Distinct types of plexiform lesions identified by synchrotron-based phase-contrast micro-CT

Abstract

In pulmonary arterial hypertension, plexiform lesions are associated with severe arterial obstruction and right ventricular failure. Exploring their structure and position is crucial for understanding the interplay between hemodynamics and vascular remodeling. The aim of this research was to use synchrotron-based phase contrast micro-CT to study the three-dimensional structure of plexiform lesions. Archived paraffin-embedded tissue-samples from 14 patients with pulmonary arterial hypertension (13 idiopathic, 1 with known BMPR2-mutation) were imaged. Clinical data showed high median PVR (12,5 WU) and mPAP (68 mmHg). Vascular lesions with more than one lumen were defined as plexiform. Prior radiopaque dye injection in some samples facilitated 3D-rendering. Four distinct types of plexiform lesions were identified: (1) localized within or derived from monopodial branches (supernumerary arteries), often with connection to the vasa vasorum; (2) localized between pulmonary arteries and larger airways as a tortuous transformation of intrapulmonary bronchopulmonary anastomoses; (3) as spherical structures at unexpected abrupt ends of distal pulmonary arteries; and (4) as occluded pulmonary arteries with re-canalization. By appearance and localization, types 1-2 potentially relieve pressure via the bronchial circulation, as pulmonary arteries in these patients were almost invariably occluded distally. In addition, types 1-3 were often surrounded by dilated thin-walled vessels, often connected to pulmonary veins, peri-bronchial vessels or the vasa vasorum. Collaterals, by-passing completely occluded pulmonary arteries, were also observed to originate within plexiform lesions. In conclusion, synchrotron-based imaging revealed significant plexiform lesion heterogeneity, resulting in a novel classification. The four types likely have different effects on hemodynamics and disease progression.

Structure of the myenteric plexus in normal and diseased human ileum analyzed by X-ray virtual histology slices

“…Furthermore, because the ganglia of the ENS are very sparse, especially in patients with dysmotility, and the myenteric plexus can fold and curve beneath what is visible on the surface of the block, it is very difficult to correctly punch the tissue of interest based on a histological section. Hence, multi-scale X-ray phase-contrast tomography, which involves scanning a tissue block with a mm-sized field-of-view at µm-resolution and then imaging specific features of interest in greater detail using local nanotomography on the full block (instead of extracting biopsy punches as in this work), would be preferable and has been proven to be feasible at different synchrotron beamlines, such as TOMCAT[ 27 , 28 ] and P10/GINIX[ 29 - 31 ].…”

A multiscale X-ray phase-contrast tomography dataset of a whole human left lung

“…The compatibility of X-ray phase-contrast imaging with existing X-ray sources will facilitate its gradual adoption and transition from preclinical research to clinical diagnostics 6 , 11 , 12 . At synchrotron facilities, systematic upgrades 13 , 14 in the X-ray source and imaging techniques over the past decades provide the means to tackle biological questions across meaningful scales and resolution 11 , 15 – 20 . Although synchrotron-based X-ray imaging can access finer anatomical detail than laboratory micro-CT 19 , 21 – 23 , many bioimaging scenarios require further upscaling of the imaging throughput and accommodation of large sample size while maintaining microscopic resolution 24 , 25 .…”

From Macroscopy to Ultrastructure: An Integrative Approach to Pulmonary Pathology

“…Synchrotron imaging of paraffin embedded samples on the other hand has been used by another group to study morphological changes in the vascularity in pulmonary vascular diseases. Westroo and colleagues leveraged synchrotron imaging to demonstrate a previously unappreciated plexiform lesion heterogeneity, the pathological hallmark of (idiopathic) pulmonary hypertension ( 18 ). The same group also used synchrotron-based phase-contrast microCT in combination with vascular dye injection to investigate the vascular morphology in alveolar capillary dysplasia with misaligned pulmonary veins, with vascular dye injection being of significant help in the analysis and further segmentation of the vascular structures ( 19 ).…”