The temporal and spatial patterns of nanoparticle that ferry both imaging and therapeutic agent in solid tumors is significantly influenced by target tissue movement, low spatial resolution, and inability to accurately define regions of interest (ROI) at certain tissue depths. These combine to limit and define nanoparticle untreated regions in tumors. Utilizing graph and matrix theories, the objective of this project was to develop a novel spectral Fiedler field (SFF) based-computational technology for nanoparticle mapping in tumors. The novelty of SFF lies in the utilization of the changes in the tumor topology from baseline for contrast variation assessment. Data suggest that SFF can enhance the spatiotemporal contrast compared to conventional method by 2-3 folds in tumors. Additionally, the SFF contrast is readily translatable for assessment of tumor drug distribution. Thus, our SFF computational platform has the potential for integration into devices that allow contrast and drug delivery applications.