ObjectiveTo explain adult-type diffuse gliomas heterogeneity through diffusion kurtosis imaging-based habitat characteristics and develop and validate a comprehensive model for predicting isocitrate dehydrogenase (IDH) status.Materials and methodsIn this prospective secondary analysis, 103 participants (mean age, 52 years; range, 21-77; 54 [52%] male) pathologically diagnosed with adult-type diffuse gliomas were enrolled between June 2018 and February 2022. The Otsu method was used to generate habitat maps with mean diffusivity (MD) and mean kurtosis (MK) for a total of 4 subhabitats containing 16 habitat features. Habitat heatmaps were created based on the Pearson correlation coefficient. The Habitat imAging aNd clinicraD INtegrated prEdiction SyStem (HANDINESS) was created by combining clinical features, conventional MRI morphological features, and habitat image features. ROC, calibration curve, and decision curve analyses were used to select the optimal model after 32 pipelines for model training and validation.ResultsIn the restricted diffusion and high-density subhabitat, MK was highly correlated with MD (R2 = 0.999), volume (0.608) and percentage of volume (0.663), and this region had the highest MK value (P<.001). The unrestricted diffusion and low-density subhabitat had the highest MD value (P<.001). When MK was less than the Otsu threshold, there was still a difference between restricted diffusion and low-density and unrestricted diffusion and low-density subhabitats (P<.01). The HANDINESS enabled more accurate prediction of the IDH status in the training (AUC=0.951 [0.902-0.987]) and internal validation cohorts (0.938 [0.881-0.949]). AUC values for single-modality models and independent factors ranged from 0.593 to 0.916. Calibration and decision curve analyses showed that the HANDINESS demonstrated a high level of clinical applicability and predictive consistency.ConclusionDiffusion kurtosis imaging-based habitat analysis provides additional important information on microscopic tumor spatial heterogeneity. The HANDINESS has higher diagnostic performance and robustness than single-modality models.