Vessel Penetration Research Articles

Placenta‐Derived Mesenchymal Stromal‐Like Cells Promote 3D‐Engineered Muscle Tissue Differentiation and Vessel Network Maturation

Placental‐derived stromal‐like cells (PLX‐PAD) have been shown to facilitate muscle tissue recovery after injury and stimulate angiogenesis. This work assesses the impact of PLX‐PAD cells on the vascularization and maturation of engineered skeletal muscle tissue. Specifically, their effects in direct co‐culture with endothelial cells, pericytes, and myoblasts seeded within microporous 3D scaffolds are characterized. Additionally, the impact of hypoxic PLX‐PAD cell‐conditioned medium (CM) on vascularization and muscle differentiation of engineered tissue is monitored. Co‐culture of PLX‐PAD with myocytes stimulated myocyte differentiation while PLX‐PAD CM promoted the formation of vascular networks. Implantation of a multi‐culture system of vascularized human skeletal muscle tissue and PLX‐PAD into a rectus abdominal defect in nude mice promoted myocyte differentiation, host vessel penetration, and tissue integration. These findings indicate the ability of placenta‐derived cells to induce the formation of vascularized engineered muscle constructs with potential therapeutic applications.

Adverse Effects Associated with Dermal Filler Treatments: Part II Vascular Complication.

Vascular complications arising from dermal filler treatments pose significant risks, including ischemia, tissue necrosis, and severe outcomes like blindness and pulmonary embolism. This study investigates the mechanisms of vascular complications, categorizing them into extravascular compression and intravascular emboli. Extravascular compression occurs when injected fillers compress adjacent blood vessels, leading to ischemia and potential necrosis, while intravascular emboli result from fillers entering blood vessels, causing blockages. The study emphasizes the importance of anatomical knowledge, careful injection techniques, and early intervention. Management strategies include the use of hyaluronidase to dissolve HA fillers, vasodilators to improve blood circulation, and hyperbaric oxygen therapy. The regions most susceptible to complications align with major arterial pathways, particularly the nasolabial folds and nasal region. The study also highlights the need for meticulous injection techniques, the use of cannulas over needles in high-risk areas, and the aspiration test to detect vessel penetration. Early detection and immediate intervention are crucial to mitigate adverse outcomes. Continuous education and training for practitioners, along with advancements in filler materials and injection methods, are essential for improving the safety of cosmetic procedures. This comprehensive understanding aids in preventing and managing vascular complications, ensuring better patient outcomes. The field of dermal filler treatments is advancing with new techniques and technologies, such as High-Resolution Ultrasound, Infrared Imaging, self-crossing hyaluronic acid filler, biodegradable microspheres, and microinjection.

Developing an explainable diagnosis system utilizing deep learning model: a case study of spontaneous pneumothorax

Objective. The trend in the medical field is towards intelligent detection-based medical diagnostic systems. However, these methods are often seen as ‘black boxes’ due to their lack of interpretability. This situation presents challenges in identifying reasons for misdiagnoses and improving accuracy, which leads to potential risks of misdiagnosis and delayed treatment. Therefore, how to enhance the interpretability of diagnostic models is crucial for improving patient outcomes and reducing treatment delays. So far, only limited researches exist on deep learning-based prediction of spontaneous pneumothorax, a pulmonary disease that affects lung ventilation and venous return. Approach. This study develops an integrated medical image analysis system using explainable deep learning model for image recognition and visualization to achieve an interpretable automatic diagnosis process. Main results. The system achieves an impressive 95.56% accuracy in pneumothorax classification, which emphasizes the significance of the blood vessel penetration defect in clinical judgment. Significance. This would lead to improve model trustworthiness, reduce uncertainty, and accurate diagnosis of various lung diseases, which results in better medical outcomes for patients and better utilization of medical resources. Future research can focus on implementing new deep learning models to detect and diagnose other lung diseases that can enhance the generalizability of this system.

