MRI analysis to map interstitial flow in the brain tumor microenvironment.

Area of Science:

• Neuro-oncology
• Biophysics
• Medical Imaging

Background:

• Glioblastoma (GBM) is an aggressive brain tumor characterized by extensive invasion.
• Interstitial fluid flow (IFF) is implicated in GBM cell invasion, but its characteristics in vivo are poorly understood.
• Characterizing IFF is crucial for elucidating GBM invasion mechanisms.

Purpose of the Study:

• To develop and validate a noninvasive technique for measuring interstitial fluid flow velocities in glioma models.
• To characterize the velocity, direction, and heterogeneity of IFF within the glioma microenvironment.
• To compare the developed method with traditional markers like Evans blue.

Main Methods:

• Development of a dynamic contrast-enhanced MRI (DCE-MRI) technique to measure IFF velocities.
• Utilized in vitro phantom models and in silico velocity vector field models for validation.
• Applied the method to four human GBM cell line xenograft models in mice.
• Compared MRI-derived IFF data with Evans blue staining.

Main Results:

• The DCE-MRI technique successfully measured average interstitial flow velocities and reconstructed velocity directions in glioma models.
• IFF velocity magnitudes were consistent across different GBM xenografts and not correlated with tumor size.
• Fluid flow direction was heterogeneous within and around tumors, not uniformly outward.
• Evans blue was validated as a marker for high/low IFF rates and outward flow.

Conclusions:

• This novel DCE-MRI approach provides unprecedented insights into interstitial fluid flow dynamics in glioma models.
• The findings reveal complex and heterogeneous IFF patterns, challenging assumptions about uniform outward flow.
• The translatable technique offers a valuable tool for preclinical and clinical research in brain tumors.