signal-to-noise ratio for slow flow measurement.

Purpose of the Study:

• To determine TIF flow rate in human breast tumor xenografts using advanced PC-MRI.
• To investigate the relationship between contrast agent distribution and TIF flow rate.
• To understand how TIF velocity influences drug delivery within tumors.

Main Methods:

• Utilized a vertical plane echo PC-MRI sequence (Velocity Mapping) to measure TIF flow rate.
• Injected two contrast agents of different sizes (DTPA-Gd and NaGdF4-PEG) intravenously.
• Correlated contrast agent distribution patterns with TIF flow velocity maps.

Main Results:

• Small-molecule DTPA-Gd distribution correlated positively with high TIF flow areas near the tumor margin.
• Nanoparticle NaGdF4-PEG distribution peaked at 3 hours and correlated negatively with high TIF flow regions.
• Demonstrated distinct distribution patterns based on contrast agent size and TIF flow dynamics.

Conclusions:

• TIF flow velocity is a critical factor influencing the distribution of intravenously administered agents.
• Understanding TIF flow dynamics can optimize drug delivery strategies for solid tumors.
• Advanced MRI techniques offer valuable insights into tumor microenvironment and therapeutic delivery.