About the Seminar:
Pulmonary diseases (e.g., emphysema and fibrosis) are leading causes of mortality worldwide, and the incidence these disorders is thought to be rising. While strides have been made in elucidating the molecular events underlying lung disease, the pathological changes in respiratory physiology responsible for disease progression remain poorly characterized. This poor understanding can be attributed to the complex fractal structure of the lungs and complicated dynamics of pulmonary gas transport. However, at its most basic level proper pulmonary function involves carefully matching fluid flow (gas via ventilation and blood via perfusion) to facilitate mass transport by diffusion and ultimately the reaction of metabolic gases (CO2 and O2) with hemoglobin. As such, the various aspects of lung function and lung dysfunction are intrinsically quantifiable, provided appropriate, non-invasive tools can be developed. To this end, research in the Cleveland lab focuses on developing techniques to assess lung structure and gas transport in animal models and human subjects using nuclear magnetic resonance (NMR) spectroscopy and MR imaging (MRI).
The structural imaging tools being developed are based on ultra-short echo-time (UTE) MRI, which allows MR signal to be encoded in microseconds (i.e., much faster than the intrinsically short T2* relaxation time of 0.8 ms in lung tissue). To assess gas transport processes, we use an atomic physics technique called alkali metal vapor spin exchange optical pumping to generate highly non-equilibrium nuclear magnetization in a noble gas—typically the nuclear spin I = ½ isotope 129Xe. The MR signal of these “hyperpolarized” gases yield MR signal that is enhanced ~10,000-fold over that of gases with equilibrium nuclear polarization. With this enhanced signal, we are able to directly visualize and quantify regional ventilation within the lungs. Using diffusion encoding MRI sequences (akin to the pulsed-field gradient techniques used in conventional NMR), it is possible to measure restricted diffusion within the lungs. The restriction allows us to directly quantity the dimensions of the pulmonary microstructure, and thus measure alveolar growth during normal development and assess early emphysematous alveolar destruction. Additionally, 129Xe is moderately soluble in tissues (Oswald solubility ~10%) and possesses and enormous chemical shift range of >200 ppm in vivo, allowing regional gas exchange to be measured regionally used spectral resolved imaging. Together, these techniques will provide a comprehensive set of tools to assess of physiology in animal models of lung disease and in human patients ranging in from neonates to the elderly.
About the Speaker:
Zack Cleveland is an Assistant Professor in the Division of Pulmonary Medicine and the Department of Radiology at Cincinnati Children’s Hospital Medical Center and in the Departments of Pediatrics and Biomedical Engineering at the University of Cincinnati. He received his B.S. in chemistry from The University of Montana and his Ph.D. in physical chemistry from Colorado State University in 2008, working with Prof. Thomas Meersmann in the area of NMR and hyperpolarization. He then accepted a postdoctoral fellowship in the Department of Radiology at Duke University Medical Center, working with Professor Bastiaan Driehuys where he developed preclinical lung MRI techniques and helped conduct a Phase I Clinical Trial for hyperpolarized 129Xe MRI. After receiving a NIH K99/R00 “Pathway to Independence” Award from the NIH, he was promoted to Research Scientist at Duke. In 2014, he recruited to help build the newly formed Center for Pulmonary Imaging Research (CPIR) at CCHMC. In 2017 he and other members of the CPIR were received the “Team Research Award” from the Cincinnati Children’s Research Foundation, and in 2018 he received the “Rising Star of Research Award” from the American Thoracic Society. He currently receives funding from the Cincinnati Children’s Research Foundation, the NIH (R00, R01 and R44 mechanisms), and the Cystic Fibrosis Foundation.