RESUMEN
The fetus is thought to be protected from exposure to foreign antigens, yet CD45RO+ T cells reside in the fetal intestine. Here we combined functional assays with mass cytometry, single-cell RNA sequencing and high-throughput T cell antigen receptor (TCR) sequencing to characterize the CD4+ T cell compartment in the human fetal intestine. We identified 22 CD4+ T cell clusters, including naive-like, regulatory-like and memory-like subpopulations, which were confirmed and further characterized at the transcriptional level. Memory-like CD4+ T cells had high expression of Ki-67, indicative of cell division, and CD5, a surrogate marker of TCR avidity, and produced the cytokines IFN-γ and IL-2. Pathway analysis revealed a differentiation trajectory associated with cellular activation and proinflammatory effector functions, and TCR repertoire analysis indicated clonal expansions, distinct repertoire characteristics and interconnections between subpopulations of memory-like CD4+ T cells. Imaging mass cytometry indicated that memory-like CD4+ T cells colocalized with antigen-presenting cells. Collectively, these results provide evidence for the generation of memory-like CD4+ T cells in the human fetal intestine that is consistent with exposure to foreign antigens.
Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Feto/inmunología , Memoria Inmunológica/inmunología , Intestinos/inmunología , Células Presentadoras de Antígenos/citología , Células Presentadoras de Antígenos/inmunología , Células Presentadoras de Antígenos/metabolismo , Linfocitos T CD4-Positivos/citología , Linfocitos T CD4-Positivos/metabolismo , Antígenos CD5/genética , Antígenos CD5/inmunología , Antígenos CD5/metabolismo , Células Cultivadas , Feto/citología , Feto/metabolismo , Citometría de Flujo , Perfilación de la Expresión Génica/métodos , Regulación del Desarrollo de la Expresión Génica/inmunología , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Memoria Inmunológica/genética , Inmunofenotipificación , Intestinos/citología , Intestinos/embriología , Antígeno Ki-67/genética , Antígeno Ki-67/inmunología , Antígeno Ki-67/metabolismoRESUMEN
The primary motor cortex (M1) is essential for voluntary fine-motor control and is functionally conserved across mammals1. Here, using high-throughput transcriptomic and epigenomic profiling of more than 450,000 single nuclei in humans, marmoset monkeys and mice, we demonstrate a broadly conserved cellular makeup of this region, with similarities that mirror evolutionary distance and are consistent between the transcriptome and epigenome. The core conserved molecular identities of neuronal and non-neuronal cell types allow us to generate a cross-species consensus classification of cell types, and to infer conserved properties of cell types across species. Despite the overall conservation, however, many species-dependent specializations are apparent, including differences in cell-type proportions, gene expression, DNA methylation and chromatin state. Few cell-type marker genes are conserved across species, revealing a short list of candidate genes and regulatory mechanisms that are responsible for conserved features of homologous cell types, such as the GABAergic chandelier cells. This consensus transcriptomic classification allows us to use patch-seq (a combination of whole-cell patch-clamp recordings, RNA sequencing and morphological characterization) to identify corticospinal Betz cells from layer 5 in non-human primates and humans, and to characterize their highly specialized physiology and anatomy. These findings highlight the robust molecular underpinnings of cell-type diversity in M1 across mammals, and point to the genes and regulatory pathways responsible for the functional identity of cell types and their species-specific adaptations.
Asunto(s)
Corteza Motora/citología , Neuronas/clasificación , Análisis de la Célula Individual , Animales , Atlas como Asunto , Callithrix/genética , Epigénesis Genética , Epigenómica , Femenino , Neuronas GABAérgicas/citología , Neuronas GABAérgicas/metabolismo , Perfilación de la Expresión Génica , Glutamatos/metabolismo , Humanos , Hibridación Fluorescente in Situ , Masculino , Ratones , Persona de Mediana Edad , Corteza Motora/anatomía & histología , Neuronas/citología , Neuronas/metabolismo , Especificidad de Órganos , Filogenia , Especificidad de la Especie , TranscriptomaRESUMEN
Elucidating the cellular architecture of the human cerebral cortex is central to understanding our cognitive abilities and susceptibility to disease. Here we used single-nucleus RNA-sequencing analysis to perform a comprehensive study of cell types in the middle temporal gyrus of human cortex. We identified a highly diverse set of excitatory and inhibitory neuron types that are mostly sparse, with excitatory types being less layer-restricted than expected. Comparison to similar mouse cortex single-cell RNA-sequencing datasets revealed a surprisingly well-conserved cellular architecture that enables matching of homologous types and predictions of properties of human cell types. Despite this general conservation, we also found extensive differences between homologous human and mouse cell types, including marked alterations in proportions, laminar distributions, gene expression and morphology. These species-specific features emphasize the importance of directly studying human brain.
