Drivers and barriers in the consistency approach for vaccine batch release testing: Report of an international workshop.

Safety and potency assessment for batch release testing of established vaccines still relies partly on animal tests. An important avenue to move to batch release without animal testing is the consistency approach. This approach is based on thorough characterization of the vaccine, and the principle that the quality of subsequent batches is the consequence of the application of consistent production of batches monitored by a GMP quality system.

Local versus global aortic pulse wave velocity in early atherosclerosis: An animal study in ApoE-/--mice using ultrahigh field MRI.

Increased aortic stiffness is known to be associated with atherosclerosis and has a predictive value for cardiovascular events. This study aims to investigate the local distribution of early arterial stiffening due to initial atherosclerotic lesions. Therefore, global and local pulse wave velocity (PWV) were measured in ApoE-/- and wild type (WT) mice using ultrahigh field MRI.

The vaccines consistency approach project: an EPAA initiative.

The consistency approach for release testing of established vaccines promotes the use of in vitro, analytical, non-animal based systems allowing the monitoring of quality parameters during the whole production process. By using highly sensitive non-animal methods, the consistency approach has the potential to improve the quality of testing and to foster the 3Rs (replacement, refinement and reduction of animal use) for quality control of established vaccines. This concept offers an alternative to the current quality control strategy which often requires large numbers of laboratory animals.

Local arterial stiffening assessed by MRI precedes atherosclerotic plaque formation.

Background: Atherosclerosis is known to impair vascular function and cause vascular stiffening. The aim of this study was to evaluate the potential predictive role of vascular stiffening in the early detection of atherosclerosis. Therefore, we investigated the time course of early functional and morphological alterations of the vessel wall in a murine atherosclerosis model.

Regional in vivo transit time measurements of aortic pulse wave velocity in mice with high-field CMR at 17.6 Tesla.

Background: Transgenic mouse models are increasingly used to study the pathophysiology of human cardiovascular diseases. The aortic pulse wave velocity (PWV) is an indirect measure for vascular stiffness and a marker for cardiovascular risk.

Results: This study presents a cardiovascular magnetic resonance (CMR) transit time (TT) method that allows the determination of the PWV in the descending murine aorta by analyzing blood flow waveforms.

Intracellular and extracellular T1 and T2 relaxivities of magneto-optical nanoparticles at experimental high fields.

This study reports the T(1) and T(2) relaxation rates of rhodamine-labeled anionic magnetic nanoparticles determined at 7, 11.7, and 17.6 T both in solution and after cellular internalization.

In vivo measurement of local aortic pulse-wave velocity in mice with MR microscopy at 17.6 Tesla.

Transgenic mouse models of human diseases have gained increasing importance in the pathophysiology of cardiovascular diseases (CVD). As an indirect measure of vascular stiffness, aortic pulse-wave velocity (PWV) is an important predictor of cardiovascular risk. This study presents an MRI approach that uses a flow area method to estimate local aortic pulse-wave velocity at different sites in the murine aorta.

Murine atherosclerotic plaque imaging with the USPIO Ferumoxtran-10.

In this study we intended to image plaque inflammation in a murine model of atherosclerosis with MRI and Ferumoxtran-10 (Sinerem, Guerbet, France). 8 apoE-/- mice were injected 500 micromol Fe/kg or 1000 micromol Fe/kg Ferumoxtran-10. 2 apoE-/- mice were injected NaCl.

In vivo comparison of atherosclerotic plaque progression with vessel wall strain and blood flow velocity in apoE(-/-) mice with MR microscopy at 17.6 T.

Object: At present, in vivo plaque characterization in mice by MRI is typically limited to the visualization of vascular lesions with no accompanying analysis of vessel wall function. The aim of this study was to analyze the influence of atherosclerotic plaque development on the morphological and mechanical characteristics of the aortic vessel wall in a pre-clinical murine model of atherosclerosis.

Materials And Methods: Groups of apolipoprotein E-deficient (apoE(-/-)) and C57BL/6J control mice fed a high-fat diet were monitored over a 12-week time period by high-field MRI.

Control of susceptibility-related image contrast by spin-lock techniques.

Macroscopic magnetic field inhomogeneities might lead to image distortions, while microscopic field inhomogeneities, due to susceptibility changes in tissues, cause spin dephasing and decreasing T(2)() relaxation time. The latter effects are especially observed in the trabecular bone and in regions adjacent to air-containing cavities when gradient-echo sequences are applied. In conventional MRI, these susceptibility-related signal voids can be avoided by applying spin-echo (SE) techniques.

Functional assessment of isolated right heart failure by high resolution in-vivo cardiovascular magnetic resonance in mice.

Precise and noninvasive characterization of the development of the cardiac phenotype in murine models of heart failure has been widely demanded in modern cardiovascular research. High-resolution cardiovascular magnetic resonance (CMR) has been proven to be a powerful tool for the accurate and reproducible assessment of LV and RV parameters in healthy mice. Whereas changes in LV parameters in models of heart failure have been thoroughly evaluated, RV dysfunction has not.

