Repeated Injection of Very Small Superparamagnetic Iron Oxide Particles (VSOPs) in Murine Atherosclerosis: A Safety Study.

Citrate-coated electrostatically stabilized very small superparamagnetic iron oxide particles (VSOPs) have been successfully tested as magnetic resonance angiography (MRA) contrast agents and are promising tools for molecular imaging of atherosclerosis. Their repeated use in the background of pre-existing hyperlipidemia and atherosclerosis has not yet been studied. This study aimed to investigate the effect of multiple intravenous injections of VSOPs in atherosclerotic mice.

Inorganic Phosphate-Induced Extracellular Vesicles from Vascular Smooth Muscle Cells Contain Elevated Levels of Hyaluronic Acid, Which Enhance Their Interaction with Very Small Superparamagnetic Iron Oxide Particles.

Patients with chronic kidney disease (CKD) have a high prevalence of hyperphosphatemia, where uremic toxins like inorganic phosphate (Pi) induce a cardiovascular remodeling. Related disorders like atherosclerosis bear the risk of increased morbidity and mortality. We previously found that Pi stimulates the synthesis and sulfation of the negatively charged glycosaminoglycans (GAGs) heparan sulfate and chondroitin sulfate in vascular smooth muscle cells (VSMC).

Uremic Toxin-Induced Exosome-like Extracellular Vesicles Contain Enhanced Levels of Sulfated Glycosaminoglycans which Facilitate the Interaction with Very Small Superparamagnetic Iron Oxide Particles.

Uremic toxins exert pathophysiological effects on cells and tissues, such as the generation of a pro-calcifying subtype of exosome-like extracellular vesicles (EVs) in vascular cells. Little is known about the effects of the toxins on the surface structure of EVs. Thus, we studied the effects of uremic toxins on the abundance of sulfated glycosaminoglycans (GAGs) in EVs, and the implications for binding of ligands such as very small superparamagnetic iron oxide particles (VSOPs) which could be of relevance for radiological EV-imaging.

Remote Monitoring Compared With In-Office Surveillance of Blood Pressure in Patients With Pregnancy-Related Hypertension: A Randomized Controlled Trial.

Objective: To compare the rate of blood pressure ascertainment within 10 days of postpartum discharge among individuals with hypertensive disorders of pregnancy randomized either to in-office blood pressure assessment or at-home monitoring.

Methods: This was a multisite randomized controlled trial of postpartum patients diagnosed with a hypertensive disorder of pregnancy before discharge between April 2021 and September 2021 and was performed at two academic training institutions. Patients were randomized to either an in-office blood pressure check or remote monitoring through a web-enabled smartphone platform.

Characterization of renal fibrosis in rats with chronic kidney disease by in vivo tomoelastography.

Chronic kidney disease (CKD) is characterized by structural changes, such as tubular atrophy, renal fibrosis, and glomerulosclerosis, all of which affect the viscoelastic properties of biological tissues. However, detection of renal viscoelasticity changes because diagnostic markers by in vivo elastography lack histopathological validation through animal models. Therefore, we investigated in vivo multiparametric magnetic resonance imaging (mp-MRI), including multifrequency magnetic resonance elastography-based tomoelastography, in the kidneys of 10 rats with adenine-induced CKD and eight healthy controls.

The role of elagolix in the suppression of ovulation in donor oocyte cycles.

Objective: To study the clinical use of elagolix in ovarian stimulation and its effect on premature ovulation in a cohort of women undergoing oocyte donation.

Design: A prospective cohort study with the use of historical controls.

Setting: A private reproductive endocrinology and infertility clinic.

Visualization of Inflammation in Experimental Colitis by Magnetic Resonance Imaging Using Very Small Superparamagnetic Iron Oxide Particles.

Inflammatory bowel diseases (IBD) comprise mainly ulcerative colitis (UC) and Crohn´s disease (CD). Both forms present with a chronic inflammation of the (gastro) intestinal tract, which induces excessive changes in the composition of the associated extracellular matrix (ECM). In UC, the inflammation is limited to the colon, whereas it can occur throughout the entire gastrointestinal tract in CD.

Bare Metal Stents on Resveratrol-Coated Balloons in Porcine Coronary and Peripheral Arteries.

Balloon angioplasty and stent implantation are standard techniques to reopen stenotic vessels. Often, balloons or stents coated with cytostatic drugs are used to prevent re-occlusion of the arteries. Resveratrol, which is known for its numerous beneficial effects on cardiovascular health, is used as an antioxidant additive on paclitaxel-coated balloon catheters.