Acute Abdominal Pain Caused by Hemorrhagic Corpus Lutheum in Reproductive-Aged Women: A Case Series

Hemorrhage of corpus luteum is a rare condition in women of reproductive age. It is possible for a woman's corpus luteum to have asymptomatic hemorrhaging as a result of blood vessel penetration through the wall of the corpus luteum during the second half of her menstrual cycle. There have been very few occurrences of it growing to be too large and then rupturing. Those who suffer from polycystic ovarian syndrome (PCOS) are at risk for developing this condition. Polycystic ovarian syndrome is characterized by an inflammation of the body's hormonal function, which results in the development of larger ovaries that also include a number of small follicular cysts. The development of cysts on the ovaries, which contribute to the appearance of larger ovaries, is brought on by an abundance of androgen hormones in the body. In a minority of cases, this enlargement also has the potential to rupture, which is an additional concern. The predominant symptom that presented clinically was sharp pain in the lower abdomen. Because to the fact that HCL may present similarly to other conditions, diagnosis might be difficult. We present and discuss three cases of young female patients who presented with acute abdominal pain, large-volume of hemoperitoneum, and anemia. Laparoscopic examination in each case showed a hemorrhagic corpus luteal cyst.

Integration of micro-CT and histology data for vasculature morpho-functional analysis in tissue regeneration

The demand for artificial or bioartificial engineered tissues is increasing today in regenerative medicine techniques to replace and restore the physiological function of damaged tissues. Such engineered constructs hold different properties depending on the tissue to be replicated. As for vascularized tissues, complex biocompatible structures, namely scaffolds, play a key role in supporting oxygen and nutrient supply, thus sustaining tissue neoformation and integration with the host. Scaffold architecture significantly impacts its regenerative potential, while preclinical trials are essential to define scaffold-host interactions. In compliance with the 3 R principle, there is a clear need to optimize both the procedures to evaluate scaffold performance and the analysis methodology decreasing the number of animals required to gain consistent data. In parallel, current technologies used in preclinical research generate huge amounts of data that need to be elaborated and interpreted correctly. Therefore, we designed this study to evaluate the results of scaffold integration with the host tissue after implantation in a mouse subcutaneous pocket model. We evaluated the angiogenic response developed by the host and the degree of scaffold integration by using a combined morphometric approach based on both histological and micro-CT analyses. Six-layer scaffolds, made of polycaprolactone (PCL) microspheres, with an ordered structure were produced by thermal sintering. Scaffolds were then implanted in BALB/c mice and retrieved 21 days post-implantation when the animals were deeply anesthetized and perfused with Microfil, a contrast agent for micro-CT. Here, we describe a method to extract quantitative data from micro-CT reconstructions such as (i) total vessel volume; (ii)% of vessel penetration; (iii) distribution of vessel diameters. The general principle of this approach is the refinement of the region of interest (ROI), thus producing a volume of interest (VOI) that matches scaffold volume. This VOI serves as a dataset from which to extract volumetric information. Then VOIs are divided into three identical parts, proximal, median, and distal, to follow the vessel progression into the scaffold, thus obtaining their depth of penetration (DoP). By this methodology, we observed in mean, among the analyzed samples, a vessel invasion for 1,38 mm3 corresponding to the 1,53% of the scaffold volume. We then looked at the diameter distribution being this value a key indicator of vessel maturity, highlighting that 55% of vessels fall into the range from 5,99–53.99 µm while the remaining 45% are distributed into intervals from 54 to 136 µm. In parallel, to evaluate tissue integration in detail, histological and immunofluorescent analyses were performed to look at vessel distribution and collagen synthesis. Histological results strongly correlate with the micro-CT data providing, however, an overview of the ingrowth tissues. In addition, by immunofluorescent analysis we demonstrate that newly formed vessels are mature at the considered time point and tissue collagen deposition is widespread within the scaffolds. Collectively, we propose a new method to track vessel formation by using a multi-modal approach posing the basis for: i) the fabrication of novel scaffolds for Tissue Engineering; ii) the integration of detailed information for a wide range of morphological and functional analyses.

