The broad and long-term objective of this application is to decipher lung airway function and progression of pulmonary vascular remodeling in unprecedented details using the newly available Notting Hill Devices (NHD) Preclinical Scanner. This patented Australian technology also known as 4-Dimensional X-ray Velocimetry (4DXV) is based on the wind tunnel technology known as particle image velocimetry. The penetrating nature of X-rays is used to capture a series of temporal phase-contrast images of the lungs. Velocimetry is used to determine the movement of an anatomical structure from one image to the next, providing information on both velocity and direction of movement. Images are paired and discretized into small sub-regions and cross- correlations performed between the sub-regions in consecutive images. The resulting 4-dimentional lung images provide functional airflow and pulmonary vasculature data of the lungs with detailed quantification of airflow and vasculature in specific regions of the airways, superimposed with high-resolution phase contrast enhanced CT. This 4DXV scanner provides a safe, quick, and inexpensive tool that provides detailed, regional quantification of lung function superimposed with lung structure. Hence, the scanner will enable a paradigm shift in lung research. The equipment will be utilized by a group of nine NIH-funded, established, senior pulmonary investigators organized in two active asthma Program Project Grants and three R01's in pulmonary arterial hypertension constituting the first application of this technology to conduct basic research in these two critical fields. The NHD Preclinical Scanner is an indispensable necessity for the asthma translational Program Project in which we propose to use this scanner to discover which specific area(s) of the lung novel classes of asthma drugs are acting. The scanner will be housed in a well-established program project Animal Model and Imaging Core. The Cleveland Clinic has made a strong commitment to establish an institutional Preclinical Lung and Heart Physiology Shared Laboratory to ensure long-term maintenance and operation of the instrument.
