The purpose of this proposal is to provide a unique, quantitative, functional biomarker of airway inflammation by directly measuring bronchial wall enhancement following iodinated contrast administration using dual-energy computed tomography (DECT). Key to our hypothesis is the well established fact that inflammation leads to bronchial arterial hyperemia previously requiring either invasive angiography or sophisticated laboratory techniques rarely utilized. A large number of diseases, both acquired and inherited, result in chronic airway inflammation, conditions for which diagnosis and especially management represent important and common clinical challenges. Although high resolution CT plays an important role in establishing and monitoring these diseases, to date, CT interpretation has exclusively relied on morphologic assessment and is often subjective. We propose a new diagnostic paradigm by emphasizing quantitative, functional assessment of the extent and severity of airway inflammation with the ultimate aim of applying this approach to a wide range of causes of airway inflammation - with important implications for accurately assessing both routine treatment as well as importantly providing a biomarker for potential new therapeutic approaches . The truly innovative aspect of this proposal is the use of recently introduced dual energy CT scanners that now enable the simultaneous acquisition of CT data at two different energy levels allowing differentiation of materials by their unique chemical composition. This includes the specific ability to separately map the distribution of iodine within tissues, and hence quantitatively measure contrast enhancement within segmental and subsegmental airway walls. To validate our hypothesis, we propose to study patients with documented Mycobarterial avium complex (MAC) lung disease as an apt model of conditions associated with chronic airway inflammation. MAC is increasingly prevalent and is associated with considerable morbidity and mortality. While criteria for diagnosis are well defined, indications for treatment remain highly controversial, requiring a prolonged 3-4 drug regimen causing numerous side-effects. Finally, guidelines for managing therapy have proved especially problematic, lacking specific and reliable quantitative, functional markers. For this study, specifically, we propose to evaluate a total of 60 patients with MAC, 30 of whom will require therapy, with sequential DECT's obtained in place of routinely acquired follow-up CT exams, with the intent to document the potential of DECT to provide a novel biomarker in patients with conditions causing chronic airway inflammation.
The purpose of this study is to evaluate a new, innovative method that we have developed employing dual energy computed tomography (DECT) to evaluate patients with diseases characterized by chronic airway inflammation by assessing changes in airway wall vascularity, thereby providing a quantitative, functional biomarker of disease. To validate our approach we intend to study patients with infections due to Mycobacterial avium complex (MAC) as a particularly apt representative of an increasingly common disease that has proved especially difficult to diagnose and especially treat, with the expectation that use of a quantitative, functional method for assessing disease extent and activity will have a profound impact on daily management of this important group of patients. It is further anticipated that this same technique will prove of value for virtually all other diseases associated with chronic airway inflammation, hence providing a new paradigm for the use of computed tomography to evaluate the airways.