Asunto(s)
Astrocitos/clasificación , Evolución Biológica , Corteza Cerebral/citología , Corteza Cerebral/metabolismo , Neuronas/clasificación , Adolescente , Adulto , Anciano , Animales , Astrocitos/citología , Femenino , Humanos , Masculino , Ratones , Persona de Mediana Edad , Inhibición Neural , Neuronas/citología , Análisis de Componente Principal , RNA-Seq , Análisis de la Célula Individual , Especificidad de la Especie , Transcriptoma/genética , Adulto JovenRESUMEN
OBJECTIVE: The present study evaluated the effect of endovascular administration of calcium chloride to the carotid artery of swines, to create a model of arterial calcification. METHODS: Fifteen Large White pigs were used for the study. Via endovascular treatment, carotid arteries were exposed during 9 min to either calcium chloride (experimental artery) or saline (control artery) with the use of the TAPAS catheter. Intravascular ultrasound (IVUS) imaging was obtained at baseline, postprocedure and at 30 days. Optical coherence tomography (OCT) imaging was obtained in vitro after carotids were harvested. Longitudinally cut parallel arterial segments were placed in a system of delicate clamps and underwent uniaxial strain test. All arteries underwent histopathological examination. RESULTS: Calcium chloride treated segments showed extensive circumferential parietal calcification evident on both IVUS and OCT. Reduction in minimal lumen area on IVUS was evident in experimental arteries both at 24 hr and 30 days postprocedure. Histopathologic assessment (Von Kossa stain) confirmed medial calcification with mild intimal thickening. Biomechanical testing showed treated segments to have smaller breaking strength and less elastic deformation than controls. CONCLUSION: We developed a nonexpensive, reproducible model of early carotid medial calcification in pigs. Our model has the potential to help the development of research to unravel mechanisms underlying arterial calcification, the use of current or new devices to treat calcified lesions as well as to serve as an option for training interventionalists on the use of such devices.
Asunto(s)
Cloruro de Calcio , Enfermedades de las Arterias Carótidas/inducido químicamente , Arteria Carótida Común/patología , Calcificación Vascular/inducido químicamente , Animales , Fenómenos Biomecánicos , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/patología , Arteria Carótida Común/diagnóstico por imagen , Modelos Animales de Enfermedad , Elasticidad , Masculino , Neointima , Sus scrofa , Factores de Tiempo , Tomografía de Coherencia Óptica , Ultrasonografía Intervencional , Calcificación Vascular/diagnóstico por imagen , Calcificación Vascular/patologíaRESUMEN
BACKGROUND: The optimal implantation technique for the bioresorbable scaffold (Absorb, Abbott Vascular) is still a matter of debate. The purpose of the present study was to evaluate the effect of implantation technique on strut embedment and scaffold expansion.MethodsâandâResults:Strut embedment depth and scaffold expansion index assessed by optical coherence tomography (OCT) (minimum scaffold area/reference vessel area) were evaluated in the ABSORB Japan trial (OCT subgroup: 87 lesions) with respect to implantation technique using either quantitative coronary angiography (QCA) or OCT. Strut embedment was assessed at the strut level (n=667), while scaffold expansion was assessed at the lesion level (n=81). The mean embedment depth was 63±59 µm. Balloon sizing and inflation pressure had no direct effect on strut embedment. Plaque morphology affected strut embedment [nonatherosclerotic (58.9±54.3 µm), fibroatheroma (73.3±59.6 µm), fibrous plaque (59.7±51.1 µm), and fibrocalcific plaque (-3.1±61.6 µm, negative value means malapposition), P <0.001]. The balloon-artery ratio positively correlated with the expansion index. This relationship was stronger when the OCT-derived reference vessel diameter (RVD) was used as a reference for balloon selection rather than the QCA-derived one [predilatation (Pearson correlation r: QCA: 0.167 vs. OCT: 0.552), postdilatation (QCA: 0.316 vs. OCT: 0.717)]. CONCLUSIONS: Underlying plaque morphology influenced strut embedment, whereas implantation technique had no direct effect on it. Optimal balloon sizing based on OCT-derived RVD might be recommended. However, the safety of such a strategy should be investigated in a prospective trial. (Circ J 2016; 80: 2317-2326).
