Validity of apparent diffusion coefficient hyperpolarized 3He-MRI using MSCT and pulmonary function tests as references
Introduction
Pulmonary emphysema is defined by pathological criteria as an abnormal permanent enlargement of the airspaces distal to the terminal bronchioles, accompanied by destruction of the alveolar walls, and without obvious fibrosis [1]. Since the introduction of Computed Tomography (CT) showing lung parenchyma destruction in emphysema as low attenuation areas [2], many attempts have been made to establish a method for the diagnosis of early low grade emphysema. Evaluation and quantification of its distribution in an early stage are also important from a clinical point of view.
In clinical practice, pulmonary function tests (PFT) are widely used for diagnosis and monitoring of patients with chronic obstructive pulmonary disease (COPD). However, PFT represent global measurements of lung function and the distribution and extent of emphysema cannot be obtained with certainty.
High resolution computed tomography (HRCT) is currently the gold standard in morphologic lung imaging. Even though three slices have been claimed to be enough to obtain the overall extent of emphysema [3] this approach has limitations concerning early diagnosis of emphysema, as well as assessment of the severity and especially spatial distribution. The reason for limiting the examination to only three slices is mainly to minimize the radiation burden. As a consequence it has been proposed [4], [5] that multislice CT (MSCT) scanning could be an option. This proposal is based on the major advantage that the entire thorax is imaged during one single breath-hold. At the same time, three-dimensional reconstructions, lung volume measurements and quantification of lung disorders can be obtained as shown by the National Emphysema Treatment Trial [6]. Comparison of lung volumes measured by MSCT with those measured by plethysmography has been made [7]. Recently, comparison of indices from MSCT, using an appropriate radiation dose, and macroscopic and microscopic morphometry has suggested the possibility of a standardization of the examination [8]. Different software-based solutions have been developed [5], [9] to quantitatively analyze the early onset of emphysema, but as yet there is no international agreement on how to do this.
Since the mid 1990s, magnetic resonance imaging (MRI) with hyperpolarized gases has been used to evaluate different lung diseases. 3He is a non-toxic inert gas and is not taken up in the blood, lessening the possibility of systemic effects and restricting its distribution to the airspaces. Much of the current research is focused on technical developments such as the production of the hyperpolarized gas itself, both with an on-site production method and a central production method with a network distribution [10]. Most of the studies have been performed in 1.5 T scanners. However, as the polarization (“magnetization”) is achieved outside of the scanner the field strength does not determine the signal to noise ratio (SNR). MR imaging with hyperpolarized 3He requires some special hardware, i.e., a multiband radiotransmitter and special coils to transmit and receive at the frequency of 3He. Adequate software for post-processing is also essential.
It is possible to achieve several different types of functional information with 3He-MRI. There are four types of image acquisition feasible in patient studies, each one, providing different lung function information: Static ventilation imaging or spin density imaging is used to assess the distribution of gas and thereby ventilation after a single 3He inhalation. Dynamic ventilation imaging is used to assess airflow on a regional basis during a single 3He inhalation. Diffusion imaging utilizes the property of 3He to move about within the gas spaces of the lung during a breath hold. This is accomplished by adding a magnetic field gradient to the second image in a pair. The image pair is thereby sensitized to the movement of the 3He atom and the apparent diffusion coefficient (ADC) of the 3He atoms cam be calculated. This parameter in turn reflects the geometry of the structures that compartmentalize the gas within the lung as the distance the atoms move is related to the size of the space in which they are confined. Finally, oxygen sensitive imaging can be used to calculate absolute values of oxygen partial pressures and oxygen consumption during a breath hold in inspiration.
Thus, 3He-MRI opens up new ways to image airways and alveolar spaces with high spatial and temporal resolution. It offers great potential to further increase our understanding of the structure and dynamic function of the lung with the additional advantage of the lack of exposure to ionizing radiation. Diffusion-weighted 3He-MRI techniques allow assessment of alveolar dimensions by measuring the ADC [11]. Good image quality, reproducibility, feasibility and safety of the technique have been demonstrated [12], [13]. As this technique is non-invasive and does not involve radiation exposure, it may be ideal for assessment of disease progression and response to treatment in a variety of diseases such as emphysema, asthma, cystic fibrosis and bronchiolitis obliterans syndrome following lung transplant surgery.
The aim of this study was to assess the enlargement of distal airspaces in patients with early emphysema using measurement of the ADC and to compare the results with emphysema indices from MSCT and pulmonary function tests.
Section snippets
Materials and methods
Written informed consent was obtained and documented from each subject. All studies were performed in accordance with the principles of the Declaration of Helsinki, with the approval of the local Research and Ethics Committee.
Results
All results presented in the tables are with the population divided in the two groups: established emphysema and pre-clinical emphysema.
Table 1 shows the demographics and results of PFT for all subjects.
The principal results of mean ADC from HP 3He-MRI and results from MSCT are summarized in Table 2. Group mean of the mean ADC was clearly different between groups; 0.392 ± 0.119 cm2/s for established emphysema and 0.216 ± 0.046 cm2/s for pre-clinical emphysema. Group mean EI differed; 11 ± 12% for
Discussion
Diffusion weighted hyperpolarized 3He-MRI provides a new measure for pulmonary microstructure because the degree of restriction of the Brownian motion of the 3He atoms, as measured by diffusion-weighted MRI, reflects lung structure. Regions in which the diffusive motion of 3He atoms is severely restricted by physical barriers, e.g., alveolar walls, are characterized by a low ADC, whereas regions in which the diffusive motion of 3He is relatively unimpeded, e.g., emphysema bulla, are
Acknowledgements
The authors thank Curt Johansson M.Sc. Department of Radiology Malmö, Isabella Björk M.Sc. Department of Respiratory Medicine Malmö, Göran Pettersson Ph.D., and Sven Månsson Ph.D., Amersham Health R&D AB for their valuable assistance and Berend C. Stoel Ph.D., Division of Image Processing, Department of Radiology, Leiden University Medical Centre, The Netherlands, for the evaluation of MSCT data.
The study was sponsored by Amersham Health, now GE Healthcare, Little Chalfont, UK and Pfizer Inc.,
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