Magnetic Particle Imaging-Guided Thermal Simulations for Magnetic Particle Hyperthermia.

Magnetic particle hyperthermia (MPH) enables the direct heating of solid tumors with alternating magnetic fields (AMFs). One challenge with MPH is the unknown particle distribution in tissue after injection. Magnetic particle imaging (MPI) can measure the nanoparticle content and distribution in tissue after delivery. The objective of this study was to develop a clinically translatable protocol that incorporates MPI data into finite element calculations for simulating tissue temperatures during MPH. To verify the protocol, we conducted MPH experiments in tumor-bearing mouse cadavers. Five 8-10-week-old female BALB/c mice bearing subcutaneous 4T1 tumors were anesthetized and received intratumor injections of Synomag®-S90 nanoparticles. Immediately following injection, the mice were euthanized and imaged, and the tumors were heated with an AMF. We used the Mimics Innovation Suite to create a 3D mesh of the tumor from micro-computerized tomography data and spatial index MPI to generate a scaled heating function for the heat transfer calculations. The processed imaging data were incorporated into a finite element solver, COMSOL Multiphysics®. The upper and lower bounds of the simulated tumor temperatures for all five cadavers demonstrated agreement with the experimental temperature measurements, thus verifying the protocol. These results demonstrate the utility of MPI to guide predictive thermal calculations for MPH treatment planning.

Multiplexed ion beam imaging (MIBI) for characterization of the tumor microenvironment across tumor types.

An ability to characterize the cellular composition and spatial organization of the tumor microenvironment (TME) using multiplexed IHC has been limited by the techniques available. Here we show the applicability of multiplexed ion beam imaging (MIBI) for cell phenotype identification and analysis of spatial relationships across numerous tumor types. Formalin-fixed paraffin-embedded (FFPE) samples from tumor biopsies were simultaneously stained with a panel of 15 antibodies, each labeled with a specific metal isotope. Multi-step processing produced images of the TME that were further segmented into single cells. Frequencies of different cell subsets and the distributions of nearest neighbor distances between them were calculated using this data. A total of 50 tumor specimens from 15 tumor types were characterized for their immune profile and spatial organization. Most samples showed infiltrating cytotoxic T cells and macrophages present amongst tumor cells. Spatial analysis of the TME in two ovarian serous carcinoma images highlighted differences in the degree of mixing between tumor and immune cells across samples. Identification of admixed PD-L1+ macrophages and PD-1+ T cells in an urothelial carcinoma sample allowed for the detailed observations of immune cell subset spatial arrangement. These results illustrate the high-parameter capability of MIBI at a sensitivity and resolution uniquely suited to understanding the complex tumor immune landscape including the spatial relationships of immune and tumor cells and expression of immunoregulatory proteins.