Nearly all patients receiving radiotherapy for lung cancer develop some degree of lung injury detectable by radiographic studies, they suffer loss of pulmonary function, and such injuries kill some patients. Consequently, the standard tolerable radiation dose for the treatment of locally advanced non-small cell lung cancer (NSCLC) is inadequate. Local control based on bronchoscopic biopsy is achieved in less than 20% of patients with standard radiotherapy doses. This is one reason for the poor survival rate in these patients. A recent phase I radiation dose escalation study for NSCLC which stratified patients based on risk of pulmonary toxicity found higher radiation dose associated with improved overall survival. If the risk of lung injury can be reduced for all patients, then a greater fraction of NSCLC patients can benefit from higher radiation doses. Delivery of radiotherapy through hypoperfused pulmonary regions for lung cancer treatment has been shown to result in less pulmonary injury in a prospective trial. This finding suggests a strategy for image-guided radiotherapy utilizing physiological images in radiotherapy treatment planning for image guidance to avoid the irradiation of highly functional regions and minimize the injury and/or loss following radiotherapy. Image guided radiotherapy seeks to apply imaging modalities for improved tumor targeting or normal tissue avoidance leading to improved tumor control or a reduction of complications. However, pulmonary functional imaging based on single photon emission tomography (SPECT) is not broadly available for treatment planning in radiation oncology clinics. An ideal functional imaging method would utilize the imaging equipment already present in radiation oncology clinics for the treatment planning process. Recently, four dimensional computed tomography (4D CT) imaging was developed for tumor motion evaluation in treatment planning. In this study we develop a novel ventilation imaging method, extracting physiological image information from 4D CT images already routinely acquired for tumor targeting. This ventilation imaging is better suited and utilizes imaging equipment more broadly available for image guided radiotherapy than SPECT pulmonary functional imaging methods. Our hypothesis: The 4D CT derived ventilation imaging technique developed by the principal investigator will provide an accurate assessment of pulmonary function for evaluation of regional lung injury and reveal regions of pulmonary dysfunction for use in image guided thoracic radiation therapy. Nearly all patients receiving radiotherapy for lung cancer develop some degree of lung injury from their treatment, some patients die from these injuries. A recent study for lung cancer treatment found higher radiation dose would improve lung cancer survival. If the risk of lung injury can be reduced for all patients, then we can use higher radiation doses and improve survival. Image guided radiotherapy seeks to apply images for improved tumor targeting or to spare normal tissue leading to improved tumor control or reduced complications. Recently, a new CT imaging method was developed which essentially obtains a 3D movie of the lungs breathing. We have developed a method to extract a map of where the breathing occurs, ventilation, from those 3D movies of the lungs breathing. Our new imaging method uses equipment already available in almost every radiation oncology clinic. This study seeks to validate our new ventilation imaging with the present standard method. ? ? ?