All-fiber miniature non-contact photoacoustic probe based on photoacoustic remote sensing microscopy for vascular imaging in vivo.

Photoacoustic (PA) remote sensing (PARS) microscopy represents a significant advancement by eliminating the need for traditional acoustic coupling media in PA microscopy (PAM), thereby broadening its potential applications. However, current PARS microscopy setups predominantly rely on free-space optical components, which can be cumbersome to implement and limit the scope of imaging applications. In this study, we develop an all-fiber miniature non-contact PA probe based on PARS microscopy, utilizing a 532-nm excitation wavelength, and showcase its effectiveness in in vivo vascular imaging. Our approach integrates various fiber-optic components, including a wavelength division multiplexer, a mode field adaptor, a fiber lens, and an optical circulator, to streamline the implementation of the PARS microscopy system. Additionally, we have successfully developed a miniature PA probe with a diameter of 4 mm. The efficacy of our imaging setup is demonstrated through in vivo imaging of mouse brain vessels. By introducing this all-fiber miniature PA probe, our work may open up new opportunities for non-contact PAM applications.

Shine and darkle the blood vessels: Multiparameter hypersensitive MR angiography for diagnosis of panvascular diseases.

Magnetic resonance angiography (MRA) is pivotal for diagnosing panvascular diseases. However, single-modality MRA falls short in diagnosing diverse vascular abnormalities. Thus, contrast agents combining T1 and T2 effects are sought for multiparameter MRA with clinical promise, yet achieving a balance in T1 and T2 contrast enhancement effects remains a scientific challenge. Herein, we developed a hypersensitive multiparameter MRA strategy using dual-modality NaGdF4 nanoparticles. Because of the longer tumbling time (τR), NaGdF4 nanoparticles can improve the longitudinal relaxivity (r1), brightening vessels in T1-weighted sequences. Simultaneously, the regular arrangement of Gd3+ in the crystal induces magnetic anisotropy, creating local static magnetic field heterogeneity and generating negative signals in T2-weighted sequences. Consequently, the efficacy of NaGdF4-enhanced high-resolution multiparameter MRA has been validated in diagnosing ischemic stroke and Alzheimer's disease in rodent models. In addition, the dual-contrast imaging has been realized on swine with a clinical 3.0-T magnetic resonance imaging scanner, highly emphasizing the clinical translation prospect.

A Custom-Developed Device for Testing Tensile Strength and Elasticity of Vascular and Intestinal Tissue Samples for Anastomosis Regeneration Research.

Optimizing the regeneration process of surgically created anastomoses (blood vessels, intestines, nerves) is an important topic in surgical research. One of the most interesting parameter groups is related to the biomechanical properties of the anastomoses. Depending on the regeneration process and its influencing factors, tensile strength and other biomechanical features may change during the healing process. Related to the optimal specimen size, the range and accuracy of measurements, and applicability, we have developed a custom-tailored microcontroller-based device. In this paper, we describe the hardware and software configuration of the latest version of the device, including experiences and comparative measurements of tensile strength and elasticity of artificial materials and biopreparate tissue samples. The machine we developed was made up of easily obtainable parts and can be easily reproduced on a low budget. The basic device can apply a force of up to 40 newtons, and can grasp a 0.05-1 cm wide, 0.05-1 cm thick tissue. The length of the test piece on the rail should be between 0.3 and 5 cm. Low production cost, ease of use, and detailed data recording make it a useful tool for experimental surgical research.

Myonuclear position and blood vessel organization during skeletal muscle postnatal development.