Contribution of Tissue Inflammation and Blood-Brain Barrier Disruption to Brain Softening in a Mouse Model of Multiple Sclerosis.

Neuroinflammatory processes occurring during multiple sclerosis cause disseminated softening of brain tissue, as quantified by magnetic resonance elastography (MRE). However, inflammation-mediated tissue alterations underlying the mechanical integrity of the brain remain unclear. We previously showed that blood-brain barrier (BBB) disruption visualized by MRI using gadolinium-based contrast agent (GBCA) does not correlate with tissue softening in active experimental autoimmune encephalomyelitis (EAE).

Tailored Magnetic Multicore Nanoparticles for Use as Blood Pool MPI Tracers.

For the preclinical development of magnetic particle imaging (MPI) in general, and the exploration of possible new clinical applications of MPI in particular, tailored MPI tracers with surface properties optimized for the intended use are needed. Here we present the synthesis of magnetic multicore particles (MCPs) modified with polyethylene glycol (PEG) for use as blood pool MPI tracers. To achieve the stealth effect the carboxylic groups of the parent MCP were activated and coupled with pegylated amines (mPEG-amines) with different PEG-chain lengths from 2 to 20 kDa.

Uraemic extracellular vesicles augment osteogenic transdifferentiation of vascular smooth muscle cells via enhanced AKT signalling and PiT-1 expression.

Extracellular vesicles (EV) function as messengers between endothelial cells (EC) and vascular smooth muscle cells (VSMC). Since chronic kidney disease (CKD) increases the risk for vascular calcifications, we investigated whether EV derived from uraemic milieu-stimulated EC and derived from uraemic rats impact the osteogenic transdifferentiation/calcification of VSMC. For that purpose, human EC were treated with urea and indoxyl sulphate or left untreated.

Evaluation of the Physicochemical Properties of the Iron Nanoparticle Drug Products: Brand and Generic Sodium Ferric Gluconate.

Complex iron nanoparticle-based drugs are one of the oldest and most frequently administered classes of nanomedicines. In the US, there are seven FDA-approved iron nanoparticle reference drug products, of which one also has an approved generic drug product (i.e.

Microdistribution of Magnetic Resonance Imaging Contrast Agents in Atherosclerotic Plaques Determined by LA-ICP-MS and SR-μXRF Imaging.

Purpose: Contrast-enhanced magnetic resonance imaging (MRI) has the potential to replace angiographic evaluation of atherosclerosis. While studies have investigated contrast agent (CA) uptake in atherosclerotic plaques, exact CA spatial distribution on a microscale is elusive. The purpose of this study was to investigate the microdistribution of gadolinium (Gd)- and iron (Fe) oxide-based CA in atherosclerotic plaques of New Zealand White rabbits.

Biodegradable Polydioxanone Microspheres for Transcatheter Arterial Embolization: Proof of Principle.

Purpose: To evaluate feasibility, embolization success, biodegradability, reperfusion, and biocompatibility of biodegradable microspheres (MS) made from polydioxanone (PDO) for transcatheter arterial embolization.

Materials And Methods: Unilateral selective renal embolization of a segmental artery was performed in 16 New Zealand White rabbits with PDO-MS (100-150 μm and 90-315 μm). Animals were randomly assigned to different observation periods and underwent control digital subtraction angiography (DSA) and MR imaging immediately (n = 3), 1 week (n = 2), 4 weeks (n = 2), 8 weeks (n = 2), 12 weeks (n = 5), and 16 weeks (n = 2) after embolization.

In vivo magnetic particle imaging: angiography of inferior vena cava and aorta in rats using newly developed multicore particles.

Magnetic Particle Imaging (MPI) is a new imaging modality, which maps the distribution of magnetic nanoparticles (MNP) in 3D with high temporal resolution. It thus may be suited for cardiovascular imaging. Its sensitivity and spatial resolution critically depend on the magnetic properties of MNP.

Hybrid MPI-MRI System for Dual-Modal In Situ Cardiovascular Assessments of Real-Time 3D Blood Flow Quantification-A Pre-Clinical In Vivo Feasibility Investigation.

Non-invasive quantification of functional parameters of the cardiovascular system, in particular the heart, remains very challenging with current imaging techniques. This aspect is mainly due to the fact, that the spatio-temporal resolution of current imaging methods, such as Magnetic Resonance Imaging (MRI) or Positron Emission Tomography (PET), does not offer the desired data repetition rates in the context of real-time data acquisition and thus, can cause artifacts and misinterpretations in accelerated data acquisition approaches. We present a fast non-invasive and quantitative dual-modal in situ cardiovascular assessment using a hybrid imaging system which combines the new imaging modality Magnetic Particle Imaging (MPI) and MRI.

