Mapping cell density and hypoxia in glioblastoma using time-dependent diffusion MRI: improved cell density assessment...

Area of Science:

• Radiology
• Oncology
• Medical Imaging

Background:

• Tumor heterogeneity, including cell density and hypoxic fraction, impacts radiation therapy (RT) efficacy.
• Quantitative imaging biomarkers (QIBs) are crucial for personalizing RT through adaptive strategies.
• Time-dependent diffusion MRI (TDD-MRI) metrics offer potential for characterizing tissue microstructure.

Purpose of the Study:

• To biologically validate the novel Time-dependent diffusion contrast (TDDC) MRI method in glioblastoma patients.
• To compare the efficacy of TDDC as a biomarker against conventional diffusion MRI metrics.
• To assess the potential of TDDC for guiding adaptive radiation therapy.

Main Methods:

• 12 glioblastoma patients underwent pre-operative TDD-MRI.
• 27 image-guided biopsy specimens were collected for histological analysis of cell density and hypoxic fraction.
• TDDC, apparent diffusion coefficient (ADC), mean diffusivity (MD), and mean kurtosis (MK) were calculated at biopsy locations.

Main Results:

• TDDC showed a significant correlation with glioblastoma cell density (ρ=0.71, p=0.003).
• Conventional diffusion metrics (ADC, MD, MK) did not significantly correlate with cell density.
• No significant correlations were found between hypoxic fraction and any diffusion metrics.

Conclusions:

• TDDC is a clinically implementable TDD-MRI method that correlates with glioblastoma cell density.
• TDDC demonstrates superior performance as a cell density biomarker compared to conventional diffusion metrics.
• TDDC shows potential as a QIB for biologically guided adaptive radiation therapy.