Fitting prelingually deafened adult cochlear implant users based on electrode discrimination performance.

Objective: This study investigated the hypotheses that (1) prelingually deafened CI users do not have perfect electrode discrimination ability and (2) the deactivation of non-discriminable electrodes can improve auditory performance.

Design: Electrode discrimination difference limens were determined for all electrodes of the array. The subjects' basic map was subsequently compared to an experimental map, which contained only discriminable electrodes, with respect to speech understanding in quiet and in noise, listening effort, spectral ripple discrimination and subjective appreciation.

Molecular imaging of angiogenesis after myocardial infarction by (111)In-DTPA-cNGR and (99m)Tc-sestamibi dual-isotope myocardial SPECT.

Background: CD13 is selectively upregulated in angiogenic active endothelium and can serve as a target for molecular imaging tracers to non-invasively visualise angiogenesis in vivo. Non-invasive determination of CD13 expression can potentially be used to monitor treatment response to pro-angiogenic drugs in ischemic heart disease. CD13 binds peptides and proteins through binding to tripeptide asparagine-glycine-arginine (NGR) amino acid residues.

Plaque-associated vasa vasorum in aged apolipoprotein E-deficient mice exhibit proatherogenic functional features in vivo.

Objective: Neovascularization of human atherosclerotic plaques is implicated in plaque progression and destabilization, although its functional implications are yet unresolved. Here, we aimed to elucidate functional and morphological properties of plaque microvessels in mice in vivo.

Methods And Results: Atherosclerotic carotid arteries from aged (>40 weeks) apolipoprotein E-deficient mice were imaged in vivo using multiphoton laser scanning microscopy.

CD36 inhibition prevents lipid accumulation and contractile dysfunction in rat cardiomyocytes.

An increased cardiac fatty acid supply and increased sarcolemmal presence of the long-chain fatty acid transporter CD36 are associated with and contribute to impaired cardiac insulin sensitivity and function. In the present study we aimed at preventing the development of insulin resistance and contractile dysfunction in cardiomyocytes by blocking CD36-mediated palmitate uptake. Insulin resistance and contractile dysfunction were induced in primary cardiomyocytes by 48 h incubation in media containing either 100 nM insulin (high insulin; HI) or 200 μM palmitate (high palmitate; HP).

Optical molecular imaging of atherosclerosis using nanoparticles: shedding new light on the darkness.

The application of optical nanoparticles in cardiovascular research is increasing because of the high spatiotemporal resolution and high sensitivity of optical techniques as compared with other imaging platforms. The major cause of cardiovascular events is atherosclerosis, which is a chronic inflammation of the arterial wall. Interestingly, the composition rather than the size of nonstenotic atherosclerotic plaques and severe plaques with >90% stenosis are indicators for high-risk vulnerability to rupture and acute cardiovascular events.

Gadolinium-labeled quantum dots for molecular magnetic resonance imaging: R1 versus R2 mapping.

Quantum dots labeled with paramagnetic gadolinium chelates can be applied as contrast agent for preclinical molecular MRI combined with fluorescence microscopy. Besides increasing the longitudinal relaxation rate, gadolinium-labeled quantum dots may increase the transverse relaxation rate, which might be related to their magnetic properties. Furthermore, molecular MRI experiments are primarily conducted at high magnetic fields, where longitudinal relaxation rate becomes less effective, and the use of transverse relaxation rate as a source of contrast may become attractive.

Evaluation of magnetic resonance vessel size imaging by two-photon laser scanning microscopy.

MR vessel size imaging (MR-VSI) is increasingly applied to noninvasively assess microvascular properties of tumors and to evaluate tumor response to antiangiogenic treatment. MR-VSI provides measures for the microvessel radius and fractional blood volume of tumor tissue. However, data have not yet been evaluated with three-dimensional microscopy techniques.

Molecular magnetic resonance imaging of myocardial angiogenesis after acute myocardial infarction.

Background: Angiogenesis is a natural mechanism to restore perfusion to the ischemic myocardium after acute myocardial infarction (MI). Therapeutic angiogenesis is being explored as a novel treatment for MI patients; however, sensitive, noninvasive in vivo measures of therapeutic efficacy are lacking and need to be developed. Here, a molecular magnetic resonance imaging method is presented to noninvasively image angiogenic activity in vivo in a murine model of MI with cyclic Asn-Gly-Arg (cNGR)-labeled paramagnetic quantum dots (pQDs).

