Nanoparticle Contrast Agents for Dark-Field X-ray Imaging

The poor soft tissue contrast of X-ray CT necessitates contrast agent use to improve diagnosis across disease applications, yet their poor detection sensitivity requires high injected doses, which restrict use in at-risk populations. Dark-field X-ray imaging is emerging as a more sensitive alternative to traditional attenuation-based imaging, leveraging scattered radiation to produce contrast. Yet aside from large, short-lived microbubbles, the alternate physics of dark-field detection has yet to be exploited for contrast agent development. Here we demonstrate that high-Z nanoparticles can provide a new means to producing dark-field image contrast, promoting scatter via a higher rather than lower electron density compared to microbubbles, increasing detection sensitivity compared to attenuation-based detection of a clinical iodine-based agent at an equivalent X-ray dose. As the use of dark-field X-ray imaging expands into more common clinical usage, this will support the development of a new class of nanoparticulate contrast agents.