Abstract

The overall long-term goal of these studies is to understand the mechanisms by which pulmonary blood flow is controlled, and how that control contributes to gas exchange defects or optimization in health and disease. The specific goal is to use a novel MRI technique to quantify the spatial and temporal dynamics of blood flow in the normal human lung. Temporal heterogeneity in a number of physiological systems has been found to be a mark of healthy function, yet little is known about the temporal dynamics of blood flow in the human lung because the appropriate tools for measuring temporal heterogeneity have not been available. Recently we developed a noninvasive MRI technique that provides quantitative measurements of pulmonary blood flow with a spatial resolution of <1 cm3 and a temporal resolution of ~10 s in the human lung, permitting us to examine spatial-temporal heterogeneity in the human lung for the first time.
The Specific Aims are designed to systematically explore the normal spectrum of spatial-temporal heterogeneity, testing: 1) the effects of altered inspired gas (O2 and CO2) in healthy subjects;2) the effects of exercise;3) the effects of ageing;and 4) the effects of altered O2 and CO2 in the lungs of subjects susceptible to high altitude pulmonary edema. This will be the first systematic, quantitative study of the spatial and temporal dynamics of pulmonary blood flow in human subjects, and will lay a foundation for applying these methods in the early detection and characterization of disease.

Public Health Relevance

Oxygenation of the blood in the lungs depends on a close matching of ventilation and blood flow: fresh gas and blood flow need to be at the same place and at the same time. We have developed a novel imaging technique for measuring the distribution of blood flow in the human lung not only spatially, but also over time, a measurement that has not been possible before. In this work we will explore the normal dynamics of blood flow as a foundation for applying these methods to identify, and to better understand, the underlying mechanisms of disease.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL104118-03
Application #
8447023
Study Section
Respiratory Integrative Biology and Translational Research Study Section (RIBT)
Program Officer
Peavy, Hannah H
Project Start
2011-04-01
Project End
2015-03-31
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
3
Fiscal Year
2013
Total Cost
$599,755
Indirect Cost
$212,816

  Institution

Name
University of California San Diego
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093

  Publications

Walker, Shane C; Asadi, Amran K; Hopkins, Susan R et al. (2015) A statistical clustering approach to discriminating perfusion from conduit vessel signal contributions in a pulmonary ASL MR image. NMR Biomed 28:1117-24
Thompson, Bruce R; Ellis, Matthew J; Stuart-Andrews, Christopher et al. (2015) Early bronchiolitis obliterans syndrome shows an abnormality of perfusion not ventilation in lung transplant recipients. Respir Physiol Neurobiol 216:28-34
Miller, G Wilson; Mugler 3rd, John P; Sá, Rui C et al. (2014) Advances in functional and structural imaging of the human lung using proton MRI. NMR Biomed 27:1542-56
Sá, Rui Carlos; Asadi, Amran K; Theilmann, Rebecca J et al. (2014) Validating the distribution of specific ventilation in healthy humans measured using proton MR imaging. J Appl Physiol (1985) 116:1048-56
Dharmakumara, Mahesh; Prisk, G Kim; Royce, Simon G et al. (2014) The effect of gas exchange on multiple-breath nitrogen washout measures of ventilation inhomogeneity in the mouse. J Appl Physiol (1985) 117:1049-54
Henderson, A Cortney; Sá, Rui Carlos; Theilmann, Rebecca J et al. (2013) The gravitational distribution of ventilation-perfusion ratio is more uniform in prone than supine posture in the normal human lung. J Appl Physiol (1985) 115:313-24
Asadi, Amran K; Cronin, Matthew V; Sá, Rui Carlos et al. (2013) Spatial-temporal dynamics of pulmonary blood flow in the healthy human lung in response to altered FI(O2). J Appl Physiol (1985) 114:107-18
Prisk, G Kim; Robertson, H Thomas (2012) Seeing may be believing. J Appl Physiol 113:315-6
Burrowes, K S; Buxton, R B; Prisk, G K (2012) Assessing potential errors of MRI-based measurements of pulmonary blood flow using a detailed network flow model. J Appl Physiol 113:130-41
Robertson, H Thomas; Buxton, Richard B (2012) Imaging for lung physiology: what do we wish we could measure? J Appl Physiol (1985) 113:317-27

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