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1.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 47(8): 1075-1081, 2022 Aug 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-36097775

RESUMO

OBJECTIVES: Central serous chorioretinopathy (CSC) is generally a common fundus disease in young and middle-aged Asian men. Acute and chronic CSC can lead to different degrees of injury to the retinal blood flow. This study aims to observe and compare the blood flow density in different retinal capillary layers in patients with acute and chronic CSC using optical coherence tomography angiography (OCTA) technology. METHODS: Twelve patients with acute CSC and 8 patients with chronic CSC including 12 eyes with acute CSC (acute CSC eye group), 11 eyes with chronic CSC (chronic CSC eye group), and 17 normal eyes (normal eye group) were enrolled in this study. All patients underwent 3 mm×3 mm, 6 mm×6 mm macular OCTA scanning. The retinal microvascu-lature was divided into superficial vascular complexes (SVC), intermediate capillary plexuses (ICP), and deep capillary plexuses (DCP) using the projection resolved-OCTA algorithm. Inner retina includes SVC, ICP, and DCP. The vessel density in each retinal layer and the inner retina were calculated and compared. RESULTS: Macular OCTA scanning of 3 mm×3 mm showed that there was no significant difference in blood flow density of SVC and ICP among the 3 groups (both P>0.05); blood flow density of DCP and inner retina in the chronic CSC eye group was significantly lower than that in the acute CSC eye group and the normal eye group (all P<0.05); there was no significant difference in retinal blood flow density of different layer between the acute CSC eye group and the normal eye group (all P>0.05). Macular OCTA scanning of 6 mm×6 mm showed that inner retinal blood flow density of the chronic CSC eye group was significantly lower than that of the acute CSC eye group and the normal eye group (both P<0.05); there was no significant difference in blood flow density of SVC among the 3 groups (P>0.05). CONCLUSIONS: The vessel density of DCP and inner retina in the eyes with chronic CSC are significantly reduced, which may result in impaired visual function. Therefore, we recommend that patients with acute CSC should be properly treated to avoid progressing into chronic CSC.


Assuntos
Coriorretinopatia Serosa Central , Coriorretinopatia Serosa Central/diagnóstico por imagem , Angiofluoresceinografia/métodos , Humanos , Masculino , Microvasos/diagnóstico por imagem , Pessoa de Meia-Idade , Retina , Tomografia de Coerência Óptica/métodos
2.
Commun Biol ; 5(1): 908, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36064747

RESUMO

The blood-tumor barrier (BTB) contributes to poor therapeutic efficacy by limiting drug uptake; therefore, elevating BTB permeability is essential for glioma treatment. Here, we prepared astrocyte microvascular endothelial cells (ECs) and glioma microvascular ECs (GECs) as in vitro blood-brain barrier (BBB) and BTB models. Upregulation of METTL3 and IGF2BP3 in GECs increased the stability of CPEB2 mRNA through its m6A methylation. CPEB2 bound to and increased SRSF5 mRNA stability, which promoted the ETS1 exon inclusion. P51-ETS1 promoted the expression of ZO-1, occludin, and claudin-5 transcriptionally, thus regulating BTB permeability. Subsequent in vivo knockdown of these molecules in glioblastoma xenograft mice elevated BTB permeability, promoted doxorubicin penetration, and improved glioma-specific chemotherapeutic effects. These results provide a theoretical and experimental basis for epigenetic regulation of the BTB, as well as insight into comprehensive glioma treatment.


Assuntos
Neoplasias Encefálicas , Glioma , Metiltransferases , Proteínas de Ligação a RNA , Fatores de Processamento de Serina-Arginina , Animais , Astrócitos/metabolismo , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Células Endoteliais/metabolismo , Epigênese Genética , Glioma/tratamento farmacológico , Glioma/genética , Glioma/metabolismo , Humanos , Metilação , Metiltransferases/genética , Metiltransferases/metabolismo , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Microvasos/metabolismo , Permeabilidade , Fatores de Processamento de RNA/genética , Fatores de Processamento de RNA/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Fatores de Processamento de Serina-Arginina/genética , Fatores de Processamento de Serina-Arginina/metabolismo , Proteína da Zônula de Oclusão-1/genética , Proteína da Zônula de Oclusão-1/metabolismo
3.
Retina ; 42(10): 1939-1949, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-36129267

