Misinterpretations about CT numbers, material decomposition, and elemental quantification

Background: Quantitative CT imaging, particularly iodine and calcium quantification, is an important CT-based biomarker.

Purpose: This study quantifies sources of errors in quantitative CT imaging in both single-energy and spectral CT.

Materials and methods: This work examines the theoretical relationship between CT numbers, linear attenuation coefficient, and material quantification. We derive four understandings: (1) CT numbers are not proportional with element mass in vivo, (2) CT numbers are proportional with element mass only when contained in a voxel of pure water, (3) iodine-water material decomposition is never accurate in vivo, and (4) for error-free material decomposition a voxel must only consist of the basis decomposition vectors. Misinterpretation-based errors are calculated using the National Institute of Standards and Technology (NIST) XCOM database for: tissue chemical compositions, clinical concentrations of hydroxyapatite (HAP), and iodine. Quantification errors are also demonstrated experimentally using phantoms.

Results: In single-energy CT, misinterpretation-induced errors for HAP density in adipose, muscle, lung, soft tissue, and blood ranged from 0-132%, i.e., a mass error of 0-749 mg/cm³. In spectral CT, errors with iodine in the same tissues resulted in a range of < 0.1-33% error, resulting in a mass error of < 0.1-1.2 mg/mL.

Conclusion: Our work demonstrates material quantification is fundamentally limited when measured in vivo due to measurement conditions differing from assumed and the errors are at or above detection limits for bone mineral density (BMD) and spectral iodine quantification. To define CT-derived biomarkers, the errors we demonstrate should either be avoided or built into uncertainty bounds.

Clinical relevance statement: Improving error bounds in quantitative CT biomarkers, specifically in iodine and BMD quantification, could lead to improvements in clinical care aspects based on quantitative CT.

Key points: CT numbers are only proportional with element mass only when contained in a voxel of pure water, therefore iodine-water material decomposition is never accurate in vivo. Misinterpretation-induced errors ranged from 0-132% for HAP density and < 0.1-33% in spectral CT with iodine. For error-free material decomposition, a voxel must only consist of the basis decomposition vectors.