Abstract

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.

Highlights

  • The proposed spectral Fiedler field (SFF) methodology utilize graph and matrix theories to assess changes in surface topology from baseline

  • A typical example of such artifacts and noise is highlighted in Fig. 3b–e over a 20 min imaging period. These are complicated further by imperfect matching of the skin surface during the motion compensation. Both of these spurious contrast signal are removed by the SFF-US imaging method (Fig. 3f–i)

  • The objective of this study was to test the feasibility of SFF-US methodology for tumor mapping of nanoparticle in a murine colon cancer model

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Summary

Introduction

The proposed SFF methodology utilize graph and matrix theories to assess changes in surface topology from baseline. The deviations from reference geometry (i.e. subtle contrast changes vs baseline) are transformed as quantifiable-flooded contour plots following nanoparticle injection. This innovative feature of SFF precisely measures the mismatch in tumor contrast in solid tumors over-time. When stabilized by a lipid shell, the Laplace pressure, which is the pressure difference between the inside and the outside of an ultrasound (US) contrast agent (perfluoropentane, PFP) changes with the boiling temperature[18] Their poor resolution in the liquid state, and dynamic changes in the contrast with temperature can be an excellent model system for understanding the feasibility of SFF imaging approaches of nanoparticles in solid tumors. Our in vivo data suggest that the innovative SFF topological imaging approach has high sensitivity of detection for clinical applications

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