Origins of and lessons from quantitative functional X-ray computed tomography of the lung

Functional CT of the lung has emerged from quantitative CT (qCT). Structural details extracted at multiple lung volumes offer indices of function. Additionally, single volumetric images, if acquired at standardized lung volumes and body posture, can be used to model function by employing such engineering techniques as computational fluid dynamics. With the emergence of multispectral CT imaging including dual energy from energy integrating CT scanners and multienergy binning using the newly released photon counting CT technology, function is tagged via use of contrast agents. Lung disease phenotypes have previously been lumped together by the limitations of spirometry and plethysmography. QCT and its functional embodiment have been imbedded into studies seeking to characterize chronic obstructive pulmonary disease, severe asthma, interstitial lung disease and more. Reductions in radiation dose by an order of magnitude or more have been achieved. At the same time, we have seen significant increases in spatial and density resolution along with methodologic validations of extracted metrics. Together, these have allowed attention to turn towards more mild forms of disease and younger populations. In early applications, clinical CT offered anatomic details of the lung. Functional CT offers regional measures of lung mechanics, the assessment of functional small airways disease, as well as regional ventilation-perfusion matching (V/Q) and more. This paper will focus on the use of quantitative/functional CT for the non-invasive exploration of dynamic three-dimensional functioning of the breathing lung and beating heart within the unique negative pressure intrathoracic environment of the closed chest.