Integrating engineered macro vessels with self-assembled capillaries in 3D implantable tissue for promoting vascular integration in-vivo

A functional multi-scale vascular network can promote 3D engineered tissue growth and improve transplantation outcome. In this work, by using a combination of living cells, biological hydrogel, and biodegradable synthetic polymer we fabricated a biocompatible, multi-scale vascular network (MSVT) within thick, implantable engineered tissues. Using a templating technique, macro-vessels were patterned in a 3D biodegradable polymeric scaffold seeded with endothelial and support cells within a collagen gel. The lumen of the macro-vessel was lined with endothelial cells, which further sprouted and anastomosed with the surrounding self-assembled capillaries. Anastomoses between the two-scaled vascular systems displayed tightly bonded cell junctions, as indicated by vascular endothelial cadherin expression. Moreover, MSVT functionality and patency were demonstrated by dextran passage through the interconnected multi-scale vasculature. Additionally, physiological flow conditions were applied with home-designed flow bioreactors, to achieve a MSVT with a natural endothelium structure. Finally, implantation of a multi-scale-vascularized graft in a mouse model resulted in extensive host vessel penetration into the graft and a significant increase in blood perfusion via the engineered vessels compared to control micro-scale-vascularized graft. Designing and fabricating such multi-scale vascular architectures within 3D engineered tissues may benefit both in vitro models and therapeutic translation research.

Discriminating invasive adenocarcinoma among lung pure ground-glass nodules: a multi-parameter prediction model.

BackgroundPatients with consistent lung pure ground-glass nodules (pGGNs) have a high incidence of lung adenocarcinoma that can be classified as adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), or invasive adenocarcinoma (IAC). Regular follow-up is recommended for AIS and MIA, while surgical resection should be considered for IAC. This study sought to develop a multi-parameter prediction model to increase the diagnostic accuracy in discriminating between IAC and AIS or MIA.MethodsThe training data set comprised consecutive patients with lung pGGNs who underwent resection from January to December 2017 at the Zhongshan Hospital. Of the 370 resected pGGNs, 344 were pathologically confirmed to be AIS, MIA, or IAC and were included in the study. The 26 benign pGGNs were excluded. We compared differences in the clinical features (e.g., age and gender), the content of serum tumor biomarkers, the computed tomography (CT) parameters (e.g., nodule size and the maximal CT value), and the morphologic characteristics of nodules (e.g., lobulation, spiculation, pleura indentation, vacuole sign, and normal vessel penetration or abnormal vessel) between the pathological subtypes of AIS, MIA, and IAC. An abnormal vessel was defined as “vessel curve” or “vessel enlargement”. Statistical analyses were performed using the chi-square test, analysis of variance (ANOVA), and rank test. The IAC prediction model was constructed via a multivariate logistical regression. Our prediction model for lung pGGNs was further validated in a data set comprising consecutive patients from multiple medical centers in China from July to December 2018. In total, 345 resected pGGNs were pathologically diagnosed as lung adenocarcinoma in the validation data set.ResultsIn the training data set, patients with pGGNs ≥10 mm in size had a high incidence (74.5%) of IAC. The maximal CT value of IAC [–416.1±121.2 Hounsfield unit (HU)] was much higher than that of MIA (–507.7±138.0 HU) and AIS (–602.6±93.3 HU) (P<0.001). IAC was more common in pGGNs that displayed any of the following CT manifestations: lobulation, spiculation, pleura indentation, vacuole sign, and vessel abnormality. The IAC prediction model was constructed using the parameters that were assessed as risk factors (i.e., the nodule size, maximal CT value, and CT signs). The receiver operating characteristic (ROC) analysis showed that the area under the curve (AUC) of this model for diagnosing IAC was 0.910, which was higher than that of the AUC for nodule size alone (0.891) or the AUC for the maximal CT value alone (0.807) (P<0.05, respectively). A multicenter validation data set was used to validate the performance of our prediction model in diagnosing IAC, and our model was found to have an AUC of 0.883, which was higher than that of the AUC of 0.827 for the module size alone model or the AUC of 0.791 for the maximal CT value alone model (P<0.05, respectively).ConclusionsOur multi-parameter prediction model was more accurate at diagnosing IAC than models that used only nodule size or the maximal CT value alone. Thus, it is an efficient tool for identifying the IAC of malignant pGGNs and deciding if surgery is needed.

