Regional contrast agent quantification in a mouse model of myocardial infarction using 3D cardiac T1 mapping

<p>Abstract</p> <p>Background</p> <p>Quantitative relaxation time measurements by cardiovascular magnetic resonance (CMR) are of paramount importance in contrast-enhanced studies of experimental myocardial infarction. First, compared to qualitative measurements based on signal intensity changes, they are less sensitive to specific parameter choices, thereby allowing for better comparison between different studies or during longitudinal studies. Secondly, T₁measurements may allow for quantification of local contrast agent concentrations. In this study, a recently developed 3D T₁mapping technique was applied in a mouse model of myocardial infarction to measure differences in myocardial T₁before and after injection of a liposomal contrast agent. This was then used to assess the concentration of accumulated contrast agent.</p> <p>Materials and methods</p> <p>Myocardial ischemia/reperfusion injury was induced in 8 mice by transient ligation of the LAD coronary artery. Baseline quantitative T₁maps were made at day 1 after surgery, followed by injection of a Gd-based liposomal contrast agent. Five mice served as control group, which followed the same protocol without initial surgery. Twenty-four hours post-injection, a second T₁measurement was performed. Local ΔR₁values were compared with regional wall thickening determined by functional cine CMR and correlated to <it>ex vivo </it>Gd concentrations determined by ICP-MS.</p> <p>Results</p> <p>Compared to control values, pre-contrast T₁of infarcted myocardium was slightly elevated, whereas T₁of remote myocardium did not significantly differ. Twenty-four hours post-contrast injection, high ΔR₁values were found in regions with low wall thickening values. However, compared to remote tissue (wall thickening > 45%), ΔR₁was only significantly higher in severe infarcted tissue (wall thickening < 15%). A substantial correlation (<it>r </it>= 0.81) was found between CMR-based ΔR₁values and Gd concentrations from <it>ex vivo </it>ICP-MS measurements. Furthermore, regression analysis revealed that the effective relaxivity of the liposomal contrast agent was only about half the value determined <it>in vitro</it>.</p> <p>Conclusions</p> <p>3D cardiac T₁mapping by CMR can be used to monitor the accumulation of contrast agents in contrast-enhanced studies of murine myocardial infarction. The contrast agent relaxivity was decreased under <it>in vivo </it>conditions compared to <it>in vitro </it>measurements, which needs consideration when quantifying local contrast agent concentrations.</p

Switching on the Lights for Gene Therapy

Strategies for non-invasive and quantitative imaging of gene expression in vivo have been developed over the past decade. Non-invasive assessment of the dynamics of gene regulation is of interest for the detection of endogenous disease-specific biological alterations (e.g., signal transduction) and for monitoring the induction and regulation of therapeutic genes (e.g., gene therapy). To demonstrate that non-invasive imaging of regulated expression of any type of gene after in vivo transduction by versatile vectors is feasible, we generated regulatable herpes simplex virus type 1 (HSV-1) amplicon vectors carrying hormone (mifepristone) or antibiotic (tetracycline) regulated promoters driving the proportional co-expression of two marker genes. Regulated gene expression was monitored by fluorescence microscopy in culture and by positron emission tomography (PET) or bioluminescence (BLI) in vivo. The induction levels evaluated in glioma models varied depending on the dose of inductor. With fluorescence microscopy and BLI being the tools for assessing gene expression in culture and animal models, and with PET being the technology for possible application in humans, the generated vectors may serve to non-invasively monitor the dynamics of any gene of interest which is proportionally co-expressed with the respective imaging marker gene in research applications aiming towards translation into clinical application

Personalized Feedback on Staff Dose in Fluoroscopy-Guided Interventions: A New Era in Radiation Dose Monitoring

Radiation safety and protection are a key component of fluoroscopy-guided interventions. We hypothesize that providing weekly personal dose feedback will increase radiation awareness and ultimately will lead to optimized behavior. Therefore, we designed and implemented a personalized feedback of procedure and personal doses for medical staff involved in fluoroscopy-guided interventions. Medical staff (physicians and technicians, n = 27) involved in fluoroscopy-guided interventions were equipped with electronic personal dose meters (PDMs). Procedure dose data including the dose area product and effective doses from PDMs were prospectively monitored for each consecutive procedure over an 8-month period (n = 1082). A personalized feedback form was designed displaying for each staff individually the personal dose per procedure, as well as relative and cumulative doses. This study consisted of two phases: (1) 1-5th months: Staff did not receive feedback (n = 701) and (2) 6-8th months: Staff received weekly individual dose feedback (n = 381). An anonymous evaluation was performed on the feedback and occupational dose. Personalized feedback was scored valuable by 76% of the staff and increased radiation dose awareness for 71%. 57 and 52% reported an increased feeling of occupational safety and changing their behavior because of personalized feedback, respectively. For technicians, the normalized dose was significantly lower in the feedback phase compared to the prefeedback phase: [median (IQR) normalized dose (phase 1) 0.12 (0.04-0.50) A mu Sv/Gy cm(2) versus (phase 2) 0.08 (0.02-0.24) A mu Sv/Gy cm(2), p = 0.002]. Personalized dose feedback increases radiation awareness and safety and can be provided to staff involved in fluoroscopy-guided interventions

