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Electron density is the most important tissue property influencing photon and ion dose distributions in radiotherapy patients. Dual-energy computed tomography (DECT) enables the determination of electron density by combining the information on photon attenuation obtained at two different effective x-ray energy spectra. Most algorithms suggested so far use the CT numbers provided after image reconstruction as input parameters, i.e., are imaged-based. To explore the accuracy that can be achieved with these approaches, we quantify the intrinsic methodological and calibration uncertainty of the seemingly simplest approach.In the studied approach, electron density is calculated with a one-parametric linear superposition (‘alpha blending’) of the two DECT images, which is shown to be equivalent to an affine relation between the photon attenuation cross sections of the two x-ray energy spectra. We propose to use the latter relation for empirical calibration of the spectrum-dependent blending parameter. For a conclusive assessment of the electron density uncertainty, we chose to isolate the purely methodological uncertainty component from CT-related effects such as noise and beam hardening.Analyzing calculated spectrally weighted attenuation coefficients, we find universal applicability of the investigated approach to arbitrary mixtures of human tissue with an upper limit of the methodological uncertainty component of 0.2%, excluding high-Z elements such as iodine. The proposed calibration procedure is bias-free and straightforward to perform using standard equipment. Testing the calibration on five published data sets, we obtain very small differences in the calibration result in spite of different experimental setups and CT protocols used. Employing a general calibration per scanner type and voltage combination is thus conceivable.Given the high suitability for clinical application of the alpha-blending approach in combination with a very small methodological uncertainty, we conclude that further refinement of image-based DECT-algorithms for electron density assessment is not advisable.