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Although widely used as a preclinical model for studying cardiovascular diseases, there is a scarcity of in vivo hemodynamic measurements of the naïve murine system in multiple arterial and venous locations, from head-to-toe, and across sex and age. The purpose of this study is to quantify cardiovascular hemodynamics in mice at different locations along the vascular tree while evaluating the effects of sex and age. Male and female, adult and aged mice were anesthetized and underwent magnetic resonance imaging. Data were acquired from four co-localized vessel pairs (carotid/jugular, suprarenal and infrarenal aorta/inferior vena cava (IVC), femoral artery/vein) at normothermia (core temperature 37 ± 0.2 °C). Influences of age and sex on average velocity differ by location in arteries. Average arterial velocities, when plotted as a function of distance from the heart, decrease nearly linearly from the suprarenal aorta to the femoral artery (adult and aged males: − 0.33 ± 0.13, R2 = 0.87; − 0.43 ± 0.10, R2 = 0.95; adult and aged females: − 0.23 ± 0.07, R2 = 0.91; − 0.23 ± 0.02, R2 = 0.99). Average velocity of aged males and average volumetric flow of aged males and females tended to be larger compared to adult comparators. With cardiovascular disease as the leading cause of death and with the implications of cardiovascular hemodynamics as important biomarkers for health and disease, this work provides a foundation for sex and age comparisons in pathophysiology by collecting and analyzing hemodynamic data for the healthy murine arterial and venous system from head-to-toe, across sex and age. [ABSTRACT FROM AUTHOR]

Purpose: In this study, we compared firefly luciferase (Fluc) reporter gene and superparamagnetic iron oxide (Feridex) as cell markers for longitudinal monitoring of cardiomyoblast graft survival using optical bioluminescence imaging (BLI) and magnetic resonance imaging (MRI), respectively.Procedures: Rats (n = 31) underwent an intramyocardial injection of cardiomyoblasts (2 x 10(6)) labeled with Fluc, Feridex, or no marker (control) or an injection of Feridex alone (75 microg). Afterward, rats were serially imaged with BLI or MRI and killed at different time points for histological analysis.Results: BLI revealed a drastically different cell survival kinetics (half-life = 2.65 days over 6 days) than that revealed by MRI (half-life = 16.8 days over 80 days). Injection of Feridex alone led to prolonged tissue retention of Feridex (> or =16 days) and persistent MR signal (> or =42 days).Conclusions: Fluc BLI reporter gene imaging is a more accurate gauge of transplanted cell survival as compared to MRI of Feridex-labeled cells. [ABSTRACT FROM AUTHOR]

Purpose: Expression of cell adhesion molecule integrin alpha(v)beta(3) is significantly up-regulated during tumor growth, and sprouting of tumor vessels and correlates well with tumor aggressiveness. The purpose of this study was to visualize tumor integrin alpha(v)beta(3) expression in vivo by using near-infrared fluorescence (NIRF) imaging of Cy5.5-linked cyclic arginine-glycine-aspartic acid (RGD) peptide in an orthotopic brain tumor model.Procedures: U87MG glioma cells transfected with the firefly luciferase gene were stereotactically injected into nude mice in the right frontal lobe. Bioluminescence imaging (BLI) using D: -luciferin substrate and small animal magnetic resonance imaging (MRI) using gadolinium contrast enhancement were conducted weekly after tumor cell inoculation to monitor intracranial tumor growth. Integrin alpha(v)beta(3) expression was assessed by using a three-dimensional optical imaging system (IVIS 200) 0-24 hours after administration of 1.5 nmol monomeric Cy5.5-RGD via the tail vein. Animals were injected intravenously with both Texas Red-tomato lectin and Cy5.5-RGD prior to sacrifice to visualize peptide localization to tumor vasculature using histology.Results: Fluorescence microscopy demonstrated specific Cy5.5-RGD binding to both U87MG tumor vessels and tumor cells with no normal tissue binding. NIRF imaging showed highest tumor uptake and tumor to normal brain tissue ratio two hours postinjection (2.64 +/- 0.20). Tumor uptake of Cy5.5-RGD was effectively blocked by using unlabeled c(RGDyK), and injection of Cy5.5 dye alone showed nonspecific binding.Conclusions: Optical imaging via BLI and NIRF offer a simple, effective, and rapid technique for noninvasive in vivo monitoring and semiquantitative analysis of intracranial tumor growth and integrin alpha(v)beta(3) expression. This study suggests that NIRF via fluorescently labeled RGD peptides may provide enhanced surveillance of tumor angiogenesis and anti-integrin treatment efficacy in orthotopic brain tumor models. