Integration of Spectral CT with PET and SPECT: Bringing Tissue Composition Information to Molecular Imaging

Molecular imaging has been transformed by integrating positron emission tomography (PET) or single-photon emission computed tomography (SPECT) with x-ray computed tomography (CT). However, x-ray CT in hybrid imaging is used primarily for anatomical localization and for attenuation and scatter correction of emission data. Its ability to characterize tissue composition remains underutilized. Spectral CT, including dual-energy CT (DECT) and photon-counting CT (PCCT), can provide material-specific information, such as images of iodine concentration, bone or calcium fractions, electron-density, effective atomic number and other spatially-varying material properties. These capabilities create an opportunity to bring tissue-composition information into molecular imaging. In addition, spectral CT can also reduce CT artifacts and provide more accurate corrections for emission data. In this review, we discuss the technical basis, integration pathways, and translational opportunities for combining spectral CT with molecular imaging. We review sequential and integrated PET/DECT approaches, emerging PET/PCCT concepts, PET-enabled spectral CT, and extensions to SPECT/CT. We then examine how spectral CT information may improve attenuation correction, scatter correction, tissue-fraction correction, positron range correction, reconstruction priors, and dosimetry. Clinical and translational applications include contrast-enhanced molecular imaging, vascular and perfusion imaging, quantitative bone marrow imaging, musculoskeletal imaging, and theranostics. Overall, spectral CT integration may move hybrid molecular imaging toward tissue-composition-informed molecular imaging, in which radiotracer signals are interpreted within their material context.