Skeletal muscle development is a complex process involving myoblast fusion to generate multinucleated fibers. Myonuclei first align in the center of the myotubes before migrating to the periphery of the myofiber. Blood vessels (BVs) are important contributors to the correct development of skeletal muscle, and myonuclei are found next to BVs in adult muscle. Here, we show that most myonuclear migration to the periphery occurs between embryonic day 17.5 and postnatal day 1 in mouse. Furthermore, myonuclear accretion after postnatal day 7 does not result in centrally nucleated myofibers as observed in the embryo. Instead, myonuclei remain at the periphery of the myofiber without moving to the center. Finally, we show that hypovascularization of skeletal muscle alters the interaction between myonuclei and BVs, suggesting that BVs may contribute to myonuclear positioning during skeletal muscle postnatal development. Overall, this work provides a comprehensive analysis of skeletal muscle development during the highly dynamic postnatal period, bringing new insights about myonuclear positioning and its interaction with BVs.

3D-printed blood vessels engineered to more closely mimic human vasculature.

Novel bioprinting technique offers strategy for building dense organ systems with complex multilayered vascular networks. Building on a technique called "sacrificial writing in functional tissue," researchers have developed immature organ systems capable of maintaining rudimentary function and maintaining viability owing to an intricate vascular network.

Autophagy as a Guardian of Vascular Niche Homeostasis.

The increasing burden of vascular dysfunction on healthcare systems worldwide results in higher morbidity and mortality rates across pathologies, including cardiovascular diseases. Vasculopathy is suggested to be caused by the dysregulation of vascular niches, a microenvironment of vascular structures comprising anatomical structures, extracellular matrix components, and various cell populations. These elements work together to ensure accurate control of the vascular network. In recent years, autophagy has been recognized as a crucial regulator of the vascular microenvironment responsible for maintaining basic cell functions such as proliferation, differentiation, replicative senescence, and apoptosis. Experimental studies indicate that autophagy activation can be enhanced or inhibited in various pathologies associated with vascular dysfunction, suggesting that autophagy plays both beneficial and detrimental roles. Here, we review and assess the principles of autophagy organization and regulation in non-tumor vascular niches. Our analysis focuses on significant figures in the vascular microenvironment, highlighting the role of autophagy and summarizing evidence that supports the systemic or multiorgan nature of the autophagy effects. Finally, we discuss the critical organizational and functional aspects of the vasculogenic niche, specifically in relation to autophagy. The resulting dysregulation of the vascular microenvironment contributes to the development of vascular dysfunction.

The role of vascular and lymphatic networks in bone and joint homeostasis and pathology.

The vascular and lymphatic systems are integral to maintaining skeletal homeostasis and responding to pathological conditions in bone and joint tissues. This review explores the interplay between blood vessels and lymphatic vessels in bones and joints, focusing on their roles in homeostasis, regeneration, and disease progression. Type H blood vessels, characterized by high expression of CD31 and endomucin, are crucial for coupling angiogenesis with osteogenesis, thus supporting bone homeostasis and repair. These vessels facilitate nutrient delivery and waste removal, and their dysfunction can lead to conditions such as ischemia and arthritis. Recent discoveries have highlighted the presence and significance of lymphatic vessels within bone tissue, challenging the traditional view that bones are devoid of lymphatics. Lymphatic vessels contribute to interstitial fluid regulation, immune cell trafficking, and tissue repair through lymphangiocrine signaling. The pathological alterations in these networks are closely linked to inflammatory joint diseases, emphasizing the need for further research into their co-regulatory mechanisms. This comprehensive review summarizes the current understanding of the structural and functional aspects of vascular and lymphatic networks in bone and joint tissues, their roles in homeostasis, and the implications of their dysfunction in disease. By elucidating the dynamic interactions between these systems, we aim to enhance the understanding of their contributions to skeletal health and disease, potentially informing the development of targeted therapeutic strategies.

[3D bioprinting: classification, evaluation, and application in vascular tissue engineering].

