PROJECT SUMMARY/ABSTRACT The overall objectives of this NIH S10 Instrumentation grant application is to request funds to purchase a newly available Notting Hill Devices (NHD) Preclinical Scanner. This instrument will allow investigators with unprecedented quantitative imaging of lung function and vascular changes for deciphering lung airway disease along with evaluation of cardiothoracic vascular remodeling in small animal models. 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 and is the only commercially available device for ultra-high resolution imaging and quantification of cardiothoracic disease models. The penetrating nature of X-rays is used to capture a series of temporal phase-contrast images of the lungs, heart and associated vascular. 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 show arteries and lungs and provides functional airflow and pulmonary vasculature data of the lungs with detailed quantification of airflow and vasculature in specific regions of the airways. The 4DX scanner provides a safe, quick, and inexpensive tool that not only provides high-resolution images but also yields detailed, regional information on lung function. The University of Michigan Center for Molecular Imaging has a rich history of contributions in basic science and in medicine and provides overall imaging support to the entire academic institution through establishment and maintenance of a small animal imaging core facility historically focused on cancer models. The addition of the 4DXV instrument equipment will be utilized by a group of NIH-funded, established, senior investigators. The 4DXV Preclinical Scanner is an indispensable necessity for the cardiothoracic translational research efforts which include evaluation of novel classes of drugs focused on treatment of cardiothoracic diseases. The scanner will be housed is a well-established Animal Model and Imaging Core with strong commitment from the University of Michigan Center for Molecular Imaging to establish an institutional Preclinical Lung and Heart Physiology Shared Laboratory to ensure long-term maintenance and operation of the instrument. Importantly, the scanner will provide for a paradigm shift in lung research and diagnostics. 4DVX is a promising and powerful technology for assessment of cardiothoracic diseases. The University of Michigan presents a near ideal environment in which to initiate such a research program within an established small animal imaging core facility.