Asunto(s)
Implantes Absorbibles , Implantación de Prótesis Vascular/métodos , Prótesis Vascular , Angiografía Coronaria , Placa Aterosclerótica , Poliésteres , Andamios del Tejido , Femenino , Humanos , Masculino , Placa Aterosclerótica/diagnóstico por imagen , Placa Aterosclerótica/cirugíaRESUMEN
BACKGROUND: Quantitative light intensity analysis of the strut core by optical coherence tomography (OCT) may enable assessment of changes in the light reflectivity of the bioresorbable polymeric scaffold from polymer to provisional matrix and connective tissues, with full disappearance and integration of the scaffold into the vessel wall. The aim of this report was to describe the methodology and to apply it to serial human OCT images post procedure and at 6, 12, 24 and 36 months in the ABSORB cohort B trial. METHODS AND RESULTS: In serial frequency-domain OCT pullbacks, corresponding struts at different time points were identified by 3-dimensional foldout view. The peak and median values of light intensity were measured in the strut core by dedicated software. A total of 303 corresponding struts were serially analyzed at 3 time points. In the sequential analysis, peak light intensity increased gradually in the first 24 months after implantation and reached a plateau (relative difference with respect to baseline [%Dif]: 61.4% at 12 months, 115.0% at 24 months, 110.7% at 36 months), while the median intensity kept increasing at 36 months (%Dif: 14.3% at 12 months, 75.0% at 24 months, 93.1% at 36 months). CONCLUSIONS: Quantitative light intensity analysis by OCT was capable of detecting subtle changes in the bioresorbable strut appearance over time, and could be used to monitor the bioresorption and integration process of polylactide struts.
Asunto(s)
Implantes Absorbibles , Prótesis Vascular , Enfermedad de la Arteria Coronaria/patología , Enfermedad de la Arteria Coronaria/cirugía , Monitoreo Fisiológico/métodos , Tomografía de Coherencia Óptica , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Humanos , MasculinoRESUMEN
Exploration and analysis of high-dimensional data are important tasks in many fields that produce large and complex data, like the financial sector, systems biology, or cultural heritage. Tailor-made visual analytics software is developed for each specific application, limiting their applicability in other fields. However, as diverse as these fields are, their characteristics and requirements for data analysis are conceptually similar. Many applications share abstract tasks and data types and are often constructed with similar building blocks. Developing such applications, even when based mostly on existing building blocks, requires significant engineering efforts. We developed ManiVault, a flexible and extensible open-source visual analytics framework for analyzing high-dimensional data. The primary objective of ManiVault is to facilitate rapid prototyping of visual analytics workflows for visualization software developers and practitioners alike. ManiVault is built using a plugin-based architecture that offers easy extensibility. While our architecture deliberately keeps plugins self-contained, to guarantee maximum flexibility and re-usability, we have designed and implemented a messaging API for tight integration and linking of modules to support common visual analytics design patterns. We provide several visualization and analytics plugins, and ManiVault's API makes the integration of new plugins easy for developers. ManiVault facilitates the distribution of visualization and analysis pipelines and results for practitioners through saving and reproducing complete application states. As such, ManiVault can be used as a communication tool among researchers to discuss workflows and results. A copy of this paper and all supplemental material is available at osf.io/9k6jw, and source code at github.com/ManiVaultStudio.