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma is the third leading cause of cancer-related deaths worldwide. Many patients are not eligible for curative therapies, such as surgical resection of the tumor or a liver transplant. Transarterial embolization is one therapy clinically used in these cases; however, this requires a long procedure and careful placement of an intraarterial catheter. Gas embolization has been proposed as a fast, easily administered, more spatially selective, and less invasive alternative. Here, we demonstrate the feasibility and efficacy of using acoustic droplet vaporization to noninvasively generate gas emboli within vasculature. Intravital microscopy experiments were performed using the rat cremaster muscle to visually observe the formation of occlusions. Large gas emboli were produced within the vasculature in the rat cremaster, effectively occluding blood flow. Following these experiments, the therapeutic efficacy of gas embolization was investigated in an ectopic xenograft model of hepatocellular carcinoma in mice. The treatment group exhibited a significantly lower final tumor volume (ANOVA, p = 0.008) and growth rate than control groups – tumor growth was completely halted. Additionally, treated tumors exhibited significant necrosis as determined by histological analysis. To our knowledge, this study is the first to demonstrate the therapeutic efficacy of gas embolotherapy in a tumor model. [ABSTRACT FROM AUTHOR]

Potentiation of neutrophil extracellular trap (NET) release is one mechanism by which antiphospholipid antibodies (aPL Abs) effect thrombotic events in patients with antiphospholipid syndrome (APS). Surface adenosine receptors trigger cyclic AMP (cAMP) formation in neutrophils, and this mechanism has been proposed to regulate NETosis in some contexts. Here we report that selective agonism of the adenosine A2A receptor (CGS21680) suppresses aPL Ab-mediated NETosis in protein kinase A-dependent fashion. CGS21680 also reduces thrombosis in the inferior vena cavae of both control mice and mice administered aPL Abs. The antithrombotic medication dipyridamole is known to potentiate adenosine signaling by increasing extracellular concentrations of adenosine and interfering with the breakdown of cAMP. Like CGS21680, dipyridamole suppresses aPL Ab-mediated NETosis via the adenosine A2A receptor and mitigates venous thrombosis in mice. In summary, these data suggest an anti-inflammatory therapeutic paradigm in APS, which may extend to thrombotic disease in the general population. Antiphospholipid syndrome is characterised by increased neutrophil extracellular trap formation (NETosis) and, consequently, increased thrombotic events. Here Ali et al. show that treatment with adenosine receptor agonists suppresses NETosis and venous thrombosis in mouse models of antiphospholipid syndrome. [ABSTRACT FROM AUTHOR]

Purpose: Clinical adoption of NK cell immunotherapy is underway for medulloblastoma and osteosarcoma, however there is currently little feedback on cell fate after administration. We propose magnetic particle imaging (MPI) may have applications for the quantitative detection of NK cells.Human-derived NK-92 cells were labeled by co-incubation with iron oxide nanoparticles (VivoTrax™) for 24 h then excess nanoparticles were washed with centrifugation. Cytolytic activity of labeled versus unlabeled NK-92 cells was assessed after 4 h of co-incubation with medulloblastoma cells (DAOY) or osteosarcoma cells (LM7 or OS17). Labeled NK-92 cells at two different doses (0.5 or 1 × 106) were administered to excised mouse brains (cerebellum), fibulas, and lungs then imaged by 3D preclinical MPI (MOMENTUM™) for detection relative to fiducial markers. NK-92 cells were also imaged by clinical-scale MPI under development at Magnetic Insight Inc.NK-92 cells were labeled with an average of 3.17 pg Fe/cell with no measurable effects on cell viability or cytolytic activity against 3 tumor cell lines. MPI signal was directly quantitative with the number of labeled NK-92 cells, with preclinical limit of detection of 3.1 × 104 cells on MOMENTUM imager. Labeled NK-92 cells could be accurately localized in mouse brains, fibulas, and lungs within < 1 mm of stereotactic injection coordinates with preclinical scanner. Feasibility for detection on a clinical-scale MPI scanner was demonstrated using 4 × 107 labeled NK-92 cells, which is in the range of NK cell doses administered in our previous clinical trial.MPI can provide sensitive, quantitative, and accurate spatial information on NK cells soon after delivery, showing initial promise to address a significant unmet clinical need to track NK cell fate in patients.Procedures: Clinical adoption of NK cell immunotherapy is underway for medulloblastoma and osteosarcoma, however there is currently little feedback on cell fate after administration. We propose magnetic particle imaging (MPI) may have applications for the quantitative detection of NK cells.Human-derived NK-92 cells were labeled by co-incubation with iron oxide nanoparticles (VivoTrax™) for 24 h then excess nanoparticles were washed with centrifugation. Cytolytic activity of