Pharmacokinetics of contrast agents targeted to the tumor vasculature in molecular magnetic resonance imaging.

Molecular magnetic resonance imaging (MRI) is increasingly used to investigate tumor angiogenic activity non-invasively. However, the pharmacokinetic behavior and tumor penetration of the often large contrast agent particles is thus far unknown. Here, pharmacokinetic analysis of cyclic asparagine-glycine-arginine (cNGR) labeled paramagnetic quantum dots (pQDs) was developed to quantify the contrast agent's homing efficacy to activated endothelial cells of angiogenic tumor vessels using dynamic contrast-enhanced (DCE) MRI.

Nanoparticles for optical molecular imaging of atherosclerosis.

Molecular imaging contributes to future personalized medicine dedicated to the treatment of cardiovascular disease, the leading cause of mortality in industrialized countries. Endoscope-compatible optical imaging techniques would offer a stand-alone alternative and high spatial resolution validation technique to clinically accepted imaging techniques in the (intravascular) assessment of vulnerable atherosclerotic lesions, which are predisposed to initiate acute clinical events. Efficient optical visualization of molecular epitopes specific for vulnerable atherosclerotic lesions requires targeting of high-quality optical-contrast-enhancing particles.

Quantitative molecular magnetic resonance imaging of tumor angiogenesis using cNGR-labeled paramagnetic quantum dots.

The objective of this study was to develop and apply cyclic Asn-Gly-Arg (cNGR)-labeled paramagnetic quantum dots (cNGR-pQDs) for the noninvasive assessment of tumor angiogenic activity using quantitative in vivo molecular magnetic resonance imaging (MRI). cNGR was previously shown to colocalize with CD13, an aminopeptidase that is highly overexpressed on angiogenic tumor endothelium. Because angiogenesis is important for tumor growth and metastatization, its in vivo detection and quantification may allow objective diagnosis of tumor status and evaluation of treatment response.

Imaging the hypoxia surrogate marker CA IX requires expression and catalytic activity for binding fluorescent sulfonamide inhibitors.

Background And Purpose: Carbonic anhydrase (CA) IX expression is increased in response to hypoxia. Recently, sulfonamide based carbonic anhydrase inhibitors (CAI) showing specificity for CA IX have been designed. Aim was to investigate the CAI binding properties under normoxia, hypoxia and reoxygenation.

Two-photon lifetime imaging of fluorescent probes in intact blood vessels: a window to sub-cellular structural information and binding status.

Fluorescence lifetime imaging (FLIM) provides a complementary contrast mechanism to fluorescence intensity and ratio imaging in intact tissue. With FLIM the time-resolved decay in fluorescence intensity of (interacting) fluorophores can be quantified by means of time correlated single photon counting (TCSPC). Here we focus on fluorescence lifetime imaging in intact blood vessels.

Optical and magnetic resonance imaging of cell death and platelet activation using annexin a5-functionalized quantum dots.

A quantum-dot-based nanoparticle is presented, allowing visualization of cell death and activated platelets with fluorescence imaging and MRI. The particle exhibits intense fluorescence and a large MR relaxivity (r1) of 3000-4500 mM-1 s-1 per nanoparticle due to a newly designed construct increasing the gadolinium-DTPA load. The nanoparticle is suitable for both anatomic and subcellular imaging of structures in the vessel wall and is a promising bimodal contrast agent for future in vivo imaging studies.

Liposome-enhanced MRI of neointimal lesions in the ApoE-KO mouse.

Conventional high-resolution MRI is capable of detecting lipid-rich atherosclerotic plaques in both human atherosclerosis and animal models of atherosclerosis. In this study we induced neointimal lesions in ApoE-KO mice by placing a constrictive collar around the right carotid artery. The model was imaged with conventional multispectral MRI, and the thickened wall could not be distinguished from surrounding tissue.

Two-photon microscopy for imaging of the (atherosclerotic) vascular wall: a proof of concept study.

Background: Understanding atherogenesis will benefit significantly from simultaneous imaging, both ex vivo and in vivo, of structural and functional information at the (sub)cellular level within intact arteries. Due to limited penetration depth and loss of resolution with depth, intravital and confocal fluorescence microscopy are not suitable to study (sub)cellular details in arteries with wall thicknesses above 50 microm.

Methods: Using two-photon laser scanning microscopy (TPLSM), which combines 3D resolution and large penetration depth, we imaged mouse carotid arteries.