Cardiovascular diseases are major diseases, and there is lack of artificial blood vessels with small diameters which can be applied in coronary artery bypass surgery. The conventional vascular scaffold preparation techniques in tissue engineering have shortcomings in regulating the diameter, geometric shape, and interconnectivity of the scaffold. 3D bioprinting can simulate the natural structure of the vascular tissue, accurately print live cells and biomaterials, and regulate the microstructure and porosity of scaffolds on the nanoscale, providing new ideas for vascular tissue engineering. This article systematically evaluates the classification of 3D bioprinting technologies and reviews the latest research progress of 3D bioprinting in vascular tissue engineering. It summarizes the advantages of 3D bioprinting and points out the problems that need to be solved, such as the immune rejection of blood vessel materials, providing reference for the further research.

In vivo video microscopy of the rupturing process of thin blood vessels to clarify the mechanism of bruising caused by blunt impact: an animal study.

BACKGROUND: The thresholds of mechanical inputs for bruising caused by blunt impact are important in the fields of machine safety and forensics. However, reliable data on these thresholds remain inadequate owing to a lack of in vivo experiments, which are crucial for investigating the occurrence of bruising. Since experiments involving live human participants are limited owing to ethical concerns, finite-element method (FEM) simulations of the bruising mechanism should be used to compensate for the lack of experimental data by estimating the thresholds under various conditions, which requires clarifying the mechanism of formation of actual bruises. Therefore, this study aimed to visualize the mechanism underlying the formation of bruises caused by blunt impact to enable FEM simulations to estimate the thresholds of mechanical inputs for bruising. METHODS: In vivo microscopy of a transparent glass catfish subjected to blunt contact with an indenter was performed. The fish were anesthetized by immersing them in buffered MS-222 (75-100 mg/L) and then fixed on a subject tray. The indenter, made of transparent acrylic and having a rectangular contact area with dimensions of 1.0 mm × 1.5 mm, was loaded onto the lateral side of the caudal region of the fish. Blood vessels and surrounding tissues were examined through the transparent indenter using a microscope equipped with a video camera. The contact force was measured using a force-sensing table. RESULTS: One of the processes of rupturing thin blood vessels, which are an essential component of the bruising mechanism, was observed and recorded as a movie. The soft tissue surrounding the thin blood vessel extended in a plane perpendicular to the compressive contact force. Subsequently, the thin blood vessel was pulled into a straight configuration. Next, it was stretched in the axial direction and finally ruptured. CONCLUSION: The results obtained indicate that the extension of the surrounding tissue in the direction perpendicular to the contact force as well as the extension of the thin blood vessels are important factors in the bruising mechanism, which must be reproduced by FEM simulation to estimate the thresholds.

Identification of transcriptional signature change and critical transcription factors involved during the differentiation of mouse trophoblast stem cell into maternal blood vessel associated trophoblast giant cell.

The placenta is essential organ for oxygen and nutrient exchange between the mother and the developing fetus. Trophoblast lineage differentiation is closely related to the normal function of the placenta. Trophoblast stem cells (TSCs) can differentiate into all placental trophoblast subtypes and are widely used as in vitro stem cell models to study placental development and trophoblast lineage differentiation. Although extensive research has been conducted on the differentiation of TSCs, the possible parallels between trophoblast giant cells (TGCs) that are differentiated from TSCs in vitro and the various subtypes of TGC lineages in vivo are still poorly understood. In this study, mouse TSCs (mTSCs) were induced to differentiate into TGCs, and our mRNA sequencing (RNA-seq) data revealed that mTSCs and TGCs have distinct transcriptional signatures. We conducted a comparison of mTSCs and TGCs transcriptomes with the published transcriptomes of TGC lineages in murine placenta detected by single-cell RNA-seq and found that mTSCs tend to differentiate into maternal blood vessel-associated TGCs in vitro. Moreover, we identified the transcription factor (TF) ZMAT1, which may be responsible for the differentiation of mTSCs into sinusoid TGCs, and the TFs EGR1 and MITF, which are likely involved in the differentiation of mTSCs into spiral artery-associated TGCs. Thus, our findings provide a valuable resource for the mechanisms of trophoblast lineage differentiation and placental deficiency-associated diseases development.

