Tumor macrophage response to therapy is conventionally detected with iron nanoparticle-enhanced MRI. However, endogenous cellular iron detection methods exist that can bypass caveats intrinsic to contrast agent use. We demonstrate that contrast-agent free multi-gradient echo R2* relaxometry iron MRI and machine vision analysis approaches can map tumor macrophage iron deposits and detect cellular response to metabolic and immunotherapy in preclinical models of breast cancer. Feasibility of endogenous macrophage imaging is shown, and the value of the cellular MRI biomarker is demonstrated as a function of treatment and tumor model.
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