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Molecular imaging of the atherosclerotic plaque using positron emission tomography
摘要： Accurately assessing an individual’s risk of myocardial infarction or stroke using currently available risk stratification tools remains a challenge, even in patients with symptomatic disease. Inflammation, micro-calcification and intra-plaque angiogenesis occur during the development and ultimate rupture of vulnerable plaques. Molecular imaging techniques such as combined positron emission tomography and computed tomography (PET/CT) offer the opportunity to target these key cellular processes within atheroma and identify high-risk lesions. In this review we will set out the studies that have demonstrated the feasibility of PET/CT imaging in assessing atherosclerotic plaque inflammation, micro-calcification and angiogenesis. We will also discuss the potential of PET/CT molecular imaging as both a screening tool for novel therapeutic interventions and as a means of improving cardiovascular risk stratification.
关键词： inflammation,angiogenesis,vulnerable plaque,positron emission tomography,micro-calcification
更新于2025-09-10 09:29:36
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Anterior segment optical coherence tomography in acute anterior uveitis
摘要： Purpose: To analyze the corneal thickness and anterior chamber (AC) angle using anterior segment optical coherence tomography (AS-OCT) in patients with acute anterior uveitis (AAU). Methods: Twenty two patients (24 eyes) were included. All patients underwent complete ophthalmological examination, applanation tonometry and AS-OCT at diagnosis and fifteen days after treatment. Results: Average corneal thickness before treatment was 564.2 ± 44.2 μm, 580.0 ± 44.3 μm and 580.1 ± 2.9 μm, respectively in central, pericentral and paracentral cornea. Fifteen days after treatment a significant decrease of corneal thickness was observed, with 529.5 ± 33.1 μm (p=0.0091) and 542.6 ± 33.6 μm (p=0.0068), respectively in central and pericentral cornea; paracentral corneal thickness (557.8 ± 35.3 μm) thinning did not reach statistical significance (p=0.1253). There was no significant change in temporal AC angle between visits, 44.3 ± 14.4 degrees before treatment and 44.7 ± 14.7 degrees fifteen days after (p=0.9343), and mean intraocular pressure, 10.8 ± 4.5 mmHg before treatment and 12.3 ± 3.0 mmHg fifteen days after (p=0.1874). Conclusion: In the studied group, AS-OCT detected a decrease of corneal thickness after AAU treatment. Temporal AC angle and intraocular pressure did not change during the studied period.
关键词： Corneal pachymetry,Anterior eye segment,Inflammation,Tomography, optical coherence,Uveitis, anterior/diagnosis
更新于2025-09-10 09:29:36
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Dissociation of 19F and fluorescence signal upon cellular uptake of dual-contrast perfluorocarbon nanoemulsions
摘要： Objective Perfluorocarbon nanoemulsions (PFCs) tagged with fluorescence dyes have been intensively used to confirm the in vivo 19F magnetic resonance imaging (MRI) localization of PFCs by post mortem histology or flow cytometry. However, only limited data are available on tagged PFCs and the potential dissociation of fluorescence and 19F label after cellular uptake over time. Materials and methods PFCs were coupled to rhodamine (Rho) or carboxyfluorescein (Cfl) and their fate was analyzed after in vitro uptake by J774, RAW and CHO cells by flow cytometry and 19F MRI. In separate in vivo experiments, the dual-labelled emulsions were intravenously applied into mice and their distribution was monitored in spleen and liver over 24 h. In a final step, time course of fluorescence and 19F signals from injected emulsions were tracked in a local inflammation model making use of a subcutaneous matrigel depot doped with LPS (lipopolysaccharide). Results Internalization of fluorescence-labelled PFCs was associated with a substantial whitening over 24 h in all macrophage cell lines while the 19F signal remained stable over time. In all experiments, CflPFCs were more susceptible to bleaching than RhoPFCs. After intravenous injection of RhoPFCs, the fluorescence signal in spleen and liver peaked after 30 min and 2 h, respectively, followed by a successive decrease over 24 h, whereas the 19F signal continuously increased during this observation period. Similar results were found in the matrigel/LPS model, where we observed increasing 19F signals in the inflammatory hot spot over time while the fluorescence signal of immune cells isolated from the matrigel depot 24 h after its implantation was only marginally elevated over background levels. This resulted in a massive underestimation of the true PFC deposition in the reticuloendothelial system and at inflammatory hot spots. Conclusion Cellular uptake of fluorescently tagged PFCs leads to a dissociation of the fluorescence and the 19F label signal over time, which critically impacts on interpretation of long-term experiments validated by histology or flow cytometry.
