Molecular imaging with spectral CT nanoprobes

X-ray contrast agents have heretofore been dominated by iodinated molecules imaged with computed tomography (CT) using traditional energy integrating detectors. Hardware and software developments in CT now present the option for dual-energy detection systems, which still retain the integrator detector approach. However, a new era of detectors called photon-counting detectors used for spectral CT has recently overcome many of the technical imaging barriers precluding clinical translation while offering a trade-off between higher image resolution or better signal to noise as well as lower radiation exposure. While these attributes are highly desirable, the unmet potential for Spectral CT is molecular imaging due to the energy discriminating properties of these systems. To date, contrast imaging is based on X-ray attenuation as seen routinely when high calcium content, such as in bone, appears white on the image. With spectral CT, individual metals, particularly gold, tantalum, bismuth, and ytterbium have emerged as the basis for new contrast media, which are referred to as K-edge contrast agents. These new agents could be used to localize and quantify important biomarkers to extend CT tissue characterization into the realm of molecular imaging. While many of the prototype attempts at such agents will likely not be translational to patients, an array of concepts, reviewed herein, could lead to clinical products in the not too distant future.