Switching on the Lights for Gene Therapy

Strategies for non-invasive and quantitative imaging of gene expression in vivo have been developed over the past decade. Non-invasive assessment of the dynamics of gene regulation is of interest for the detection of endogenous disease-specific biological alterations (e.g., signal transduction) and for monitoring the induction and regulation of therapeutic genes (e.g., gene therapy). To demonstrate that non-invasive imaging of regulated expression of any type of gene after in vivo transduction by versatile vectors is feasible, we generated regulatable herpes simplex virus type 1 (HSV-1) amplicon vectors carrying hormone (mifepristone) or antibiotic (tetracycline) regulated promoters driving the proportional co-expression of two marker genes. Regulated gene expression was monitored by fluorescence microscopy in culture and by positron emission tomography (PET) or bioluminescence (BLI) in vivo. The induction levels evaluated in glioma models varied depending on the dose of inductor. With fluorescence microscopy and BLI being the tools for assessing gene expression in culture and animal models, and with PET being the technology for possible application in humans, the generated vectors may serve to non-invasively monitor the dynamics of any gene of interest which is proportionally co-expressed with the respective imaging marker gene in research applications aiming towards translation into clinical application

Research data

Research data on radiation safety of ultraportable X-ray systems for TB screenin

Targeting of ICAM-1 on vascular endothelium under static and shear stress conditions using a liposomal Gd-based MRI contrast agent

Contains fulltext : 109692.pdf (publisher's version ) (Open Access)ABSTRACT: BACKGROUND: The upregulation of intercellular adhesion molecule-1 (ICAM-1) on the endothelium of bloodvessels in response to pro-inflammatory stimuli is of major importance for the regulation oflocal inflammation in cardiovascular diseases such as atherosclerosis, myocardial infarctionand stroke. In vivo molecular imaging of ICAM-1 will improve diagnosis and follow-up ofpatients by non-invasive monitoring of the progression of inflammation. RESULTS: A paramagnetic liposomal contrast agent functionalized with anti-ICAM-1 antibodies formultimodal magnetic resonance imaging (MRI) and fluorescence imaging of endothelialICAM-1 expression is presented. The ICAM-1-targeted liposomes were extensivelycharacterized in terms of size, morphology, relaxivity and the ability for binding to ICAM-1-expressing endothelial cells in vitro. ICAM-1-targeted liposomes exhibited strong binding toendothelial cells that depended on both the ICAM-1 expression level and the concentration ofliposomes. The liposomes had a high longitudinal and transversal relaxivity, which enableddifferentiation between basal and upregulated levels of ICAM-1 expression by MRI. Theliposome affinity for ICAM-1 was preserved in the competing presence of leukocytes andunder physiological flow conditions. CONCLUSION: This liposomal contrast agent displays great potential for in vivo MRI of inflammation-relatedICAM-1 expression

Internalization of paramagnetic phosphatidylserine-containing liposomes by macrophages

Abstract Background Inflammation plays an important role in many pathologies, including cardiovascular diseases, neurological conditions and oncology, and is considered an important predictor for disease progression and outcome. In vivo imaging of inflammatory cells will improve diagnosis and provide a read-out for therapy efficacy. Paramagnetic phosphatidylserine (PS)-containing liposomes were developed for magnetic resonance imaging (MRI) and confocal microscopy imaging of macrophages. These nanoparticles also provide a platform to combine imaging with targeted drug delivery. Results Incorporation of PS into liposomes did not affect liposomal size and morphology up to 12 mol% of PS. Liposomes containing 6 mol% of PS showed the highest uptake by murine macrophages, while only minor uptake was observed in endothelial cells. Uptake of liposomes containing 6 mol% of PS was dependent on the presence of Ca2+ and Mg2+. Furthermore, these 6 mol% PS-containing liposomes were mainly internalized into macrophages, whereas liposomes without PS only bound to the macrophage cell membrane. Conclusions Paramagnetic liposomes containing 6 mol% of PS for MR imaging of macrophages have been developed. In vitro these liposomes showed specific internalization by macrophages. Therefore, these liposomes might be suitable for in vivo visualization of macrophage content and for (visualization of) targeted drug delivery to inflammatory cells.</p

The right touch:design of artificial antigen-presenting cells to stimulate the immune system

\u3cp\u3eWith the ever expanding possibilities to build supramolecular structures, chemists are challenged to mimic nature including the construction of artificial cells or functions thereof. Within the field of immunology, effective immunotherapy critically depends on efficient production of antigen-specific cytotoxic T-cells. Herein lies an opportunity for chemists to design and synthesize so-called artificial antigen presenting cells (aAPCs) that can promote T-cell activation and their subsequent expansion. In this review we discuss the current status of aAPC development, also focusing on developments in nanoscience which might improve future designs. As synthetic mimics of natural antigen-presenting cells, aAPCs encompass three basic signals required for T-cell activation: MHC-antigen complexes, costimulatory molecules and soluble immune modulating compounds. Both spatial and temporal organization of these signals during aAPC/T-cell contact is important for efficient T-cell activation. We discuss how signals have been incorporated in several aAPC designs, but also how physical properties such as size and shape are essential for targeting the aAPCs to T-cell rich areas in vivo.\u3c/p\u3