Experimental hybrid spectral CT with Cramer-Rao lower bound-optimized weighting for quantitative iodine imaging

Spectral computed tomography (CT) is a burgeoning quantitative imaging technique with applications in oncologic diagnostics, prognostic prediction, tissue perfusion studies, and treatment follow-up. While normalized iodine concentration values have been correlated with microenvironmental biophysical changes, obtaining accurate iodine concentrations, particularly at low concentrations remains difficult due to varying spectral CT instrumentation performance. Hybrid spectral CT systems, combining multiple spectral CT instrumentation techniques, address these quantitation insufficiencies by increasing spectral separation but have not been evaluated on a clinically analogous platform. We validate a hybrid spectral CT system, comprised of clinical-grade components, acquiring four distinct effective spectra and applying efficient noise-reducing weighting schemes to compare iodine noise and bias against conventional kVp-Switching (kVp-S). Two tube current levels (50, 350 mA) and three duty cycle ratios (33/67, 50/50, 75/25) were implemented to elucidate radiation dose exposure and kVp-S parameterization impact. A standard quality assurance (QA) and patient-derived, abdominal IodinePrint phantom were scanned on the system. The average absolute bias in iodine density images of the QA phantom was comparable across acquisition techniques, below 0.5 mg/mL, while quantitative noise improved by 22% using noise-optimized weighting schemes. In the IodinePrint phantom aorta and pancreas structures, the noise-optimized weighting scheme increased signal-to-noise ratio (SNR) by 1.3x compared to kVp-S alone. These results highlight the increased precision of hybrid, multi-channel spectral CT systems and motivate CT designs that enable robust CT biomarker development.