The evaluation of functional small intestinal submucosa for abdominal wall defect repair in a rat model: Potent effect of sequential release of VEGF and TGF-β1 on host integration

Ineffective vessel penetration and extracellular matrix (ECM) remodeling are responsible for the failure of porcine small intestinal submucosa (SIS)-repaired abdominal wall defects. Combined growth factors could be used as directing signals in a nature-mimicking strategy to improve this repair through mesh functionalization. In this work, vascular endothelial growth factor (VEGF) and transforming growth factor β1 (TGF-β1) were incorporated into a silk fibroin membrane via coaxial aqueous electrospinning to exploit their benefits of biological interactions. The membrane was sandwiched into the SIS bilayer as a functional mesh to repair partial-thickness defects in a rat model. Membrane characterization demonstrated that the core-shell structure ensured the independent distribution and sequential release of two regulators and protection of their bioactivities, which were confirmed by cell viability and protein expression. The mesh was further assessed to facilitate vasculature formation and collagen secretion in vitro, and exhibited better host integration than VEGF- or TGF-β1-containing mesh and developed reinforced mechanical properties compared with the VEGF-containing mesh after 28 days in vivo. Determination of the underlying biological interactions revealed that rapid VEGF release promotes angiogenesis and collagen secretion but initially potentiates the inflammatory response. Sustained TGF-β1 release at relatively low concentrations promoted VEGF for vessel permeation and maturation and steadily induced ECM remodeling under milder foreign body reactions. The functionalization of SIS improves repair by sufficient integration with timely remodeling and helps elucidate the related regulatory interactions.

Rebirth of Aspirin Synthesis By‐Product: Prickly Poly(salicylic acid) Nanoparticles as Self‐Anticancer Drug Carrier

AbstractAs a great drug, aspirin has been used to treat many important diseases. To expand the biomedical applications of the aspirin material family, in this report, the authors polymerized salicylic acid (functional part of aspirin) into poly (salicylic acid) (PSA), which was once a by‐product during aspirin synthesis. PSA can be formulated into sub‐100 nm prickly nanoparticles (NPs) via a nanoprecipitation self‐assembly procedure. The PSA NPs are found to be nontoxic to normal cells and cancer cells, but can inhibit tumor growth in the CT26 mouse model. The anticancer drug can be effectively loaded into PSA NPs and the drug‐loaded PSA NPs show ultra‐high blood vessel penetration, tumor penetration, and tumor accumulation due to the special prickly nanostructure. With these combined advantages, including the self‐therapeutic effects, high biosafety, and high tumor accumulation performance, drug‐loaded PSA NPs achieved a significant tumor inhibition efficacy without causing any side effects. Therefore, a new poly (salicylic acid) NP platform is successfully developed from a byproduct of aspirin synthesis, expanding the biomedical applications of aspirin‐related materials.

Optimization of Marine Debris Collection Routing for Solar and Diesel Hybrid Power Vessels

With the increase of marine debris and the serious destruction of the ecological environment, marine debris collection has become an urgent task facing us. In this paper, the logistics network is used to optimize the routing of marine debris collection vessels. In order to reduce carbon emissions, we choose to use new energy waste collection vessels which have solar and diesel hybrid power. The objection of this paper is to minimize the total cost. The constraints include time window, vessel capacity and carbon emissions, which are solved by large-scale neighborhood search algorithm. Taking the East China Sea as an example, the results show that the total cost and total time can be saved by 20.58% and 17.43% respectively by choosing the best debris collection time. Under different environmental conditions, when the photovoltaic penetration of solar hybrid vessel reaches 75%, the cost can be saved by 22.14%, and the carbon emission can be reduced by 74.7%. Through the analysis of different types of vessels, it is found that 11.85% of the cost can be saved by selecting the best vessel type.

