On the molecular relationship between Hounsfield Unit (HU), mass density, and electron density in computed tomography (CT)

Accurate determination of physical/mass and electron densities are critical to accurate spatial and dosimetric delivery of radiotherapy for photon and charged particles. In this manuscript, the biology, chemistry, and physics that underly the relationship between computed tomography (CT) Hounsfield Unit (HU), mass density, and electron density was explored. In standard radiation physics practice, quantities such as mass and electron density are typically calculated based off a single kilovoltage CT (kVCT) scan assuming a one-to-one relationship between HU and density. It is shown that, in absence of mass density assumptions on tissues, the relationship between HU and density is not one-to-one with uncertainties as large as 7%. To mitigate this uncertainty, a novel multi-dimensional theoretical approach is defined between molecular (water, lipid, protein, and mineral) composition, HU, mass density, and electron density. Empirical parameters defining this relationship are x-ray beam energy/spectrum dependent and, in this study, two methods are proposed to solve for them including through a tissue mimicking phantom calibration process. As a proof of concept, this methodology was implemented in a separate in-house created tissue mimicking phantom and it is shown that sub 1% accuracy is possible for both mass and electron density. As molecular composition is not always known, the sensitivity of this model to uncertainties in molecular composition was investigated and it was found that, for soft tissue, sub 1% accuracy is achievable assuming nominal organ/tissue compositions. For boney tissues, the uncertainty in mineral content may lead to larger errors in mass and electron density compared with soft tissue. In this manuscript, a novel methodology to directly determine mass and electron density based off CT HU and knowledge of molecular compositions is presented. If used in conjunction with a methodology to determine molecular compositions, mass and electron density can be accurately calculated from CT HU.