RESUMO

PURPOSE: The study aimed to evaluate the macular microvasculature of X-linked retinoschisis (XLRS) and identify correlations between vascular changes, structural changes, and functional outcome. METHODS: Genetically confirmed XLRS patients and heathy control subjects underwent complete ophthalmic examination, dilated funduscopic examination, optical coherence tomography, and optical coherence tomography angiography. Schisis distribution, outer plexiform layer discontinuation, photoreceptor layer thickness, and photoreceptor outer segment length were reviewed using optical coherence tomography. Vascular flow density and foveal thickness at foveal and parafoveal area were measured using optical coherence tomography angiography. RESULTS: A total of 17 eyes of 9 XLRS patients and 22 eyes of 11 control subjects were examined from July 2018 to August 2020. Flow density in the deep capillary plexus at foveal and parafoveal area decreased in XLRS patients compared with control subjects (P = 0.014 and 0.001, respectively), whereas foveal avascular zone area and perimeter remarkably increased (P = 0.015 and 0.001, respectively). Although outer and total retinal layers were significantly thicker in XLRS, inner retinal layer was thinner with reduced photoreceptor layer thickness and shortened photoreceptor outer segment length (P < 0.001 and P < 0.001, respectively). Foveal flow loss in deep capillary plexus, foveal avascular zone enlargement, thinner inner retina and photoreceptor layer thickness, and shortened photoreceptor outer segment length correlated with best-corrected visual acuity. CONCLUSION: X-linked retinoschisis eyes exhibit decreased flow density in the deep capillary plexus and variable foveal avascular zone with enlarged perimeter. Structural deterioration of the photoreceptor best reflects the degenerative changes, whereas microvascular alteration shows considerable correlation with functional outcome in XLRS.


Assuntos
Retinosquise , Angiofluoresceinografia/métodos , Fóvea Central , Humanos , Microvasos , Vasos Retinianos/diagnóstico por imagem , Retinosquise/diagnóstico por imagem , Retinosquise/genética , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos , Acuidade Visual
4.
Front Endocrinol (Lausanne) ; 13: 973058, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36060954

RESUMO

Protein kinase C (PKC) is a family of serine/threonine protein kinases, the activation of which plays an important role in the development of diabetic microvascular complications. The activation of PKC under high-glucose conditions stimulates redox reactions and leads to an accumulation of redox stress. As a result, various types of cells in the microvasculature are influenced, leading to changes in blood flow, microvascular permeability, extracellular matrix accumulation, basement thickening and angiogenesis. Structural and functional disorders further exacerbate diabetic microvascular complications. Here, we review the roles of PKC in the development of diabetic microvascular complications, presenting evidence from experiments and clinical trials.


Assuntos
Angiopatias Diabéticas , Proteína Quinase C , Permeabilidade Capilar/efeitos dos fármacos , Permeabilidade Capilar/fisiologia , Diabetes Mellitus , Angiopatias Diabéticas/tratamento farmacológico , Angiopatias Diabéticas/etiologia , Angiopatias Diabéticas/metabolismo , Humanos , Microvasos/efeitos dos fármacos , Microvasos/metabolismo , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Proteína Quinase C/efeitos adversos , Proteína Quinase C/metabolismo
5.
Cells ; 11(16)2022 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-36010546

RESUMO

Organ function relies on microvascular networks to maintain homeostatic equilibrium, which varies widely in different organs and during different physiological challenges. The endothelium role in this critical process can only be evaluated in physiologically relevant contexts. Comparing the responses to oxygen flux in primary murine microvascular EC (MVEC) obtained from brain and lung tissue reveals that supra-physiological oxygen tensions can compromise MVEC viability. Brain MVEC lose mitochondrial activity and undergo significant alterations in electron transport chain (ETC) composition when cultured under standard, non-physiological atmospheric oxygen levels. While glycolytic capacity of both lung and brain MVEC are unchanged by environmental oxygen, the ability to trigger a metabolic shift when oxygen levels drop is greatly compromised following exposure to hyperoxia. This is particularly striking in MVEC from the brain. This work demonstrates that the unique metabolism and function of organ-specific MVEC (1) can be reprogrammed by external oxygen, (2) that this reprogramming can compromise MVEC survival and, importantly, (3) that ex vivo modelling of endothelial function is significantly affected by culture conditions. It further demonstrates that physiological, metabolic and functional studies performed in non-physiological environments do not represent cell function in situ, and this has serious implications in the interpretation of cell-based pre-clinical models.


