An optical system for noninvasive microscopy of psoriatic mice in vivo.

Psoriasis is a chronic inflammatory skin disease involved with both complex morphological changes of skin and immune processes. The clinical diagnostics and research of psoriasis often require invasive biopsy which lacks their real-time dynamics in vivo. Here we report a noninvasive microscopic system developed by combining in vivo fluorescent microscopy, optical clearing, and immunolabeling to enable real-time imaging of immune cells and cytokines in blood flow in psoriatic animal models. The vascular morphology and time-lapse kinetics of interleukin (IL)-23, IL-17, tumor necrosis factor-α, and CD4+ cells in blood are captured at submicron resolution through the thickening epidermis and opaque scales during the development of psoriasis in vivo. Our data suggest IL-23 recruits CD4+ cells to release IL-17 in blood that further leaks out in the psoriatic skin area. This optical system enables noninvasive and real-time assessment of immune molecules and cells in vivo, providing good potential for medical researches on psoriasis.

Roles of DWI and T2-weighted MRI volumetry in the evaluation of lymph node metastasis and lymphovascular invasion of stage IB-IIA cervical cancer.

AIM: To determine whether magnetic resonance imaging volumetry on T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) could be used to assess lymph node metastases (LNM) and lymphovascular invasion (LVSI) in resectable cervical cancer. MATERIAL AND METHODS: Sixty-five consecutive patients with cervical cancer were enrolled retrospectively. Tumour size, including maximum transverse diameter, tumour length, and gross tumour volume (GTV), was evaluated on DWI and T2WI. Apparent diffusion coefficient (ADC) values were measured. Univariate, multivariate, and receiver operating characteristic (ROC) curve analyses were performed to determine whether tumour size and ADC could be used to assess LNM and LVSI. RESULTS: Tumour length on both T2WI and DWI, and T2WI-based and DWI-based GTVs could be used to assess LNM (p=0.002, 0.004, 0.001, and <0.001, respectively). Tumour length on T2WI, T2WI-based GTV, DWI-based GTV, and ADC value could be used assess LVSI (p=0.039, 0.038, 0.012, 0.039, respectively). Multivariate analyses showed both T2WI-based GTV (odds ratio [OR] = 1.044; p=0.008) and DWI-based GTV (OR=1.941; p=0.019) were independent risk factors for LNM. T2WI-based GTV (OR=1.023, p=0.038) and DWI-based GTV (OR=3.275, p=0.008) were independent risk factors for LVSI. No statistically significant difference was identified between the area under the ROC curve (AUC) of the DWI-based GTV and the T2WI-based GTV (0.790 versus 0.775, p=0.113), or the tumour length on both T2WI (0.790 versus 0.734, p=0.185) and DWI (0.790 versus 0.737, p=0.333) for LNM. For LVSI, the AUC of DWI-based GTV was higher than T2WI-based GTV (0.720 versus 0.682, p=0.006). CONCLUSION: GTV on both T2WI and DWI could be used assess LNM and LVSI. DWI-based GTV might show the greatest potential for assessing LNM and LVSI in resectable cervical cancer.

Impact of image averaging on vessel detection using optical coherence tomography angiography in eyes with macular oedema and in healthy eyes.

PURPOSE: To assess the repeatability of multiple automatic vessel density (VD) measurements and the effect of image averaging on vessel detection by optical coherence tomography angiography (OCTA). METHODS: An observational study was conducted in a series of healthy volunteers and patients with macular oedema. Five sequential OCTA images were acquired for each eye using the OptoVue HD device. The effect of the averaging of the 5 acquisitions on vessel detection was analysed quantitatively using a pixel-by-pixel automated analysis. In addition, two independent retina experts qualitatively assessed the change in vessel detection in averaged images segmented in 9 boxes and compared to the first non-averaged image. RESULTS: The automatic VD measurement in OCTA images showed a good repeatability with an overall mean intra-class correlation coefficient (ICC) of 0.924. The mean ICC was higher in healthy eyes compared to eyes with macular oedema (0.877 versus 0.960; p < 0.001) and in the superficial vascular plexus versus the deep vascular complex (0.967 versus 0.888; p = 0.001). The quantitative analysis of the effect of the averaging showed that averaged images had a mean gain of 790.4 pixels/box, located around or completing interruptions in the vessel walls, and a mean loss of 727.2 pixels/box. The qualitative analysis of the averaged images showed that 99.6% of boxes in the averaged images had a gain in vessel detection (i.e., vessels detected in the averaged image but not in the non-averaged image). The loss of pixels was due to a reduction in background noise and motion artifacts in all cases and no case of loss of vessel detection was observed. CONCLUSION: The automatic VD measurement using the OptoVue HD device showed a good repeatability in 5 acquisitions in a row setting. Averaging images increased vessel detection, and in about a third of boxes, decreased the background noise, both in healthy eyes and, in a greater proportion, in eyes with macular oedema.