Liquid-phase ASEM imaging of cellular and structural details in cartilage\xa0and bone formed during endochondral ossification: Keap1-deficient osteomalacia

Chondrogenesis and angiogenesis drive endochondral ossification. Using the atmospheric scanning electron microscopy (ASEM) without decalcification and dehydration, we directly imaged angiogenesis-driven ossification at different developmental stages shortly after aldehyde fixation, using aqueous radical scavenger glucose solution to preserve water-rich structures. An embryonic day 15.5 mouse femur was fixed and stained with phosphotungstic acid (PTA), and blood vessel penetration into the hypertrophic chondrocyte zone was visualised. We observed a novel envelope between the perichondrium and proliferating chondrocytes, which was lined with spindle-shaped cells that could be borderline chondrocytes. At postnatal day (P)1, trabecular and cortical bone mineralisation was imaged without staining. Additional PTA staining visualised surrounding soft tissues; filamentous connections between osteoblast-like cells and osteocytes in cortical bone were interpreted as the osteocytic lacunar-canalicular system. By P10, resorption pits had formed on the tibial trabecular bone surface. The applicability of ASEM for pathological analysis was addressed using knockout mice of Keap1, an oxidative-stress sensor. In Keap1−/− femurs, we observed impaired calcification and angiogenesis of epiphyseal cartilage, suggesting impaired bone development. Overall, the quick ASEM method we developed revealed mineralisation and new structures in wet bone tissue at EM resolution and can be used to study mineralisation-associated phenomena of any hydrated tissue.

Abstract 5997: Increased connexin 43 expression and gap junction communication correlates with invasion following reduced glucose metabolism in breast cancer cells

Abstract Dysregulation of gap junction intercellular communication (GJIC) is a common feature during cancer progression. GJIC is a means of direct cell-cell communication mediated by regulated membrane channels composed of connexin proteins. This communication is frequently lost between primary tumor cells but may be upregulated at secondary metastatic sites with stromal cells. Control of this process by cancer cells has been shown to facilitate aggressive qualities both in vitro and in vivo. During the process of metastasis, cells encounter numerous metabolic challenges that must be overcome, particularly during growth of primary tumors. In this study, we set out to evaluate if changes to cancer cell metabolism affect GJIC in breast cancer cells. To address this question, we generated a metabolic variant of the MDA-MB-231 cell line conditioned to grow in glucose-limiting conditions. These cells were grown in FBS supplemented RPMI with &amp;lt;0.130mM glucose compared to 2mM in control conditions for more than 4 weeks. Substantial cell death over this time revealed a small population of cells capable of surviving in glucose reduced conditions. Growth of these cells normalized following a period of quiescence and exhibited stable viability and proliferative capacity. Following STR validation, these cells were designated MDA-MB-231LG for their ability to grow in low glucose media. MDA-MB-231LG exhibited a larger and more rounded morphologic appearance with formation of strong cell-cell contacts as demonstrated by scanning electron microscopy in contrast to parental cells which showed a higher degree of membrane overlap. Further comparison of the two cell lines through western blot and immunofluorescence analysis of connexin 43, a major connexin expressed in breast tissue, revealed higher levels in MDA-MB-231LG and increased membrane localization. Using a double label dye transfer technique, the gap junction permeable fluorescent dye calcein showed increased movement from CM-DiI labeled donor cells into neighboring cells in MDA-MB-231LG indicating functional gap junction coupling while MDA-MB-231 had little to no dye movement. To evaluate phenotypic qualities, both cell lines were grown in Matrigel and MDA-MB-231LG displayed increased stellate morphology. Use of a Matrigel invasion chamber assay confirmed the increased invasive qualities with significantly more MDA-MB-231LG invading through the lower portion of the membrane compared to MDA-MB-231 parental cells. Our data demonstrate a clear upregulation of gap junction activity following metabolic adaptation to reduced glucose availability. It also suggests a possible connection between GJIC and invasive qualities in breast cancer cells and may represent an inducible phenotype that occurs in primary tumors when tumor growth limits blood vessel penetration and nutrient availability. Citation Format: Jennifer C. Jones, Amanda M. Miceli, Mary M. Chaudhry, Mallika A. Jai, Romel N. Pancho, Alan Lazzar, Bradley S. Taylor, Vishnupriya Bodempudi, Prarthana P. Jain, Sheeri Hanjra, Alexander E. Urban, Brian Zanotti, Ellen K. Kohlmeir, Thomas M. Bodenstine. Increased connexin 43 expression and gap junction communication correlates with invasion following reduced glucose metabolism in breast cancer cells [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5997.

