Purpose: We propose a one-step tissue characterization method for spectral photon-counting computed tomography (SPCCT) using eigentissue decomposition (ETD), tailored for highly accurate human tissue characterization in radiotherapy.

Methods: The approach combines a Poisson likelihood, a spatial prior, and a quantitative prior constraining eigentissue fractions based on expected values for tabulated tissues. There are two regularization parameters: α for the quantitative prior, and β for the spatial prior. The approach is validated in a realistic simulation environment for SPCCT. The impact of α and β is evaluated on a virtual phantom. The framework is tested on a virtual patient and compared with two sinogram-based two-step methods [using respectively filtered backprojection (FBP) and an iterative method for the second step] and a post-reconstruction approach with the same quantitative prior. All methods use ETD.

Results: Optimal performance with respect to bias or RMSE is achieved with different combinations of α and β on the cylindrical phantom. Evaluated in tissues of the virtual patient, the one-step framework outperforms two-step and post-reconstruction approaches to quantify proton-stopping power (SPR). The mean absolute bias on the SPR is 0.6% (two-step FBP), 0.6% (two-step iterative), 0.6% (post-reconstruction), and 0.2% (one-step optimized for low bias). Following the same order, the RMSE on the SPR is 13.3%, 2.5%, 3.2%, and 1.5%.

Conclusions: Accurate and precise characterization with ETD can be achieved with noisy SPCCT data without the need to rely on post-reconstruction methods. The one-step framework is more accurate and precise than two-step methods for human tissue characterization.