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Molecular imaging & biology (2021). doi:10.1007/s11307-021-01623-y, Published by Springer Nature Switzerland, Cham

Theranostics 7(6), 1499-1510 (2017). doi:10.7150/thno.17263, Published by Ivyspring, Wyoming, NSW

Myocardial infarction and stroke are frequent after surgical procedures and consume a considerable amount of benefit of surgical therapy. Perioperative stress, induced by surgery, is composed of hemodynamic and inflammatory reactions. The effects of perioperative stress on atherosclerotic plaques are ill-defined. Murine models to investigate the influence of perioperative stress on plaque stability and rupture are not available. We developed a model to investigate the influence of perioperative stress on plaque growth and stability by exposing apolipoprotein-E-deficient mice, fed a high cholesterol diet for 7 weeks, to a double hit consisting of 30 min of laparotomy combined with a substantial blood loss (approximately 20% of total blood volume; 400 mu l). The innominate artery was harvested 72 h after the intervention. Control groups were sham and baseline controls. Interleukin-6 (IL-6) and serum amyloid A (SAA) plasma levels were determined. Plaque load, vascular smooth muscle cell (VSMC) and macrophage content were quantified. Plaque stability was assessed using the Stary score and frequency of signs of plaque rupture were assessed. High-dose atorvastatin (80 mg/kg body weight/day) was administered for 6 days starting 3 days prior to the double hit. A single dose of an IL-6-neutralizing antibody or the fusion protein gp130-Fc selectively targeting IL-6 trans-signaling was subcutaneously injected. IL-6 plasma levels increased, peaking at 6 h after the intervention. SAA levels peaked at 24 h (n=4, P

Myocardial infarction and stroke are frequent after surgical procedures and consume a considerable amount of benefit of surgical therapy. Perioperative stress, induced by surgery, is composed of hemodynamic and inflammatory reactions. The effects of perioperative stress on atherosclerotic plaques are ill-defined. Murine models to investigate the influence of perioperative stress on plaque stability and rupture are not available. We developed a model to investigate the influence of perioperative stress on plaque growth and stability by exposing apolipoprotein-E-deficient mice, fed a high cholesterol diet for 7 weeks, to a double hit consisting of 30 min of laparotomy combined with a substantial blood loss (approximately 20% of total blood volume; 400 µl). The innominate artery was harvested 72 h after the intervention. Control groups were sham and baseline controls. Interleukin-6 (IL-6) and serum amyloid A (SAA) plasma levels were determined. Plaque load, vascular smooth muscle cell (VSMC) and macrophage content were quantified. Plaque stability was assessed using the Stary score and frequency of signs of plaque rupture were assessed. High-dose atorvastatin (80 mg/kg body weight/day) was administered for 6 days starting 3 days prior to the double hit. A single dose of an IL-6-neutralizing antibody or the fusion protein gp130-Fc selectively targeting IL-6 trans-signaling was subcutaneously injected. IL-6 plasma levels increased, peaking at 6 h after the intervention. SAA levels peaked at 24 h (n=4, P, Summary: We developed a model to study the dynamics of atherosclerotic plaque growth and stability following surgery, and show that IL-6 inhibition and statins beneficially affect plaque volume and complexity.

Fluorescence-mediated tomography (FMT) enables longitudinal and quantitative determination of the fluorescence distribution in vivo and can be used to assess the biodistribution of novel probes and to assess disease progression using established molecular probes or reporter genes. The combination with an anatomical modality, e.g., micro computed tomography (µCT), is beneficial for image analysis and for fluorescence reconstruction. We describe a protocol for multimodal µCT-FMT imaging including the image processing steps necessary to extract quantitative measurements. After preparing the mice and performing the imaging, the multimodal data sets are registered. Subsequently, an improved fluorescence reconstruction is performed, which takes into account the shape of the mouse. For quantitative analysis, organ segmentations are generated based on the anatomical data using our interactive segmentation tool. Finally, the biodistribution curves are generated using a batch-processing feature. We show the applicability of the method by assessing the biodistribution of a well-known probe that binds to bones and joints.

Theranostics 4(10), 960-971 (2014). doi:10.7150/thno.9293, Published by Ivyspring, Wyoming, NSW