Beyond Fixed Thresholds: Cluster-Derived MRI Boundaries Improve Assessment of Crohn’s Disease Activity

<b>Background/Objectives:</b> Crohn's disease (CD) requires precise, noninvasive monitoring to guide therapy and support treat-to-target management. Magnetic resonance enterography (MRE), particularly diffusion-weighted imaging (DWI), is the preferred cross-sectional technique for assessing small-bowel inflammation. Indices such as the Magnetic Resonance Index of Activity (MaRIA) and its diffusion-weighted variant (DWI MaRIA) are widely used for grading disease activity. This study evaluated whether unsupervised clustering of MRI-derived features can complement these indices by providing more coherent and biologically grounded stratification of disease activity. <b>Materials and Methods:</b> Fifty patients with histologically confirmed CD underwent 1.5 T MRE. Of 349 bowel segments, 84 were pathological and classified using literature-based thresholds (MaRIA, DWI MaRIA) and unsupervised clustering. Differences between inactive, active, and severe disease were analyzed using multivariate analysis of variance (MANOVA), analysis of variance (ANOVA), and <i>t</i>-tests. Mahalanobis distances were calculated to quantify and compare separation between categories. <b>Results:</b> Using MaRIA thresholds, 5, 16, and 63 segments were classified as inactive, active, and severe (Mahalanobis distances 2.60, 4.95, 4.12). Clustering redistributed them into 22, 37, and 25 (9.26, 24.22, 15.27). For DWI MaRIA, 21, 14, and 49 segments were identified under thresholds (3.59, 5.72, 2.85) versus 21, 37, and 26 with clustering (7.40, 16.35, 9.41). Wall thickness dominated cluster-derived separation, supported by diffusion metrics and the apparent diffusion coefficient (ADC). <b>Conclusions:</b> Cluster-derived classification yielded clearer and more biologically consistent separation of disease-activity groups than fixed thresholds, emphasizing its potential to refine boundary definition, enhance MRI-based assessment, and inform future AI-driven diagnostic modeling.