In vivo lung morphometry with hyperpolarized³He diffusion MRI in canines with induced emphysema: disease progression and comparison with computed tomography

Abstract

Despite a long history of development, diagnostic tools for in vivo regional assessment of lungs in patients with pulmonary emphysema are not yet readily available. Recently, a new imaging technique, in vivo lung morphometry, was introduced by our group. This technique is based on MRI measurements of diffusion of hyperpolarized 3 He gas in lung air spaces and provides quantitative in vivo tomographic information on lung microstructure at the level of the acinar airways. Compared with standard diffusivity measurements that strongly depend on pulse sequence parameters (mainly diffusion time), our approach evaluates a "hard number," the average acinar airway radius. For healthy dogs, we find here a mean acinar airway radius of ~0.3 mm compared with 0.36 mm in healthy humans. The purpose of the present study is the application of this technique for quantification of emphysema progression in dogs with experimentally induced disease. The diffusivity measurements and resulting acinar airway geometrical characteristics were correlated with the local lung density and local lung-specific air volume calculated from quantitative computed tomography data obtained on the same dogs. The results establish an important association between the two modalities. The observed sensitivity of our method to emphysema progression suggests that this technique has potential for the diagnosis of emphysema and tracking of disease progression or improvement via a pharmaceutical intervention. Keywords hyperpolarized gases; magnetic resonance imaging; diffusionPulmonary emphysema, which is defined as "a condition of the lung characterized by abnormal, permanent enlargement of airspaces distal to the terminal bronchioles, accompanied by destruction of their walls, without fibrosis" (23), is a major medical problem worldwide. There are several conventional methods of diagnosing and evaluating emphysema: pulmonary function tests, chest radiography, and computed tomography (CT). These methods in general provide a gross assessment of the degree of emphysema and are used for qualitative, clinical applications. Pulmonary function tests are reportedly insensitive to early, mild changes of emphysema (24); the same is true for conventional chest radiography (25). CT is more sensitive

In vivo lung morphometry with hyperpolarized 3He diffusion MRI: Theoretical background

“…As an example, we have re-analyzed previously published data obtained with 3 He diffusion MRI in a dog model of unilateral emphysema [26]. The theoretical model Eqs.…”

An Official Research Policy Statement of the American Thoracic Society/European Respiratory Society: Standards for Quantitative Assessment of Lung Structure

“…The ADC value of hyperpolarized 3 He gas in unrestricted air (0.8 cm 2 /s) is reduced to 0.2 cm 2 /s in a normal living human lung, and increases in severe emphysema-0.6 cm 2 /s is common (199,200); the corresponding values are lower in small animals (198,201). Applying intersection and point counting to histologic lung specimens related to the MRI permits interpretation of the ADC with respect to morphometric characteristics of peripheral airspaces (71,119,201,202), namely, the alveolar surface-tovolume ratio or its reciprocal, L m (SECTION 6.6). Both the ADC and L m estimate the mean free distance within the combined airspaces of alveolar sacs and ducts.…”

Stem Cells and Cell Therapies in Lung Biology and Diseases: Conference Report

“…Because airway structures will limit the diffusion of gas, measurement of the atomic motion will provide information about the lung microstructure. Both gases have been used in humans, large animals, and, more recently, small animals in both healthy and diseased conditions and have provided important insights into the three-dimensional structure of the lungs (64)(65)(66)(67)(68)(69)(70)(71)(72)(73). The usefulness of this approach to treatment of human disease is obvious, with greater ability to determine the changes in lung microstructure as a function of disease and over time.…”