关键词： Inflammation,19F MRI,Contrast media,Fluorescence,Perfluorocarbons
更新于2025-09-10 09:29:36
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Integrin Alpha-9 Mediates Lymphatic Valve Formation in Corneal Lymphangiogenesis
摘要： PURPOSE. We recently reported that corneal lymphatic vessels develop integrin alpha-9 (Itga-9)-positive valves during inflammatory lymphangiogenesis. The purpose of this study was to further investigate the role of Itga-9 in corneal lymphatic valve formation in vivo and lymphatic endothelial cell (LEC) functions in vitro. METHODS. Standard murine suture placement model was used to study the effect of Itga-9 blockade on lymphatic valve formation in vivo using Itga-9 neutralizing antibody. Whole-mount corneas were harvested for immunofluorescent microscopic analysis. Additionally, human LEC culture system was used to examine the effect of Itga-9 gene knockdown on cell functions using small interfering RNAs (siRNAs). RESULTS. Itga-9 blockade in vivo significantly reduced the number of lymphatic valves formed in the inflamed cornea. Moreover, Itga-9 gene knockdown in human LECs suppresses cell functions of proliferation, adhesion, migration, and tube formation. CONCLUSIONS. Itga-9 is critically involved in corneal lymphatic valve formation. Further investigation of the Itga-9 pathway may provide novel strategies to treat lymphatic-related diseases occurring both inside and outside the eye.
关键词： lymphangiogenesis,lymphatic valve,inflammation,integrin alpha-9
更新于2025-09-09 09:28:46
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Association between microRNAs expression and signaling pathways of inflammatory markers in diabetic retinopathy
摘要： Diabetic retinopathy is one of the common and serious microvascular complications of diabetes mellitus, as hyperglycemia has metabolic effects on the retina. Hyperglycemia induces increased oxidative stress, which stimulates inflammation pathways and promotes vascular dysfunction of the retina that leads to increased capillary permeability and vascular leakage. One of the main factors involving diabetic retinopathy is the inflammation signaling pathways. In contemporary times, microRNAs (miRNAs) are identified as functional biomarkers for early detection and treatment of numerous diseases specifically diabetic retinopathy. MiRNAs can modulate gene expression through regulation of transcriptional and posttranscriptional of target genes. With that, miRNAs can regulate almost every cellular and developmental process, including the regulation of instinct immune responses and inflammation. The aim of this study is to investigate the role of miRNAs in inflammation pathways and the pathogenesis of diabetic retinopathy.
关键词： miRNAs,inflammation pathway,diabetic retinopathy
更新于2025-09-09 09:28:46
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Connexin43 Mimetic Peptide Improves Retinal Function and Reduces Inflammation in a Light-Damaged Albino Rat Model
摘要： PURPOSE. Drugs that regulate connexin43 (Cx43) gap junction channels can reduce the spread of injury and improve functional outcomes after nervous system trauma. In the eye, Cx43 expression increases in the choroid following light damage. The aim of this study was to investigate whether Cx43 hemichannel block could preserve retinal function postinjury. METHODS. Light damage was induced by exposure of adult albino Sprague-Dawley rats to 2700 Lux light for 24 hours. Intravitreal injections of a Cx43 mimetic peptide hemichannel blocker, Peptide5, or sham were administered 2 hours after the onset and at the end of the light damage period. Retinal function was assessed by electroretinogram and inflammatory responses in the choroid and retina were assessed using immunohistochemistry (ionized calcium binding adaptor molecule 1 [Iba-1], leukocyte common antigen [CD45], glial fibrillary acidic protein [GFAP]). RESULTS. Light-damaged rat eyes had (1) reduced neuronal responses in both the rod and cone pathways and (2) marked inflammatory responses in the choroid and retina. Peptide5 significantly preserved function of photoreceptoral and postphotoreceptoral neurons in these animals. This was evident 24 hours after injury and 2 weeks later, as shown by improved mixed a-wave and mixed b-wave amplitudes, isolated rod PII and PIII amplitudes, and cone PII responses when compared with sham-treated controls. Retinal thinning and inflammation were also significantly reduced in Peptide5-treated eyes when compared with sham-treated controls. CONCLUSIONS. Blocking Cx43 hemichannels after light damage can significantly improve functional outcomes of neurons in both the rod and cone photo-transduction pathways in the light-damaged animal model, likely by reducing choroid inflammation and suppressing the glial-mediated inflammatory response. These data may have relevance for the treatment of conditions such as diabetic retinopathy and age-related macular degeneration.
