A Mechanistic Evaluation of Diffusion MRI for Glioma Cellularity
Abstract
Purpose
Cellular density (CD) in gliomas is of great clinical importance to guide treatment. A commonly used approach for estimating CD is based on imaging, by using Apparent Diffusion Coefficient (ADC) measurements derived from diffusion MRI. Cell membranes hindering diffusion, posits an inverse theoretic relationship between CD and ADC: as CD rises, ADC is expected to decrease. We set out to assess this relationship empirically. Materials and
Methods
Spatially localized biopsies (52 evaluable) were collected from 23 patients with untreated gliomas who underwent biopsy as part of a clinical trial, average 2.26 biopsies/patient, CD for each biopsy was measured as number of nuclei/mm2 with quantitative histopathology. The sample set was overweight for tumor and abnormal brain, and for balance, 52 mirror sites from contralateral normal appearing white matter were selected as “virtual biopsies”, with CD inferred from the published literature. CD predicted theoretically was compared and contrasted to empiric data.
Results
We found the inverse from what was expected theoretically, specifically, CD and ADC were moderately positively correlated. The theoretical approach predicts a negative correlation between cell density and ADC. Empiric data shows the slope to be positive.
Conclusion
Empiric correlations between cellular density and ADC values in glioma are at odds with one commonly used current theoretical framework, with empiric correlations reversed in sign from the expected. Revision of the current theoretical framework would be justified. Histopathological ground truth using empirical datasets are essential to inform future models.