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

BACKGROUND The enteric nervous system(ENS)is situated along the entire gastrointestinal tract and is divided into myenteric and submucosal plexuses in the small and large intestines.The ENS consists of neurons,glial cells,and nerves assembled into ganglia,surrounded by telocytes,interstitial cells of Cajal,and connective tissue.Owing to the complex spatial organization of several interconnections with nerve fascicles,the ENS is difficult to examine in conventional histological sections of 3-5μm.AIM To examine human ileum full-thickness biopsies using X-ray phase-contrast nanotomography without prior staining to visualize the ENS.METHODS Six patients were diagnosed with gastrointestinal dysmotility and neuropathy based on routine clinical and histopathological examinations.As controls,fullthickness biopsies were collected from healthy resection ileal regions after hemicolectomy for right colon malignancy.From the paraffin blocks,4-μm thick sections were prepared and stained with hematoxylin and eosin for localization of the myenteric ganglia under a light microscope.A 1-mm punch biopsy(up to 1 cm in length)centered on the myenteric plexus was taken and placed into a Kapton®tube for mounting in the subsequent investigation.X-ray phase-contrast tomography was performed using two custom-designed laboratory setups with micrometer resolution for overview scanning.Subsequently,selected regions of interest were scanned at a synchrotron-based end-station,and high-resolution slices were reported.In total,more than 6000 virtual slices were analyzed from nine samples.RESULTS In the overview scans,the general architecture and quality of the samples were studied,and the myenteric plexus was localized.High-resolution scans revealed details,including the ganglia,interganglional nerve fascicles,and surrounding tissue.The ganglia were irregular in shape and contained neurons and glial cells.Spindle-shaped cells with very thin cellular projections could be observed on the surface of the ganglia,which appeared to build a network.In the patients,there were no alterations in the general architecture of the myenteric ganglia.Nevertheless,several pathological changes were observed,including vacuolar degeneration,autophagic activity,the appearance of sequestosomes,chromatolysis,and apoptosis.Furthermore,possible expulsion of pyknotic neurons and defects in the covering cellular network could be observed in serial slices.These changes partly corresponded to previous light microscopy findings.CONCLUSION The analysis of serial virtual slices could provide new information that cannot be obtained by classical light microscopy.The advantages,disadvantages,and future possibilities of this method are also discussed.

Long-term effects of biodegradable versus durable polymer-coated sirolimus-eluting stents on coronary arterial wall morphology assessed by virtual histology intravascular ultrasound

Background The durable presence of polymer coating on drug-eluting stent （DES） surface may be one of the principal reasons for stent thrombosis. The long-term coronary arterial response to biodegradable polymer-coated sirolimus-eluting stent （BSES） in vivo remained unclear.Methods Forty-one patients were enrolled in this study and virtual histology intravascular ultrasound （VH-IVUS） was performed to assess the native artery vascular responses to BSES compared with durable polymer-coated SES （DSES） during long-term follow-up （median： 8 months）. The incidence of necrotic core abutting to the lumen was evaluated at follow-up.Results With similar in-stent late luminal loss （0.15 mm （0.06-0.30 mm） vs. 0.19 mm （0.03-0.30 mm）, P=0.772）, the overall incidence of necrotic core abutting to the lumen was significantly less in BSES group than in DSES group （44% vs.63%, P 〈0.05） （proximal 18%, stented site 14% and distal 12% in BSES group, proximal 19%, stented site 28% and distal 16% in DSES group）. The DSES-treated segments had a significant higher incidence of necrotic core abutting to the lumen through the stent struts （73% vs. 36%, P 〈0.01）. In addition, more multiple necrotic core abutting to the lumen was observed in DSES group （overall： 63% vs. 36%, P 〈0.05）. Furthermore, when the stented segments with necrotic core abutting to the lumen had been taken into account only, DSES-treated lesions tended to contain more multiple necrotic core abutting to the lumen through the stent struts than BSES-treated lesions （74% vs. 33%）, although there was no statistically significant difference between them （P=0.06）.Conclusions By VH-IVUS analysis at follow-up, a greater frequency of stable lesion morphometry was shown in lesions treated with BSESs compared with lesions treated with DSESs. The major reason was BSES produced less toxicity to the arterial wall and facilitated neointimal healing as a result of polymer coating on DES surface biodegraded as time went by.

