Assessment of Intratumor Heterogeneity in Parametric Dynamic Contrast-Enhanced MR Images: A Comparative Study of Novel and Established Methods

Intratumor heterogeneity is associated with aggressive disease and poor survival rates in several types of cancer. A novel method for assessing intratumor heterogeneity in medical images, named the spatial gradient method, has been developed in our laboratory. In this study, we measure intratumor heterogeneity in K (trans) maps derived by dynamic contrast-enhanced magnetic resonance imaging using the spatial gradient method, and we compare the performance of the novel method with that of histogram analyses and texture analyses using the Haralick method. K (trans) maps of 58 untreated and sunitinib-treated pancreatic ductal adenocaricoma (PDAC) xenografts from two PDAC models were investigated. Intratumor heterogeneity parameters derived by the spatial gradient method were sensitive to tumor line differences as well as sunitinib-induced changes in intratumor heterogeneity. Furthermore, the parameters provided additional information to the median value and were not severely affected by imaging noise. The parameters derived by histogram analyses were insensitive to spatial heterogeneity and were strongly correlated to the median value, and the Haralick features were severely influenced by imaging noise and did not differentiate between untreated and sunitinib-treated tumors. The spatial gradient method was superior to histogram analyses and Haralick features for assessing intratumor heterogeneity in K (trans) maps of untreated and sunitinib-treated PDAC xenografts, and can possibly be used to assess intratumor heterogeneity in other medical images and to evaluate effects of other treatments as well.