Handling and performance characteristics of a new small caliber radiopaque embolic microsphere.

The in vitro and in vivo handling and performance characteristics of a small caliber radiopaque embolic microsphere, 40–90 μm DC Bead LUMI™ (LUMI40‐90), were studied. Microsphere drug loading and elution and effects on size, suspension, and microcatheter delivery were evaluated using established in vitro methodologies. In vivo evaluations of vascular penetration (rabbit renal artery embolization), long‐term biocompatibility and X‐ray imaging properties, pharmacokinetics and local tissue effects of both doxorubicin (Dox) and irinotecan (Iri) loaded microspheres (swine hepatic artery embolization) were conducted. Compared to 70–150 μm DC Bead LUMI (LUMI70‐150), LUMI40‐90 averaged 70 μm versus 100 μm, which was unchanged upon drug loading. Handling, suspension, and microsphere delivery studies were successfully performed. Dox loading was faster (20 min) and Iri equivalent (<10 min) while drug elution rates were similar. Contrast suspension times were longer with no delivery complications. Vascular penetration was statistically greater (rabbit) with no unexpected adverse safety findings (swine). Microspheres ± drug were visible under X‐ray imaging (CT) at 90 days. Peak plasma drug levels and area under the curve were greater for LUMI40‐90 compared to LUMI70‐150 but comparable to 70–150 μm DC BeadM1™ (DC70‐150). Local tissue effects showed extensive hepatic necrosis for Dox, whereas Iri displayed lower toxicity with more pronounced lobar fibrosis. LUMI40‐90 remains suspended for longer and have greater vessel penetration compared to the other DC Bead LUMI sizes and are similarly highly biocompatible with long‐term visibility under X‐ray imaging. Drug loading is equivalent or faster with pharmacokinetics similar to DC70‐150 for both Dox and Iri.

MRI features predict microvascular invasion in intrahepatic cholangiocarcinoma

BackgroundThe presence of microvascular invasion (MVI) in intrahepatic cholangiocarcinoma (ICC) is a significant adverse prognostic factor. This study sought to investigate the correlation between preoperative imaging parameters and MVI in ICC.MethodsA total of 108 patients with surgically resected single ICC tumors (34 MVI-positive and 74 MVI-negative lesions) who underwent MRI examination, including T1WI, T2WI, DWI, and dynamic enhancement imaging, were enrolled in this retrospective study. The following qualitative and quantitative characteristics were evaluated: tumor morphology, signal features on T1WI and T2WI, intrahepatic duct dilatation, hepatic capsule retraction, target sign on DWI, dynamic enhancement pattern, arterial phase enhancement pattern, dot−/band-like enhancement inside the tumor, visible vessel penetration inside the tumor (hepatic artery, portal vein, or hepatic vein), integrity of the enhancement edge of the arterial phase, peripheral hepatic enhancement, tumor size, maximum enhancement edge thickness, arterial edge enhancement ratio, and delayed phase enhancement ratio. Other clinicopathological features were also used to predict and evaluate MVI in ICC. Chi-square test, Fisher’s exact test, and independent t-test were used for univariate analysis to determine the relationships among the presence of MVI and these MR parameters. Logistic regression analysis was used to identify predictors of MVI among these MR parameters.ResultsAmong MRI characteristics, tumor morphology, intrahepatic duct dilatation, arterial phase enhancement pattern, visible hepatic artery penetration sign, maximum diameter of the tumor and the arterial phase edge enhancement ratio were correlated with MVI (P = 0.007, 0.003, 0.008, 0.000, 0.003, and 0.002, respectively). Furthermore, higher CA19–9 levels (≥37 U/ml) and pathological tumor grade III were also related to MVI (P = 0.014 and 0.004, respectively). However, multivariate logistic regression analysis demonstrated that none of the parameters were independent risk factors for the diagnosis of MVI in ICCs.ConclusionFor the preoperative prediction of MVI in ICC, six qualitative and quantitative data obtained on preoperative MRI, as well as one tumorigenic marker and the pathological tumor grade, were statistically significant. More research is needed to identify MR characteristics that can be used as independent risk factors.