labeled versus unlabeled NK-92 cells was assessed after 4 h of co-incubation with medulloblastoma cells (DAOY) or osteosarcoma cells (LM7 or OS17). Labeled NK-92 cells at two different doses (0.5 or 1 × 106) were administered to excised mouse brains (cerebellum), fibulas, and lungs then imaged by 3D preclinical MPI (MOMENTUM™) for detection relative to fiducial markers. NK-92 cells were also imaged by clinical-scale MPI under development at Magnetic Insight Inc.NK-92 cells were labeled with an average of 3.17 pg Fe/cell with no measurable effects on cell viability or cytolytic activity against 3 tumor cell lines. MPI signal was directly quantitative with the number of labeled NK-92 cells, with preclinical limit of detection of 3.1 × 104 cells on MOMENTUM imager. Labeled NK-92 cells could be accurately localized in mouse brains, fibulas, and lungs within < 1 mm of stereotactic injection coordinates with preclinical scanner. Feasibility for detection on a clinical-scale MPI scanner was demonstrated using 4 × 107 labeled NK-92 cells, which is in the range of NK cell doses administered in our previous clinical trial.MPI can provide sensitive, quantitative, and accurate spatial information on NK cells soon after delivery, showing initial promise to address a significant unmet clinical need to track NK cell fate in patients.Results: Clinical adoption of NK cell immunotherapy is underway for medulloblastoma and osteosarcoma, however there is currently little feedback on cell fate after administration. We propose magnetic particle imaging (MPI) may have applications for the quantitative detection of NK cells.Human-derived NK-92 cells were labeled by co-incubation with iron oxide nanoparticles (VivoTrax™) for 24 h then excess nanoparticles were washed with centrifugation. Cytolytic activity of labeled versus unlabeled NK-92 cells was assessed after 4 h of co-incubation with medulloblastoma cells (DAOY) or osteosarcoma cells (LM7 or OS17). Labeled NK-92 cells at two different doses (0.5 or 1 × 106) were administered to excised mouse brains (cerebellum), fibulas, and lungs then imaged by 3D preclinical MPI (MOMENTUM™) for detection relative to fiducial markers. NK-92 cells were also imaged by clinical-scale MPI under development at Magnetic Insight Inc.NK-92 cells were labeled with an average of 3.17 pg Fe/cell with no measurable effects on cell viability or cytolytic activity against 3 tumor cell lines. MPI signal was directly quantitative with the number of labeled NK-92 cells, with preclinical limit of detection of 3.1 × 104 cells on MOMENTUM imager. Labeled NK-92 cells could be accurately localized in mouse brains, fibulas, and lungs within < 1 mm of stereotactic injection coordinates with preclinical scanner. Feasibility for detection on a clinical-scale MPI scanner was demonstrated using 4 × 107 labeled NK-92 cells, which is in the range of NK cell doses administered in our previous clinical trial.MPI can provide sensitive, quantitative, and accurate spatial information on NK cells soon after delivery, showing initial promise to address a significant unmet clinical need to track NK cell fate in patients.Conclusion: Clinical adoption of NK cell immunotherapy is underway for medulloblastoma and osteosarcoma, however there is currently little feedback on cell fate after administration. We propose magnetic particle imaging (MPI) may have applications for the quantitative detection of NK cells.Human-derived NK-92 cells were labeled by co-incubation with iron oxide nanoparticles (VivoTrax™) for 24 h then excess nanoparticles were washed with centrifugation. Cytolytic activity of labeled versus unlabeled NK-92 cells was assessed after 4 h of co-incubation with medulloblastoma cells (DAOY) or osteosarcoma cells (LM7 or OS17). Labeled NK-92 cells at two different doses (0.5 or 1 × 106) were administered to excised mouse brains (cerebellum), fibulas, and lungs then imaged by 3D preclinical MPI (MOMENTUM™) for detection relative to fiducial markers. NK-92 cells were also imaged by clinical-scale MPI under development at Magnetic Insight Inc.NK-92 cells were labeled with an average of 3.17 pg Fe/cell with no measurable effects on cell viability or cytolytic activity against 3 tumor cell lines. MPI signal was directly quantitative with the number of labeled NK-92 cells, with preclinical limit of detection of 3.1 × 104 cells on MOMENTUM imager. Labeled NK-92 cells could be accurately localized in mouse brains, fibulas, and lungs within < 1 mm of stereotactic injection coordinates with preclinical scanner. Feasibility for detection on a clinical-scale MPI scanner was demonstrated using 4 × 107 labeled NK-92 cells, which is in the range of NK cell doses administered in our previous clinical trial.MPI can provide sensitive, quantitative, and accurate spatial information on NK cells soon after delivery, showing initial promise to address a significant unmet clinical need to track NK cell fate in patients. [ABSTRACT FROM AUTHOR]