OBJECTIVE: To determine whether diffusion tensor imaging (DTI) parameters acquired with model-based DTI and model-free generalized Q-sampling imaging (GQI) re-constructions may noninvasively predict isocitrate dehydrogenase (IDH) mutational status in patients with grade 2-4 gliomas.METHODS: Forty patients with known IDH genotype (28 IDH wild-type; 12 IDH mutant) who underwent preoperative DTI evaluation on a 3-Tesla magnetic resonance imaging scanner were analyzed retrospectively. Absolute values obtained from model-based and model-free reconstructions were compared. Using the intraclass correlation coefficient, interobserver agreement was assessed for various sampling techniques. Variables having statistically significant distributions between IDH groups were subjected to a receiver operating characteristic (ROC) analysis. Using multivariable logistic regression analysis, independent predictors, if present, were identified and a model was developed.RESULTS: Six imaging parameters (3 from model-based DTI and 3 from model-free GQI reconstructions) showed statistically significant differences between groups (P < 0.001, power >0.97), with very high correlation to each other (P< 0.001). Age difference between the groups was statistically significant (P< 0.001). The optimal logistic regression model comprised a GQI-based parameter and age, which were independent predictors as well, producing an area under the ROC curve, accuracy, sensitivity, and specificity of 0.926, 85%, 75%, and 89.3%, respectively. Using the GQI reconstruction feature alone with a cut-off of 1.60, an 85% of accuracy was also achieved with ROC analysis.CONCLUSIONS: The imaging parameters acquired from model-based DTI and model-free GQI reconstructions, combined with the clinical variable age, may have the ability to noninvasively predict the IDH genotype in gliomas, either alone or in particular combinations.