Hyperperfusion profiles after recanalization differentially associate with outcomes in a rat ischemic stroke model.

Futile recanalization hampers prognoses of ischemic stroke after successful mechanical thrombectomy, hypothetically through post-recanalization perfusion deficits, onset-to-groin delays and sex effects. Clinically, acute multiparametric imaging studies remain challenging. We assessed possible relationships between these factors and disease outcome after experimental cerebral ischemia-reperfusion, using translational MRI, behavioral testing and multi-model inference analyses.

imaging of cerebral glucose metabolism informs on subacute to chronic post-stroke tissue status - A pilot study combining PET and deuterium metabolic imaging.

Recanalization therapy after acute ischemic stroke enables restoration of cerebral perfusion. However, a significant subset of patients has poor outcome, which may be caused by disruption of cerebral energy metabolism. To assess changes in glucose metabolism subacutely and chronically after recanalization, we applied two complementary imaging techniques, fluorodeoxyglucose (FDG) positron emission tomography (PET) and deuterium (H) metabolic imaging (DMI), after 60-minute transient middle cerebral artery occlusion (tMCAO) in C57BL/6 mice.

Prolonged release of VEGF and Ang1 from intralesionally implanted hydrogel promotes perilesional vascularization and functional recovery after experimental ischemic stroke.

Injectable hydrogels can generate and support pro-repair environments in injured tissue. Here we used a slow-releasing drug carrying -forming hydrogel to promote post-stroke recovery in a rat model. Release kinetics were measured and with MRI, using gadolinium-labeled albumin (Galbumin), which demonstrated prolonged release over multiple weeks.

Magnetic resonance imaging of local and remote vascular remodelling after experimental stroke.

The pattern of vascular remodelling in relation to recovery after stroke remains largely unclear. We used steady-state contrast-enhanced magnetic resonance imaging to assess the development of cerebral blood volume and microvascular density in perilesional and exofocal areas from (sub)acutely to chronically after transient stroke in rats. Microvascular density was verified histologically after infusion with Evans Blue dye.

PECAM-1-targeted micron-sized particles of iron oxide as MRI contrast agent for detection of vascular remodeling after cerebral ischemia.

An increasing amount of studies have provided evidence for vascular remodeling, for example, angiogenesis, after cerebral ischemia, which may play a significant role in post-stroke brain plasticity and recovery. Molecular imaging can provide unique in vivo whole-brain information on alterations in the expression of specific endothelial markers. A possible target for molecular magnetic resonance imaging (MRI) of post-stroke (neo)vascularization is platelet endothelial cell adhesion molecule-1 (PECAM-1).

MRI of ICAM-1 upregulation after stroke: the importance of choosing the appropriate target-specific particulate contrast agent.

Purpose: Magnetic resonance imaging (MRI) with targeted contrast agents provides a promising means for diagnosis and treatment monitoring after cerebrovascular injury. Our goal was to demonstrate the feasibility of this approach to detect the neuroinflammatory biomarker intercellular adhesion molecule-1 (ICAM-1) after stroke and to establish a most efficient imaging procedure.

Procedures: We compared two types of ICAM-1-functionalized contrast agent: T 1-shortening gadolinium chelate-containing liposomes and T2(*)-shortening micron-sized iron oxide particles (MPIO).

Nanoclusters of iron oxide: effect of core composition on structure, biocompatibility, and cell labeling efficacy.

Inorganic nanocrystals have a variety of applications in medicine. They may serve as contrast agents, therapeutics, and for in vitro diagnostics. Frequently, the synthesis route yields hydrophobically capped nanocrystals, which necessitates their subsequent coating to render a water-soluble and biocompatible probe.

Imaging neuroinflammation after stroke: current status of cellular and molecular MRI strategies.

Cellular and molecular magnetic resonance imaging (MRI) strategies for studying the spatiotemporal profile of neuroinflammatory processes after stroke are increasingly being explored since the first reports appeared about a decade ago. These strategies most often employ (super)paramagnetic contrast agents, such as (ultra)small particles of iron oxide and gadolinium chelates, for MRI-based detection of specific leukocyte populations or molecular inflammatory markers that are involved in the pathophysiology of stroke or plasticity. In this review we describe achievements, limitations and prospects in the field of cellular and molecular MRI of neuroinflammation in preclinical and clinical stroke.

Molecular MRI of Inflammation in Atherosclerosis.

Inflammatory activity in atherosclerotic plaque is a risk factor for plaque rupture and atherothrombosis and may direct interventional therapy. Inflammatory activity can be evaluated at the (sub)cellular level using in vivo molecular MRI. This paper reviews recent progress in contrast-enhanced molecular MRI to visualize atherosclerotic plaque inflammation.

Annexin A5-functionalized bimodal nanoparticles for MRI and fluorescence imaging of atherosclerotic plaques.

Apoptosis and macrophage burden are believed to correlate with atherosclerotic plaque vulnerability and are therefore considered important diagnostic and therapeutic targets for atherosclerosis. These cell types are characterized by the exposure of phosphatidylserine (PS) at their surface. In the present study, we developed and applied a small micellar fluorescent annexin A5-functionalized nanoparticle for noninvasive magnetic resonance imaging (MRI) of PS exposing cells in atherosclerotic lesions.

Paramagnetic and fluorescent liposomes for target-specific imaging and therapy of tumor angiogenesis.

