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Principal Investigator
Name
Dmitriy Yablonskiy
Degrees
PhD
Institution
Washington University Mallinckrodt Institute of Radiology
Position Title
Professor of Radiology
Email
About this CDAS Project
Study
NLST (Learn more about this study)
Project ID
2004-90024
Initial CDAS Request Approval
Aug 6, 2004
Title
Quantitation of Lung Ventilation and Structure by 3He MR
Summary
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 previous 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. Theory of gas diffusion in lung is based on our major 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 -ung biopsy-lt;/SPAN> on a canine model of emphysema with physiology similar to the 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. More accurate selection of patients may substantially improve the outcome of LVRS.
Aims

Hyperpolarized 3He atoms entering lung acini diffuse. Acinar airways covered with alveolar sleeves serve as obstacles to the path of diffusing 3He atoms; hence diffusivity of 3He gas can provide information on the acinar airways geometry. Specific Aim 1 To develop a new technique based on 3He diffusion MRI for tomographic -ung biopsy- This technique will allow in vivo non-invasive quantitative assessment of lung microstructural parameters at the alveolar level and serve as a powerful tool for identifying emphysema. We will extend our existing mathematical model that is based on a realistic structure of lung and relates anisotropic 3He ADC measurements in lung to lung microstructural parameters at the alveolar level. We will test this model on healthy mice and canines with different levels of emphysema. The mice will be used for sophisticated multi-dimensional MR experiments that would not be possible or safe with humans. The canine model, expressing a controlled level of emphysema, has physiology similar to human and will be used (a) to establish a set of essential parameters characterizing lung microstructure that can be obtained from 3He diffusion MRI and (b) to find optimal values for 3He diffusion-sensitive MRI pulse sequence parameters for use in humans. The current imaging standard for in-vivo evaluation of emphysema - CT - quantifies the density of lung tissue but does not provide information on lung tissue microstructure and can not readily distinguish between ventilated and non-ventilated lung regions. 3He MRI is capable of providing information on both lung ventilation and microstructure. Specific Aim 2 To establish a quantitative set of relationships between regional lung ventilation as determined by 3He spin-density MRI, lung microstructural parameters as determined by 3He diffusion MRI, and X-ray linear attenuation coefficient (LAC) obtained from CT images. These relationships will provide new insightful clinical information that can be inferred from CT images. We expect correlation between these measurements (ventilation, ADCs and CT) because abnormal, permanent enlargement of acinar air-spaces, accompanied by destruction of their walls with emphysema progression results in (a) decreased lung tissue density and increased 3He diffusivity (lesser restrictions to diffusion); and (b) reduction and eventual loss of elastic lung tissue recoil and loss of lung ventilatory function. We will conduct all studies on a canine model expressing a controlled level of emphysema and human subjects with different levels of emphysema. A quantitative relationship between 3He MRI data and LAC obtained from CT will be found through image segmentation procedure based on multi-modality registration of CT data with 3He MRI data. Overall, we propose to develop further, verify on animal models, apply to patients with emphysema and test against current imaging techniques new 3He MRI methods for imaging of human lung. These methods take advantage of the MR imaging properties of hyperpolarized 3He gas and will allow quantitative evaluation of lung ventilatory function as well as lung microstructure at the alveolar level. 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. Our methods will also allow for more accurate selection of patients suitable for LVRS that might substantially improve the outcome of LVRS

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