Assuntos
Hiperóxia , Animais , Células Endoteliais/metabolismo , Hipóxia/metabolismo , Camundongos , Microvasos , Oxigênio/metabolismo
6.
Sensors (Basel) ; 22(16)2022 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-36015953

RESUMO

The diagnosis of small vessel disease is attracting interest; however, it remains difficult to visualize the microvasculature using 3 Tesla (T) magnetic resonance imaging (MRI). Therefore, this study aimed to visualize the microvascular structure and measure a slow flow on 3T MRI. We developed a microcirculation system using piezoelectric pumps connected to small tubes (0.4, 0.5, 0.8, and 1.0 mm) and evaluated various MR sequences and imaging parameters to identify the most appropriate acquisition parameters. We found that the system could image small structures with a diameter of 0.5 mm or more when using a 1 m-long tube (maximal signal intensity of 241 in 1 mm, 199 in 0.8 mm, and 133 in 0.5 mm). We also found that the highest signal-to-noise ratio (SNR) appeared on 2-dimensional time-of-flight low-resolution imaging and that the flow velocity (10.03 cm/s) was similar to the actual velocity (11.01 cm/s in a flowmeter) when velocity encoding of 30 cm/s was used in a 0.8 mm-diameter tube. In conclusion, this study demonstrates that a microcirculation system can be used to image small vessels. Therefore, our results could serve as a basis for research on vessels' anatomical structure and pathophysiological function in small vessel disease.


Assuntos
Imageamento por Ressonância Magnética , Ultrassom , Imageamento por Ressonância Magnética/métodos , Microcirculação , Microvasos/diagnóstico por imagem , Imagens de Fantasmas , Razão Sinal-Ruído
7.
Fluids Barriers CNS ; 19(1): 64, 2022 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-36028880

RESUMO

BACKGROUND: Endothelial cells (ECs) in cerebral vessels are considered the primary targets in acute hemorrhagic brain injuries. EC dysfunction can aggravate neuronal injuries by causing secondary inflammatory responses and blood-brain barrier (BBB) disruption. Previous studies have reported that enhancement of mitochondrial function within ECs may reduce BBB disruption and decrease the severity of acute brain injuries. However, the molecular signaling pathways through which enhanced EC mitochondrial function is enhanced to exert this BBB protective effect have not been fully elucidated. METHODS: To identify signaling pathways involved in linking EC-specific mitochondrial dysfunction and BBB disruption, we first performed RNA sequencing using isolated cerebral vessels from TEKCRIF1 KO mice, a mouse strain that displays EC-specific mitochondrial dysfunction. After identification, we assessed the significance of candidate signaling pathways using an intracerebral hemorrhage (ICH) mouse model. BBB integrity was assessed using an IgG leakage assay, and symptomatic changes were evaluated using behavioral assays. RESULTS: Transcriptome analyses of the TEKCRIF1 KO mouse revealed significant changes in Notch1 signaling, a pathway intimately involved in BBB maintenance. We also observed a decrease in Notch1 signaling and expression of the mitochondrial oxidative phosphorylation (OxPhos) complex in the ICH mouse model, which also exhibits BBB disruption. To further assess the function of Notch1 signaling in relation to BBB disruption, we injected ICH model mice with adropin, a protein that interacts with the Notch1 ligand NB-3 and activates Notch1 signaling. We found that adropin prevented BBB disruption and reduced the extent (area) of the injury compared with that in vehicle controls, in association with alteration of mitochondrial function. CONCLUSION: These results suggest that the Notch1 signaling pathway acts as an upstream regulator of DEGs and can be a target to regulate the changes involved with endothelial mitochondrial dysfunction-dependent BBB disruption. Thus, treatment methods that activate Notch1 may be beneficial in acute brain injuries by protecting BBB integrity.


Assuntos
Barreira Hematoencefálica , Lesões Encefálicas , Animais , Hemorragia Cerebral , Modelos Animais de Doenças , Células Endoteliais , Perfilação da Expressão Gênica , Camundongos , Microvasos , Mitocôndrias , Transdução de Sinais , Transcriptoma
8.
Am J Physiol Heart Circ Physiol ; 323(3): 490-498, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35930446