Functionalizing Collagen with Vessel-Penetrating Two-Photon Phosphorescence Probes: A New In Vivo Strategy to Map Oxygen Concentration in Tumor Microenvironment and Tissue Ischemia.

The encapsulation and/or surface modification can stabilize and protect the phosphorescence bio-probes but impede their intravenous delivery across biological barriers. Here, a new class of biocompatible rhenium (ReI ) diimine carbonyl complexes is developed, which can efficaciously permeate normal vessel walls and then functionalize the extravascular collagen matrixes as in situ oxygen sensor. Without protective agents, ReI -diimine complex already exhibits excellent emission yield (34%, λem   = 583 nm) and large two-photon absorption cross-sections (σ2   = 300 GM @ 800 nm) in water (pH 7.4). After extravasation, remarkably, the collagen-bound probes further enhanced their excitation efficiency by increasing the deoxygenated lifetime from 4.0 to 7.5 µs, paving a way to visualize tumor hypoxia and tissue ischemia in vivo. The post-extravasation functionalization of extracellular matrixes demonstrates a new methodology for biomaterial-empowered phosphorescence sensing and imaging.

A moderate dose of preoperative radiotherapy may improve resectability in myxoid liposarcoma.

BACKGROUND: Histotype specific neoadjuvant therapy response data is scarce in soft tissue sarcomas. This study aimed to assess the impact of a moderate radiotherapy (RT) dose on resectability and to correlate MRI parameters to pathological treatment response in Myxoid Liposarcoma (MLS). METHODS: This prospective, multicenter, single-arm, phase 2 trial assessed the radiological effects of 36 Gy of preoperative radiotherapy in primary non-metastatic MLS (n=34). Distance of the tumor to the neurovascular bundle, tumor dimensions, fat fraction, enhancing fraction were determined on MRI scans at baseline, after 8 and 16 fractions, and preoperatively. Pathological response was established by central pathology review. RESULTS: Preoperative radiotherapy resulted in a median increase of 2 mm (IQR 0 to 6) of the distance of the tumor to the neurovascular bundle. As compared to baseline, the median change of the tumor volume, craniocaudal diameter and axial diameter at preoperative MRI were -60% (IQR -74 to -41), -19% (IQR -23 to -7) and -20% (IQR -29 to -12), respectively. The median fat fraction of 0.1 (IQR 0.0-0.1) and enhancing fraction of 0.8 (IQR 0.6 to 0.9) at baseline, changed to 0.2 (IQR 0.1 to 0.5) and to 0.5(IQR 0.4 to 0.9) preoperatively, respectively. Radiological signs of response in terms of volume, enhancing fraction and fat fraction were correlated with specific pathological signs of response like hyalinization, necrosis and fatty maturation. CONCLUSIONS: A moderate dose of preoperative radiotherapy may improve resectability in MLS and could facilitate achievement of clear margins and function preservation. MRI features which were predictive for expressions of pathological response, can play a role in further personalization of neoadjuvant treatment strategies in order to improve outcome in MLS.

Impact of unknown incidental findings in PET/CT examinations of patients with proven or suspected vascular graft or endograft infections.

