Development of Hyperpolarized Helium for Assessing ILD

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DESCRIPTION (provided by applicant): The idiopathic diffuse parenchymal lung disorders (DPLD) are a group of disorders that are often difficult to distinguish. Those associated with inflammation (i.e. NSIP) usually have a better prognosis than those associated with fibrosis (i.e., UIP). The techniques of polarized gas MRI have never been applied to this area of pulmonary medicine. Hyperpolarized (HP) helium MRI with its ability to assess structure and function in a non-invasive manner while giving regional information has the ability to revolutionize how we diagnose and follow these disorders. HP MRI has the potential to measure three important parameters in pulmonary fibrosis: alveolar size, compliance, and the alveolar partial pressure of oxygen. There are important differences in pathology between the inflammatory and fibrotic diffuse lung disorders that lead us to believe these measurements will be different in the two conditions. Our hypothesis is that fibrotic lung disease (UIP) will be characterized by regional areas of decreased compliance with an increase in distil airway size (honeycomb lung) in contrast to inflammatory interstitial lung disease which will be characterized by areas of decreased compliance with a decrease in distil airway size. In addition, we hypothesize that the distil airways in fibrotic lung disease will have relatively maintained alveolar O2 levels while in inflammatory interstitial lung disease the distil airway/alveolar O2 levels will be decreased. Our plan is to develop HP MRI techniques for small animals so that we can apply these techniques for the evaluation and diagnosis of the DPLD. Our specific aims are: Specific Aim 1: We will optimize and assess the reproducibility of the three regional measurement techniques (regional alveolar size, lung compliance, and alveolar oxygen levels) using HP helium MRI in healthy rats Specific Aim 2:A. We will identify regional functional and structural differences between healthy rats, an inflammatory rat model, and a fibrotic rat model by performing HP helium MRI measurements of regional alveolar size, compliance, and oxygenation in the groups. B. We will compare the HP MRI measurements with standardized measurements of lung dysfunction which will include pre-MRI pulmonary function tests, and post-MRI histopathological examination of the rat lung and measurement of collagen content. PUBLIC HEALTH RELEVANCE: The work proposed in this study will address a serious pulmonary condition of unknown etiology known as the idiopathic diffuse parenchymal lung disorders (DPLD (. We will develop for the first time in normal rats and two rat models of DPLD, hyperpolarized helium MRI techniques to measure regional alveolar size, compliance and alveolar oxygen levels. We believe that these measurements can differentiate inflammatory from fibrotic DPLD and will have important diagnostic and prognostic utility in humans