Study of Diffusion Weighted Imaging Derived Diffusion Parameters as Biomarkers for the Microenvironment in Gliomas

Objectives: To explore the efficacy of diffusion weighted imaging (DWI)-derived metrics under different models as surrogate indicators for molecular biomarkers and tumor microenvironment in gliomas.

Methods: A retrospective study was performed for 41 patients with gliomas. The standard apparent diffusion coefficient (ADC_st) and ADC under ultra-high b values (ADC_uh) (b values: 2500 to 5000 s/mm²) were calculated based on monoexponential model. The fraction of fast diffusion (f), pseudo ADC (ADC_fast) and true ADC (ADC_slow) were calculated by bi-exponential model (b values: 0 to 2000 s/mm²). The apparent diffusional kurtosis (K_app) was derived from the simplified diffusion kurtosis imaging (DKI) model (b values: 200 to 3000 s/mm²). Potential correlations between DWI parameters and immunohistological indices (i.e. Aquaporin (AQP)1, AQP4, AQP9 and Ki-67) were investigated and DWI parameters were compared between high- and low-grade gliomas, and between tumor center and peritumor. Receiver operator characteristic (ROC) curve and area under the curve (AUC) were calculated to determine the performance of independent or combined DWI parameters in grading gliomas.

Results: The ADC_slow and ADC_uh at tumor center showed a stronger correlation with Ki-67 than other DWI metrics. The ADC_st, ADC_slow and ADC_uh at tumor center presented correlations with AQP1 and AQP4 while AQP9 did not correlate with any DWI metric. K_app showed a correlation with Ki-67 while no significant correlation with AQPs. ADC_st (p < 0.001) and ADC_slow (p = 0.001) were significantly lower while the ADC_uh (p = 0.006) and K_app (p = 0.005) were significantly higher in the high-grade than in the low-grade gliomas. ADC_st, f, ADC_fast, ADC_slow, ADC_uh, K_app at the tumor center had significant differences with those in peritumor when the gliomas grade became high (p < 0.05). Involving ADC_uh and K_app simultaneously into an independent ADC_st model (AUC = 0.833) could further improve the grading performance (ADC_st+ADC_uh+K_app: AUC = 0.923).

Conclusion: Different DWI metrics fitted within different b-value ranges (low to ultra-high b values) have different efficacies as a surrogate indicator for molecular expression or microstructural complexity in gliomas. Further studies are needed to better explain the biological meanings of these DWI parameters in gliomas.