Recent Advances in Higher-Order, Multimodal, Biomedical Imaging Agents.

Advances in biomedical imaging have spurred the development of integrated multimodal scanners, usually capable of two simultaneous imaging modes. The long-term vision of higher-order multimodality is to improve diagnostics or guidance through the analysis of complementary, data-rich, co-registered images. Synergies achieved through combined modalities could enable researchers to better track diverse physiological and structural events, analyze biodistribution and treatment efficacy, and compare established and emerging modalities. Higher-order multimodal approaches stand to benefit from molecular imaging probes and, in recent years, contrast agents that have hypermodal characteristics have increasingly been reported in preclinical studies. Given the chemical requirements for contrast agents representing various modalities to be integrated into a single entity, the higher-order multimodal agents reported so far tend to be of nanoparticulate form. To date, the majority of reported nanoparticles have included components that are active for magnetic resonance. Herein, recent progress in higher-order multimodal imaging agents is reviewed, spanning a range of material and structural classes, and demonstrating utility in three (or more) imaging modalities.