Voxelwise and Patientwise Correlation of 18F-FDOPA PET, Relative Cerebral Blood Volume, and Apparent Diffusion Coefficient in Treatment-Naïve Diffuse Gliomas with Different Molecular Subtypes

Abstract

Our purpose was to identify correlations between ¹⁸F-fluorodihydroxyphenylalanine (¹⁸F-FDOPA) uptake and physiologic MRI, including relative cerebral blood volume (rCBV) and apparent diffusion coefficient (ADC), in gliomas with different molecular subtypes and to evaluate their prognostic values. Methods: Sixty-eight treatment-naïve glioma patients who underwent ¹⁸F-FDOPA PET and physiologic MRI were retrospectively selected (36 with isocitrate dehydrogenase wild-type [IDH_wt], 16 with mutant 1p/19q noncodeleted [IDH_m-noncodel], and 16 with mutant codeleted [IDH_m-codel]). Fluid-attenuated inversion recovery hyperintense areas were segmented and used as regions of interest. For voxelwise and patientwise analyses, Pearson correlation coefficients (r_voxelwise and r_patientwise) between the normalized SUV (nSUV), rCBV, and ADC were evaluated. Cox regression analysis was performed to investigate the associations between overall survival and r_voxelwise, maximum or median nSUV, median rCBV, or median ADC. Results: For IDH_wt and IDH_m-noncodel gliomas, nSUV demonstrated significant positive correlations with rCBV (r_voxelwise = 0.25 and 0.31, respectively; r_patientwise = 0.50 and 0.70, respectively) and negative correlations with ADC (r_voxelwise = -0.19 and -0.19, respectively; r_patientwise = -0.58 and -0.61, respectively) in both voxelwise and patientwise analyses. IDH_m-codel gliomas demonstrated a significant positive correlation between nSUV and ADC only in voxelwise analysis (r_voxelwise = 0.18). In Cox regression analysis, r_voxelwise between nSUV and rCBV (hazard ratio, 28.82) or ADC (hazard ratio, 0.085) had significant associations with overall survival for only IDH_wt gliomas. Conclusion: IDH_m-codel gliomas showed distinctive patterns of correlations between amino acid PET and physiologic MRI. Stronger correlations between nSUV and rCBV or ADC may result in a worse prognosis for IDH_wt gliomas.

Keywords: 18F-FDOPA PET; ADC; correlation coefficient; glioma; rCBV.

Graphical abstract

FIGURE 1.

Example of postprocessing and segmentation in 36-y-old man with treatment-naïve WHO grade IV, IDH_wt, MGMT-unmethylated, and EGFR-amplified glioblastoma. ROIs of FLAIR hyperintense region are overlaid on ¹⁸F-FDOPA, rCBV, and ADC maps. A scatterplot extracted from ROI is shown with r_voxelwise between nSUV and rCBV or ADC. Median nSUV, rCBV, and ADC (green lines) are also shown.

FIGURE 2.

r_voxelwise between nSUV and rCBV (A) and between ¹⁸F-FDOPA uptake and ADC (B). All comparisons with ANOVA have P values of less than 0.002. Bars denote mean value and 95% CI. *Mean P < 0.05. **Mean P < 0.01. ***Mean P < 0.001.

FIGURE 3.

r_patientwise between median nSUV and rCBV or ADC in IDH_wt (all grades) (A), IDH_wt (grades II and III) (B), IDH_m-noncodel (C), and IDH_m-codel (D). There are no significant differences in strength of correlation coefficients for median nSUV and rCBV among different molecular subtypes. Correlation coefficient of median nSUV and ADC is significantly weaker in IDH_m-codel than in IDH_wt (all grades, P = 0.016; grades II and III, P = 0.042) or IDH_m-noncodel (P = 0.032).

FIGURE 4.

Receiver-operating-characteristic curve to differentiate IDH_m-codel from IDH_wt and IDH_m-noncodel gliomas. AUC = area under curve.