Coronary artery spasms due to tyrosine kinase inhibitors used in chronic myeloid leukemia

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(19)F MRI Imaging Strategies to Reduce Isoflurane Artifacts in In Vivo Images

PURPOSE: Isoflurane (ISO) is the most commonly used preclinical inhalation anesthetic. This is a problem in (19)F MRI of fluorine contrast agents, as ISO signals cause artifacts that interfere with unambiguous image interpretation and quantification; the two most attractive properties of heteronuclear MRI. We aimed to avoid these artifacts using MRI strategies that can be applied by any pre-clinical researcher. PROCEDURES: Three strategies to avoid ISO chemical shift displacement artifacts (CSDA) in (19)F MRI are described and demonstrated with measurements of (19)F-containing agents in phantoms and in vivo (n = 3 for all strategies). The success of these strategies is compared to a standard Rapid Acquisition with Relaxation Enhancement (RARE) sequence, with phantom and in vivo validation. ISO artifacts can successfully be avoided by (1) shifting them outside the region of interest using a narrow signal acquisition bandwidth, (2) suppression of ISO by planning a frequency-selective suppression pulse before signal acquisition or by (3) preventing ISO excitation with a 3D sequence with a narrow excitation bandwidth. RESULTS: All three strategies result in complete ISO signal avoidance (p < 0.0001 for all methods). Using a narrow acquisition bandwidth can result in loss of signal to noise ratio and distortion of the image, and a frequency-selective suppression pulse can be incomplete when B1-inhomogeneities are present. Preventing ISO excitation with a narrow excitation pulse in a 3D sequence yields the most robust results (relative SNR 151 +/- 28% compared to 2D multislice methods, p = 0.006). CONCLUSION: We optimized three easily implementable methods to avoid ISO signal artifacts and validated their performance in phantoms and in vivo. We make recommendation on the parameters that pre-clinical studies should report in their method section to make the used approach insightful

Clinically-Applicable Perfluorocarbon-Loaded Nanoparticles For In vivo Photoacoustic, (19)F Magnetic Resonance And Fluorescent Imaging

Contains fulltext : 193511.pdf (publisher's version ) (Open Access)Photoacoustic imaging (PAI) is an emerging biomedical imaging technique that is now coming to the clinic. It has a penetration depth of a few centimeters and generates useful endogenous contrast, particularly from melanin and oxy-/deoxyhemoglobin. Indocyanine green (ICG) is a Food and Drug Administration-approved contrast agents for human applications, which can be also used in PAI. It is a small molecule dye with limited applications due to its fast clearance, rapid protein binding, and bleaching effect. Methods: Here, we entrap ICG in a poly(lactic-co-glycolic acid) nanoparticles together with a perfluorocarbon (PFC) using single emulsion method. These nanoparticles and nanoparticle-loaded dendritic cells were imaged with PA, (19)F MR, and fluorescence imaging in vitro and in vivo. Results: We formulated particles with an average diameter of 200 nm. The encapsulation of ICG within nanoparticles decreased its photobleaching and increased the retention of the signal within cells, making it available for applications such as cell imaging. As little as 0.1x10(6) cells could be detected in vivo with PAI using automated spectral unmixing. Furthermore, we observed the accumulation of ICG signal in the lymph node after subcutaneous injection of nanoparticles. Conclusion: We show that we can label primary human dendritic cells with the nanoparticles and image them in vitro and in vivo, in a multimodal manner. This work demonstrates the potential of combining PAI and (19)F MRI for cell imaging and lymph node detection using nanoparticles that are currently produced at GMP-grade for clinical use

Topography of immune cell infiltration in different stages of coronary atherosclerosis revealed by multiplex immunohistochemistry.

BACKGROUND: Aim of this study was to investigate immune cells and subsets in different stages of human coronary artery disease with a novel multiplex immunohistochemistry (mIHC) technique. METHODS: Human left anterior descending coronary artery specimens were analyzed: eccentric intimal thickening (N = 11), pathological intimal thickening (N = 10), fibroatheroma (N = 9), and fibrous plaque (N = 9). Eccentric intimal thickening was considered normal, and pathological intimal thickening, fibroatheroma, and fibrous plaque were considered diseased coronary arteries. Two mIHC panels, consisting of six and five primary antibodies, autofluoresence, and DAPI, were used to detect adaptive and innate immune cells. Via semi-automated analysis, (sub)types of immune cells in whole plaques and specific plaque regions were quantified. RESULTS: Increased numbers of CD3(+) T cells (P < 0.001), CD20(+) B cells (P = 0.013), CD68(+) macrophages (P = 0.003), CD15(+) neutrophils (P = 0.017), and CD31(+) endothelial cells (P = 0.024) were identified in intimas of diseased coronary arteries compared to normal. Subset analyses of T cells and macrophages showed that diseased coronary arteries contained an abundance of CD3(+)CD8(-) non-cytotoxic T cells and CD68(+)CD206(-) non-M2-like macrophages. Proportions of CD3(+)CD45RO(+) memory T cells were similar to normal coronary arteries. Among pathological intimal thickening, fibroatheroma, and fibrous plaque, all immune cell numbers and subsets were similar. CONCLUSIONS: The type of immune response does not differ substantially between different stages of plaque development and may provide context for mechanistic research into immune cell function in atherosclerosis. We provide the first comprehensive map of immune cell subtypes across plaque types in coronary arteries demonstrating the potential of mIHC for vascular research

Nanoparticles for "two color" F-19 magnetic resonance imaging: Towards e combined imaging of biodistribution and degradation

Contains fulltext : 217381.pdf (publisher's version ) (Open Access

Adventitial adaptive immune cells are associated with ascending aortic dilatation in patients with a bicuspid aortic valve.

BACKGROUND: Bicuspid aortic valve (BAV) is associated with ascending aorta aneurysms and dissections. Presently, genetic factors and pathological flow patterns are considered responsible for aneurysm formation in BAV while the exact role of inflammatory processes remains unknown. METHODS: In order to objectify inflammation, we employ a highly sensitive, quantitative immunohistochemistry approach. Whole slides of dissected, dilated and non-dilated ascending aortas from BAV patients were quantitatively analyzed. RESULTS: Dilated aortas show a 4-fold increase of lymphocytes and a 25-fold increase in B lymphocytes in the adventitia compared to non-dilated aortas. Tertiary lymphoid structures with B cell follicles and helper T cell expansion were identified in dilated and dissected aortas. Dilated aortas were associated with an increase in M1-like macrophages in the aorta media, in contrast the number of M2-like macrophages did not change significantly. CONCLUSION: This study finds unexpected large numbers of immune cells in dilating aortas of BAV patients. These findings raise the question whether immune cells in BAV aortopathy are innocent bystanders or contribute to the deterioration of the aortic wall

Progressive Pulmonary Artery Dilatation is Associated with Type B Aortic Dissection in Patients with Marfan Syndrome

Contains fulltext : 214024.pdf (publisher's version ) (Open Access