RESUMO

Darkly pigmented individuals are at the greatest risk of hypovitaminosis D, which may result in microvascular endothelial dysfunction via reduced nitric oxide (NO) bioavailability and/or increased oxidative stress and inflammation. We investigated the associations among skin pigmentation (M-index; skin reflectance spectrophotometry), serum vitamin D concentration [25(OH)D], circulating inflammatory cytokine (TNF-α, IL-6, and IL-10) concentrations, and the NO contribution to local heating-induced cutaneous vasodilation (%NO-mediated vasodilation) in a diversely pigmented cohort of young adults. An intradermal microdialysis fiber was placed in the forearms of 33 healthy adults (14 men/19 women; 18-27 yr; M-index, 30-81 AU) for local delivery of pharmacological agents. Lactated Ringer's solution was perfused through the fiber during local heating-induced (39°C) cutaneous vasodilation. After attaining stable elevated blood flow, 15 mM NG-nitro-l-arginine methyl ester (l-NAME; NO synthase inhibiter) was infused to quantify %NO-mediated vasodilation. Red cell flux was measured (laser-Doppler flowmetry; LDF) and cutaneous vascular conductance (CVC = LDF/MAP) was normalized to maximal (%CVCmax; 28 mM sodium nitroprusside + 43°C). Serum [25(OH)D] and circulating cytokines were analyzed by ELISA and multiplex assay, respectively. M-index was negatively associated with [25(OH)D] (r = -0.57, P < 0.0001) and %NO-mediated vasodilation (r = -0.42, P = 0.02). Serum[25(OH)D] was positively related to %NO (r = 0.41, P = 0.02). Controlling for [25(OH)D] weakened the association between M-index and %NO-mediated dilation (P = 0.16, r = -0.26). There was a negative curvilinear relation between [25(OH)D] and circulating IL-6 (r = -0.56, P < 0.001), but not TNF-α or IL-10 (P ≥ 0.14). IL-6 was not associated with %NO-mediated vasodilation (P = 0.44). These data suggest that vitamin D insufficiency/deficiency may contribute to reduced microvascular endothelial function in healthy, darkly pigmented young adults.NEW & NOTEWORTHY Endothelial dysfunction, an antecedent to hypertension and overt CVD, is commonly observed in otherwise healthy Black adults, although the underlying causes remain unclear. We show that reduced vitamin D availability with increasing degrees of skin pigmentation is associated with reduced microvascular endothelial function, independent of race or ethnicity, in healthy young adults. Greater prevalence of vitamin D deficiency in more darkly pigmented individuals may predispose them to increased risk of endothelial dysfunction.


Assuntos
Deficiência de Vitamina D , Vitamina D , Feminino , Humanos , Interleucina-10 , Masculino , Microdiálise , Microvasos , NG-Nitroarginina Metil Éster , Óxido Nítrico , Fluxo Sanguíneo Regional , Pele/irrigação sanguínea , Pigmentação da Pele , Vasodilatação , Deficiência de Vitamina D/diagnóstico , Adulto Jovem
9.
Front Immunol ; 13: 945656, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35967431

RESUMO

Pneumolysin (PLY) is a bacterial pore forming toxin and primary virulence factor of Streptococcus pneumonia, a major cause of pneumonia. PLY binds cholesterol-rich domains of the endothelial cell (EC) plasma membrane resulting in pore assembly and increased intracellular (IC) Ca2+ levels that compromise endothelial barrier integrity. Caveolae are specialized plasmalemma microdomains of ECs enriched in cholesterol. We hypothesized that the abundance of cholesterol-rich domains in EC plasma membranes confers cellular susceptibility to PLY. Contrary to this hypothesis, we found increased PLY-induced IC Ca2+ following membrane cholesterol depletion. Caveolin-1 (Cav-1) is an essential structural protein of caveolae and its regulation by cholesterol levels suggested a possible role in EC barrier function. Indeed, Cav-1 and its scaffolding domain peptide protected the endothelial barrier from PLY-induced disruption. In loss of function experiments, Cav-1 was knocked-out using CRISPR-Cas9 or silenced in human lung microvascular ECs. Loss of Cav-1 significantly enhanced the ability of PLY to disrupt endothelial barrier integrity. Rescue experiments with re-expression of Cav-1 or its scaffolding domain peptide protected the EC barrier against PLY-induced barrier disruption. Dynamin-2 (DNM2) is known to regulate caveolar membrane endocytosis. Inhibition of endocytosis, with dynamin inhibitors or siDNM2 amplified PLY induced EC barrier dysfunction. These results suggest that Cav-1 protects the endothelial barrier against PLY by promoting endocytosis of damaged membrane, thus reducing calcium entry and PLY-dependent signaling.


