Nanoparticles with "K-edge" Metals Bring "Color" in Multiscale Spectral Photon Counting X-ray Imaging

Preclinical and clinical diagnostics depend greatly on medical imaging, which enables the identification of physiological and pathological processes in living subjects. It is often necessary to use contrast agents to complement anatomical data with functional information or to describe the disease phenotypically. Nanomaterials are used as contrast agents in many advanced bioimaging techniques and applications because of their high payload, physicochemical properties, improved sensitivity, and multimodality. Metals with k-edge energy within the X-ray bandwidth respond to photon counting and spectral X-ray imaging. This Perspective examines the progress made in the emerging area of nanoparticle-based k-edge contrast agents. These nano "k-edge" particles have been explored with spectral photon counting CT (SPCCT) for multiplexed molecular imaging, pushing the boundaries of resolution and capabilities of CT imaging. Design considerations, contrast properties, and biological behavior are discussed in detail. The key applications are highlighted by categorizing these nanomaterials based on their X-ray, k-edge energy, and biological properties, as well as their synthesis, functionalization, and characterization processes. The article delves into the transformative impact of nano "k-edge" particles on early disease detection and other biomedical applications. The review provides further insights into how the "k-edge signatures" of these nanoparticles combined with photon counting technique can be leveraged for quantitative, multicontrast imaging of diseases. We also discuss the status quo of clinically approved nanoparticles for imaging and highlight the challenges such as toxicity and clearance as well as promising clinical perspectives, providing a balanced view of the potential and limitations of these nanomaterials. Furthermore, we discuss the necessary future research efforts required to clinically translate nano "k-edge" particles as SPCCT contrast agents for early disease diagnosis and tracking.