Vascular graft or endograft Infections (VGEI) are rare but severe complications of vascular reconstructive surgery, and associated with significant mortality and morbidity risk. Positron emission tomography/computed tomography with 18F-fluorodeoxyglucose (PET/CT) has been shown to have a high diagnostic accuracy in the detection of VGEI. In this single-center prospective cohort study, we assessed the rate and the impact on patient management of relevant unknown incidental findings in PET/CT of patients with proven or suspected VGEI, and clinical follow-up of all patients was performed. Our study results show a comparably high rate of relevant unknown incidental findings (181 in 502 examinations), with documented direct impact on patient management in 80 of 181 (44%) of all findings. PET/CT scan- and patient-based evaluation revealed impact on patient management in 76 of 502 (17%) of all PET/CT scans, and in 59 of 162 (36%) of all patients, respectively. Furthermore, PET/CT correctly identified the final diagnosis in 20 of 36 (56%) patients without VGEI. In conclusion, in proven and suspected VGEI, PET/CT detects a high rate of relevant unknown incidental findings with high impact on patient management.

Detecting Three-Dimensional Vascular Networks in the Mouse Embryonic Hindbrain.

Blood vessel formation is a fine-regulated process and interfering with blood vessel formation causes embryonic lethality as well as associated with many diseases in the adult, including inflammatory, ischemic, and cancer metastatic diseases. Brain contains abundant blood vessels and has some unique physiological functions, such as blood-brain barrier. Due to the thickness and opaque characters of the tissues, it is a challenge to visualize the three-dimensional structures of the brain blood vessels in the mouse. Therefore, establishing a protocol to display the three-dimensional structures in the brain is required for exploring the regulatory molecular mechanisms in brain blood vessel formation. In this manuscript, we introduced a whole-mount and a vibratome thick section of mouse embryonic hindbrain to display the three-dimensional structures of brain vascular system.

CRIMSON: An open-source software framework for cardiovascular integrated modelling and simulation.

In this work, we describe the CRIMSON (CardiovasculaR Integrated Modelling and SimulatiON) software environment. CRIMSON provides a powerful, customizable and user-friendly system for performing three-dimensional and reduced-order computational haemodynamics studies via a pipeline which involves: 1) segmenting vascular structures from medical images; 2) constructing analytic arterial and venous geometric models; 3) performing finite element mesh generation; 4) designing, and 5) applying boundary conditions; 6) running incompressible Navier-Stokes simulations of blood flow with fluid-structure interaction capabilities; and 7) post-processing and visualizing the results, including velocity, pressure and wall shear stress fields. A key aim of CRIMSON is to create a software environment that makes powerful computational haemodynamics tools accessible to a wide audience, including clinicians and students, both within our research laboratories and throughout the community. The overall philosophy is to leverage best-in-class open source standards for medical image processing, parallel flow computation, geometric solid modelling, data assimilation, and mesh generation. It is actively used by researchers in Europe, North and South America, Asia, and Australia. It has been applied to numerous clinical problems; we illustrate applications of CRIMSON to real-world problems using examples ranging from pre-operative surgical planning to medical device design optimization.

Comparison of Vascular Morphometry in Jawbones and Long Bones: Micro-CT Study in a Rat Model Treated with Zoledronic Acid.

The study was aimed at investigating the effect of zoledronic acid on vascular morphometry in jawbones and long bones on a rat model. Twenty-four skeletal mature Sprague-Dawley female rats were administered oncologic dose of zoledronic acid (ZA) or normal saline for 4 weeks and then subjected to tooth extraction on the mandible and maxilla and a bone defect creation on the femur. After the surgical procedures, ZA or saline treatment was continued until sacrifice at week 2, week 4, and week 8 postoperatively. Vascular perfusion with MICROFIL was performed on all the animals. Micro-CT analysis demonstrated a tendency of decreased vessel density and vessel number in ZA-treated groups but no statistical difference. In conclusion, the neovessel formation is suppressed but not significantly by ZA treatment, indicating that angiogenesis inhibition may contribute to the development of MRONJ but does not play a key role.

The anti-angiogenic agent lenvatinib induces tumor vessel normalization and enhances radiosensitivity in hepatocellular tumors.