Feasibility of capturing vessel expansion with 4D-CTA: Phantom study to determine reproducibility, spatial and temporal resolution.

BACKGROUND: Dynamic Computed Tomography Angiography (4D CTA) has the potential of providing insight into the biomechanical properties of the vessel wall, by capturing motion of the vessel wall. For vascular pathologies, like intracranial aneurysms, this could potentially refine diagnosis, prognosis, and treatment decision-making. PURPOSE: The objective of this research is to determine the feasibility of a 4D CTA scanner for accurately measuring harmonic diameter changes in an in-vitro simulated vessel. METHODS: A silicon tube was exposed to a simulated heartbeat. Simulated heart rates between 40 and 100 beats-per-minute (bpm) were tested and the flow amplitude was varied, resulting in various changes of tube diameter. A 320-detector row CT system with ECG-gating captured three consecutive cycles of expansion. Image registration was used to calculate the diameter change. A vascular echography set-up was used as a reference, using a 9 MHz linear array transducer. The reproducibility of 4D CTA was represented by the Pearson correlation (r) between the three consecutive diameter change patterns, captured by 4D CTA. The peak value similarity (pvs) was calculated between the 4D CTA and US measurements for increasing frequencies and was chosen as a measure of temporal resolution. Spatial resolution was represented by the Sum of the Relative Percentual Difference (SRPD) between 4D CTA and US diameter change patterns for increasing amplitudes. RESULTS: The reproducibility of 4D CTA measurements was good (r ≥ 0.9) if the diameter change was larger than 0.3 mm, moderate (0.7 ≤ r < 0.9) if the diameter change was between 0.1 and 0.3 mm, and low (r < 0.7) if the diameter change was smaller than 0.1 mm. Regarding the temporal resolution, the amplitude of 4D CTA was similar to the US measurements (pvs ≥ 90%) for the frequencies of 40 and 50 bpm. Frequencies between 60 and 80 bpm result in a moderate similarity (70% ≤ pvs < 90%). A low similarity (pvs < 70%) is observed for 90 and 100 bpm. Regarding the spatial resolution, diameter changes above 0.30 mm result in SRPDs consistently below 50%. CONCLUSION: In a phantom setting, 4D CTA can be used to reliably capture reproducible tube diameter changes exceeding 0.30 mm. Low pulsation frequencies (40 or 50 bpm) provide an accurate measurement of the maximum tube diameter change.

Generation of human iPSC-derived 3D bile duct within liver organoid by incorporating human iPSC-derived blood vessel.

In fetal development, tissue interaction such as the interplay between blood vessel (BV) and epithelial tissue is crucial for organogenesis. Here we recapitulate the spatial arrangement between liver epithelial tissue and the portal vein to observe the formation of intrahepatic bile ducts (BDs) from human induced pluripotent stem cells (hiPSC). We co-culture hiPSC-liver progenitors on the artificial BV consisting of immature smooth muscle cells and endothelial cells, both derived from hiPSCs. After 3 weeks, liver progenitors within hiPSC-BV-incorporated liver organoids (BVLO) differentiate to cholangiocytes and acquire epithelial characteristics, including intercellular junctions, microvilli on the apical membrane, and secretory functions. Furthermore, liver surface transplanted-BVLO temporarily attenuates cholestatic injury symptoms. Single cell RNA sequence analysis suggests that BD interact with the BV in BVLO through TGFß and Notch pathways. Knocking out JAG1 in hiPSC-BV significantly attenuates bile duct formation, highlighting BVLO potential as a model for Alagille syndrome, a congenital biliary disease. Overall, we develop a novel 3D co-culture method that successfully establishes functional human BDs by emulating liver epithelial-BV interaction.

Quantitative microCT imaging of a whole equine placenta and its blood vessel network.

