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

Abstract

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 K trans and v e values remains insufficiently explored. Hypothesis: Two-dimensional cluster analysis may quantify the distribution of a tumor voxel subregion with a distinct range of K trans and v e 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 tumormicroenvironmental 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 K trans and v e 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 K trans at 0.040 min À1 and 0.116 min À1 , and v e 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 K trans and v e values.

Dynamic Contrast-Enhanced MRI in the Abdomen of Mice with High Temporal and Spatial Resolution Using Stack-of-Stars Sampling and KWIC Reconstruction

“…This analysis began with conversion of the time-dependent pixel intensity, S ( t ), to relaxation rate, R 1 (t) = 1/ T 1 (t), using the relation where TR is the repetition time, S 0 is the signal intensity prior to the bolus arrival, α is the flip angle used to acquire the dynamic data, and where and T 10 is the pre-contrast longitudinal relaxation time determined in the VFA experiment. The relaxation rates were then converted to contrast agent concentrations using the relation where r 1 = 4.6 s −1 mm −1 [ 36 ] is the relaxivity of the contrast agent in the tissue. Non-linear least-squares analysis was then used to fit the tissue concentration curves to the relation [ 22 ] where we have introduced the sub-script notation to indicate parameters associated with the tissue of interest (TOI) and reference region (RR), and are the adjustable parameters and values for the reference tissue parameters in muscle were assumed to be = 0.1 min −1 and = 0.1 [ 22 ].…”