RESUMEN
Background: Kidney transplantation is the preferred treatment option for patients with end-stage renal disease. However, long-term graft survival remains a challenge. The enzyme indoleamine 2,3 dioxygenase (IDO) has been reported to have immunomodulatory effects with IDO transcripts being elevated in both antibody-mediated rejection and T cell-mediated rejection. Methods: A metal-conjugated antibody panel for the staining of kidney biopsies was developed, allowing the visualization of 41 structural and immune markers on a single tissue slide to gain in-depth insight into the composition and localization of the immune cell compartment. Staining was applied to week 4 and 24 protocol biopsies of 49 patients as well as on 15 indication biopsies of the TRITON study and 4 additional transplantation biopsies with glomerulitis. Results: A highly distinctive and specific glomerular IDO expression was observed in biopsies from 3 of 49 patients in imaging mass cytometry. Immunohistochemistry confirmed IDO expression in glomeruli of 10 of 10 cases with glomerulitis. IDO was found to be expressed by CD31+ glomerular endothelial cells, accompanied by the presence of granzyme-B+Tbet+CD7+CD45RA+ natural killer cells and CD68+ macrophages. Furthermore, a proportion of both the immune cells and endothelial cells expressed Ki-67, indicative of cell proliferation, which was not observed in control glomeruli. Conclusions: Our results show glomerular IDO expression in transplanted kidneys with glomerulitis, which is accompanied by increased numbers of natural killer cells and macrophages and likely reflects local immune activation.
RESUMEN
Evolution strategies (ESs) are powerful probabilistic search and optimization algorithms gleaned from biological evolution theory. They have been successfully applied to a wide range of real world applications. The modern ESs are mainly designed for solving continuous parameter optimization problems. Their ability to adapt the parameters of the multivariate normal distribution used for mutation during the optimization run makes them well suited for this domain. In this article we describe and study mixed integer evolution strategies (MIES), which are natural extensions of ES for mixed integer optimization problems. MIES can deal with parameter vectors consisting not only of continuous variables but also with nominal discrete and integer variables. Following the design principles of the canonical evolution strategies, they use specialized mutation operators tailored for the aforementioned mixed parameter classes. For each type of variable, the choice of mutation operators is governed by a natural metric for this variable type, maximal entropy, and symmetry considerations. All distributions used for mutation can be controlled in their shape by means of scaling parameters, allowing self-adaptation to be implemented. After introducing and motivating the conceptual design of the MIES, we study the optimality of the self-adaptation of step sizes and mutation rates on a generalized (weighted) sphere model. Moreover, we prove global convergence of the MIES on a very general class of problems. The remainder of the article is devoted to performance studies on artificial landscapes (barrier functions and mixed integer NK landscapes), and a case study in the optimization of medical image analysis systems. In addition, we show that with proper constraint handling techniques, MIES can also be applied to classical mixed integer nonlinear programming problems.
Asunto(s)
Algoritmos , Vasos Coronarios/diagnóstico por imagen , UltrasonografíaRESUMEN
The intestine represents the largest immune compartment in the human body, yet its development and organisation during human foetal development is largely unknown. Here we show the immune subset composition of this organ during development, by longitudinal spectral flow cytometry analysis of human foetal intestinal samples between 14 and 22 weeks of gestation. At 14 weeks, the foetal intestine is mainly populated by myeloid cells and three distinct CD3-CD7+ ILC, followed by rapid appearance of adaptive CD4+, CD8+ T and B cell subsets. Imaging mass cytometry identifies lymphoid follicles from week 16 onwards in a villus-like structure covered by epithelium and confirms the presence of Ki-67+ cells in situ within all CD3-CD7+ ILC, T, B and myeloid cell subsets. Foetal intestinal lymphoid subsets are capable of spontaneous proliferation in vitro. IL-7 mRNA is detected within both the lamina propria and the epithelium and IL-7 enhances proliferation of several subsets in vitro. Overall, these observations demonstrate the presence of immune subset-committed cells capable of local proliferation in the developing human foetal intestine, likely contributing to the development and growth of organized immune structures throughout most of the 2nd trimester, which might influence microbial colonization upon birth.