Ex vivo magnetic particle imaging of vascular inflammation in abdominal aortic aneurysm in a murine model.

Abdominal aortic aneurysms (AAAs) are currently one of the leading causes of death in developed countries. Inflammation is crucial in the disease progression, having a substantial impact on various determinants in AAAs development. Magnetic particle imaging (MPI) is an innovative imaging modality, enabling the highly sensitive detection of magnetic nanoparticles (MNPs), suitable as surrogate marker for molecular targeting of vascular inflammation.

Novel MR-Visible, Biodegradable Microspheres for Transcatheter Arterial Embolization: Experimental Study in a Rabbit Renal Model.

Purpose: To assess feasibility, embolization success, biodegradability, reperfusion, biocompatibility and in vivo visibility of novel temporary microspheres (MS) for transcatheter arterial embolization.

Material And Methods: In 9 New Zealand white rabbits unilateral superselective embolization of the lower kidney pole was performed with biodegradable MS made of polydioxanone (PDO) (size range 90-300 and 200-500 µm) impregnated with super-paramagnetic iron oxide (SPIO). Magnetic resonance imaging (MRI) was performed post-interventionally to assess in vivo visibility.

MPI Phantom Study with A High-Performing Multicore Tracer Made by Coprecipitation.

Magnetic particle imaging (MPI) is a new imaging technique that detects the spatial distribution of magnetic nanoparticles (MNP) with the option of high temporal resolution. MPI relies on particular MNP as tracers with tailored characteristics for improvement of sensitivity and image resolution. For this reason, we developed optimized multicore particles (MCP 3) made by coprecipitation via synthesis of green rust and subsequent oxidation to iron oxide cores consisting of a magnetite/maghemite mixed phase.

Resveratrol-Coated Balloon Catheters in Porcine Coronary and Peripheral Arteries.

Angioplasty aiming at vascular dilatation causes endothelial denudation and induces complex inflammatory responses that affect vascular healing, including delayed reendothelialization and excessive neointima proliferation. Resveratrol is known for multiple beneficial effects on the vessel wall after systemic treatment or sustained release from a stent. It is also used as an additive on drug-coated balloon catheters (DCB).

Very small superparamagnetic iron oxide nanoparticles: Long-term fate and metabolic processing in atherosclerotic mice.

We investigated the biotransformation of very small superparamagnetic iron oxide nanoparticles (VSOP) in atherosclerotic LDLR mice. Transmission electron microscopy revealed an uptake of VSOP not only by macrophages but also by endothelial cells in liver, spleen, and atherosclerotic lesions and their accumulation in the lysosomal compartment. Using magnetic particle spectroscopy (MPS), we show that the majority of VSOP's superparamagnetic iron was degraded within 28 days.

Renal Denervation by Transaortic Periarterial Ethanol Injection: An Experimental Study in Porcines.

Aims: To evaluate the feasibility, safety and efficacy of renal sympathetic denervation via endoluminal transaortic periarterial ethanol injection.

Methods And Results: In 11 normotensive pigs transaortic puncture was performed with a 90-cm 21G needle with subsequent unilateral ethanol injection to the periarterial space. Needle placement was achieved using a 7F steerable sheath fluoroscopically positioned slightly above the renal artery origin.

Bioequivalence decision for nanoparticular iron complex drugs for parenteral administration based on their disposition.

Although parenteral iron products have been established to medicinal use decades before, their structure and pharmacokinetic properties are not fully characterized yet. With its' second reflection paper on intravenous iron-based nano-colloidal products (EMA/CHMP/SWP/620008/2012) the European Medicine Agency provided an extensive catalogue of methods for quality, non-clinical and pharmacokinetic studies for the comparison of nano-sized iron products to an originator (EMA, 2015). For iron distribution studies, the reflection paper assumed the use of rodents.

Novel magnetic multicore nanoparticles designed for MPI and other biomedical applications: From synthesis to first in vivo studies.

Synthesis of novel magnetic multicore particles (MCP) in the nano range, involves alkaline precipitation of iron(II) chloride in the presence of atmospheric oxygen. This step yields green rust, which is oxidized to obtain magnetic nanoparticles, which probably consist of a magnetite/maghemite mixed-phase. Final growth and annealing at 90°C in the presence of a large excess of carboxymethyl dextran gives MCP very promising magnetic properties for magnetic particle imaging (MPI), an emerging medical imaging modality, and magnetic resonance imaging (MRI).