Assuntos
Proteínas de Bactérias , Caveolina 1 , Pulmão , Pneumonia Pneumocócica , Pneumonia , Estreptolisinas , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Caveolina 1/genética , Caveolina 1/metabolismo , Colesterol/metabolismo , Endotélio Vascular/metabolismo , Humanos , Pulmão/irrigação sanguínea , Pulmão/metabolismo , Microvasos/metabolismo , Pneumonia/genética , Pneumonia/metabolismo , Pneumonia/microbiologia , Pneumonia Pneumocócica/genética , Pneumonia Pneumocócica/metabolismo , Pneumonia Pneumocócica/microbiologia , Streptococcus pneumoniae/metabolismo , Streptococcus pneumoniae/patogenicidade , Estreptolisinas/genética , Estreptolisinas/metabolismo , Doenças Vasculares/genética , Doenças Vasculares/metabolismo , Doenças Vasculares/microbiologia
10.
Transl Vis Sci Technol ; 11(8): 9, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35947369

RESUMO

Purpose: To explore the relationship between serum uric acid (SUA) and retinochoroidal microcirculation in the Chinese population. Methods: This prospective cross-sectional study was conducted among the residents of Guangzhou, southern China. A commercially available optical coherence tomography angiography (OCTA) device was used to obtain the superficial vessel density (SVD) and deep vessel density in the retina and the choriocapillaris flow deficit (CFD) in the macular region. Univariable and multivariable linear regression models were used to assess the association of hyperuricemia and SUA levels with OCTA parameters. Results: A total of 638 participants with normal SUA and 296 participants with hyperuricemia were included in the study. Parafoveal SVD was significantly reduced among the participants with hyperuricemia compared to participants with normal SUA (P < 0.001), while the parafoveal CFD was higher in hyperuricemic participants than those of normal SUA levels (P = 0.007). After adjusting for potential confounders, greater SUA levels was associated with lower SVD (ß = -0.078; P < 0.001) and greater CFD (ß = 0.015; P = 0.011). Gender difference analysis indicated that a 10-µmol/L increase in SUA levels among the female participants led to a 0.144 decrease in SVD (P < 0.001), but it was not statistically significant for the male participants (P = 0.653). Conclusions: An elevated uric acid level and its fluctuations were independently associated with impaired retinal and choroidal microcirculation using OCTA in the study population. Women appear to be more sensitive to high SUA levels than men. Translational Relevance: Elevating uric acid concentration may play a role in the development and progression of cardiovascular diseases through microvascular alteration, as demonstrated by OCTA parameters.


Assuntos
Hiperuricemia , Tomografia de Coerência Óptica , Angiografia , Corioide/irrigação sanguínea , Corioide/diagnóstico por imagem , Estudos Transversais , Feminino , Humanos , Hiperuricemia/epidemiologia , Masculino , Microvasos/diagnóstico por imagem , Estudos Prospectivos , Retina , Tomografia de Coerência Óptica/métodos , Ácido Úrico
11.
Int J Mol Sci ; 23(15)2022 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-35955533

RESUMO

Glioblastoma (GB) is the most aggressive and recurrent form of brain cancer in adults. We hypothesized that the identification of biomarkers such as certain microRNAs (miRNAs) and the circulating microvesicles (MVs) that transport them could be key to establishing GB progression, recurrence and therapeutic response. For this purpose, circulating MVs were isolated from the plasma of GB patients (before and after surgery) and of healthy subjects and characterized by flow cytometry. OpenArray profiling and the individual quantification of selected miRNAs in plasma and MVs was performed, followed by target genes' prediction and in silico survival analysis. It was found that MVs' parameters (number, EGFRvIII and EpCAM) decreased after the surgical resection of GB tumors, but the inter-patient variability was high. The expression of miR-106b-5p, miR-486-3p, miR-766-3p and miR-30d-5p in GB patients' MVs was restored to control-like levels after surgery: miR-106b-5p, miR-486-3p and miR-766-3p were upregulated, while miR-30d-5p levels were downregulated after surgical resection. MiR-625-5p was only identified in MVs isolated from GB patients before surgery and was not detected in plasma. Target prediction and pathway analysis showed that the selected miRNAs regulate genes involved in cancer pathways, including glioma. In conclusion, miR-625-5p shows potential as a biomarker for GB regression or recurrence, but further in-depth studies are needed.


Assuntos
Neoplasias Encefálicas , Glioblastoma , MicroRNAs , Adulto , Biomarcadores , Neoplasias Encefálicas/genética , Perfilação da Expressão Gênica , Glioblastoma/genética , Humanos , MicroRNAs/genética , Microvasos
12.
Sci Rep ; 12(1): 13995, 2022 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-35978040

RESUMO

The dominant consequence of irradiating biological systems is cellular damage, yet microvascular damage begins to assume an increasingly important role as the radiation dose levels increase. This is currently becoming more relevant in radiation medicine with its pivot towards higher-dose-per-fraction/fewer fractions treatment paradigm (e.g., stereotactic body radiotherapy (SBRT)). We have thus developed a 3D preclinical imaging platform based on speckle-variance optical coherence tomography (svOCT) for longitudinal monitoring of tumour microvascular radiation responses in vivo. Here we present an artificial intelligence (AI) approach to analyze the resultant microvascular data. In this initial study, we show that AI can successfully classify SBRT-relevant clinical radiation dose levels at multiple timepoints (t = 2-4 weeks) following irradiation (10 Gy and 30 Gy cohorts) based on induced changes in the detected microvascular networks. Practicality of the obtained results, challenges associated with modest number of animals, their successful mitigation via augmented data approaches, and advantages of using 3D deep learning methodologies, are discussed. Extension of this encouraging initial study to longitudinal AI-based time-series analysis for treatment outcome predictions at finer dose level gradations is envisioned.