Angiogenesis is essential for tumor growth and metastatic potential and for that reason considered an important target for tumor treatment. Noninvasive imaging technologies, capable of visualizing tumor angiogenesis and evaluating the efficacy of angiostatic therapies, are therefore becoming increasingly important. Among the various imaging modalities, magnetic resonance imaging (MRI) is characterized by a superb spatial resolution and anatomical soft-tissue contrast.

Current applications of nanotechnology for magnetic resonance imaging of apoptosis.

Apoptosis, or programmed cell death, is a morphologically and biochemically distinct form of cell death, which together with proliferation plays an important role in tissue development and homeostasis. Insufficient apoptosis is important in the pathology of various disorders such as cancer and autoimmune diseases, whereas a high apoptotic activity is associated with myocardial infarction, neurodegenerative diseases, and advanced atherosclerotic lesions. Consequently, apoptosis is recognized as an important therapeutic target, which should be either suppressed, e.

RGD peptide functionalized and reconstituted high-density lipoprotein nanoparticles as a versatile and multimodal tumor targeting molecular imaging probe.

High density lipoprotein (HDL), an endogenous nanoparticle, transports fat throughout the body and is capable of transferring cholesterol from atheroma in the vessel wall to the liver. In the present study, we utilized HDL as a multimodal nanoparticle platform for tumor targeting and imaging via nonspecific accumulation and specific binding to angiogenically activated blood vessels. We reconstituted HDL (rHDL) with amphiphilic gadolinium chelates and fluorescent dyes.

Nanoparticulate assemblies of amphiphiles and diagnostically active materials for multimodality imaging.

Modern medicine has greatly benefited from recent dramatic improvements in imaging techniques. The observation of physiological events through interactions manipulated at the molecular level offers unique insight into the function (and dysfunction) of the living organism. The tremendous advances in the development of nanoparticulate molecular imaging agents over the past decade have made it possible to noninvasively image the specificity, pharmacokinetic profiles, biodistribution, and therapeutic efficacy of many novel compounds.

Internalization of annexin A5-functionalized iron oxide particles by apoptotic Jurkat cells.

Apoptosis plays an important role in the etiology of various diseases. Several studies have reported on the use of annexin A5-functionalized iron oxide particles for the detection of apoptosis with MRI, both in vitro and in vivo. The protein annexin A5 binds with high affinity to the phospholipid phosphatidylserine, which is exposed in the outer leaflet of the apoptotic cell membrane.

Improved magnetic resonance molecular imaging of tumor angiogenesis by avidin-induced clearance of nonbound bimodal liposomes.

Angiogenic, that is, newly formed, blood vessels play an important role in tumor growth and metastasis and are a potential target for tumor treatment. In previous studies, the alpha(v)beta(3) integrin, which is strongly expressed in angiogenic vessels, has been used as a target for Arg-Gly-Asp (RGD)-functionalized nanoparticulate contrast agents for magnetic resonance imaging-based visualization of angiogenesis. In the present study, the target-to-background ratio was increased by diminishing the nonspecific contrast enhancement originating from contrast material present in the blood pool.

Kinetics of avidin-induced clearance of biotinylated bimodal liposomes for improved MR molecular imaging.

Dual labeled liposomes, carrying both paramagnetic and fluorescent lipids, were recently proposed as potent contrast agents for MR molecular imaging. These nanoparticles are coated with poly(ethylene glycol) (PEG) to increase their blood circulation half-life, which should allow extensive accumulation at the targeted site. To eliminate nonspecific blood pool signal from the MR images, the circulating liposomes should ideally be cleared from the circulation when sufficient target-specific contrast enhancement is obtained.

MRI contrast agents: current status and future perspectives.

Magnetic Resonance Imaging (MRI) is increasingly used in clinical diagnostics, for a rapidly growing number of indications. The MRI technique is non-invasive and can provide information on the anatomy, function and metabolism of tissues in vivo. MRI scans of tissue anatomy and function make use of the two hydrogen atoms in water to generate the image.

Annexin A5-conjugated quantum dots with a paramagnetic lipidic coating for the multimodal detection of apoptotic cells.

Apoptosis, or programmed cell death, plays an important role in the etiology of a variety of diseases, including cancer. Visualization of apoptosis would allow both early detection of therapy efficiency and evaluation of disease progression. To that aim we developed a novel annexin A5-conjugated bimodal nanoparticle.

Annexin A5-functionalized bimodal lipid-based contrast agents for the detection of apoptosis.

Apoptosis, or programmed cell death, plays an important role in the etiology of a variety of diseases, including cancer and myocardial infarction. Visualization of apoptosis would allow both early detection of therapy efficiency and evaluation of disease progression. To that aim, we synthesized two types of lipid-based bimodal contrast agents that enable the detection of apoptotic cells with both MRI and optical techniques.

Lipid-based nanoparticles for contrast-enhanced MRI and molecular imaging.

In the field of MR imaging and especially in the emerging field of cellular and molecular MR imaging, flexible strategies to synthesize contrast agents that can be manipulated in terms of size and composition and that can be easily conjugated with targeting ligands are required. Furthermore, the relaxivity of the contrast agents, especially for molecular imaging applications, should be very high to deal with the low sensitivity of MRI. Lipid-based nanoparticles, such as liposomes or micelles, have been used extensively in recent decades as drug carrier vehicles.