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Regional Pulmonary Blood Flow in Huma ns and Dogs by 4D Computed Tomography

Posted Jun 30, 2008 Updated Apr 7, 2023
By Jonathan H. Dakin MD , Timothy W. Evans DSc , David M. Hansell MD , Eric A. Hoffman PhD
10 min read

Rationale and Objectives

Pulmonary vascular control mechanisms are complex and likely to differ between species. We wish to quantify regional perfusion and the effects of gravity using computed tomography.

Materials and Methods

Sequential density measurements following the administration of a bolus of iodinated contrast medium were acquired from four healthy human subjects and four dogs.

Results

In humans, perfusion (Q) was linear throughout most of the range of vertical height, with an overall gradient of −2.6% cm −1 . However, when perfusion was normalized to “tissue” density (blood plus tissue: sQ t ), maximum perfusion occurred around the mid-range of vertical height, being 9% (range 1–22%) greater than either the dorsal or ventral extreme. Within discrete transverse axial sections, concentric zones of perfusion centered on blood vessels were demonstrated. The relationship between sQ t and vertical height in dogs was distinctly linear, with a gradient of −7.2% cm −1 . In dogs, the median gradient of Q was −13.6% cm −1 (range −9.7 to −17.1%).

Conclusions

Differences in regional pulmonary perfusion, particularly the vertical gradient observed in humans and dogs, may in part reflect anatomic differences between the symmetric dichotomous branching structure of the human pulmonary vasculature and the more asymmetrical structure found in dogs.

The mechanisms that regulate pulmonary vascular control are poorly understood, but assume therapeutic significance in patients with clinical conditions characterized by ventilation perfusion (V/Q) mismatch, such as pulmonary embolism and the acute respiratory distress syndrome. Regional pulmonary perfusion has been studied using radioactive tracers ( ), positron emission tomography (PET) ( ), single positron emission computed tomography ( ), and magnetic resonance imaging ( ). Computed tomography (CT), despite its superior spatial resolution and shorter acquisition times, has not been as fully explored ( ). Previous studies of pulmonary perfusion in humans using CT have been limited to discrete sampling at defined regions of interest (ROIs), and revealed increased perfusion to dependent lung regions ( ), but were not analyzed on a pixel-by-pixel basis. The aims of this study were twofold. First, using four-dimensional CT, regional pulmonary perfusion was characterized in conscious, normal human subjects, to identify the effect of gravity on perfusion gradients in the normal lung. Second, previously acquired data from dogs using the same methodology ( ) were reanalyzed using the technical modifications necessary in human subjects. This allowed interspecies comparisons to identify differences that might relate to the different vascular branching patterns in the two species. Quadrupeds have been used extensively to study pulmonary perfusion, and inference has been drawn to perfusion in humans, although equivalence of their pulmonary physiology has not been demonstrated.

Materials and methods

Study Subjects

Volunteer studies were performed in six male human subjects between the ages of 30 and 48 years) at the Royal Brompton Hospital, London, UK. All subjects were nonsmokers and self-reported to be healthy. Males were chosen to avoid exposure of breast tissue to radiation. The protocol was approved by local institutional board review, and all subjects provided informed written consent. All animal studies were performed within guidelines for animal care stipulated by the American Physiological Society and the National Institutes of Health. Dogs evaluated in this study are reported in Chon et al and preparation details are provided in that study ( ). Studies were approved by the University of Pennsylvania Institutional Animal Care and Use Committee.

Study Design

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flowvolume=ΔHU1AUCa flow

volume

=

Δ

HU

1

AUC

a

where ΔHU t = the difference between baseline and peak density in the tissue ROI (HU) and AUC a = the area under the time attenuation curve of the feeding vessel (HU). Thus, perfusion is measured as blood flow per unit voxel, and is independent of the volume of the ROI sampled. This method assumes negligible contrast washout from the parenchymal ROI before peak opacification ( ).

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Methods

Scanning Protocol

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Volunteers

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Animals

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Data Analysis

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Sampling

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Animal Studies

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Humans

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Filtering

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Figure 1, Specimen curve fits for a range of chi-squared values. Each figure illustrates a gamma variate fit typical of the given chi-squared value.

