Magnetic resonance lung function--a breakthrough for lung imaging and functional assessment? A phantom study and clinical trial

Abstract

Background: Chronic lung diseases are a major issue in public health. A serial pulmonary assessment using imaging techniques free of ionizing radiation and which provides early information on local function impairment would therefore be a considerably important development. Magnetic resonance imaging (MRI) is a powerful tool for the static and dynamic imaging of many organs. Its application in lung imaging however, has been limited due to the low water content of the lung and the artefacts evident at air-tissue interfaces. Many attempts have been made to visualize local ventilation using the inhalation of hyperpolarized gases or gadolinium aerosol responding to MRI. None of these methods are applicable for broad clinical use as they require specific equipment.

Methods: We have shown previously that low-field MRI can be used for static imaging of the lung. Here we show that mathematical processing of data derived from serial MRI scans during the respiratory cycle produces good quality images of local ventilation without any contrast agent. A phantom study and investigations in 85 patients were performed.

Results: The phantom study proved our theoretical considerations. In 99 patient investigations good correlation (r = 0.8; p < or = 0.001) was seen for pulmonary function tests and MR ventilation measurements. Small ventilation defects were visualized.

Conclusion: With this method, ventilation defects can be diagnosed long before any imaging or pulmonary function test will indicate disease. This surprisingly simple approach could easily be incorporated in clinical routine and may be a breakthrough for lung imaging and functional assessment.

Figure 1

a. Native ventilation MR image of one patient during expiration and inspiration. For precise measurement the region of interest would have to move during the respiratory cycle, we therefore include a schematic of our theoretical considerations. The four circles schematically represent four alveoli in a volume (voxel). During inspiration, tissue will be replaced by air causing a lower MR signal as shown on the right. In the same volume now only one of the "Alveoli" will give a signal. The ventilation can be derived from this signal change. b. Upper images: native (unregistered) MR ventilation images during expiration and inspiration. Measurements at the same location are almost impossible while the lung is moving as the same region of interest can not be exactly located. Note the different MR signal and the different size and shape of the lung. Lower images: Registered images. The registration process artificially changes the volume of the lung. An interpolation of the original image intensity values was used to compute the warped image when specific regions are expanded or contracted. The signal changes of the lung are then noted, the size and shape of the thorax stay the same. This way the signal change of each pixel can be measured and ventilation calculated. Note the different MR signal. In contrast to the upper images size and shape of the lung stay unchanged.

Figure 2

MR image of the phantom at "inspiration" = maximal air content and "expiration" = minimal air content. The graph shows the correlation between the air content in ml air/ml sponge measured by MRI (= MR ventilation) and that calculated from the volume of the sponge (= real ventilation). Dashed lines = regression line and 95% confidence interval.

Figure 3

Upper image and graph: patient with normal pulmonary function test. On the left, a MR ventilation image is shown with the 6 ROIs (in different colours) used for ventilation measurement, on the right are the ventilation graphs which show the ventilation (= ml air/ml lung parenchyma) in 50 images for each ROI during the respiratory cycles. The 50 measurements span a total of one minute. The colours of the graphs match the colours of the ROIs in the ventilation image to differenciate the 6 lung regions. The ventilation is similar in each of the ROIs. Note the tiring of the young patient (maximal in- and expiration at the beginning only). Ventilation measurements: Right: upper field (turquoise) 0.64 ml/cm³; middle field (violet) 0.68 ml/cm³; lower field (brown) 0.65 ml/cm³. Left: upper field (yellow) 0.67 ml/cm³; middle field (pink) 0.68 ml/cm³; lower field (blue) 0.62 ml/cm³. Middle image and graph: patient with cystic fibrosis. The total ventilation is markedly decreased compared to the healthy patient. Additionally, the different lung regions show a very different ventilation, poorest in the left middle field. Ventilation measurements: Right: upper field (turquoise) 0.27 ml/cm³; middle field (violet) 0.17 ml/cm³; lower field (brown) 0.3 ml/cm³. Left: upper field (yellow) 0.2 ml/cm³; middle field (pink) 0.32 ml/cm³; lower field (blue) 0.38 ml/cm³. Bottom Graph: Correlation of MR ventilation and vital capacity measured by conventional pulmonary function test (r = 0,8; p ≤ 0,001). Black lines = regression line and 95% confidence interval.

Figure 4

Ventilation map images. One image selected from the ventilation map video. Increase in air content is coded red (inspiration); decrease is coded green (expiration). In image b and c note the artifacts in the region of the diaphragm which occur secondary to the registration process which registers the lungs only. However, the lung is still clearly outlined. a. healthy person in inspiration. Note the homogeneous contribution of air in inspiration. b. patient with cystic fibrosis. Note the multiple ventilation defects (black areas) and the poor overall ventilation (patchy ventilation pattern and little colour coded areas). c. patient with mycoplasma pneumonia. Despite normal global lung function a large ventilation defect (Circled black area) is noted in the right lower field where conventional imaging shows a pneumonic infiltrate. d. patient with asthma and good fev1 in the pulmonary function test. Despite good fev1 this patient may require more efficient treatment as there is still an impairment of local ventilation peripherally and in the left lower field (arrows).