HighlightsActive immunotherapy is promising for the development of potent cancer therapeutics.Various types of artificial antigen-presenting cells (aAPCs) may be used as ‘off-the-shelf’ products to induce antigen-specific T cell activation both ex vivo and in vivo.Size, shape, cytokine delivery mechanism, ligand composition, ligand mobility, and ligand positioning on aAPCs all have significant effects on T cell activation, and therefore should be taken into account when designing novel constructs.
Cardiac MR T(1) mapping is a promising quantitative imaging tool for the diagnosis and evaluation of cardiomyopathy. Here, we present a new preclinical cardiac MRI method enabling three-dimensional T(1) mapping of the mouse heart. The method is based on a variable flip angle analysis of steady-state MR imaging data. A retrospectively triggered three-dimensional FLASH (fast low-angle shot) sequence (3D IntraGate) enables a constant repetition time and maintains steady-state conditions. 3D T(1) mapping of the complete mouse heart could be achieved in 20 min. High-quality, bright-blood T(1) maps were obtained with homogeneous T(1) values (1764 ± 172 ms) throughout the myocardium. The repeatability coefficient of R(1) (1/T(1) ) in a specific region of the mouse heart was between 0.14 and 0.20 s(-1) , depending on the number of flip angles. The feasibility for detecting regional differences in ΔR(1) was shown with pre- and post-contrast T(1) mapping in mice with surgically induced myocardial infarction, for which ΔR(1) values up to 0.83 s(-1) were found in the infarct zone. The sequence was also investigated in black-blood mode, which, interestingly, showed a strong decrease in the apparent mean T(1) of healthy myocardium (905 ± 110 ms). This study shows that 3D T(1) mapping in the mouse heart is feasible and can be used to monitor regional changes in myocardial T(1), particularly in relation to pathology and in contrast-enhanced experiments to estimate local concentrations of (targeted) contrast agent.
ObjectiveContrast-enhanced spectral mammography (CESM) examination results in a low-energy (LE) and contrast-enhanced image. The LE appears similar to a full-field digital mammogram (FFDM). Our aim was to evaluate LE CESM image quality by comparing it to FFDM using criteria defined by the European Reference Organization for Quality Assured Breast Screening and Diagnostic Services (EUREF).MethodsA total of 147 cases with both FFDM and LE images were independently scored by two experienced radiologists using these (20) EUREF criteria. Contrast detail measurements were performed using a dedicated phantom. Differences in image quality scores, average glandular dose, and contrast detail measurements between LE and FFDM were tested for statistical significance.ResultsNo significant differences in image quality scores were observed between LE and FFDM images for 17 out of 20 criteria. LE scored significantly lower on one criterion regarding the sharpness of the pectoral muscle (p < 0.001), and significantly better on two criteria on the visualization of micro-calcifications (p = 0.02 and p = 0.034). Dose and contrast detail measurements did not reveal any physical explanation for these observed differences.ConclusionsLow-energy CESM images are non-inferior to FFDM images. From this perspective FFDM can be omitted in patients with an indication for CESM.Key Points• Low-energy CESM images are non-inferior to FFDM images.• Micro-calcifications are significantly more visible on LE CESM than on FFDM.• There is no physical explanation for this improved visibility of micro-calcifications.• There is no need for an extra FFDM when CESM is indicated.
A first-pass myocardial perfusion sequence for mouse cardiac MRI is presented. A segmented ECG-triggered acquisition combined with parallel imaging acceleration was used to capture the first pass of a Gd-DTPA bolus through the mouse heart with a temporal resolution of 300-400 msec. The method was applied in healthy mice (N 5 5) and in mice with permanent occlusion of the left coronary artery (N 5 6). Baseline semiquantitative perfusion values of healthy myocardium showed excellent reproducibility. Infarct regions revealed a significant decrease in the semiquantitative myocardial perfusion values (0.05 6 0.02) compared to remote myocardium (0.20 6 0.04). Myocardial areas of decreased perfusion correlated well to infarct areas identified on the delayed-enhancement scans. This protocol is a valuable addition to the mouse cardiac MRI toolbox for preclinical studies of ischemic heart disease.
BackgroundThe upregulation of intercellular adhesion molecule-1 (ICAM-1) on the endothelium of blood vessels in response to pro-inflammatory stimuli is of major importance for the regulation of local inflammation in cardiovascular diseases such as atherosclerosis, myocardial infarction and stroke. In vivo molecular imaging of ICAM-1 will improve diagnosis and follow-up of patients by non-invasive monitoring of the progression of inflammation.ResultsA paramagnetic liposomal contrast agent functionalized with anti-ICAM-1 antibodies for multimodal magnetic resonance imaging (MRI) and fluorescence imaging of endothelial ICAM-1 expression is presented. The ICAM-1-targeted liposomes were extensively characterized 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 to endothelial cells that depended on both the ICAM-1 expression level and the concentration of liposomes. The liposomes had a high longitudinal and transversal relaxivity, which enabled differentiation between basal and upregulated levels of ICAM-1 expression by MRI. The liposome affinity for ICAM-1 was preserved in the competing presence of leukocytes and under physiological flow conditions.ConclusionThis liposomal contrast agent displays great potential for in vivo MRI of inflammation-related ICAM-1 expression.
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