Since many diseases or injuries can cause biomechanical or structural property changes that can alter lung function, there is great interest in measuring regional lung function by measurement of regional mechanical changes. To date, the most prevalent approach for assessing regional lung function from 4-D X-ray CT data has been a measure of Jacobian of deformation. However, although the Jacobian describes regional volume changes of the lung during deformation, it lacks any consideration of directional changes of local compressions and expansions during respiration. Herein, we propose the use of strain as a measure of regional lung function from 4-D thoracic CT and we perform correlation of principal strains of calculated deformation by s recently proposed 3-D optical flow technique (MOFID) computed from radiotherapy treatment planning 4-D X-ray CT data sets collected in seven subjects suffering from non-small cell primary lung cancer. In addition to 4-D CT data, both SPECT ventilation (VSPECT), and SPECT perfusion (QSPECT) data were acquired in all subjects. For each subject, we performed voxel-wise statistical correlation of the Jacobian as well as principal strains of deformation (CT-derived pulmonary function images) with both ventilation and perfusion SPECT. For all subjects, the maximum principal strain resulted in a higher correlation with both SPECT ventilation and SPECT perfusion than other indices including the previously established Jacobian metric.