The evaluation of angiogenesis inhibitors requires the analysis of the precise structure and function of tumor vessels. The anti-angiogenic agents lenvatinib and sorafenib are multi-target tyrosine kinase inhibitors that have been approved for the treatment of hepatocellular carcinoma (HCC). However, the different effects on tumor vasculature between lenvatinib and sorafenib are not well understood. In this study, we analyzed the effects of both drugs on vascular structure and function, including vascular normalization, and investigated whether the normalization had a positive effect on a combination therapy with the drugs and radiation using micro X-ray computed tomography with gold nanoparticles as a contrast agent, as well as immunohistochemical analysis and interstitial fluid pressure (IFP) measurement. In mice subcutaneously transplanted with mouse HCC cells, treatment with lenvatinib or sorafenib for 14 days inhibited tumor growth and reduced the tumor vessel volume density. However, analysis of integrated data on vessel density, rates of pericyte-covering and perfused vessels, tumor hypoxia, and IFP measured 4 days after drug treatment showed that treatment with 3 mg/kg of lenvatinib significantly reduced the microvessel density and normalized tumor vessels compared to treatment with 50 mg/kg of sorafenib. These results showed that lenvatinib induced vascular normalization and improved the intratumoral microenvironment in HCC tumors earlier and more effectively than sorafenib. Moreover, such changes increased the radiosensitivity of tumors and enhanced the effect of lenvatinib and radiation combination therapy, suggesting that this combination therapy is a powerful potential application against HCC.

Development of X-ray contrast agents using single nanometer-sized gold nanoparticles and lactoferrin complex and their application in vascular imaging.

The technology to accurately image the morphology of tumor vessels with X-ray contrast agents is important to clarify mechanisms underlying tumor progression and evaluate the efficacy of chemotherapy. However, in clinical practice, iodine-based contrast agents present problems such as short blood retention owing to a high clearance ability and insufficient X-ray absorption capacity when compared with other high atomic number elements. To resolve these issues, gold nanoparticles (AuNPs), with a high atomic number, have attracted a great deal of attention as contrast agents for angiography, and have been employed in small animal models. Herein, we developed novel contrast agents using AuNPs and captured changes in tumor vessel morphology with time using X-ray computed tomography (CT). First, glutathione-supported single nanometer-sized AuNPs (sAu/GSH) (diameter, 2.2 nm) were fabricated using tetrakis(hydroxymethyl)phosphonium chloride as a reducing agent. The sAu/GSH particles were intravenously injected into mice, remained in vessels for a few minutes, and were then excreted by the kidneys after 24 h, similar to the commercial contrast agent iopamidol. Next, the Au/GSH and lactoferrin (sAu/GSH-LF) (long axis size, 17.3 nm) complex was produced by adding lactoferrin to the sAu/GSH solution under the influence of a condensing agent. On intravenously administering sAu/GSH-LF to mice, the blood retention time was 1-3 h, which was considerably longer than that observed with iopamidol and sAu/GSH. Moreover, we succeeded in imaging morphological changes in identical tumor vessels for several days using X-ray CT with sAu/GSH-LF.

Densidad vascular/de perfusión en dos protocolos de angiotomografía de coherencia óptica ¿Intercambiables? / Vessel/ perfusion density in two optical coherence tomography angiography protocols. Interchangeable?

Resumen Introducción: Distintos protocolos de angiotomografía de coherencia óptica evalúan la mácula. Objetivo: R2) entre las densidades vascular y de perfusión de dos protocolos de angiotomografía de coherencia óptica, para determinar si sus mediciones podían intercambiarse. Método: Estudio observacional, comparativo, prospectivo, transversal entre dos protocolos de angiotomografía de coherencia óptica (AngioPlex, Zeiss) en sujetos sanos. Se identificó la R2 entre las densidades vascular y de perfusión central, interna y completa (protocolo de 3 x 3 mm), y central, interna, externa y completa (protocolo de 6 x 6 mm). Resultados: 78 ojos, mediana de edad 23 años. Hubo R2 altas entre las densidades interna y completa del protocolo de 3 x 3 mm (0.96), externa y completa del de 6 x 6 mm (0.96), y centrales vasculares y de perfusión (≥ 0.96); la R2 entre las densidades centrales vascular y de perfusión de distintos protocolos fue ≤ 0.71. Conclusiones: Las densidades vasculares y de perfusión tienen R2 alta dentro de un protocolo, pero no entre protocolos, porque estos miden preferentemente zonas distintas, lo cual limita intercambiar mediciones.