Placental structure is linked to function across morphological scales. In the placenta, changes to gross anatomy, such as surface area, volume, or blood vessel arrangement, are associated with suboptimal physiological outcomes. However, quantifying each of these metrics requires different laborious semi-quantitative methods. Here, we demonstrate how, with minimal sample preparation, whole-organ computed microtomography (microCT) can be used to calculate gross morphometry of the equine placenta and a range of additional metrics, including branching morphometry of placental vasculature, non-destructively from a single dataset. Our approach can be applied to quantify the gross structure of any large mammalian placenta.

Embedding Biomimetic Vascular Networks via Coaxial Sacrificial Writing into Functional Tissue.

Printing human tissues and organs replete with biomimetic vascular networks is of growing interest. While it is possible to embed perfusable channels within acellular and densely cellular matrices, they do not currently possess the biomimetic architectures found in native vessels. Here, coaxial sacrificial writing into functional tissues (co-SWIFT) is developed, an embedded bioprinting method capable of generating hierarchically branching, multilayered vascular networks within both granular hydrogel and densely cellular matrices. Coaxial printheads are designed with an extended core-shell configuration to facilitate robust core-core and shell-shell interconnections between printed branching vessels during embedded bioprinting. Using optimized core-shell ink combinations, biomimetic vessels composed of a smooth muscle cell-laden shell that surrounds perfusable lumens are coaxially printed into granular matrices composed of: 1) transparent alginate microparticles, 2) sacrificial microparticle-laden collagen, or 3) cardiac spheroids derived from human induced pluripotent stem cells. Biomimetic blood vessels that exhibit good barrier function are produced by seeding these interconnected lumens with a confluent layer of endothelial cells. Importantly, it is found that co-SWIFT cardiac tissues mature under perfusion, beat synchronously, and exhibit a cardio-effective drug response in vitro. This advance opens new avenues for the scalable biomanufacturing of vascularized organ-specific tissues for drug testing, disease modeling, and therapeutic use.

Effect of Vascular Senescence on the Efficacy and Safety of Warfarin: Insights from Rat Models and a Prospective Cohort Study.

Warfarin, with its narrow therapeutic range, requires the understanding of various influencing factors for personalized medication. Vascular senescence, marked by vascular stiffening and endothelial dysfunction, has an unclear effect on the efficacy and safety of warfarin. Based on previous studies, we hypothesized that vascular senescence increases the risk of bleeding during warfarin therapy. This study aimed to explore these effects using animal models and clinical cohorts. We established rat models of vascular senescence and calcification using d-galactose, vitamin D, and nicotine. After validating the models, we examined changes in the international normalized ratio (INR) at fixed warfarin doses (0.20 and 0.35 mg/kg). We found that vascular senescence caused significantly elevated INR values and increased bleeding risk. In the prospective clinical cohort study (NCT06428110), hospitalized warfarin patients with standard dose adjustments were divided into vascular senescence and control groups based on ultrasound and computed tomography diagnosis. Using propensity score matching to exclude the influence of confounding factors, we found that the vascular senescence group had lower steady-state warfarin doses and larger dose adjustments, with a higher probability of INR exceeding the therapeutic range. The vascular senescence group tended to experience more bleeding or thromboembolic/ischemic events during 1 year of follow-up, while there was no statistical difference. In conclusion, vascular senescence leads to unstable INR values and increases higher bleeding risk during warfarin therapy, highlighting the importance of considering vascular senescence in future precision warfarin therapies. SIGNIFICANCE STATEMENT: Many factors influence warfarin efficacy; however, the effect of vascular senescence remains unclear. This study aimed to investigate the effects of vascular senescence on the efficacy and safety of warfarin. Through both rat models and clinical cohort studies, our findings indicated that vascular senescence may compromise the stability of warfarin, presenting challenges in maintaining its efficacy and safety.

Avermectin induced vascular damage in zebrafish larvae: association with mitochondria-mediated apoptosis and VEGF/Notch signaling pathway.

