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We developed and validated a novel strategy based on subregionalization into mesenteric and antimesenteric borders on magnetic resonance enterography (MRE).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>We included 184 CD patients across two surgical and one follow-up cohorts. For 12 patients who underwent MRE and surgery (Cohort 1), MRE coregistration with ileal specimens was achieved for 88 sections using three-dimensional-printing and creeping fat information. Optimal multivariable MRE models for mesenteric border, antimesenteric border, and whole-circle regions were constructed referencing histological fibrosis and validated in another 21 patients (Cohort 2). The impact of this strategy on the prediction of disease progression was assessed in a retrospective follow-up cohort of 151 patients (Cohort 3).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Histological fibrosis scores were higher in mesenteric than antimesenteric regions in both surgical cohorts (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). MRE models showed the highest diagnostic accuracy for fibrosis in the mesenteric border (area under the receiver operating characteristic curve [AUROC] 0.91), followed by the antimesenteric border (AUROC 0.84), and the whole-circle (AUROC 0.77) regions in Surgical Cohort 1. In surgical Cohort 2, MRE also showed higher efficacy in mesenteric (AUROC 0.87) than antimesenteric border (AUROC 0.77). In Cohort 3, baseline fibrosis measurements in the mesenteric border (hazard ratio [HR] 9.25) had the greatest predictive value on disease progression\n                      <jats:italic>versus<\/jats:italic>\n                      other regions (HR 0.28\u20122.09).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Intestinal fibrosis demonstrates spatial heterogeneity. Subregionalization into mesenteric and antimesenteric borders improves MRE diagnostic power and may aid in predicting CD progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Relevance statement<\/jats:title>\n                    <jats:p>Mesenteric and antimesenteric border subregionalization on MRE advances fibrosis evaluation in CD by addressing the spatial heterogeneity of fibrosis, enabling tailored therapeutic strategies and identifying high-risk patients with disease progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Spatial heterogeneity of intestinal fibrosis in CD limits the diagnostic accuracy of conventional whole-region MRE analysis.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Fibrosis is more severe in the mesenteric than the antimesenteric border, with subregional MRE analysis outperforming whole-circle analysis in fibrosis detection.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Baseline mesenteric border fibrosis severity most strongly predicts CD progression, necessitating subregionalization for outcome prediction and management.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical Abstract<\/jats:title>\n                  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