Asunto(s)
Interleucina-7 , Intestinos , Embarazo , Femenino , Humanos , Segundo Trimestre del Embarazo , Feto , Linfocitos , Mucosa Intestinal , Subgrupos de Linfocitos TRESUMEN
With the advent of multiplex fluorescence in situ hybridization (FISH) and in situ RNA sequencing technologies, spatial transcriptomics analysis is advancing rapidly, providing spatial location and gene expression information about cells in tissue sections at single cell resolution. Cell type classification of these spatially-resolved cells can be inferred by matching the spatial transcriptomics data to reference atlases derived from single cell RNA-sequencing (scRNA-seq) in which cell types are defined by differences in their gene expression profiles. However, robust cell type matching of the spatially-resolved cells to reference scRNA-seq atlases is challenging due to the intrinsic differences in resolution between the spatial and scRNA-seq data. In this study, we systematically evaluated six computational algorithms for cell type matching across four image-based spatial transcriptomics experimental protocols (MERFISH, smFISH, BaristaSeq, and ExSeq) conducted on the same mouse primary visual cortex (VISp) brain region. We find that many cells are assigned as the same type by multiple cell type matching algorithms and are present in spatial patterns previously reported from scRNA-seq studies in VISp. Furthermore, by combining the results of individual matching strategies into consensus cell type assignments, we see even greater alignment with biological expectations. We present two ensemble meta-analysis strategies used in this study and share the consensus cell type matching results in the Cytosplore Viewer ( https://viewer.cytosplore.org ) for interactive visualization and data exploration. The consensus matching can also guide spatial data analysis using SSAM, allowing segmentation-free cell type assignment.
Asunto(s)
Corteza Visual Primaria , Transcriptoma , Animales , Ratones , Hibridación Fluorescente in Situ , Perfilación de la Expresión Génica , AlgoritmosRESUMEN
The cognitive abilities of humans are distinctive among primates, but their molecular and cellular substrates are poorly understood. We used comparative single-nucleus transcriptomics to analyze samples of the middle temporal gyrus (MTG) from adult humans, chimpanzees, gorillas, rhesus macaques, and common marmosets to understand human-specific features of the neocortex. Human, chimpanzee, and gorilla MTG showed highly similar cell-type composition and laminar organization as well as a large shift in proportions of deep-layer intratelencephalic-projecting neurons compared with macaque and marmoset MTG. Microglia, astrocytes, and oligodendrocytes had more-divergent expression across species compared with neurons or oligodendrocyte precursor cells, and neuronal expression diverged more rapidly on the human lineage. Only a few hundred genes showed human-specific patterning, suggesting that relatively few cellular and molecular changes distinctively define adult human cortical structure.
Asunto(s)
Cognición , Hominidae , Neocórtex , Lóbulo Temporal , Animales , Humanos , Perfilación de la Expresión Génica , Gorilla gorilla/genética , Hominidae/genética , Hominidae/fisiología , Macaca mulatta/genética , Pan troglodytes/genética , Filogenia , Transcriptoma , Neocórtex/fisiología , Especificidad de la Especie , Lóbulo Temporal/fisiologíaRESUMEN
BACKGROUND AND AIMS: Accurate classification of plaque composition is essential for treatment planning. Intravascular ultrasound (IVUS) has limited efficacy in assessing tissue types, while near-infrared spectroscopy (NIRS) provides complementary information to IVUS but lacks depth information. The aim of this study is to train and assess the efficacy of a machine learning classifier for plaque component classification that relies on IVUS echogenicity and NIRS-signal, using histology as reference standard. METHODS: Matched NIRS-IVUS and histology images from 15 cadaveric human coronary arteries were analyzed (10 vessels were used for training and 5 for testing). Fibrous/pathological intimal thickening (F-PIT), early necrotic core (ENC), late necrotic core (LNC), and calcific tissue regions-of-interest were detected on histology and superimposed onto IVUS frames. The pixel intensities of these tissue types from the training set were used to train a J48 classifier for plaque characterization (ECHO-classification). To aid differentiation of F-PIT from necrotic cores, the NIRS-signal was used to classify non-calcific pixels outside yellow-spot regions as F-PIT (ECHO-NIRS classification). The performance of ECHO and ECHO-NIRS classifications were validated against histology. RESULTS: 262 matched frames were included in the analysis (162 constituted the training set and 100 the test set). The