Imaging features of hepatic inflammatory pseudotumor: distinction from colorectal liver metastasis using gadoxetate disodium-enhanced magnetic resonance imaging.

To identify gadoxetate disodium-enhanced MRI features distinguishing hepatic IPT from CLM. From February 2008 to December 2019, 162 lesions (IPT, n = 31 and CLM, n = 131) from 94 patients (mean age 65.1 ± 12.2years; 65 men and 29 women) were retrospectively assessed for the presence or absence of obscure boundary, rim enhancement on arterial phase (AP), persistent rim enhancement during AP to transitional phase (TP), blood vessel penetration, peritumoral parenchymal enhancement on AP, peritumoral parenchymal hypointensity on hepatobiliary phase (HBP), peritumoral parenchymal hyperintensity on T2-weighted imaging (T2WI), biliary dilatation, central hypointensity with a relatively hyperintense periphery on HBP, peripheral hyperintensity on diffusion-weighted imaging (DWI) and T2WI, and lesion to liver signal intensity ratio (SIRlesion/liver) on HBP and DWI. Relevant features for differentiating between ITP and CLM were identified by univariate and multivariate analyses. Univariate analysis revealed significantly higher frequencies of the following features in IPT than CLM: younger age, obscure boundary, blood vessel penetration, central hypointensity with a relatively hyperintense periphery on HBP, higher SIRlesion/liver on HBP, and lower SIRlesion/liver on DWI (P < 0.001‒0.035). Rim enhancement on AP and persistent rim enhancement during AP to TP were significantly more common in CLM than in IPT (P ≤ 0.001). Multivariate analysis revealed that a central hypointensity with a relatively peripheral hyperintensity on HBP, higher SIRlesion/liver on HBP, and lower SIRlesion/liver on DWI were predictive of IPT (P = 0.003‒0.039). Central hypointensity with a relatively peripheral hyperintensity on HBP and SIRlesion/liver on HBP and DWI may be reliable gadoxetate disodium-enhanced MRI features for distinguishing IPT from CLM.

AB197. Jejunal diverticulosis—a rare cause life-threatening gastrointestinal bleeding

Background: Small bowel diverticulosis is a rare entity comprising of multiple outpouchings of the mesenteric border of the small bowel. The prevalence is reported at 0.2–1.3%. These pseudodiverticula are an acquired pathology of the small bowel, involving the mucosal and submucosal layers. It is hypothesised that they are pulsion diverticulae due to herniation at the site of blood vessel penetration through the bowel wall.

Damage tolerant analysis of corner cracks in small nozzle process penetration of the CAREM-25 reactor pressure vessel

This paper presents a damage tolerant approach assessment of corner cracks in small nozzle process penetrations in the pressure vessel of the small modular reactor CAREM-25 subjected to mechanical and thermal shock loadings during certain operation events. Fracture mechanics analyses were performed following ASME XI guidelines considering a representative geometry and specific loading conditions. Stress distributions in the uncracked component were calculated by finite element techniques, while fracture driving forces were estimated using closed form solutions. Maximum allowable corner crack sizes were calculated using linear elastic fracture mechanics and failure assessment diagram (FAD) approaches. The onset of stable crack growth and crack instability were considered as failure conditions. Additionally, fatigue crack growth estimations during the service life were performed integrating a Paris law up to the maximum allowable crack sizes. The results indicate that it seems unlikely that pre-existing cracks reach allowable sizes during the reactor's service life.

Use of 3-D Contrast-Enhanced Ultrasound to Evaluate Tumor Microvasculature After Nanoparticle-Mediated Modulation

A cost-effective method for serial in vivo imaging of tumor microvasculature has been developed. We evaluated acoustic angiography (AA) for visualizing and assessing non-small cell lung tumor (A549) microvasculature in mice before and after tumor vascular disruption by vascular-targeted gold nanoparticles and radiotherapy. Standard B-mode and microbubble-enhanced AA images were acquired at pre- and post-treatment time points. Using these modes, a new metric, 50% vessel penetration depth, was developed to characterize the 3-D spatial heterogeneity of microvascular networks. We observed an increase in tumor perfusion after radiation-induced vascular disruption, relative to control animals. This was also visualized in vessel morphology mode, which revealed a loss in vessel integrity. We found that tumors with poorly perfused vasculature at day 0 exhibited a reduced growth rate over time. This suggested a new method to reduce in-group treatment response variability using pre-treatment microvessel maps to objectively identify animals for study removal.