Abstract Introduction: Different optical coherence tomography angiography (OCTA) scanning protocols evaluate the macula. Objective: To compare the determination coefficients (R2) between vessel and perfusion densities of two OCTA scanning protocols, to learn whether their metrics could be interchanged. Method: Non-experimental, comparative, prospective, observational, cross-sectional study, between two OCTA scanning protocols (Angioplex, Zeiss) in healthy subjects. We found the R2 between central, inner, and full densities (3 x 3 mm protocol), and between central, inner, outer and full densities (6 x 6 mm protocol), both for vessel and perfusion densities. Results: 78 eyes, median age 23 years. There were high R2 between inner and full densities in the 3 x 3 mm protocol (0.96), between outer and full densities in the 6 x 6 mm protocol (0.96) and between central vessel and perfusion densities (≥0.96); R2 between central vessel and perfusion densities of different protocols (≤0.71). Conclusions: Vessel and perfusion densities have high determination coefficients within a scanning protocol, but not between protocols, because each preferentially measures different macular areas. The metrics of different protocols should not be interchanged for follow-up.

Intra-vital imaging of mesenchymal stromal cell kinetics in the pulmonary vasculature during infection.

Mesenchymal stem/stromal cells (MSCs) have demonstrated efficacy in pre-clinical models of inflammation and tissue injury, including in models of lung injury and infection. Rolling, adhesion and transmigration of MSCs appears to play a role during MSC kinetics in the systemic vasculature. However, a large proportion of MSCs become entrapped within the lungs after intravenous administration, while the initial kinetics and the site of arrest of MSCs in the pulmonary vasculature are unknown. We examined the kinetics of intravascularly administered MSCs in the pulmonary vasculature using a microfluidic system in vitro and intra-vital microscopy of intact mouse lung. In vitro, MSCs bound to endothelium under static conditions but not under laminar flow. VCAM-1 antibodies did not affect MSC binding. Intravital microscopy demonstrated MSC arrest at pulmonary micro-vessel bifurcations due to size obstruction. Retention of MSCs in the pulmonary microvasculature was increased in Escherichia coli-infected animals. Trapped MSCs deformed over time and appeared to release microvesicles. Labelled MSCs retained therapeutic efficacy against pneumonia. Our results suggest that MSCs are physically obstructed in pulmonary vasculature and do not display properties of rolling/adhesion, while retention of MSCs in the infected lung may require receptor interaction.

Clinicopathological and radiological significance of the collateral vessels of renal cell carcinoma on preoperative computed tomography.

This study aimed to investigate the clinicopathological and radiological significance of the collateral vessel of renal cell carcinoma (RCC) on preoperative computed tomography (CT). Preoperative contrast-enhanced CT of 236 consecutive patients with pathological documented RCC were retrospectively reviewed during the period of 2014. The associations of the presence of collateral vessels with perioperative clinicopathological and radiological features, as well as long term survival outcomes were analyzed. Totally, collateral vessels were detected by contrast-enhanced CT in 110 of 236 patients. The presence of collateral vessels was significantly associated with higher pathologic T stage, higher Fuhrman grade, higher overall RENAL scores, greater tumor size and enhancement, and more tumor necrosis (all P < 0.05). In patients with clear cell RCC, those harboring collateral vessels had significantly higher SSIGN scores (P < 0.001) and shorter overall survival (P = 0.01) than those without collateral vessel. The incidence of intraoperative blood loss, blood transfusion, radical nephrectomy (RN) and open surgery were also significantly higher in patients with collateral vessels (all P < 0.05). In multivariate analysis, the presence of collateral vessels was significantly associated with RN (P = 0.021) and open surgery (P = 0.012). The presence of collateral vessels was significantly associated with aggressive clinicopathological parameters and worse prognosis. It is worth paying attention to its association with the choice of RN and open surgery in clinical practice.

Preoperative misdiagnosis of pancreatic and periampullary cancer in patients undergoing pancreatoduodenectomy: A multicentre retrospective cohort study.