pixel intensities of F-PIT and ENC were similar and thus these two tissues could not be differentiated by echogenicity. With ENC and LNC as a single class, ECHO-classification showed good agreement with histology for detecting calcific and F-PIT tissues but had poor efficacy for necrotic cores (recall 0.59 and precision 0.29). Similar results were found when F-PIT and ENC were treated as a single class (recall and precision for LNC 0.78 and 0.33, respectively). ECHO-NIRS classification improved necrotic core and LNC detection, resulting in an increase of the overall accuracy of both models, from 81.4% to 91.8%, and from 87.9% to 94.7%, respectively. Comparable performance of the two models was seen in the test set where the overall accuracy of ECHO-NIRS classification was 95.0% and 95.5%, respectively. CONCLUSIONS: The combination of echogenicity with NIRS-signal appears capable of overcoming limitations of echogenicity, enabling more accurate characterization of plaque components.
Asunto(s)
Enfermedad de la Arteria Coronaria , Placa Aterosclerótica , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/patología , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/patología , Humanos , Aprendizaje Automático , Placa Aterosclerótica/patología , Valor Predictivo de las Pruebas , Espectroscopía Infrarroja Corta/métodos , Ultrasonografía , Ultrasonografía Intervencional/métodosRESUMEN
BACKGROUND: Tissue necrosis, a consequence of inadequate tissue oxygenation, is a common post-operative complication. As current surgical assessments are often limited to visual and tactile feedback, additional techniques that can aid in the interrogation of tissue viability are needed to improve patient outcomes. In this bi-institutional pilot study, the performance of a novel snapshot hyperspectral imaging camera to detect superficial cutaneous oxygen saturation (StO2) was evaluated. METHODS: Healthy human volunteers were recruited at two participating centers. Cutaneous StO2 of the forearm was determined by a snapshot hyperspectral camera on two separate study days during occlusion-reperfusion of the brachial artery and after induction of local vasodilation. To calculate the blood StO2 at each pixel in the multispectral image, spectra were selected, and fitting was performed over wavelengths ranging from 470 to 950 nm. RESULTS: Quantitative detection of physiological changes in cutaneous StO2 levels was feasible in all sixteen volunteers. A significant (P<0.001) decrease in cutaneous StO2 levels from 78.3% (SD: 15.3) at baseline to 60.6% (SD: 19.8) at the end of occlusion phase was observed, although StO2 levels returned to baseline after five minutes. Mean cutaneous StO2 values were similar in the same subjects on separate study days (Pearson R2: 0.92 and 0.77, respectively) at both centers. Local vasodilation did not yield significant changes in cutaneous StO2 values. CONCLUSIONS: This pilot study demonstrated the feasibility of a snapshot hyperspectral camera for detecting quantitative physiological changes in cutaneous StO2 in normal human volunteers, and serves as a precursor for further validation in perioperative studies.
RESUMEN
The human fetal immune system must protect the infant against the sudden exposure to a large variety of pathogens upon birth. While it is known that the fetal immune system develops in sequential waves, relatively little is known about the composition of the innate and adaptive immune system in the tissues. Here, we applied high-dimensional mass cytometry to profile the immune system in human fetal liver, spleen, and intestine. With Hierarchical Stochastic Neighbor Embedding (HSNE) we distinguished 177 distinct immune cell clusters, including both previously identified and novel cell clusters. PCA analysis indicated substantial differences between the compositions of the immune system in the different organs. Through dual t-SNE we identified tissue-specific cell clusters, which were found both in the innate and adaptive compartment. To determine the spatial location of tissue-specific subsets we developed a 31-antibody panel to reveal both the immune compartment and surrounding stromal elements through analysis of snap-frozen tissue samples with imaging mass cytometry. Imaging mass cytometry reconstructed the tissue architecture and allowed both the characterization and determination of the location of the various immune cell clusters within the tissue context. Moreover, it further underpinned the distinctness of the immune system in the tissues. Thus, our results provide evidence for early compartmentalization of the adaptive and innate immune compartment in fetal spleen, liver, and intestine. Together, our data provide a unique and comprehensive overview of the composition and organization of the human fetal immune system in several tissues.