Assuntos
Neoplasias , Radiocirurgia , Animais , Inteligência Artificial , Microvasos/diagnóstico por imagem , Microvasos/patologia , Neoplasias/diagnóstico por imagem , Neoplasias/patologia , Neoplasias/radioterapia , Radiocirurgia/métodos , Dosagem Radioterapêutica , Tomografia de Coerência Óptica/métodos
13.
Nat Methods ; 19(8): 1004-1012, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35927475

RESUMO

The advent of neuroimaging has increased our understanding of brain function. While most brain-wide functional imaging modalities exploit neurovascular coupling to map brain activity at millimeter resolutions, the recording of functional responses at microscopic scale in mammals remains the privilege of invasive electrophysiological or optical approaches, but is mostly restricted to either the cortical surface or the vicinity of implanted sensors. Ultrasound localization microscopy (ULM) has achieved transcranial imaging of cerebrovascular flow, up to micrometre scales, by localizing intravenously injected microbubbles; however, the long acquisition time required to detect microbubbles within microscopic vessels has so far restricted ULM application mainly to microvasculature structural imaging. Here we show how ULM can be modified to quantify functional hyperemia dynamically during brain activation reaching a 6.5-µm spatial and 1-s temporal resolution in deep regions of the rat brain.


Assuntos
Microscopia , Fenômenos Fisiológicos do Sistema Nervoso , Animais , Encéfalo/fisiologia , Mamíferos , Microbolhas , Microscopia/métodos , Microvasos , Ratos
14.
World J Gastroenterol ; 28(24): 2733-2747, 2022 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-35979164

RESUMO

BACKGROUND: The prognosis of hepatocellular carcinoma (HCC) remains poor and relapse occurs in more than half of patients within 2 years after hepatectomy. In terms of recent studies, microvascular invasion (MVI) is one of the potential predictors of recurrence. Accurate preoperative prediction of MVI is potentially beneficial to the optimization of treatment planning. AIM: To develop a radiomic analysis model based on pre-operative magnetic resonance imaging (MRI) data to predict MVI in HCC. METHODS: A total of 113 patients recruited to this study have been diagnosed as having HCC with histological confirmation, among whom 73 were found to have MVI and 40 were not. All the patients received preoperative examination by Gd-enhanced MRI and then curative hepatectomy. We manually delineated the tumor lesion on the largest cross-sectional area of the tumor and the adjacent two images on MRI, namely, the regions of interest. Quantitative analyses included most discriminant factors (MDFs) developed using linear discriminant analysis algorithm and histogram analysis with MaZda software. Independent significant variables of clinical and radiological features and MDFs for the prediction of MVI were estimated and a discriminant model was established by univariate and multivariate logistic regression analysis. Prediction ability of the above-mentioned parameters or model was then evaluated by receiver operating characteristic (ROC) curve analysis. Five-fold cross-validation was also applied via R software. RESULTS: The area under the ROC curve (AUC) of the MDF (0.77-0.85) outperformed that of histogram parameters (0.51-0.74). After multivariate analysis, MDF values of the arterial and portal venous phase, and peritumoral hypointensity in the hepatobiliary phase were identified to be independent predictors of MVI (P < 0.05). The AUC value of the model was 0.939 [95% confidence interval (CI): 0.893-0.984, standard error: 0.023]. The result of internal five-fold cross-validation (AUC: 0.912, 95%CI: 0.841-0.959, standard error: 0.0298) also showed favorable predictive efficacy. CONCLUSION: Noninvasive MRI radiomic model based on MDF values and imaging biomarkers may be useful to make preoperative prediction of MVI in patients with primary HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/cirurgia , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Imageamento por Ressonância Magnética/métodos , Microvasos/diagnóstico por imagem , Microvasos/patologia , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos
15.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 39(4): 740-748, 2022 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-36008338

