Development and validation of a controlled heating apparatus for long-term MRI of 3D microfluidic tumor models.

Conventional testing of novel contrast agents for magnetic resonance imaging (MRI) involves cell and animal studies. However, 2D cultures lack dynamic flow and MRI is limited by regulatory approval of long-term anesthesia use. Microfluidic tumor models (MTMs) offer a cost-effective, reproducible, and high throughput platform for bridging cell and animal models.

Structured adaptive boosting trees for detection of multicellular aggregates in fluorescence intravital microscopy.

Fluorescence intravital microscopy captures large data sets of dynamic multicellular interactions within various organs such as the lungs, liver, and brain of living subjects. In medical imaging, edge detection is used to accurately identify and delineate important structures and boundaries inside the images. To improve edge sharpness, edge detection frequently requires the inclusion of low-level features.

Caveat Emptor: Commercialized Manganese Oxide Nanoparticles Exhibit Unintended Properties.

Nano-encapsulated manganese oxide (NEMO) particles are noteworthy contrast agents for magnetic resonance imaging (MRI) due to their bright, pH-switchable signal ("OFF" to "ON" at low pH), high metal loading, and targeting capability for increased specificity. For the first time, we performed a head-to-head comparison of NEMO particles from In-house and commercialized sources (US Nano vs Nanoshel) to assess their potential as bright T MRI contrast agents. Manganese oxide nanocrystals (MnO, MnO, and MnO) were systematically evaluated for size, chemistry, release of manganese ions, and MRI signal pre- and post-encapsulation within poly(lactic--glycolic acid) (PLGA).

Short-term exposure of female BALB/cJ mice to e-cigarette aerosol promotes neutrophil recruitment and enhances neutrophil-platelet aggregation in pulmonary microvasculature.

Despite the perception that e-cigarettes are safer than conventional cigarettes, numerous findings demonstrated that e-cigarette aerosol (EC) exposure induced compromised immune functionality, vascular changes even after acute exposure, and lung injury. Notably, altered neutrophil functionality and platelet hemodynamics have been observed post-EC exposure. It was hypothesized that EC exposure initiates an inflammatory response resulting in altered neutrophil behavior and increased neutrophil-platelet interaction in the pulmonary microvasculature.

PEGylation of Metal Oxide Nanoparticles Modulates Neutrophil Extracellular Trap Formation.

Novel metal oxide nanoparticle (NP) contrast agents may offer safety and functionality advantages over conventional gadolinium-based contrast agents (GBCAs) for cancer diagnosis by magnetic resonance imaging. However, little is known about the behavior of metal oxide NPs, or of their effect, upon coming into contact with the innate immune system. As neutrophils are the body's first line of defense, we sought to understand how manganese oxide and iron oxide NPs impact leukocyte functionality.

E-Cigarette Use: Device Market, Study Design, and Emerging Evidence of Biological Consequences.

Electronic cigarettes are frequently viewed as a safer alternative to conventional cigarettes; however, evidence to support this perspective has not materialized. Indeed, the current literature reports that electronic cigarette use is associated with both acute lung injury and subclinical dysfunction to the lung and vasculature that may result in pathology following chronic use. E-cigarettes can alter vascular dynamics, polarize innate immune populations towards a proinflammatory state, compromise barrier function in the pulmonary endothelium and epithelium, and promote pre-oncogenic phenomena.

Live Imaging of the Lung.

Live imaging is critical to determining the dynamics and spatial interactions of cells within the tissue environment. In the lung, this has proven to be difficult due to the motion brought about by ventilation and cardiac contractions. A previous version of this Current Protocols in Cytometry article reported protocols for imaging ex vivo live lung slices and the intact mouse lung.

Tuning the size and composition of manganese oxide nanoparticles through varying temperature ramp and aging time.

Manganese oxide (MnO) nanoparticles (NPs) can serve as robust pH-sensitive contrast agents for magnetic resonance imaging (MRI) due to Mn2+ release at low pH, which generates a ~30 fold change in T1 relaxivity. Strategies to control NP size, composition, and Mn2+ dissolution rates are essential to improve diagnostic performance of pH-responsive MnO NPs. We are the first to demonstrate that MnO NP size and composition can be tuned by the temperature ramping rate and aging time used during thermal decomposition of manganese(II) acetylacetonate.

Manganese Oxide Nanoparticle Synthesis by Thermal Decomposition of Manganese(II) Acetylacetonate.

