New Cluster Analysis Method for Quantitative Dynamic Contrast‐Enhanced MRI Assessing Tumor Heterogeneity Induced by a Tumor‐Microenvironmental Ameliorator (E7130) Treatment to a Breast Cancer Mouse Model

Background Dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) can provide insight into tumor perfusion. However, a method that can quantitatively measure the intra‐tumor distribution of tumor voxel clusters with a distinct range of Ktrans and ve values remains insufficiently explored. Hypothesis Two‐dimensional cluster analysis may quantify the distribution of a tumor voxel subregion with a distinct range of Ktrans and ve values in human breast cancer xenografts. Study Type Prospective longitudinal study. Animal Model Twenty‐two female athymic nude mice with MCF‐7 xenograft, treated with E7130, a tumor‐microenvironmental ameliorator, or saline. Field Strength/Sequence 9.4 Tesla, turbo rapid acquisition with relaxation enhancement, and spoiled gradient‐echo sequences. Assessment We performed two‐dimensional k‐means clustering to identify tumor voxel clusters with a distinct range of Ktrans and ve values on Days 0, 2, and 5 after treatment, calculated the ratio of the number of tumor voxels in each cluster to the total number of tumor voxels, and measured the normalized distances defined as the ratio of the distance between each tumor voxel and the nearest tumor margin to a tumor radius. Statistical Tests Unpaired t‐tests, Dunnett's multiple comparison tests, and Chi‐squared test were used. Results The largest and second largest clusters constituted 44.4% and 27.5% of all tumor voxels with cluster centroid values of Ktrans at 0.040 min−1 and 0.116 min−1, and ve at 0.131 and 0.201, respectively. At baseline (Day 0), the average normalized distances for the largest and second largest clusters were 0.33 and 0.24, respectively. E7130‐treated group showed the normalized distance of the initial largest cluster decreasing to 0.25, while that of the second largest cluster increasing to 0.31. Saline‐treated group showed no change. Data Conclusion A two‐dimensional cluster analysis might quantify the spatial distribution of a tumor subregion with a distinct range of Ktrans and ve values. Level of Evidence 1 Technical Efficacy Stage 1