In vivo quantitative three-dimensional motion mapping of the murine myocardium with PC-MRI at 17.6 T.

This work presents a method that allows for the assessment of 3D murine myocardial motion in vivo at microscopic resolution. Phase-contrast (PC) magnetic resonance imaging (MRI) at 17.6 T was applied to map myocardial motion in healthy mice along three gradient directions.

Primary semi-constrained arthroplasty for chronic fracture-dislocations of the elbow.

We present six patients with chronic dislocation of the elbow who were treated by primary semiconstrained total elbow arthroplasty. All were women with a mean age of 65 years (51 to 76), the mean interval between dislocation and surgery was 17 weeks (5 to 52) and the mean follow-up 58 months (24 to 123). The most dramatic improvement was in function.

In vivo assessment of absolute perfusion and intracapillary blood volume in the murine myocardium by spin labeling magnetic resonance imaging.

The absolute perfusion and the intracapillary or regional blood volume (RBV) in murine myocardium were assessed in vivo by spin labeling magnetic resonance imaging. Pixel-based perfusion and RBV maps were calculated at a pixel resolution of 469 x 469 mum and a slice thickness of 2 mm. The T(1) imaging module was a segmented inversion recovery snapshot fast low angle shot sequence with velocity compensation in all three gradient directions.

High-resolution MRI with cardiac and respiratory gating allows for accurate in vivo atherosclerotic plaque visualization in the murine aortic arch.

Genetically engineered mouse models provide enormous potential for investigation of the underlying mechanisms of atherosclerotic disease, but noninvasive imaging methods for analysis of atherosclerosis in mice are currently limited. This study aimed to demonstrate the feasibility of MRI to noninvasively visualize atherosclerotic plaques in the thoracic aorta in mice deficient in apolipoprotein-E, who develop atherosclerotic lesions similar to those observed in humans. To freeze motion, MR data acquisition was both ECG- and respiratory-gated.

In vivo time-resolved quantitative motion mapping of the murine myocardium with phase contrast MRI.

Myocardial motion of healthy mice and mice with myocardial infarction was assessed in vivo by phase contrast (PC) cine MRI. The imaging module was a segmented fast low angle shot (FLASH) sequence with velocity compensation in all three gradient directions. To accomplish additional motion encoding, the spin phase was prepared using bipolar gradient pulses, which resulted in a linear dependence between the voxel velocity and spin phase.

In vivo assessment of absolute perfusion in the murine skeletal muscle with spin labeling MRI. Magnetic resonance imaging.

Purpose: To assess absolute perfusion in the skeletal muscle of mice in vivo with spin labeling magnetic resonance imaging (MRI) under normal and stress conditions.

Materials And Methods: Absolute perfusion in the skeletal muscle of 27 C57BL/6 mice was assessed in vivo non-invasively by spin labeling MRI at 7.05 T.

Analysis of right ventricular function in healthy mice and a murine model of heart failure by in vivo MRI.

Because of its complex geometry, assessment of right ventricular (RV) function is more difficult than it is for the left ventricle (LV). Because gene-targeted mouse models of cardiomyopathy may involve remodeling of the right heart, the purpose of this study was to develop high-resolution functional magnetic resonance imaging (MRI) for in vivo quantification of RV volumes and global function in mice. Thirty-three mice of various age were studied under isoflurane anesthesia by electrocardiogram-triggered cine-MRI at 7 T.

Dobutamine-stress magnetic resonance microimaging in mice : acute changes of cardiac geometry and function in normal and failing murine hearts.

The aim of this study was to assess the capability of MRI to characterize systolic and diastolic function in normal and chronically failing mouse hearts in vivo at rest and during inotropic stimulation. Applying an ECG-gated FLASH-cine sequence, MRI at 7 T was performed at rest and after administration of 1.5 microgram/g IP dobutamine.

Developmental changes of cardiac function and mass assessed with MRI in neonatal, juvenile, and adult mice.

Cardiovascular transgenic mouse models with an early phenotype or even premature death require noninvasive imaging methods that allow for accurate visualization of cardiac morphology and function. Thus the purpose of our study was to assess the feasibility of magnetic resonance imaging (MRI) to characterize cardiac function and mass in newborn, juvenile, and adult mice. Forty-five C57bl/6 mice from seven age groups (3 days to 4 mo after birth) were studied by MRI under isoflurane anesthesia.

Beyond k-space: spectral localization using higher order gradients.

Chemical shift imaging (CSI) often suffers from the inconvenient shape of its spatial response function (SRF), which affects both localization and signal-to-noise ratio. Replacing the magnetic field gradients for phase encoding by higher order magnetic fields allows a better adjustment of the SRF to the structures in the sample. We combined this principle with the SLOOP (spectral localization with optimal pointspread function) technique to simultaneously obtain spectra from several arbitrarily shaped compartments within a sample.