Dataset Information

Quantitative analysis of monocyte subpopulations in murine atherosclerotic plaques by multiphoton microscopy.

ABSTRACT: The progressive accumulation of monocyte-derived cells in the atherosclerotic plaque is a hallmark of atherosclerosis. However, it is now appreciated that monocytes represent a heterogeneous circulating population of cells that differ in functionality. New approaches are needed to investigate the role of monocyte subpopulations in atherosclerosis since a detailed understanding of their differential mobilization, recruitment, survival and emigration during atherogenesis is of particular importance for development of successful therapeutic strategies. We present a novel methodology for the in vivo examination of monocyte subpopulations in mouse models of atherosclerosis. This approach combines cellular labeling by fluorescent beads with multiphoton microscopy to visualize and monitor monocyte subpopulations in living animals. First, we show that multiphoton microscopy is an accurate and timesaving technique to analyze monocyte subpopulation trafficking and localization in plaques in excised tissues. Next, we demonstrate that multiphoton microscopy can be used to monitor monocyte subpopulation trafficking in atherosclerotic plaques in living animals. This novel methodology should have broad applications and facilitate new insights into the pathogenesis of atherosclerosis and other inflammatory diseases.

SUBMITTER: Haka AS

PROVIDER: S-EPMC3443108 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Quantitative analysis of monocyte subpopulations in murine atherosclerotic plaques by multiphoton microscopy.

Haka Abigail S AS Potteaux Stephane S Fraser Haley H Randolph Gwendalyn J GJ Maxfield Frederick R FR

PloS one 20120914 9

The progressive accumulation of monocyte-derived cells in the atherosclerotic plaque is a hallmark of atherosclerosis. However, it is now appreciated that monocytes represent a heterogeneous circulating population of cells that differ in functionality. New approaches are needed to investigate the role of monocyte subpopulations in atherosclerosis since a detailed understanding of their differential mobilization, recruitment, survival and emigration during atherogenesis is of particular importanc ...[more]

PMID: 23024767

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Project description:BackgroundDuodenal gastrinomas (DGASTs) are neuroendocrine tumors that develop in the submucosa of the duodenum and produce the hormone gastrin. Surgical resection of DGASTs is complicated by the small size of these tumors and the tendency for them to develop diffusely in the duodenum. Endoscopic mucosal resection of DGASTs is an increasingly popular method for treating this disease due to its low complication rate but suffers from poor rates of pathologically negative margins. Multiphoton microscopy can capture high-resolution images of biological tissue with contrast generated from endogenous fluorescence (autofluorescence [AF]) through two-photon excited fluorescence (2PEF). Second harmonic generation is another popular method of generating image contrast with multiphoton microscopy (MPM) and is a light-scattering phenomenon that occurs predominantly from structures such as collagen in biological samples. Some molecules that contribute to AF change in abundance from processes related to the cancer disease process (e.g., metabolic changes, oxidative stress, and angiogenesis).Study design/materials and methodsMPM was used to image 12 separate patient samples of formalin-fixed and paraffin-embedded duodenal gastrinoma slides with a second-harmonic generation (SHG) channel and four 2PEF channels. The excitation and emission profiles of each 2PEF channel were tuned to capture signal dominated by distinct fluorophores with well-characterized fluorescent spectra and known connections to the physiologic changes that arise in cancerous tissue.ResultsWe found that there was a significant difference in the relative abundance of signal generated in the 2PEF channels for regions of DGASTs in comparison to the neighboring tissues of the duodenum. Data generated from texture feature extraction of the MPM images were used in linear discriminant analysis models to create classifiers for tumor versus all other tissue types before and after principal component analysis (PCA). PCA improved the classifier accuracy and reduced the number of features required to achieve maximum accuracy. The linear discriminant classifier after PCA distinguished between tumor and other tissue types with an accuracy of 90.6%-93.8%.ConclusionsThese results suggest that multiphoton microscopy 2PEF and SHG imaging is a promising label-free method for discriminating between DGASTs and normal duodenal tissue which has implications for future applications of in vivo assessment of resection margins with endoscopic MPM.

Project description:Background and purposeIntracranial atherosclerosis is one of the main causes of stroke, and high-resolution magnetic resonance imaging provides useful imaging biomarkers related to the risk of ischemic events. This study aims to evaluate differences in histogram features between culprit and nonculprit intracranial atherosclerosis using high-resolution magnetic resonance imaging.MethodsTwo hundred forty-seven patients with intracranial atherosclerosis who underwent high-resolution magnetic resonance imaging sequentially between January 2015 and December 2016 were recruited. Quantitative features, including stenosis, plaque burden, minimum luminal area, intraplaque hemorrhage, enhancement ratio, and dispersion of signal intensity (coefficient of variation), were analyzed based on T2-, T1-, and contrast-enhanced T1-weighted images. Step-wise regression analysis was used to identify key determinates differentiating culprit and nonculprit plaques and to calculate the odds ratios (ORs) with 95% CIs.ResultsIn total, 190 plaques were identified, of which 88 plaques (37 culprit and 51 nonculprit) were located in the middle cerebral artery and 102 (57 culprit and 45 nonculprit) in the basilar artery. Nearly 90% of culprit lesions had a degree of luminal stenosis of <70%. Multiple logistic regression analyses showed that intraplaque hemorrhage (OR, 16.294 [95% CI, 1.043-254.632]; P=0.047), minimum luminal area (OR, 1.468 [95% CI, 1.032-2.087]; P=0.033), and coefficient of variation (OR, 13.425 [95% CI, 3.987-45.204]; P<0.001) were 3 significant features in defining culprit plaques in middle cerebral artery. The enhancement ratio (OR, 9.476 [95% CI, 1.256-71.464]; P=0.029), intraplaque hemorrhage (OR, 2.847 [95% CI, 0.971-10.203]; P=0.046), and coefficient of variation (OR, 10.068 [95% CI, 2.820-21.343]; P<0.001) were significantly associated with plaque type in basilar artery. Coefficient of variation was a strong independent predictor in defining plaque type for both middle cerebral artery and basilar artery with sensitivity, specificity, and accuracy being 0.79, 0.80, and 0.80, respectively.ConclusionsFeatures characterized by high-resolution magnetic resonance imaging provided complementary values over luminal stenosis in defined lesion type for intracranial atherosclerosis; the dispersion of signal intensity in histogram analysis was a particularly effective predictive parameter.

Dataset Information

Quantitative analysis of monocyte subpopulations in murine atherosclerotic plaques by multiphoton microscopy.

Publications

Quantitative analysis of monocyte subpopulations in murine atherosclerotic plaques by multiphoton microscopy.

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