关键词： retina,choroid,light damage,inflammation,connexin43,electroretinogram
更新于2025-09-09 09:28:46
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Imaging Spectrum and Pitfalls of <sup>11</sup> C-Methionine Positron Emission Tomography in a Series of Patients with Intracranial Lesions
摘要： 11C-methionine (Met) positron emission tomography (PET) is one of the most commonly used PET tracers for evaluating brain tumors. However, few reports have described tips and pitfalls of 11C-Met PET for general practitioners. Physiological 11C-Met uptake, anatomical variations, vascular disorders, non-tumorous lesions such as inflammation or dysplasia, benign brain tumors and patient condition during 11C-Met PET examination can potentially affect the image interpretation and cause false positives and negatives. These pitfalls in the interpretation of 11C-Met PET images are important for not only nuclear medicine physicians but also general radiologists. Familiarity with the spectrum and pitfalls of 11C-Met images could help prevent unfavorable clinical results caused by misdiagnoses.
关键词： Inflammation,Methionine,Positron-emission tomography,Brain tumors,Vascular diseases
更新于2025-09-09 09:28:46
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<sup>111</sup> In-DANBIRT <i>In Vivo</i> Molecular Imaging of Inflammatory Cells in Atherosclerosis
摘要： Atherosclerosis-related morbidity and mortality remain a global concern. Atherosclerotic disease follows a slow and silent progression, and the transition from early-stage lesions to vulnerable plaques remains difficult to diagnose. Inflammation is a key component of the development of atherosclerotic plaque and consequent life-threatening complications. This study assessed 111In-DANBIRT as an in vivo, noninvasive SPECT/CT imaging probe targeting an inflammatory marker, Lymphocyte Function Associated Antigen-1 (LFA-1), in atherosclerotic plaques. Methods. Selective binding of 111In-DANBIRT was assessed using Sprague-Dawley rats exposed to filtered air and ozone (1 ppm) by inhalation for 4 hours to induce a circulating leukocytosis and neutrophilia in peripheral blood. After 24 hours, whole blood was collected and incubated with radiolabeled DANBIRT (68Ga-DANBIRT and 111In-DANBIRT). Isolated cell component smeared slides using cytospin technique were stained with Wright-Giemsa stain. Apolipoprotein E-deficient (apoE?/?) mice were fed either a normal diet or a high-fat diet (HFD) for 8 weeks. Longitudinal SPECT/CT imaging was performed 3 hours after administration at baseline, 4, and 8 weeks of HFD diet, followed by tissue harvesting for biodistribution, serum lipid analysis, and histology. 3D autoradiography was performed in both groups 24 hours after administration of 111In-DANBIRT. Results. Increased specific uptake of radiolabeled DANBIRT by neutrophils in the ozone-exposed group was evidenced by the acute immune response due to 4-hour ozone exposure. Molecular imaging performed at 3 hours using SPECT/CT imaging evidenced an exponential longitudinal increase in 111In-DANBIRT uptake in atherosclerosis lesions in HFD-fed mice compared to normal-diet-fed mice. Such results were consistent with increased immune response to vascular injury in cardiovascular and also immune tissues, correlated by 24 hours after administration of 3D autoradiography. Histologic analysis confirmed atherosclerotic disease progression with an increased vascular lesion area in HFD-fed mice compared to normal-diet-fed mice. Conclusion. 111In-DANBIRT is a promising molecular imaging probe to assess inflammation in evolving atheroma and atherosclerotic plaque.
