A form of lung function imaging is emerging that uses phase-resolved four-dimensional CT (4DCT or breath-hold CT) images along with image processing techniques to generate lung function maps that provide a surrogate of lung ventilation. CT-based ventilation (referred to as CT-ventilation) research has gained momentum in Radiation Oncology because many lung cancer patients undergo four-dimensional CT simulation as part of the standard treatment planning process. Therefore, generating CT-ventilation images provides functional information without burdening the patient with an extra imaging procedure. CT-ventilation has progressed from an image processing calculation methodology, to validation efforts, to retrospective demonstration of clinical utility in Radiation Oncology. In particular, CT-ventilation has been proposed for two main clinical applications: functional avoidance radiation therapy and thoracic dose–response assessment. The idea of functional avoidance radiation therapy is to preferentially spare functional portions of the lung (as measured by CT-ventilation) during radiation therapy with the hypothesis that reducing dose to functional portions of the lung will lead to reduced rates of radiation-related thoracic toxicity. The idea of imaging-based dose–response assessment is to evaluate pre- to post-treatment CT-ventilation-based imaging changes. The hypothesis is that early, imaging-change-based response can be an early predictor of subsequent thoracic toxicity. Based on the retrospective evidence, the clinical applications of CT-ventilation have progressed from the retrospective setting to on-going prospective clinical trials. This review will cover basic CT-ventilation calculation methodologies, validation efforts, presentation of clinical applications, summarize on-going clinical trials, review potential uncertainties and shortcomings of CT-ventilation, and discuss future directions of CT-ventilation research.
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