INTRODUCTION: Whereas neoadjuvant chemo(radio)therapy is increasingly used in pancreatic cancer, it is currently not recommended for other periampullary (non-pancreatic) cancers. This has important implications for the relevance of the preoperative diagnosis for pancreatoduodenectomy. This retrospective multicentre cohort study aimed to determine the frequency of clinically relevant misdiagnoses in patients undergoing pancreatoduodenectomy for pancreatic or other periampullary cancer. METHODS: Data from all consecutive patients who underwent a pancreatoduodenectomy between 2014 and 2018 were obtained from the prospective Dutch Pancreatic Cancer Audit. The preoperative diagnosis as concluded by the multidisciplinary team (MDT) meeting was compared with the final postoperative diagnosis at pathology to determine the rate of clinically relevant misdiagnosis (defined as missed pancreatic cancer or incorrect diagnosis of pancreatic cancer). RESULTS: In total, 1244 patients underwent pancreatoduodenectomy of whom 203 (16%) had a clinically relevant misdiagnosis preoperatively. Of all patients with a final diagnosis of pancreatic cancer, 13% (87/679) were preoperatively misdiagnosed as distal cholangiocarcinoma (n = 41, 6.0%), ampullary cancer (n = 27, 4.0%) duodenal cancer (n = 16, 2.4%), or other (n = 3, 0.4%). Of all patients with a final diagnosis of periampullary (non-pancreatic) cancer, 21% (116/565) were preoperatively incorrectly diagnosed as pancreatic cancer. Accuracy of preoperative diagnosis was 84% for pancreatic cancer, 71% for distal cholangiocarcinoma, 73% for ampullary cancer and 73% for duodenal cancer. A prediction model for the preoperative likelihood of pancreatic cancer (versus other periampullary cancer) prior to pancreatoduodenectomy demonstrated an AUC of 0.88. DISCUSSION: This retrospective multicentre cohort study showed that 16% of patients have a clinically relevant misdiagnosis that could result in either missing the opportunity of neoadjuvant chemotherapy in patients with pancreatic cancer or inappropriate administration of neoadjuvant chemotherapy in patients with non-pancreatic periampullary cancer. A preoperative prediction model is available on www.pancreascalculator.com.

Ultrasound-visualized, site-specific vascular embolization using magnetic protein microcapsules.

Imaging-guided vascular embolization is frequently performed on patients with advanced hepatocellular carcinoma (HCC) to alleviate symptoms and extend their survival time. Current operation procedures are not only painful for patients, but are also inaccurate in tumor targeting after the release of embolic agents from the catheter, leading to injury to healthy tissues simultaneously. In this study, we developed an ultrasound-visualized, site-specific vascular embolization strategy with magnetic protein microcapsules (MPMs). MPMs were fabricated using a rapid emulsification method, giving it a smooth surface and a core-shell structure. Their diameters could be controlled within 10 µm, allowing them to pass through capillaries. The core-shell structure and loading of magnetic Fe3O4 endowed MPMs with good contrast under ultrasound imaging and magnetically inducible targeting properties, as well as aggregation response even under flowing conditions. In vitro cytotoxicity and hemolysis evaluation demonstrated good biocompatibility of the MPMs. Furthermore, mock embolization showed that cell death could be induced by aggregation of the MPMs. Such a combination of real-time monitoring using ultrasound and control on targeted vascular embolization might be a breakthrough in the treatment of advanced HCC.

A new imaging sign in COVID-19 pneumonia: vascular changes and their correlation with clinical severity of the disease.

PURPOSE: It has come to our attention that specific vascular changes (VCs) appear more frequently in chest computed tomography (CT) of patients with coronavirus disease 2019 (COVID-19). In this study, we aimed to investigate if these specific VCs in chest CT correlate with clinical severity of the disease. METHODS: CT images of 102 patients who underwent low-dose noncontrast chest CT due to COVID-19 between 11 March 2020 and 11 April 2020 were evaluated retrospectively. The patients were divided into two groups based on the presence of VCs in CT images. VCs in chest CT of patients with COVID-19 were defined using the following descriptors: decreased lumen caliber, vascular wall irregularity, angulation in the course of the vessel, vascular disruption, and/or interruption. The relationship of these VCs with disease symptoms (fever, cough, shortness of breath), comorbid conditions (diabetes, hypertension, asthma), smoking habit, disease-specific laboratory changes (white blood cell-lymphocyte count, neutrophil/lymphocyte ratio, C-reactive protein [CRP], D-dimer, lactate dehydrogenase [LDH], ferritin, procalcitonin), lung parenchymal infiltration pattern (ground-glass opacity, crazy-paving pattern, consolidation) and its distribution (peripheral, central, mixed, upper lobes, lower lobes, right middle lobe) on CT were investigated by comparison of these variables between patients with and without VCs in chest CT. RESULTS: VCs were observed in 18 out of 102 patients (18%) with typical parenchymal involvement for COVID-19. There was no significant difference in terms of age and sex. We found an irregularity in the wall of the vascular structures in the distal branches and decreased lumen caliber of the vessels related to ground-glass opacities in 15 patients, concentric luminal narrowing in annular form in 4 patients, angulation/traction or springiness in the vascular structures towards the active lesions in 3 patients, and interruptions along the vascular course in 1 patient. VCs were significantly correlated with fever (12/18, 66.7%) and shortness of breath (7/18, 39%). These changes were significantly more remarkable in common disease involving both upper and lower lobes (10/18, 56%). In these cases, there was a substantial increase in CRP (15/18, 83%; mean, 5.7±6.3 mg/dL) and LDH (8/18, 44%) values compared to those who did not have any VCs. CONCLUSION: The results of this study suggest that specific VCs observed in chest CT may predict the disease severity in cases of COVID-19 pneumonia. These changes may be related to respiratory distress in the disease.

