Pulmonary vascular morphology as an imaging biomarker in chronic thromboembolic pulmonary hypertension

Abstract

Patients with chronic thromboembolic pulmonary hypertension (CTEPH) have morphologic changes to the pulmonary vasculature. These include pruning of the distal vessels, dilation of the proximal vessels, and increased vascular tortuosity. Advances in image processing and computer vision enable objective detection and quantification of these processes in clinically acquired computed tomographic (CT) scans. Three-dimensional reconstructions of the pulmonary vasculature were created from the CT angiograms of 18 patients with CTEPH diagnosed using imaging and hemodynamics as well as 15 control patients referred to our Dyspnea Clinic and found to have no evidence of pulmonary vascular disease. Compared to controls, CTEPH patients exhibited greater pruning of the distal vasculature (median density of small-vessel volume: 2.7 [interquartile range (IQR): 2.5-3.0] vs. 3.2 [3.0-3.8]; P = 0.008), greater dilation of proximal arteries (median fraction of blood in large arteries: 0.35 [IQR: 0.30-0.41] vs. 0.23 [0.21-0.31]; P = 0.0005), and increased tortuosity in the pulmonary arterial tree (median: 4.92% [IQR: 4.85%-5.21%] vs. 4.63% [4.39%-4.92%]; P = 0.004). CTEPH was not associated with dilation of proximal veins or increased tortuosity in the venous system. Distal pruning of the vasculature was correlated with the cardiac index (R = 0.51, P = 0.04). Quantitative models derived from CT scans can be used to measure changes in vascular morphology previously described subjectively in CTEPH. These measurements are also correlated with invasive metrics of pulmonary hemodynamics, suggesting that they may be used to assess disease severity. Further work in a larger cohort may enable the use of such measures as a biomarker for diagnostic, phenotyping, and prognostic purposes.

Keywords: arterial; chronic thromboembolic pulmonary hypertension; computed tomography; tortuosity.

Figure 1

Examples of vascular reconstruction for 2 control subjects (top) and 2 patients with chronic thromboembolic pulmonary hypertension (bottom). Some patients exhibited patchy disease (bottom left), whereas others exhibited diffuse disease throughout the vascular tree (bottom right).

Figure 2

Volume distribution profiles for CTEPH and control subjects. A, Whole-lung profile. Note the rightward and downward shift of the peak for subjects with CTEPH, indicating loss of small vasculature. B, Individual lung profiles. C, D, The two computed measures of small-vessel loss, the small-vessel volume fraction BV5/TBV (C) and small-vessel volume density ρBV5 (D). BV5: blood vessel volume for vessels with a cross-sectional area ≤ 5 mm²; CTEPH: chronic thromboembolic pulmonary hypertension; TBV: total blood vessel volume; ρBV5: BV5/lung volume.

Figure 3

A, B, Example of an arterial-venous-segmented vascular tree is shown for a patient with CTEPH (A) and a control subject (B), with the arterial phase shown in blue and the venous phase shown in red. C–F, The proximal vasculature (C, D) and the distal vasculature (E, F), separated by size, are shown under the respective images. Note the loss of smaller vessels in E, in comparison with F, and the dilation of the large proximal vasculature in the arterial, as compared to venous, proximal vessels in C. G, Relative volume distribution profiles combined for each cohort for both the arterial (top) and venous (bottom) phases. Note the rightward shift of the vascular profile in the subjects with CTEPH (black lines) compared to controls (red lines), as also demonstrated in Figure 2. In the arterial system, the CTEPH cohort also has increased distribution in the large vessels (cross-sectional area > 10 mm²). H, Comparisons of large vessels (BV>10) and small vessels (BV5) are shown for both groups, highlighting the difference in arterial/venous (Art/Vein) ratios in the two different vessel sizes. BV5: blood vessel volume for vessels with a cross-sectional area ≤ 5 mm²; BV>10: blood vessel volume for vessels with a cross-sectional area > 10 mm²; CTEPH: chronic thromboembolic pulmonary hypertension.

Figure 4

A, B, Examples of the right-lung proximal arterial vasculature in a control (A) and a patient with CTEPH and evidence of increased tortuosity (B). C, The proximal venous system, with less-tortuous vessels in the same CTEPH patient. D, E, The most tortuous arterial (D) and venous (E) proximal vessels in the right lower lobe of another patient with CTEPH, illustrating the significant tortuosity in the arterial but not the venous system. Proximal vessels are shown for ease of visualization. F, Comparison between the CTEPH and control cohorts. G, H, Relationships between segment tortuosity and segment length (G) and between segment tortuosity and segment cross-sectional area (H). Note that arterial tortuosity in CTEPH remains higher than arterial tortuosity in controls and venous tortuosity in both groups. CTEPH: chronic thromboembolic pulmonary hypertension.

Figure 5

A–D, Logistic regression–based receiver operating curves (ROCs) based on four of the key morphologic measures distinguishing CTEPH and control subjects (combined whole lungs): BV5/TBV (A), ρBV5 (B), BV>10_ART/BV>10_VEIN(C), and arterial tortuosity (D). Of these, the arterial/venous ratio of the larger vessels has the strongest discriminating ability, as measured by the area under the curve. E, Model combining all four parameters. BV5: blood vessel volume for vessels with a cross-sectional area ≤ 5 mm²; BV>10: blood vessel volume for vessels with a cross-sectional area > 10 mm²; CTEPH: chronic thromboembolic pulmonary hypertension; TBV: total blood vessel volume; ρBV5: BV5/lung volume.