For biomedical applications, metal oxide nanoparticles such as iron oxide and manganese oxide (MnO), have been used as biosensors and contrast agents in magnetic resonance imaging (MRI). While iron oxide nanoparticles provide constant negative contrast on MRI over typical experimental timeframes, MnO generates switchable positive contrast on MRI through dissolution of MnO to Mn at low pH within cell endosomes to 'turn ON' MRI contrast. This protocol describes a one-pot synthesis of MnO nanoparticles formed by thermal decomposition of manganese(II) acetylacetonate in oleylamine and dibenzyl ether.

Neutrophil extracellular traps in breast cancer and beyond: current perspectives on NET stimuli, thrombosis and metastasis, and clinical utility for diagnosis and treatment.

The formation of neutrophil extracellular traps (NETs), known as NETosis, was first observed as a novel immune response to bacterial infection, but has since been found to occur abnormally in a variety of other inflammatory disease states including cancer. Breast cancer is the most commonly diagnosed malignancy in women. In breast cancer, NETosis has been linked to increased disease progression, metastasis, and complications such as venous thromboembolism.

Intelligent and automatic in vivo detection and quantification of transplanted cells in MRI.

Purpose: Magnetic resonance imaging (MRI)-based cell tracking has emerged as a useful tool for identifying the location of transplanted cells, and even their migration. Magnetically labeled cells appear as dark contrast in T2*-weighted MRI, with sensitivities of individual cells. One key hurdle to the widespread use of MRI-based cell tracking is the inability to determine the number of transplanted cells based on this contrast feature.

Quantitative intravital two-photon excitation microscopy reveals absence of pulmonary vaso-occlusion in unchallenged Sickle Cell Disease mice.

Sickle cell disease (SCD) is a genetic disorder that leads to red blood cell (RBC) sickling, hemolysis and the upregulation of adhesion molecules on sickle RBCs. Chronic hemolysis in SCD results in a hyper-inflammatory state characterized by activation of circulating leukocytes, platelets and endothelial cells even in the absence of a crisis. A crisis in SCD is often triggered by an inflammatory stimulus and can lead to the acute chest syndrome (ACS), which is a type of lung injury and a leading cause of mortality among SCD patients.

Poly(lactic-co-glycolic acid) encapsulated gadolinium oxide nanoparticles for MRI-based cell tracking.

Superparamagnetic iron oxide particles have proven useful for cell tracking applications by monitoring cell transplantation and migration in living organisms. However, one perceived drawback is that these particles cause dark contrast in MRI, sometimes yielding confusion with other biological phenomena, which also yield dark contrast. To that end, researchers have investigated the use of gadolinium oxide (Gd2O3) based contrast agents for MRI-based cell tracking, as Gd2O3 has favorable r1 molar relaxivity.

Clinically viable magnetic poly(lactide-co-glycolide) particles for MRI-based cell tracking.

Purpose: To design, fabricate, characterize, and in vivo assay clinically viable magnetic particles for MRI-based cell tracking.

Methods: Poly(lactide-co-glycolide) (PLGA) encapsulated magnetic nano and microparticles were fabricated. Multiple biologically relevant experiments were performed to assess cell viability, cellular performance, and stem cell differentiation.

Specific chemotaxis of magnetically labeled mesenchymal stem cells: implications for MRI of glioma.

Purpose: Glioblastoma multiforme (GBM) is a lethal disease marked by infiltration of cancerous cells into the surrounding normal brain. The dire outcome of GBM patients stems in part from the limitations of current neuroimaging methods. Notably, early cancer detection methodologies are lacking, without the ability to identify aggressive, metastatic tumor cells.

Biocompatible and pH-sensitive PLGA encapsulated MnO nanocrystals for molecular and cellular MRI.

Inorganic manganese-based particles are becoming attractive for molecular and cellular imaging, due to their ability to provide bright contrast on MRI, as opposed to the dark contrast generated from iron-based particles. Using a single emulsion technique, we have successfully fabricated pH-sensitive poly(lactic-co-glycolic acid) (PLGA)-encapsulated manganese oxide (MnO) nanocrystals. Two classes of particles were fabricated at ∼140 nm and 1.

Nanotechnology for delivery of drugs to the brain for epilepsy.

Epilepsy results from aberrant electrical activity that can affect either a focal area or the entire brain. In treating epilepsy with drugs, the aim is to decrease seizure frequency and severity while minimizing toxicity to the brain and other tissues. Antiepileptic drugs (AEDs) are usually administered by oral and intravenous routes, but these drug treatments are not always effective.