Osteogenic and angiogenic tissue formation in high fidelity nanocomposite Laponite-gelatin bioinks

Bioprinting of living cells is rapidly developing as an advanced biofabrication approach to engineer tissues. Bioinks can be extruded in three-dimensions (3D) to fabricate complex and hierarchical constructs for implantation. However, a lack of functionality can often be attributed to poor bioink properties. Indeed, advanced bioinks encapsulating living cells should: (i) present optimal rheological properties and retain 3D structure post fabrication, (ii) promote cell viability and support cell differentiation, and (iii) localise proteins of interest (e.g. vascular endothelial growth factor (VEGF)) to stimulate encapsulated cell activity and tissue ingrowth upon implantation. In this study, we present the results of the inclusion of a synthetic nanoclay, Laponite® (LPN) together with a gelatin methacryloyl (GelMA) bioink and the development of a functional cell-instructive bioink. A nanocomposite bioink displaying enhanced shape fidelity retention and interconnected porosity within extrusion-bioprinted fibres was observed. Human bone marrow stromal cell (HBMSC) viability within the nanocomposite showed no significant changes over 21 days of culture in LPN-GelMA (85.60 ± 10.27%), compared to a significant decrease in GelMA from 7 (95.88 ± 2.90%) to 21 days (55.54 ± 14.72%) (p < 0.01). HBMSCs were observed to proliferate in LPN-GelMA with a significant increase in cell number over 21 days (p < 0.0001) compared to GelMA alone. HBMSC-laden LPN-GelMA scaffolds supported osteogenic differentiation evidenced by mineralised nodule formation, including in the absence of the osteogenic drug dexamethasone. Ex vivo implantation in a chick chorioallantoic membrane model, demonstrated excellent integration of the bioink constructs in the vascular chick embryo after 7 days of incubation. VEGF-loaded LPN-GelMA constructs demonstrated significantly higher vessel penetration than GelMA-VEGF (p < 0.0001) scaffolds. Integration and vascularisation was directly related to increased drug absorption and retention by LPN-GelMA compared to LPN-free GelMA. In summary, a novel light-curable nanocomposite bioink for 3D skeletal regeneration supportive of cell growth and growth factor retention and delivery, evidenced by ex vivo vasculogenesis, was developed with potential application in hard and soft tissue reparation.

Mature vessel networks in engineered tissue promote graft–host anastomosis and prevent graft thrombosis

Graft vascularization remains one of the most critical challenges facing tissue-engineering experts in their attempt to create thick transplantable tissues and organs. In vitro prevascularization of engineered tissues has been suggested to promote rapid anastomosis between the graft and host vasculatures; however, thrombotic events have been reported upon graft implantation. Here, we aimed to determine whether in vitro vessel maturation in transplantable grafts can accelerate vascular integration and graft perfusion and prevent thrombotic events in the grafts. To this end, endothelial cells and fibroblasts were cocultured on 3D scaffolds for 1, 7, or 14 d to form vasculature with different maturation degrees. Monitoring graft-host interactions postimplantation demonstrated that the 14-d in vitro-cultured grafts, bearing more mature and complex vessel networks as indicated by elongated and branched vessel structures, had increased graft-host vessel anastomosis; host vessel penetration into the graft increased approximately eightfold, and graft perfusion increased sixfold. The presence of developed vessel networks prevented clot accumulation in the grafts. Conversely, short-term cultured constructs demonstrated poor vascularization and increased thrombus formation. Elevated expression levels of coagulation factors, von Willebrand factor (vWF), and tissue factor (TF), were demonstrated in constructs bearing less mature vasculature. To conclude, these findings demonstrate the importance of establishing mature and complex vessel networks in engineered tissues before implantation to promote anastomosis with the host and accelerate graft perfusion.