Vertical gradients in regional lung density and perfusion in the supine human lung: the Slinky effect

Abstract

In vivo radioactive tracer and microsphere studies have differing conclusions as to the magnitude of the gravitational effect on the distribution of pulmonary blood flow. We hypothesized that some of the apparent vertical perfusion gradient in vivo is due to compression of dependent lung increasing local lung density and therefore perfusion/volume. To test this, six normal subjects underwent functional magnetic resonance imaging with arterial spin labeling during breath holding at functional residual capacity, and perfusion quantified in nonoverlapping 15 mm sagittal slices covering most of the right lung. Lung proton density was measured in the same slices using a short echo 2D-Fast Low-Angle SHot (FLASH) sequence. Mean perfusion was 1.7 +/- 0.6 ml x min(-1) x cm(-3) and was related to vertical height above the dependent lung (slope = -3%/cm, P < 0.0001). Lung density averaged 0.34 +/- 0.08 g/cm3 and was also related to vertical height (slope = -4.9%/cm, P < 0.0001). By contrast, when perfusion was normalized for regional lung density, the slope of the height-perfusion relationship was not significantly different from zero (P = 0.2). This suggests that in vivo variations in regional lung density affect the interpretation of vertical gradients in pulmonary blood flow and is consistent with a simple conceptual model: the lung behaves like a Slinky (Slinky is a registered trademark of Poof-Slinky Incorporated), a deformable spring distorting under its own weight. The greater density of lung tissue in the dependent regions of the lung is analogous to a greater number of coils in the dependent portion of the vertically oriented spring. This implies that measurements of perfusion in vivo will be influenced by density distributions and will differ from excised lungs where density gradients are reduced by processing.

Figures

Figure 1

Figure 1A shows an ASL measure of regional pulmonary blood flow (in ml/min/cm3) after correction for coil heterogeneity and absolute quantification of perfusion in a representative subject lying supine in the MR scanner. This is a sagittal slice of the mid-right lung at functional residual capacity. The posterior lung is at the bottom of the image and region adjacent to the diaphragm is visible as the concave region on the left side of the image. The division of the right lung unto upper, middle and lower lobes is visible. The signal intensity of the images scales as a function of perfusion with brighter regions representing areas of greater blood flow. Figure 1B shows FLASH proton density (g/cm3) measures of regional lung density in the lung same slice as Figure 1A. A vertical gradient in proton density is visible as brighter voxels in the dependent portion of the lung. Figure 1C shows data from the same lung slice as Figure 1 A and B after absolute quantification of perfusion and density, image registration, and division of the ASL measure of perfusion by the FLASH density to give a measure of density normalized perfusion (ml/min/g).

Figure 2

The data in the left column in Figure 2 shows perfusion (A), density (D) and density normalized perfusion (G) per voxel graphed as a function of distance from the most dependent portion of the lung for all 3 lung slices in all 6 subjects. Note that the x and y axes have been reversed in the images so that vertical height increases up the figure. In each of these three figures the white line is the fit of the linear regression encompassing all data points. The middle column (B,E,H) shows the same data averaged for voxels lying within the same gravitational plane. The right hand column (C,F,I) shows the same data divided into 3 planes of equal height. It can be appreciated that the vertical slope in perfusion seen in Figure B is substantially altered when the significant vertical gradient in density (E) is accounted for, and in H the slope of the vertical relationship between density normalized perfusion and height is not significantly different from zero. Similarly, there was a significant difference in perfusion between lung gravitational regions (C) and perfusion was least in the non-dependent region and greatest in the intermediate lung region. Density was significantly less in the non-dependent region and greater in the gravitationally dependent region (F). When perfusion was normalized for density (I) perfusion in the middle region of the lung was significantly greater than either the dependent or non-dependent regions. However in contrast to the perfusion data which was not corrected for density (C), the non-dependent lung regions did not differ significantly from the dependent lung regions. (see text for details). * = significantly different from middle and dependent region, # = significantly different from dependent and non-dependent region, + = significantly different from non-dependent and middle region, all p

Figure 3

A Slinky®-type deformable spring during parabolic flight. In A, taken in zero G, the coils of the spring are uniform, whereas in B taken in 2 G the effects of gravity on the distribution of the coils are clearly visible.