Confocal laser endomicroscopy in the “in vivo” histological diagnosis of the gastrointestinal tract

Recent technological advances in miniaturization have allowed for a confocal scanning microscope to be integrated into a conventional flexible endoscope,or into trans-endoscopic probes,a technique now known as confocal endomicroscopy or confocal laser endomicroscopy.This newly-developed technology has enabled endoscopists to collect real-time in vivo histological images or "virtual biopsies" of the gastrointestinal mucosa during endoscopy,and has stimulated significant interest in the application of this technique in clinical gastroenterology.This review aims to evaluate the current data on the technical aspects and the utility of this new technology in clinical gastroenterology and its potential impact in the future,particularly in the screening or surveillance of gastrointestinal neoplasia.

Coronary plaque characterization of nonculprit or nontarget lesions assessed by analysis of in vivo intracoronary ultrasound radio-frequency data

Background Unheralded sudden death and acute myocardial infarction are common manifestations of coronary atherosclerosis. Such events are related to thrombotic occlusion at the site of non-flow limiting atherosclerotic plaques in epicardial coronary arteries. This study aimed to assess plaque characterization of nonculprit lesions in patients with acute coronary syndrome （ACS） compared with those with stable angina pectoris （SAP） determined by analysis of intravascular ultrasound （IVUS） radiofrequency （RF） data. Methods In 81 patients, nonculprit vessels with 〈50% diameter stenosis and nontarget segment of culprit vessels with 〈50% diameter stenosis were studied with IVUS. Tissue maps were reconstructed from RF data using IVUS-Virtual Histology software. Results Mean lipid core percentage was significantly higher in patients with ACS than in those with SAP （（25.78±6.30）% vs （9.11±4.90）%, P 〈0.001）. In addition, patients with SAP showed more fibrotic vessels （（59.66±16.87）% vs （49.07±10.20）%, P 〈0.001）. There was no significant difference in either mean calcium （（4.37±2.40）% vs （5.12±3.00）%, P=-0.225） or fibrolipid （（24.94±9.40）% vs （25.82±13.60）%, P=0.731） percentages in nonculprit vessels, but the mean calcium percentage was significantly higher in nontarget lesions of culprit vessels （（5.51±3.29）% vs （3.57±2.10）%, P=0.003）. In addition, there was a positive correlation between lipid core and remodeling index （RI） （r=0.847, P〈0.001） and a negative correlation between fibrous tissue and RI （r= -0.946, P〈0.001）. Conclusions In this study, in both nonculprit vessels and nontarget lesion of culprit vessels, plaque characterization of nonculprit lesions determined by spectral analysis of IVUS RF data was significantly different in patients with ACS. The percentage of lipid core was significantly higher in patients with ACS than in those with SAP. Conversely, SAP patients showed more fibrotic content. In vivo plaque composition and morphological changes were related to remodeling of the coronary artery tree.

Ex vivo evaluation of IVUS-VH imaging and the role of plaque structure on peripheral artery disease

Peripheral artery disease(PAD)results from the buildup of atherosclerotic plaque in the arterial wall,can progress to severe ischemia and lead to tissue necrosis and limb amputation.We evaluated a means of assessing PAD mechanics ex vivo using ten human peripheral arteries with PAD.Pressure-inflation testing was performed at six physiological pressure intervals ranging from 10 to 200 mmHg.These vessels were imaged with IVUS-VH to determine plaque composition and change in vessel structure with pressure.Statistical analysis was performed to determine which plaque structures and distributions of these structures had the greatest influence on wall deformation.We found that fibrous plaque,necrotic core,and calcification had a statistically significant effect on all variables(p<0.05).The presence of large concentrations of fibrous plaque was linked to reduced vessel compliance and ellipticity,which could lead to stent fractures and restenosis.For the plaque distribution we found that clustered necrotic core increased overall compliance while clustered calcification decreased overall compliance.The effect of plaque distribution on vessel wall deformation must be considered equally important to plaque concentration.