INTRODUCTION: Despite the use of modern minimally invasive surgical techniques, post-operative complications following lung cancer resection remain common and challenging to predict. Pulmonary ventilation imaging modalities offer detailed regional assessment of airflow obstruction and are highly sensitive to subclinical airway and/or parenchymal disease. Nevertheless, ventilation imaging is seldom integrated into pre-operative lung function assessment and risk stratification procedures. Therefore, the objective of this thesis was to quantify the burden of ventilation defects observed by Technegas SPECT and 129Xe MRI before lung cancer resection and establish their association with the occurrence and clinical impact of post-operative complications. METHODS: Patients undergoing lung cancer resection at St. Joseph’s Healthcare Hamilton were recruited into a prospective, proof-of-concept, six-week observational study. Participants were evaluated prior to resection surgery to document baseline demographics and clinical characteristics, performed standard pulmonary function tests and sputum induction, and underwent Technegas SPECT and 129Xe MRI to assess ventilation. Abnormal ventilation was quantified as the ventilation defect percent (VDP) and was considered abnormal if VDP was ≥mean+2 standard deviations of a healthy population. Following surgery, participants were followed for 4 weeks to document the incidence of post-operative complications, as specified by the Ottawa TM&M categorization system, and the length of hospital stay. RESULTS: One hundred and twenty-three participants were enrolled, of whom 103 were evaluated pre-operatively and followed for post-operative outcomes. Of the 103 participants (69±8 years, 58% female), 89% (92/103) underwent minimally invasive surgery, and 74% (76/103) underwent lobectomy. Abnormal ventilation was observed pre-operatively by Technegas SPECT and 129Xe MRI for 59% (58/99) and 84% (82/98) of participants, respectively. In a subset of 69 participants in whom sputum was collected, 51% (35/69) had intraluminal inflammation. A total of 64 post-operative complications occurred; 16 (25%) were pulmonary, and 48 (75%) were pleural complications. A post-operative complication occurred in 42% (41/103) of participants. Pre-operative Technegas SPECT and 129Xe MRI VDP were higher for participants with post-operative complications compared to those without (Technegas SPECT: 26±17% vs 19±7%, p=0.02; 129Xe MRI: 13±12% vs 7±6% p=0.003) and were positively correlated with post-operative length of hospital stay (Technegas SPECT: r=0.43, p<0.0001; 129Xe MRI: r=0.49, p<0.0001). Multivariable regression models revealed that preoperative Technegas SPECT and 129Xe MRI VDP were predictors of post-operative complications (Technegas SPECT: Odds ratio=1.08, p=0.005; 129Xe MRI: Odds ratio=1.16, p=0.002) and post-operative length of hospital stay (Technegas SPECT: unstandardized β=0.13, p<0.001; 129Xe MRI: unstandardized β=0.24, p<0.001). CONCLUSIONS: Abnormal ventilation, quantified by Technegas SPECT and 129Xe MRI VDP, is prevalent prior to lung cancer resection and a predictor of post-operative complications and length of hospital stay. / Thesis / Master of Science (MSc) / Post-operative complications are frequent adverse events following lung cancer resection, resulting in substantial patient morbidity and mortality that have a significant clinical and economic impact. Despite this, post-operative complications remain inadequately predicted, and limited research has been dedicated to reducing the risk of pulmonary complications after lung cancer resection. Standard clinical screening tools, such as pulmonary function tests, are used for patient selection in lung cancer resection surgery; however, they provide a global estimate of a complex multicompartment organ and may lack the sensitivity to detect subclinical lung pathology that influences post-operative outcomes. Thus, using high-resolution medical imaging modalities such as single photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI), we investigated the prevalence and clinical relevance of abnormal ventilation, a functional consequence of airway and/or parenchymal disease. One hundred and three participants were enrolled in a six-week prospective, proof-of-concept observational study. Participants performed pre-operative imaging and were followed for four weeks post-operatively to document post-operative complications and relevant clinical outcomes. Pre-operative SPECT and MRI revealed a high prevalence of abnormal ventilation. The pre-operative ventilation defect burden was greater in participants who developed one or more complications during the four-week post-operative period and was an independent predictor of both the incidence of post-operative complications and the length of hospital stay. These observations provide proof-of-concept evidence that abnormal ventilation, assessed by two ventilation imaging modalities, is prevalent and clinically relevant prior to lung cancer resection. Taken together, this thesis establishes that ventilation imaging may have implications for risk stratification and risk modification in patients scheduled to undergo lung cancer resection.