RESUMO

The design of wall filter in ultrasonic microvascular imaging directly affects the resolution of blood flow imaging. We compared the traditional polynomial regression wall filter algorithm and two algorithms based on singular value decomposition (SVD), Full-SVD algorithm and RS-RSVD algorithm (random sampling based on random singular value decomposition) through experiments with simulated data and human renal entity data imaging experiments. The experimental results showed that the filtering effect of the traditional polynomial regression wall filter algorithm was limited, however, Full-SVD algorithm and RS-RSVD algorithm could better extract the micro blood flow signal from the tissue or noise signal. When RS-RSVD algorithm was randomly divided into 16 blocks, the signal-to-noise ratio was the same as that of Full-SVD algorithm, reduces the contrast-to-noise ratio by 2.05 dB, and reduces the execution time by 90.41%. RS-RSVD algorithm can improve the operation efficiency and is more conducive to the real-time imaging of high frame rate ultrasound microvessels.


Assuntos
Algoritmos , Ultrassom , Humanos , Microvasos/diagnóstico por imagem , Razão Sinal-Ruído , Ultrassonografia/métodos
16.
J Am Heart Assoc ; 11(15): e25226, 2022 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-35876422

RESUMO

Background The associations of time-averaged cumulative blood pressure (BP) from midlife to late life with microvasculature expressed as retinal vessel diameters is not well studied. The aim of this study was to evaluate the association of cumulative systolic BP and diastolic BP (DBP) with retinal vessel calibers, focusing on race differences. Methods and Results The analysis included 1818 adults from the ARIC (Atherosclerosis Risk in Communities) study attending the fifth visit (2011-2013; age 77±5 years, 17.1% Black participants). Time-averaged cumulative BPs were calculated as the sum of averaged BPs from adjacent consecutive visits (visits 1-5) indexed to total observation time (24±1 years). Summarized estimates for central retinal arteriolar equivalent and central retinal venular equivalent at the fifth visit represent average retinal vessel diameters. The arteriole:venule ratio was calculated. We tested for effect modification by race. Results from multiple linear regression models suggested that higher time-averaged cumulative DBP (ß [95% CI] per 1-SD increase: -1.78 [-2.53, -1.02], P<0.001 and -0.005 [-0.009, -0.002], P=0.004, respectively) but not systolic BP (-0.52 [-1.30, 0.26], P=0.189 and 0.001 [-0.002, 0.005], P=0.485, respectively) was associated with smaller central retinal arteriolar equivalent and arteriole:venule ratio. The association between time-averaged cumulative DBP and arteriole:venule ratio was strongest in White participants (interaction P=0.007). The association of cumulative systolic BP and DBP with central retinal venular equivalent was strongest in Black participants (interaction P=0.015 and 0.011, respectively). Conclusions Exposure to higher BP levels, particularly DBP, from midlife to late life is associated with narrower retinal vessel diameters in late life. Furthermore, race moderated the association of cumulative BP exposure with retinal microvasculature.


Assuntos
Pressão Sanguínea , Hipertensão , Microvasos , Vasos Retinianos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Arteríolas/fisiopatologia , Negros , Pressão Sanguínea/fisiologia , Diástole , Humanos , Hipertensão/complicações , Hipertensão/diagnóstico , Hipertensão/etnologia , Hipertensão/fisiopatologia , Microvasos/fisiopatologia , Artéria Retiniana/fisiopatologia , Veia Retiniana/fisiopatologia , Vasos Retinianos/fisiopatologia , Sístole , Fatores de Tempo , Vênulas/fisiopatologia , Brancos
17.
Ultrasound Med Biol ; 48(10): 2095-2109, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35882573

RESUMO

The morphological features of vasculature in diseased tissue differ significantly from those in normal tissue. Therefore, vasculature quantification is crucial for disease diagnosis and staging. Ultrasound microvessel imaging (UMI) with ultrafast ultrasound acquisitions has been determined to have potential in clinical applications given its superior sensitivity in blood flow detection. However, the presence of spatial-dependent noise caused by a low imaging signal-to-noise ratio and incoherent clutter artifacts caused by moving hyperechoic scatterers degrades the performance of UMI and the reliability of vascular quantification. To tackle these issues, we proposed an improved UMI technique along with an adaptive vessel segmentation workflow for robust vessel identification and vascular feature quantification. A previously proposed sub-aperture cross-correlation technique and a normalized cross-correlation technique were applied to equalize the spatially dependent noise level and suppress the incoherent clutter artifact. A square operator and non-local means filter were then used to better separate the blood flow signal from residual background noise. On the de-noised ultrasound microvessel image, an automatic and adaptive vessel segmentation method was developed based on the different spatial patterns of blood flow signal and background noise. The proposed workflow was applied to a CIRS phantom, to a Doppler flow phantom and to an inflammatory bowel, kidney and liver, to validate its feasibility. Results revealed that automatic adaptive, and robust vessel identification performance can be achieved using the proposed method without the subjectivity caused by radiologists/operators.


