Emphysema is a major medical problem in the US and worldwide. Diagnostic methods for the evaluation of emphysema should be sensitive to regional lung structure at the alveolar level. Diffusion MRI with hyperpolarized 3He gas that evaluates the 3He-gas ADC (apparent diffusion coefficient) can provide this sensitivity. It offers information on lung microstructure and function not provided by traditional imaging modalities and pulmonary function tests. With 3He diffusion MRI, alveolar size and the integrity of alveolar walls can be evaluated, even though the alveoli are too small to be resolved by direct imaging. This points to the large potential for clinical application of ADC measurements with hyperpolarized 3He gas. However, until recently it was not clear what specific features of lung structure are probed by 3He gas ADC measurements. Recently we proposed a theoretical model based on a large body of histology data that provides this explanation. However, substantial questions must be answered if we are to understand the 3He ADC measurement and optimally exploit its diagnostic potential. In this proposal we will extend our mathematical model that relates anisotropic ADC measurements in lung to lung microstructural parameters. The mathematical model is based on a realistic structure of lung at the acinar level described in terms of acinar airways covered with alveolar sleeves. The theory of gas diffusion in lung is based on our key concept of anisotropic diffusion in lung acinar airways. We will conduct sophisticated multi-dimensional MR experiments on sacrificed mice with healthy lungs to test the fundamental feature of our mathematical model, the anisotropy of ADC. We will develop further and test our new diffusion 3He MRI technique for tomographic """"""""lung biopsy"""""""" on a canine model of emphysema with physiology similar to human and establish a quantitative relationship between the severity of emphysema as determined by CT and the 3He anisotropic diffusivities. We will use 3He diffusion and ventilation MRI together with CT to study normal human subjects and patients with emphysema. Inter-comparison of these three techniques will establish quantitative relationships between CT, lung ventilation and anisotropic ADC measurements and will open up possibilities for new interpretations of results obtained by each modality. The potential implications are significant. A comprehensive clinical picture of emphysema progression, from initial onset of the alveolar deformation to the final stage, characterized by dramatic loss of lung function, will be established. New methods will be sensitive enough to allow early diagnosis of emphysema that will improve patient treatment. PERFORMANCESITE(S)(organization,city, state) Washington University, St. Louis, MO 63110 KEY PERSONNEL.See instructionson Page 11. Use continuationpages as neededto providethe requiredinformationinthe format shownbelow. Name Organization Roleon Project Dmitriy A. Yablonskiy, PhD Washington University Principal Investigator Mark S. Conradi, PhD Washington University Co-Investigator David Gierada, MD Washington University Co-Investigator Joel D. Cooper, M.D. Washington University Co-Investigator Stephen S. Lefrak, MD Washington University Co-Investigator Amir A. Amini, PhD Washington University Co-Investigator G. Larry Brethhorst, PhD Washington University Co-Investigator Kyongtae Ty Bae, MD, PhD Washington University Co-Investigator Charles F. Hildebolt, DDS Washington University Statistician ? PHS 398 (Rev. 05/01) Page 2 Form Page 2? Principal Investigator/Program Director (Last, first, middle): Yablonskiy, Dmitriy, A. Type the name of the principal investigator/program director at the top of each printed page and each continuation page. (For type specifications, see instructions on page 6.) RESEARCH GRANT TABLE OF CONTENTS Page Numbers Face Page .............................................................................................................................................................................................. 1 Description,

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL070037-05
Application #
7151964
Study Section
Diagnostic Imaging Study Section (DMG)
Program Officer
Croxton, Thomas
Project Start
2002-12-15
Project End
2009-11-30
Budget Start
2006-12-01
Budget End
2009-11-30
Support Year
5
Fiscal Year
2007
Total Cost
$362,679
Indirect Cost
Name
Washington University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Yablonskiy, Dmitriy A; Sukstanskii, Alexander L; Quirk, James D (2017) Diffusion lung imaging with hyperpolarized gas MRI. NMR Biomed 30:
Fishman, Emily F; Quirk, James D; Sweet, Stuart C et al. (2017) What makes a good pediatric transplant lung: Insights from in vivo lung morphometry with hyperpolarized3He magnetic resonance imaging. Pediatr Transplant 21:
Quirk, James D; Sukstanskii, Alexander L; Woods, Jason C et al. (2016) Experimental evidence of age-related adaptive changes in human acinar airways. J Appl Physiol (1985) 120:159-65
Chang, Yulin V; Quirk, James D; Yablonskiy, Dmitriy A (2015) In vivo lung morphometry with accelerated hyperpolarized (3) He diffusion MRI: a preliminary study. Magn Reson Med 73:1609-14
Lu, Jianhua; Zhou, Jinyuan; Cai, Congbo et al. (2015) Observation of true and pseudo NOE signals using CEST-MRI and CEST-MRS sequences with and without lipid suppression. Magn Reson Med 73:1615-22
Quirk, James D; Chang, Yulin V; Yablonskiy, Dmitriy A (2015) In vivo lung morphometry with hyperpolarized (3) He diffusion MRI: reproducibility and the role of diffusion-sensitizing gradient direction. Magn Reson Med 73:1252-7
Sukstanskii, Alexander L; Quirk, James D; Yablonskiy, Dmitriy A (2014) Probing lung microstructure with hyperpolarized 3He gradient echo MRI. NMR Biomed 27:1451-60
Yablonskiy, Dmitriy A; Sukstanskii, Alexander L; Conradi, Mark S (2014) Commentary on ""The influence of lung airways branching structure and diffusion time on measurements and models of short-range 3He gas MR diffusion"". J Magn Reson 239:139-42
Pennati, Francesca; Quirk, James D; Yablonskiy, Dmitriy A et al. (2014) Assessment of regional lung function with multivolume (1)H MR imaging in health and obstructive lung disease: comparison with (3)He MR imaging. Radiology 273:580-90
Yablonskiy, Dmitriy A; Sukstanskii, Alexander L; Quirk, James D et al. (2014) Probing lung microstructure with hyperpolarized noble gas diffusion MRI: theoretical models and experimental results. Magn Reson Med 71:486-505

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