Combined Dw-Mri and Dw-MRS Sensitivity to Glioma Tumour Microenvironment: A Preliminary Study

AIMS The glioma tumor microenvironment (TME) plays a major role in tumourigenesis of gliomas, encompassing a complex network of cells and biomolecules that contribute to radio-resistance and poor outcomes. Diffusion-weighted (DW) MRI probes tissue microstructure non-invasively with high sensitivity but lacks cel- lular specificity. However, metabolite diffusion-weighted MR spectroscopy (DW-MRS) sensitises MR spectra to diffusion of intracellular metabolites, providing information about specific cellular morphology. Here we com- bine DW-MRI and DW-MRS to non-invasively characterise cell-specific TME changes in patients diagnosed with a spectrum of gliomas. METHODS 10 patients (5 male, mean age 47.7 years, range 22-76 years with newly diagnosed glioma were recruited and imaged on 3T Philips Ingenia CX system following informed consent. DW-MRS analysis: Data were combined per DW condition and averaged over gradient direction for b-value. The LCModel estimates for total NAA (tNAA), total creatine (tCr) and total choline (tCho) were used to calculate the ADC for these metabolites. DW-MRI analysis: NODDI model was fitted to the last two shells (b=711 and b=2500s/mm2) to estimate neurite orientation disperson index, odiNODDI and intra-neurite volume fraction ficvfNODDI. VERDICT model was fitted to b values using in-house Matlab code to obtain: intracellular signal fraction ficvfVERDICT, cell radius RVERDICT, ex- tracellular and extravascular signal fraction feesVERDICT, radial and axial extracellular diffusivities diVERDICT and dhVERDICT. RESULTS Tumour tNAA’s ADC decreased compared to contralateral NAWM suggesting neuronal loss with a trend of de- creasing tNAA’s ADC with increased WHO grade. We also observed increased feesVERDICT, dhVERDICT and decreased ficvfNODDI with WHO grade suggesting TME-specific cellular loss. Tumour tCho’s ADC was slightly increased com- pared to NAWM suggesting glial activation/reaction but was stable across WHO grade. CONCLUSION Combined DW-MRI and DW-MRS measurements potentially offer novel characterization of the glioma TME, essential for understanding mechanisms of radio-resistance and for developing more effective therapies.