Assuntos
Processamento de Imagem Assistida por Computador , Microvasos , Imagens de Fantasmas , Reprodutibilidade dos Testes , Razão Sinal-Ruído , Ultrassonografia
18.
J Physiol ; 600(17): 3921-3929, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35869823

RESUMO

Heart failure (HF) is characterised by abnormal conduit and resistance artery function in humans. Microvascular function in HF is less well characterised, due in part to the lack of tools to image these vessels in vivo. The skin microvasculature is a surrogate for systemic microvascular function and health and plays a key role in thermoregulation, which is dysfunctional in HF. We deployed a novel optical coherence tomography (OCT) technique to visualise and quantify microvascular structure and function in 10 subjects with HF and 10 age- and sex-matched controls. OCT images were obtained from the ventral aspect of the forearm, at baseline (33°C) and after 30 min of localised skin heating. At rest, OCT-derived microvascular density (20.3 ± 8.7%, P = 0.004), diameter (35.1 ± 6.0 µm, P = 0.006) and blood flow (82.9 ± 41.1 pl/s, P = 0.021) were significantly lower in HF than CON (27.2 ± 8.0%, 40.4 ± 5.8 µm, 110.8 ± 41.9 pl/s), whilst blood speed was not significantly lower (74.3 ± 11.0 µm/s vs. 81.3 ± 9.9 µm/s, P = 0.069). After local heating, the OCT-based density, diameter, blood speed and blood flow of HF patients were similar (all P > 0.05) to CON. Although abnormalities exist at rest which may reflect microvascular disease status, patients with HF retain the capacity to dilate cutaneous microvessels in response to localised heat stress. This is a novel in vivo human observation of microvascular dysfunction in HF, illustrating the feasibility of OCT to directly visualise and quantify microvascular responses to physiological stimuli in vivo. KEY POINTS: Microvessels in the skin are critical to human thermoregulation, which is compromised in participants with heart failure (HF). We have developed a powerful new non-invasive optical coherence tomography (OCT)-based approach for the study of microvascular structure and function in vivo. Our approach enabled us to observe and quantify abnormal resting microvascular function in participants with HF. Patients with HF were able to dilate skin microvessels in response to local heat stress, arguing against an underlying structural abnormality. This suggests that microvascular functional regulation is the primary abnormality in HF. OCT can be used to directly visualise and quantify microvascular responses to physiological stimuli in vivo.


Assuntos
Insuficiência Cardíaca , Tomografia de Coerência Óptica , Administração Cutânea , Insuficiência Cardíaca/diagnóstico por imagem , Humanos , Microvasos/diagnóstico por imagem , Pele/irrigação sanguínea , Pele/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos
19.
Bull Math Biol ; 84(8): 85, 2022 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-35802265

RESUMO

We analyse mathematical models in order to understand how microstructural features of vascular networks may affect blood flow dynamics, and to identify particular characteristics that promote the onset of self-sustained oscillations. By focusing on a simple three-node motif, we predict that network "redundancy", in the form of a redundant vessel connecting two main flow-branches, together with differences in haemodynamic resistance in the branches, can promote the emergence of oscillatory dynamics. We use existing mathematical descriptions for blood rheology and haematocrit splitting at vessel branch-points to construct our flow model; we combine numerical simulations and stability analysis to study the dynamics of the three-node network and its relation to the system's multiple steady-state solutions. While, for the case of equal inlet-pressure conditions, a "trivial" equilibrium solution with no flow in the redundant vessel always exists, we find that it is not stable when other, stable, steady-state attractors exist. In turn, these "nontrivial" steady-state solutions may undergo a Hopf bifurcation into an oscillatory state. We use the branch diameter ratio, together with the inlet haematocrit rate, to construct a two-parameter stability diagram that delineates regimes in which such oscillatory dynamics exist. We show that flow oscillations in this network geometry are only possible when the branch diameters are sufficiently different to allow for a sufficiently large flow in the redundant vessel, which acts as the driving force of the oscillations. These microstructural properties, which were found to promote oscillatory dynamics, could be used to explore sources of flow instability in biological microvascular networks.


Assuntos
Conceitos Matemáticos , Modelos Biológicos , Hemodinâmica , Microvasos/fisiologia , Modelos Teóricos
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