All Publications

  • Unstable Inflation Causing Injury Insight from Prone Position and Paired Computed Tomography Scans AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE Xin, Y., Cereda, M., Hamedani, H., Pourfathi, M., Siddiqui, S., Meeder, N., Kadlecek, S., Duncan, I., Profka, H., Rajaei, J., Tustison, N. J., Gee, J. C., Kavanagh, B. P., Rizi, R. R. 2018; 198 (2): 197–207


    It remains unclear how prone positioning improves survival in acute respiratory distress syndrome. Using serial computed tomography (CT), we previously reported that "unstable" inflation (i.e., partial aeration with large tidal density swings, indicating increased local strain) is associated with injury progression.We prospectively tested whether prone position contains the early propagation of experimental lung injury by stabilizing inflation.Injury was induced by tracheal hydrochloric acid in rats; after randomization to supine or prone position, injurious ventilation was commenced using high tidal volume and low positive end-expiratory pressure. Paired end-inspiratory (EI) and end-expiratory (EE) CT scans were acquired at baseline and hourly up to 3 hours. Each sequential pair (EI, EE) of CT images was superimposed in parametric response maps to analyze inflation. Unstable inflation was then measured in each voxel in both dependent and nondependent lung. In addition, five pigs were imaged (EI and EE) prone versus supine, before and (1 hour) after hydrochloric acid aspiration.In rats, prone position limited lung injury propagation and increased survival (11/12 vs. 7/12 supine; P = 0.01). EI-EE densities, respiratory mechanics, and blood gases deteriorated more in supine versus prone rats. At baseline, more voxels with unstable inflation occurred in dependent versus nondependent regions when supine (41 ± 6% vs. 18 ± 7%; P < 0.01) but not when prone. In supine pigs, unstable inflation predominated in dorsal regions and was attenuated by prone positioning.Prone position limits the radiologic progression of early lung injury. Minimizing unstable inflation in this setting may alleviate the burden of acute respiratory distress syndrome.

    View details for PubMedID 29420904

  • Hyperpolarized Gas Diffusion MRI of Biphasic Lung Inflation in Short and Long Term Emphysema Models. American journal of physiology. Lung cellular and molecular physiology Xin, Y., Cereda, M., Kadlecek, S., Emami, K., Hamedani, H., Duncan, I., Rajaei, J., Hughes, L., Meeder, N., Naji, J., Profka, H., Bolognese, B. J., Foley, J. P., Podolin, P. L., Rizi, R. R. 2017: ajplung 00048 2017-?


    During lung-inflation, airspace dimensions are affected non-linearly by both alveolar expansion and recruitment, potentially confounding the identification of emphysematous lung by hyperpolarized helium-3 diffusion magnetic resonance imaging (HP MRI). This study aimed to characterize lung inflation over a broad range of inflation volume and pressure values in two different models of emphysema, as well as in normal lungs. Elastase-treated rats (n=7) and healthy controls (n=7) were imaged with HP MRI. Gradual inflation was achieved by incremental changes to both inflation volume and airway pressure. The apparent diffusion coefficient (ADC) was measured at each level of inflation and fitted to the corresponding airway pressures as the second order response equation, with minimizing residue (2<0.001). A biphasic ADC response was detected, with an initial ADC increase followed by a decrease at airway pressures >18 cmH2O. Discrimination between treated and control rats was optimal when airway pressure was intermediate (between 10-11 cmH2O). Similar findings were confirmed in mice following long-term exposure to cigarette smoke, where optimal discrimination between treated and healthy mice occurred at a similar airway pressure as in the rats. We subsequently explored the evolution of ADC measured at the intermediate inflation level in mice after prolonged smoke exposure, and found a significant increase (P<0.01) in ADC over time. Our results demonstrate that measuring ADC at intermediate inflation enhances the distinction between healthy and diseased lungs, thereby establishing a model that may improve the diagnostic accuracy of future HP gas diffusion studies.

    View details for DOI 10.1152/ajplung.00048.2017

    View details for PubMedID 28473321

  • C] pyruvate. Magnetic resonance in medicine Pourfathi, M., Xin, Y., Kadlecek, S. J., Cereda, M. F., Profka, H., Hamedani, H., Siddiqui, S. M., Ruppert, K., Drachman, N. A., Rajaei, J. N., Rizi, R. R. 2017


    To investigate pulmonary metabolic alterations during progression of acute lung injury.Using hyperpolarized [1-(13) C] pyruvate imaging, we measured pulmonary lactate and pyruvate in 15 ventilated rats 1, 2, and 4 h after initiation of mechanical ventilation. Lung compliance was used as a marker for injury progression. 5 untreated rats were used as controls; 5 rats (injured-1) received 1 ml/kg and another 5 rats (injured-2) received 2 ml/kg hydrochloric acid (pH 1.25) in the trachea at 70 min.The mean lactate-to-pyruvate ratio of the injured-1 cohort was 0.15 ± 0.02 and 0.15 ± 0.03 at baseline and 1 h after the injury, and significantly increased from the baseline value 3 h after the injury to 0.23 ± 0.02 (P = 0.002). The mean lactate-to-pyruvate ratio of the injured-2 cohort decreased from 0.14 ± 0.03 at baseline to 0.08 ± 0.02 1 h after the injury and further decreased to 0.07 ± 0.02 (P = 0.08) 3 h after injury. No significant change was observed in the control group. Compliance in both injured groups decreased significantly after the injury (P < 0.01).Our findings suggest that in severe cases of lung injury, edema and hyperperfusion in the injured lung tissue may complicate interpretation of the pulmonary lactate-to-pyruvate ratio as a marker of inflammation. However, combining the lactate-to-pyruvate ratio with pulmonary compliance provides more insight into the progression of the injury and its severity. Magn Reson Med, 2017. © 2017 International Society for Magnetic Resonance in Medicine.

    View details for DOI 10.1002/mrm.26604

    View details for PubMedID 28074497