Asunto(s)
Feto/inmunología , Citometría de Flujo/métodos , Sistema Inmunológico/inmunología , Análisis de la Célula Individual/métodos , Inmunidad Adaptativa/inmunología , Linaje de la Célula/inmunología , Análisis por Conglomerados , Feto/citología , Humanos , Sistema Inmunológico/citología , Sistema Inmunológico/embriología , Inmunidad Innata/inmunología , Intestinos/citología , Intestinos/embriología , Intestinos/inmunología , Hígado/citología , Hígado/embriología , Hígado/inmunología , Análisis de Componente Principal , Bazo/citología , Bazo/embriología , Bazo/inmunología , Linfocitos T/clasificación , Linfocitos T/inmunologíaRESUMEN
PURPOSE: Intravascular optical coherence tomography (OCT) is widely used for analysis of the coronary artery disease. Its high spatial resolution allows for visualization of arterial tissue components in detail. There are different OCT systems on the market, each of which produces data characterized by its own intensity range and distribution. These differences should be taken into account for the development of image processing algorithms. In order to overcome this difference in the intensity range and distribution, we developed a framework for matching intensities based on the exact histogram matching technique. METHODS: In our method, the key step for using the exact histogram matching is to determine the target histogram. For this, we proposed two schemes: a global scheme that uses a single histogram as the target histogram for all the pullbacks, and a local scheme that selects for each single image a target histogram from a predefined database. These two schemes are compared on a unique dataset containing pairs of pullbacks that were acquired shortly after each other with systems from two vendors, St. Jude and Terumo. Pullbacks were aligned according to anatomical landmarks, and a database of matched histogram pairs was created. A leave-one-out cross validation was used to compare performance of the two schemes. The matching accuracy was evaluated by comparing: (a) histograms using Euclidean (dx2 ) and Kolmogorov-Smirnov (dKS ) distances, and (b) median intensity level within anatomical regions of interest. RESULTS: Leave-one-out validation indicated that both matching schemes yield comparably high accuracies across the entire validation dataset. The local scheme outperforms the global scheme with marginally lower dissimilarities at both histogram level and intensity level. High visual similarity was observed when comparing the matched images to their aligned counterparts. CONCLUSION: Both local and global schemes are robust and produce accurate intensity matching. While local scheme performs marginally better than the global scheme, it requires a predefined histogram dataset and is more time consuming. Thus, for offline standardization of the images, the local scheme should be preferred for being more accurate. For online standardization or when another system is involved, the global scheme can be used as a simple and nearly-as-accurate alternative.
RESUMEN
AIMS: We aimed to assess possible differences in neointimal quality after everolimus-eluting bioresorbable scaffold (BVS) implantation in comparison with cobalt-chromium everolimus-eluting scaffold (CoCr-EES) implantation by optical frequency domain imaging (OFDI). METHODS AND RESULTS: This study is a post hoc analysis of the TROFI II trial assessing neointimal quality six months after the implantation of BVS (N=82) and CoCr-EES (N=87) in STEMI patients. Neointimal light property analysis by OFDI fully automatically computed light attenuation, backscatter and light intensity for superficial and deep neointima. High light attenuation/backscatter and high light intensity are reportedly associated with lipidic change and tissue maturation, respectively. Superficial and deep neointima in BVS presented lower light attenuation than CoCr-EES (superficial: 0.77±0.15 vs. 1.27±0.55 mm-1, p<0.001; deep: 0.88±0.20 vs. 1.17±0.27 mm-1, p<0.001). Superficial neointima in BVS showed comparable backscatter to that of CoCr-EES (4.81±0.52 vs. 4.94±0.61, p=0.141), while deep neointima in BVS showed lower backscatter than that of CoCr-EES (4.60±0.62 vs. 4.97±0.62, p<0.001). Light intensity of superficial neointima was comparable between both arms (139±13 vs. 144±30, p=0.236), whereas light intensity of deep neointima in BVS was lower than CoCr-EES (129±14 vs. 138±21, p<0.001). CONCLUSIONS: The present OFDI comparison suggested that tissue maturation was comparable but lipidic change of neointima was less prominent after BVS than after CoCr-EES implantation.
