Optical Coherence Tomography of Pulmonary Arterial Walls in Humans and Pigs (Sus scrofa domesticus)

Pulmonary arterial hypertension (PAH) is a devastating disorder characterized by progressive elevation of the pulmonary pressures that, in the absence of therapy, results in chronic right-heart failure and premature death. The vascular pathology of PAH is characterized by progressive loss of small (diameter, less than 50 μm) peripheral pulmonary arteries along with abnormal medial thickening, neointimal formation, and intraluminal narrowing of the remaining pulmonary arteries. Vascular pathology correlates with disease severity, given that hemodynamic effects and disease outcomes are worse in patients with advanced compared with lower-grade lesions. Novel imaging tools are urgently needed that demonstrate the extent of vascular remodeling in PAH patients during diagnosis and treatment monitoring. Optical coherence tomography (OCT) is a catheter-based intravascular imaging technique used to obtain high-resolution 2D and 3D cross-sectional images of coronary arteries, thus revealing the extent of vascular wall pathology due to diseases such as atherosclerosis and in-stent restenosis; its utility as a diagnostic tool in the assessment of the pulmonary circulation is unknown. Here we show that OCT provides high-definition images that capture the morphology of pulmonary arterial walls in explanted human lungs and during pulmonary arterial catheterization of an adult pig. We conclude that OCT may facilitate the evaluation of patients with PAH by disclosing the degree of wall remodeling present in pulmonary vessels. Future studies are warranted to determine whether this information complements the hemodynamic and functional assessments routinely performed in PAH patients, facilitates treatment selection, and improves estimates of prognosis and outcome.Abbreviations: OCT, optical coherence tomography; PAC, pulmonary artery catheter; PAH, pulmonary arterial hypertensionPulmonary arterial hypertension (PAH) is a devastating disorder characterized by progressive elevation of pulmonary pressures that, when untreated, can lead to chronic right heart failure and death.¹⁴ The vascular pathology of PAH is characterized by neointimal formation, medial thickening, intravascular thrombi and, in severe cases, intravascular clusters of disorganized endothelial cells that give rise to tortuous endovascular channels.⁸ Most of the early vascular lesions are found in small (diameter, less than 50 μm) pulmonary arteries. However, as the disease advances, pulmonary arteries (diameter, 50 μm or larger) proximal to these lesions also display evidence of luminal narrowing and medial thickening.^7,8,15 Most patients with PAH are younger than those with chronic systemic vascular disorders (that is, coronary artery disease, peripheral vascular disease, systemic hypertension), whose vascular pathology involves mostly large to medium-sized arteries. However, both patient populations demonstrate various pathologic features, including vascular smooth-cell accumulation, neointimal formation, inflammation, luminal narrowing, and alterations in the composition of the extracellular matrix.^6,17The only definite way to diagnose PAH is through right heart catheterization to directly measure the pressure in the pulmonary circulation. Although pulmonary angiography during right heart catheterization cannot be used to diagnose PAH, it provides supportive evidence of PAH by demonstrating significant peripheral small vessel loss and luminal narrowing in the remaining central vessels. Angiography can help clinicians visualize pulmonary vessels in real time, but this diagnostic technique has important limitations. The use of ionized contrast can cause allergic reactions and may trigger acute renal failure due to contrast-induced nephropathy.²⁶ In addition, pulmonary angiography provides information regarding gross vessel appearance and small vessel perfusion but not about the state of vascular wall remodeling or the extent of luminal narrowing associated with PAH at any stage.^5,16 Therefore, imaging techniques are urgently needed that complement the hemodynamic information obtained via right heart catheterization with a safe and reproducible method to assess vascular wall pathology, thereby allowing clinicians to correlate the clinical evolution of PAH with the progression of vascular pathology.The last decade has seen tremendous progress in the development of intravascular imaging modalities that can identify patients at risk for developing complications related to systemic vascular disease and therefore prevent disease-related morbidity and mortality.⁴ One such modality is optical coherence tomography (OCT), an imaging technique that uses a thin (diameter, 1.0 mm) wire and near-infrared light to capture micrometer-resolution, 3D images from within optical scattering media (for example, biologic tissue).¹ Superior to other intravascular imaging techniques, OCT is frequently used in patients with coronary artery disease, where it provides high-resolution images of the coronary arterial wall that correlate highly with pathology seen in explanted vessels.^10,11,21 To date, several small studies have demonstrated the application of OCT to the evaluation of vascular remodeling in both idiopathic PAH and chronic thromboembolic PAH.^7,21 However, despite OCT''s obvious advantages in the characterization of vascular remodeling in discrete segments of the pulmonary circulation, whether OCT provides anatomic information across the length of the pulmonary artery has not been tested.Here, we report the capacity of OCT to obtain both longitudinal and cross-sectional images that provide accurate anatomic information on healthy pulmonary arteries in explanted human lungs and during the pulmonary arterial catheterization of a live adult pig (Sus scrofa domesticus).