Radiologic Evaluation and Structured Reporting Form for Extrahepatic Bile Duct Cancer: 2019 Consensus Recommendations from the Korean Society of Abdominal Radiology.

Radiologic imaging is important for evaluating extrahepatic bile duct (EHD) cancers; it is used for staging tumors and evaluating the suitability of surgical resection, as surgery may be contraindicated in some cases regardless of tumor stage. However, the published general recommendations for EHD cancer and recommendations guided by the perspectives of radiologists are limited. The Korean Society of Abdominal Radiology (KSAR) study group for EHD cancer developed key questions and corresponding recommendations for the radiologic evaluation of EHD cancer and organized them into 4 sections: nomenclature and definition, imaging technique, cancer evaluation, and tumor response. A structured reporting form was also developed to allow the progressive accumulation of standardized data, which will facilitate multicenter studies and contribute more evidence for the development of recommendations.

A General Strategy for Development of Activatable NIR-II Fluorescent Probes for In Vivo High-Contrast Bioimaging.

Organic dye based NIR-II fluorescent probes, owing to their high signal-to-background ratio and deeper penetration, are highly useful for deep-tissue high-contrast imaging in vivo. However, it is still a challenge to design activatable NIR-II fluorescent probes. Here, a novel class of polymethine dyes (NIRII-RTs), with bright (quantum yield up to 2.03 %), stable, and anti-solvent quenching NIR-II emission, together with large Stokes shifts, was designed. Significantly, the novel NIR-II dyes NIRII-RT3 and NIRII-RT4, equipped with a carboxylic acid group, can serve as effective NIR-II platforms for the design of activatable bioimaging probes with high contrast. As a proof of concept, a series of target-activatable NIRII-RT probes (NIRII-RT-pH, NIRII-RT-ATP and NIRII-RT-Hg) for pH, adenosine triphosphate (ATP), and metal-ion detection, were synthesized. By applying the NIRII-RT probe, the real-time monitoring of drug-induced hepatotoxicity was realized.

An Ultrahigh-Field-Tailored T1 -T2 Dual-Mode MRI Contrast Agent for High-Performance Vascular Imaging.

The assessment of vascular anatomy and functions using magnetic resonance imaging (MRI) is critical for medical diagnosis, whereas the commonly used low-field MRI system (≤3 T) suffers from low spatial resolution. Ultrahigh field (UHF) MRI (≥7 T), with significantly improved resolution and signal-to-noise ratio, shows great potential to provide high-resolution vasculature images. However, practical applications of UHF MRI technology for vascular imaging are currently limited by the low sensitivity and accuracy of single-mode (T1 or T2 ) contrast agents. Herein, a UHF-tailored T1 -T2 dual-mode iron oxide nanoparticle-based contrast agent (UDIOC) with extremely small core size and ultracompact hydrophilic surface modification, exhibiting dually enhanced T1 -T2 contrast effect under the 7 T magnetic field, is reported. The UDIOC enables clear visualization of microvasculature as small as ≈140 µm in diameter under UHF MRI, extending the detection limit of the 7 T MR angiography. Moreover, by virtue of high-resolution UHF MRI and a simple double-checking process, UDIOC-based dual-mode dynamic contrast-enhanced MRI is successfully applied to detect tumor vascular permeability with extremely high sensitivity and accuracy, providing a novel paradigm for the precise medical diagnosis of vascular-related diseases.