Asunto(s)
Stents Liberadores de Fármacos , Neointima/etiología , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Implantes Absorbibles , Stents Liberadores de Fármacos/efectos adversos , Everolimus , Humanos , Infarto del Miocardio con Elevación del ST/cirugía , Stents , Tomografía de Coherencia Óptica , Resultado del TratamientoRESUMEN
An important application of intravascular optical coherence tomography (IVOCT) for atherosclerotic tissue analysis is using it to estimate attenuation and backscatter coefficients. This work aims at exploring the potential of the attenuation coefficient, a proposed backscatter term, and image intensities in distinguishing different atherosclerotic tissue types with a robust implementation of depth-resolved (DR) approach. Therefore, the DR model is introduced to estimate the attenuation coefficient and further extended to estimate the backscatter-related term in IVOCT images, such that values can be estimated per pixel without predefining any delineation for the estimation. In order to exclude noisy regions with a weak signal, an automated algorithm is implemented to determine the cut-off border in IVOCT images. The attenuation coefficient, backscatter term, and the image intensity are further analyzed in regions of interest, which have been delineated referring to their pathology counterparts. Local statistical values were reported and their distributions were further compared with a two-sample t-test to evaluate the potential for distinguishing six types of tissues. Results show that the IVOCT intensity, DR attenuation coefficient, and backscatter term extracted with the reported implementation are complementary to each other on characterizing six tissue types: mixed, calcification, fibrous, lipid-rich, macrophages, and necrotic core.
Asunto(s)
Algoritmos , Aterosclerosis/diagnóstico por imagen , Tomografía de Coherencia Óptica/métodos , Tejido Adiposo/diagnóstico por imagen , Calcinosis/diagnóstico por imagenRESUMEN
BACKGROUND: Pancreatic cancer is the fourth leading cause of cancer-related mortality in the United States. The minority of patients can undergo curative-intended surgical therapy due to progressive disease stage at time of diagnosis. Nonetheless, tumor involvement of surgical margins is seen in up to 70% of resections, being a strong negative prognostic factor. Real-time intraoperative imaging modalities may aid surgeons to obtain tumor-free resection margins. Full-field optical coherence tomography (FF-OCT) is a promising diagnostic tool using high-resolution white-light interference microscopy without tissue processing. Therefore, we composed an atlas of FF-OCT images of malignant and benign pancreatic tissue, and investigated the accuracy with which the pathologists could distinguish these. MATERIALS AND METHODS: One hundred FF-OCT images were collected from specimens of 29 patients who underwent pancreatic resection for various indications between 2014 and 2016. One experienced gastrointestinal pathologist and one pathologist in training scored independently the FF-OCT images as malignant or benign blinded to the final pathology conclusion. Results were compared to those obtained with standard hematoxylin and eosin (H&E) slides. RESULTS: Overall, combined test characteristics of both pathologists showed a sensitivity of 72%, specificity of 74%, positive predictive value of 69%, negative predictive value of 79% and an overall accuracy of 73%. In the subset of pancreatic ductal adenocarcinoma patients, 97% of the FF-OCT images (n = 35) were interpreted as tumor by at least one pathologist. Moreover, normal pancreatic tissue was recognised in all cases by at least one pathologist. However, atrophy and fibrosis, serous cystadenoma and neuroendocrine tumors were more often wrongly scored, in 63%, 100% and 25% respectively. CONCLUSION: FF-OCT could distinguish normal pancreatic tissue from pathologic pancreatic tissue in both processed as non-processed specimens using architectural features. The accuracy in pancreatic ductal adenocarcinoma is promising and warrants further evaluation using improved assessment criteria.