Abnormal expression of Vascular Endothelial Growth Factor (VEGF) is found in emphysema, oronchopulmonary dysplasia, pulmonary fibrosis, and asthma. The precise mechanism by which anomalous VEGF expression contributes to the pathogenesis of parenchyma! lung disease is poorly understood. Although animal models of altered pulmonary VEGF expression now exists, methods for longitudinal studies of these model systems limit our ability to investigate the disease process. The goal of this R21 proposal is to establish MRI techniques for quantitative, longitudinal assessment of the lung in VEGF over and under expressing mice. MRI provides a wide range of powerful tools for longitudinal assessment of altered gene function in other organ systems. The combination of low spin density, cardiac and respiratory motion and significant susceptibility distortions generated at air/tissue interfaces make MRI studies extremely difficult to perform in the lung. Overcoming the air/tissue MR susceptibility effect in vivo will advance the field and allow a much wider range of functional, structural, biochemical and perfusion MRI measurements to be applied to the lung. We will develop Perfluorocarbon-Emulsion MRI (PEMRI), allowing liquid ventilation for in-vivo pujmonary MRI in mice. We will determine the optimum perfluorocarbon emulsion for safe liquid ventilation and delineation of parenchyma! structures. To delineate the pulmonary vasculature, we will develop high resolution Gadolinium-enhanced Perfluorocarbon-Emulsion magnetic resonance angiography (PEMRA). We will also evaluate intra and intersubject reproducibility of the technique. We will apply the PEMRI and PEMRA techniques to demonstrate the feasibility of longitudinal in vivo detection and characterization of differences in lung morphology between normal and VEGF-altered mice. The expected outcomes of this study are: 1)The development, optimization and test/retest evaluation of a new in-vivo MRI techniques for assessment of lung disease; and 2) Completion of an initial pilot study demonstrating the ability of these techniques in mouse models to characterize the pathophysiological and structural effects of manipulation of pulmonary VEGF expression. This proposed work is important, providing a method for longitudinal in vivo studies of altered pulmonary VEGF expression, which model clinical asthma and emphysema. The PEMRI technique essentially allows the lung to be imaged as if it is a solid organ. This makes it possible for other dynamic, physiological, biochemical, and structural MRI data to be collected in the lung for the first time. Long term, potential clinical applications of this technique include assessment of lung viability from MRI perfusion studies, and evaluation of lung maturity in PFC ventilated premature infants using MR spectroscopy. ? ? ?
| Darquenne, Chantal; Borja, Maria G; Oakes, Jessica M et al. (2014) Increase in relative deposition of fine particles in the rat lung periphery in the absence of gravity. J Appl Physiol (1985) 117:880-6 |
| Oakes, Jessica M; Breen, Ellen C; Scadeng, Miriam et al. (2014) MRI-based measurements of aerosol deposition in the lung of healthy and elastase-treated rats. J Appl Physiol (1985) 116:1561-8 |
| Oakes, Jessica M; Scadeng, Miriam; Breen, Ellen C et al. (2013) Regional distribution of aerosol deposition in rat lungs using magnetic resonance imaging. Ann Biomed Eng 41:967-78 |
| Oakes, Jessica M; Scadeng, Miriam; Breen, Ellen C et al. (2012) Rat airway morphometry measured from in situ MRI-based geometric models. J Appl Physiol (1985) 112:1921-31 |
| Michiue, Hiroyuki; Eguchi, Akiko; Scadeng, Miriam et al. (2009) Induction of in vivo synthetic lethal RNAi responses to treat glioblastoma. Cancer Biol Ther 8:2306-13 |
| Rao, Karumanchi V; Na, Min Kyun; Cook, Jennifer C et al. (2008) Kahalalides V-Y isolated from a Hawaiian collection of the sacoglossan mollusk Elysia rufescens. J Nat Prod 71:772-8 |
