Intravital Imaging of Thrombosis Models in Mice.

Intravital microscopy is a powerful tool to study thrombosis in real time. The kinetics of thrombus formation and progression in vivo is studied after inflicting damage to the endothelium through mechanical, chemical, or laser injury. Mouse models of atherosclerosis are also used to induce thrombus formation. Vessels of different sizes and from different vascular beds such as carotid artery or vena cava, mesenteric or cremaster arterioles, can be targeted. Using fluorescent dyes, antibodies, or reporter mouse strains allows to visualize key cells and factors mediating the thrombotic processes. Here, we review the latest literature on using intravital microscopy to study thrombosis as well as thromboinflammation following transient middle cerebral artery occlusion, infection-induced immunothrombosis, and liver ischemia reperfusion.

Beyond Hemostasis: Platelet Innate Immune Interactions and Thromboinflammation.

There is accumulating evidence that platelets play roles beyond their traditional functions in thrombosis and hemostasis, e.g., in inflammatory processes, infection and cancer, and that they interact, stimulate and regulate cells of the innate immune system such as neutrophils, monocytes and macrophages. In this review, we will focus on platelet activation in hemostatic and inflammatory processes, as well as platelet interactions with neutrophils and monocytes/macrophages. We take a closer look at the contributions of major platelet receptors GPIb, αIIbß3, TLT-1, CLEC-2 and Toll-like receptors (TLRs) as well as secretions from platelet granules on platelet-neutrophil aggregate and neutrophil extracellular trap (NET) formation in atherosclerosis, transfusion-related acute lung injury (TRALI) and COVID-19. Further, we will address platelet-monocyte and macrophage interactions during cancer metastasis, infection, sepsis and platelet clearance.

Comparison of prostate MRI-3D transrectal ultrasound fusion biopsy for first-time and repeat biopsy patients with previous atypical small acinar proliferation.

INTRODUCTION: This study evaluates the clinical benefit of magnetic resonance-transrectal ultrasound (MR-TRUS) fusion biopsy over systematic biopsy between first-time and repeat prostate biopsy patients with prior atypical small acinar proliferation (ASAP). MATERIALS: 100 patients were enrolled in a single-centre prospective cohort study: 50 for first biopsy, 50 for repeat biopsy with prior ASAP. Multiparameteric magnetic resonance imaging (MP-MRI) and standard 12-core ultrasound biopsy (Std-Bx) were performed on all patients. Targeted biopsy using MRI-TRUS fusion (Fn-Bx) was performed f suspicious lesions were identified on the pre-biopsy MP-MRI. Classification of clinically significant disease was assessed independently for the Std-Bx vs. Fn-Bx cores to compare the two approaches. RESULTS: Adenocarcinoma was detected in 49/100 patients (26 first biopsy, 23 ASAP biopsy), with 25 having significant disease (17 first, 8 ASAP). Fn-Bx demonstrated significantly higher per-core cancer detection rates, cancer involvement, and Gleason scores for first-time and ASAP patients. However, Fn-Bx was significantly more likely to detect significant cancer missed on Std-Bx for ASAP patients than first-time biopsy patients. The addition of Fn-Bx to Std-Bx for ASAP patients had a 166.7% relative risk reduction for missing Gleason ≥ 3 + 4 disease (number needed to image with MP-MRI=10 patients) compared to 6.3% for first biopsy (number to image=50 patients). Negative predictive value of MP-MRI for negative biopsy was 79% for first-time and 100% for ASAP patients, with median followup of 32.1 ± 15.5 months. CONCLUSIONS: MR-TRUS Fn-Bx has a greater clinical impact for repeat biopsy patients with prior ASAP than biopsy-naïve patients by detecting more significant cancers that are missed on Std-Bx.

Feasibility of simultaneous whole-brain imaging on an integrated PET-MRI system using an enhanced 2-point Dixon attenuation correction method.

PURPOSE: To evaluate a potential approach for improved attenuation correction (AC) of PET in simultaneous PET and MRI brain imaging, a straightforward approach that adds bone information missing on Dixon AC was explored. METHODS: Bone information derived from individual T1-weighted MRI data using segmentation tools in SPM8, were added to the standard Dixon AC map. Percent relative difference between PET reconstructed with Dixon+bone and with Dixon AC maps were compared across brain regions of 13 oncology patients. The clinical potential of the improved Dixon AC was investigated by comparing relative perfusion (rCBF) measured with arterial spin labeling to relative glucose uptake (rPETdxbone) measured simultaneously with (18)F-flurodexoyglucose in several regions across the brain. RESULTS: A gradual increase in PET signal from center to the edge of the brain was observed in PET reconstructed with Dixon+bone. A 5-20% reduction in regional PET signals were observed in data corrected with standard Dixon AC maps. These regional underestimations of PET were either reduced or removed when Dixon+bone AC was applied. The mean relative correlation coefficient between rCBF and rPETdxbone was r = 0.53 (p < 0.001). Marked regional variations in rCBF-to-rPET correlation were observed, with the highest associations in the caudate and cingulate and the lowest in limbic structures. All findings were well matched to observations from previous studies conducted with PET data reconstructed with computed tomography derived AC maps. CONCLUSION: Adding bone information derived from T1-weighted MRI to Dixon AC maps can improve underestimation of PET activity in hybrid PET-MRI neuroimaging.