关键词： Molecular imaging,Atherosclerosis,Inflammation,SPECT/CT,111In-DANBIRT,LFA-1
更新于2025-09-08 09:54:20
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Transforming Weakness into Strength: Photothermal‐Therapy‐Induced Inflammation Enhanced Cytopharmaceutical Chemotherapy as a Combination Anticancer Treatment
摘要： A new synergistic treatment that combines photothermal therapy (PTT) and inflammation-mediated active targeting (IMAT) chemotherapy based on cytopharmaceuticals is developed. During PTT, the photothermal tumor ablation is accompanied by an inflammatory effect and upregulation of inflammatory factors at the tumor site, which may accelerate tumor regeneration. Moreover, PTT-induced inflammation can also recruit neutrophils (NEs) to the tumor site. To convert the disadvantages of PTT-induced inflammation into strengths, NEs are investigated as cytopharmaceuticals for IMAT chemotherapy to further inhibit the tumor recurrence after PTT due to the chemotaxis of NEs to the inflammatory sites. In this study, PEGylated gold nanorods (PEG-GNRs) are explored as the photothermal agent and paclitaxel-loaded cytopharmaceuticals of NEs as the IMAT chemotherapeutic agent. PTT is conducted at 72 h postinjection of PEG-GNRs, followed by cytopharmaceuticals for IMAT chemotherapy. It is demonstrated that the cytopharmaceuticals effectively accumulate in the tumor sites after PTT, which leads to a significant enhancement of antitumor efficacy and a reduction in systemic toxicity. These studies suggest that PTT-induced inflammation further enhances the chemotherapy of cytopharmaceuticals, and the combination of PTT and IMAT chemotherapy may be a promising synergistic strategy for targeted cancer therapy.
关键词： combination cancer therapy,inflammation,photothermal therapy,cytopharmaceuticals,neutrophils
更新于2025-09-04 15:30:14
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Automated Analysis of Vitreous Inflammation Using Spectral-Domain Optical Coherence Tomography
摘要： Purpose: To develop an automated method for quantifying vitreous signal intensity on optical coherence tomography (OCT), with particular application for use in the assessment of vitreous inflammation. Methods: This retrospective, observational case-control series comprised 30 patients (30 eyes), with vitreous haze secondary to intermediate, posterior, or panuveitis; 12 patients (12 eyes) with uveitis without evidence of vitreous haze; and 18 patients (18 eyes) without intraocular inflammation or vitreoretinal disease. The presence and severity of vitreous haze was classified according to the National Eye Institute system; other inflammatory indices and clinical parameters were also documented. Spectral-domain OCT images were analyzed using custom VITreous ANalysis software (termed ‘VITAN’), which is fully automated and avoids the need for manual segmentation. Results: VITAN performed accurate segmentation in all scans. Automated measurements of the vitreous:retinal pigment epithelium (RPE) signal ratio showed a moderate correlation with clinical vitreous haze scores (r ? 0.585, P , 0.001), comparable to that reported using manual segmentation in our previous study (r ? 0.566, P ? 0.0001). The novel parameter of vitreous:RPE textural ratio showed a marginally stronger correlation (r ? 0.604, P , 0.001) with clinical vitreous haze scores than the Vitreous:RPE signal ratio. Conclusions: The custom OCT image analysis software (VITAN) allows rapid and automated measurement of vitreous parameters, that is comparable to our previously reported vitreous:RPE index, and correlates with clinically measured disease activity. Such OCT-based indices may provide the much needed objective markers of vitreous activity, which may be used in both clinical assessment, and as outcome measures in clinical trials for intermediate, posterior, and panuveitis.
关键词： optical coherence tomography,vitreous inflammation,uveitis automated segmentation
更新于2025-09-04 15:30:14