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Statistical Analysis

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Results

Volunteers

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Table 1

Subject Demographic Data

MC EM LP SS Mean Age (y) 30 33 35 30 34 Mass (kg) 73 89 76 81 82 Height (m) 1.82 1.83 1.68 1.83 1.81

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Figure 2, Distribution of (a) perfusion (Q/mL/min −1mL −1 ), (b) air fraction, and (c) normalized perfusion (sQ tmL/min −1g −1 ) in a volunteer subject (L.P.).

Table 2

Radiologic and Physiologic Parameters

Human Dog Adjacent Grid Overlapping Grid_N_ 76,515 2,163 60,503 Baseline −745 −663 −665 Opacification 37 123 124 Chi-squared 83 139 136 MTT 0.3 6.1 −91.2 Rise time 3.3 2.1 2 F air 0.75 0.66 0.67 Q 1.5 2.4 2.4 sQ t 5.6 6.8 6.6

n , number of gamma variate fits; baseline, baseline attenuation before opacification with contrast (Hounsfield units); opacification, difference between baseline and peak attenuation during opacification (Hounsfield units); chi-squared, goodness of fit of gamma variate to tissue opacification/time curve; MTT, mean transit time of contrast bolus in tissue ROI; rise time, time of arrival of contrast bolus in tissue ROI; F air , air fractional content of tissue ROI; Q, perfusion; sQ t m, perfusion normalized to “water” fraction; ROI, region of interest.

Data are intersubject means of radiologic and physiologic parameters.

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Figure 3, Distribution of normalized perfusion (sQ t ) along the z axis for human scans. Box and whisker plots show the distribution of values of sQ t measured within each z axial plane. Central dot, median value, extremes of box indicate upper and lower quartiles. Whiskers are drawn at a standard span from each quartile. The slice at 20 mm was positioned on the pulmonary artery bifurcation, with other slices reading caudally.

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Figure 4, Distribution of perfusion along the vertical axis in humans. Distribution of Q/perfusion (upper panel) and sQ tnormalized perfusion (lower panel) along the vertical axis in volunteer subjects.

Figure 5, Topographic distribution of iso-sQt points in human lung. Topographic distribution of iso-sQ t points (points with equal normalized perfusion) in human lung. Each plot represents an octile in the distribution of values of sQ t . The points plotted are those whose sQ t lies within the range indicated on the panel header strip (mL/min −1g −1 ). The lung outline indicated within each panel is the same slice of the left lung subject (L.P.).

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Dogs

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Figure 6, Color map showing distribution of normalized perfusion (sQ t mL/min −1g −1 ) in a supine dog.

Figure 7, Distribution of sQ t along the vertical axis in dogs. Distribution of normalized perfusion (sQ t ) along the vertical axis in dogs using nonoverlapping (upper panel) and overlapping (lower panel) translational methods of sampling. Each plot within the trellis represents a different animal subject.

Figure 8, Topographic distribution of iso sQt points in dog lungs. Topographic distribution of iso sQ t points (points with equal normalized perfusion) in dog lungs using nonoverlapping (upper panel) and overlapping (lower panel) translational methods of sampling. Each plot within the trellis represents an octile in the distribution of values of sQ t . The points plotted are those whose sQ t lies within the range indicated on the panel header strip (mL/min −1g −1 ). The lung outline indicated within each panel is the same slice of the left lung of one subject.

Table 3

Derived Parameters for Linear Regression of Q on Vertical Height for Dog Studies

Subject Intercept Gradient_r 2_P X1030 11.8 −9.1 0.76 0 X1346 9.9 −9.6 0.95 0 X1606 7.3 −3.2 0.75 <10 −5 X3522 7.8 −7.1 0.83 0 Median 8.85 −8.1 0.8 0

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Discussion

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Methodologic Considerations

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Regional Distribution of Perfusion

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Intraregional Distribution of Perfusion

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Comparison of Human Data to Animal Species

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Acknowledgments

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