Avermectin is a highly effective insecticide that has been widely used in agriculture since the 1990s. In recent years, the safety of avermectin for non-target organisms has received much attention. The vasculature is important organs in the body and participate in the composition of other organs. However, studies on the vascular safety of avermectin are lacking. The vasculature of zebrafish larvae is characterized by ease of observation and it is a commonly used model for vascular studies. Therefore, zebrafish larvae were used to explore the potential risk of avermectin on the vasculature. The results showed that avermectin induced vascular damage throughout the body of zebrafish larvae, including the head, eyes, intestine, somite, tail and other vasculature. The main forms of damage are reduction in vascular diameter, vascular area and vascular abundance. Meanwhile, avermectin induced a decrease in the number of endothelial cells and apoptosis within the vasculature. In addition, vascular damage may be related to impairment of mitochondrial function and mitochondria-mediated apoptosis. Finally, exploration of the molecular mechanisms revealed abnormal alterations in the expression of genes related to the VEGF/Notch signaling pathway. Therefore, the VEGF/Notch signaling pathway may be an important mechanism for avermectin-induced vascular damage in zebrafish larvae. This study demonstrates the vascular toxicity of avermectin in zebrafish larvae and reveals the possible molecular mechanism, which would hopefully draw more attention to the safety of avermectin in non-target organisms.

Neural Regulation of Vascular Development: Molecular Mechanisms and Interactions.

As a critical part of the circulatory system, blood vessels transport oxygen and nutrients to every corner of the body, nourishing each cell, and also remove waste and toxins. Defects in vascular development and function are closely associated with many diseases, such as heart disease, stroke, and atherosclerosis. In the nervous system, the nervous and vascular systems are intricately connected in both development and function. First, peripheral blood vessels and nerves exhibit parallel distribution patterns. In the central nervous system (CNS), nerves and blood vessels form a complex interface known as the neurovascular unit. Second, the vascular system employs similar cellular and molecular mechanisms as the nervous system for its development. Third, the development and function of CNS vasculature are tightly regulated by CNS-specific signaling pathways and neural activity. Additionally, vascular endothelial cells within the CNS are tightly connected and interact with pericytes, astrocytes, neurons, and microglia to form the blood-brain barrier (BBB). The BBB strictly controls material exchanges between the blood and brain, maintaining the brain's microenvironmental homeostasis, which is crucial for the normal development and function of the CNS. Here, we comprehensively summarize research on neural regulation of vascular and BBB development and propose directions for future research.

Cross-Anatomy Transfer Learning via Shape-Aware Adaptive Fine-Tuning for 3D Vessel Segmentation.

Deep learning methods have recently achieved remarkable performance in vessel segmentation applications, yet require numerous labor-intensive labeled data. To alleviate the requirement of manual annotation, transfer learning methods can potentially be used to acquire the related knowledge of tubular structures from public large-scale labeled vessel datasets for target vessel segmentation in other anatomic sites of the human body. However, the cross-anatomy domain shift is a challenging task due to the formidable discrepancy among various vessel structures in different anatomies, resulting in the limited performance of transfer learning. Therefore, we propose a cross-anatomy transfer learning framework for 3D vessel segmentation, which first generates a pre-trained model on a public hepatic vessel dataset and then adaptively fine-tunes our target segmentation network initialized from the model for segmentation of other anatomic vessels. In the framework, the adaptive fine-tuning strategy is presented to dynamically decide on the frozen or fine-tuned filters of the target network for each input sample with a proxy network. Moreover, we develop a Gaussian-based signed distance map that explicitly encodes vessel-specific shape context. The prediction of the map is added as an auxiliary task in the segmentation network to capture geometry-aware knowledge in the fine-tuning. We demonstrate the effectiveness of our method through extensive experiments on two small-scale datasets of coronary artery and brain vessel. The results indicate the proposed method effectively overcomes the discrepancy of cross-anatomy domain shift to achieve accurate vessel segmentation for these two datasets.