Hyperpolarized 3He diffusion MRI and histology in pulmonary emphysema

Abstract

Diffusion MRI of hyperpolarized (3)He shows that the apparent diffusion coefficient (ADC) of (3)He gas is highly restricted in the normal lung and becomes nearly unrestricted in severe emphysema. The nature of this restricted diffusion provides information about lung structure; however, no direct comparison with histology in human lungs has been reported. The purpose of this study is to provide information about (3)He gas diffusivity in explanted human lungs, and describe the relationship between (3)He diffusivity and the surface area to lung volume ratio (SA/V) and mean linear intercept (L(m)) measurements--the gold standard for diagnosis of emphysema. Explanted lungs from patients who were undergoing lung transplantation for advanced COPD, and donor lungs that were not used for transplantation were imaged via (3)He diffusion MRI. Histological measurements were made on the same specimens after they were frozen in the position of study. There is an inverse correlation between diffusivity and SA/V (and a positive correlation between diffusivity and L(m)). An important result is that restricted (3)He diffusivity separated normal from emphysematous lung tissue more clearly than the morphometric analyses. This effect may be due to the smaller histologic sampling size compared to the MRI voxel sizes.

FIG. 1

Photo of a typical transverse slice of one of the control lungs, showing four holes where samples were taken for processing, and measurements of the SA/V and L_m intercept. A photomicrograph is shown at right, overlaid by the sampling grid. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]

FIG. 2

Sample histological slides for various degrees of emphysema. a: For the sample from a nominally healthy lung, L_m = 0.027 cm, SA/V = 204 cm^-1, and ADC = 0.23 cm²/s. b: For the moderately diseased lung sample, L_m = 0.041 cm, SA/V = 134 cm^-1, and ADC = 0.42 cm²/s. c: For the severely diseased sample, L_m = 0.062 cm, SA/V = 89.5 cm^-1, and ADC = 0.63 cm²/s.

FIG. 3

Diffusivity maps for two control lungs and four lungs with severe COPD. The differences between the two groups are apparent from the images and color scale. Orientation differs slightly from image to image, but the apex is to the left and the diaphragmatic surface is to the right in these approximately sagittal slices. While all of the emphysematous lungs studied had large areas of severe disease, there was a significant range of tissue destruction at different locations within each of the several diseased lungs.

FIG. 4

Comparison of average SA/V and ADC values (each point is an average over a single lung). Here the SA/V value is the average over all histological samples from the given lung, and the ADC value is the average over the data from the image voxels corresponding to the sampled regions. The correlation is strong (R = 0.96).

FIG. 5

Graphs comparing both SA/V and L_m as functions of the diffusivity in all individual samples from control and emphysematous explanted lungs. Both histological measures show correlations with ³He diffusivity and ADC.

FIG. 6

Histograms of SA/V (top) and ³He diffusivity (bottom) for the nine lungs studied. While there is significant overlap of the two groups for the histologic measure of emphysema (SA/V), restricted diffusion of ³He very clearly separates them. (The histograms of L_m and ADC are very similar.)