The Patlak model is most suited for describing carotid plaque enhancement. Correlation with histologic findings validated K(trans) as an indicator of plaque microvasculature, and the reproducibility of K(trans) was good.

Increased understanding of the pathophysiology of ischemic acute kidney injury in renal transplantation may lead to novel therapies that improve early graft function. Therefore, we studied the renal microcirculation in ischemically injured kidneys from donors after cardiac death (DCD) and in living donor kidneys with minimal ischemia. During transplant surgery, peritubular capillaries were visualized by sidestream darkfield imaging. Despite a profound reduction in creatinine clearance, total renovascular resistance of DCD kidneys was similar to that of living donor kidneys. In contrast, renal microvascular perfusion in the early reperfusion period was 42% lower in DCD kidneys compared with living donor kidneys, which was accounted for by smaller blood vessel diameters in DCD kidneys. Furthermore, DCD kidneys were characterized by smaller red blood cell exclusion zones in peritubular capillaries and by greater production of syndecan-1 and heparan sulfate (main constituents of the endothelial glycocalyx) compared with living donor kidneys, providing strong evidence for glycocalyx degradation in these kidneys. We conclude that renal ischemia and reperfusion is associated with reduced capillary blood flow and loss of glycocalyx integrity. These findings form the basis for development of novel interventions to prevent ischemic acute kidney injury. ischemia-reperfusion injury; endothelial glycocalyx KIDNEY TRANSPLANTATION IS inevitably associated with ischemia and reperfusion injury. Depending on the severity of injury, 20 -80% of recipients of deceased donor kidneys require dialysis treatment in the first week after transplantation, which is referred to as delayed graft function (26). This condition complicates patient management and is associated with a 40% increased rate of graft loss in kidneys from donors after brain death (45). Liberal use of donations after cardiac death greatly expands the number of available donor kidneys and may even eliminate transplant waiting lists (37). However, kidneys from these donors suffer extensive ischemic injury from circulatory arrest until organ preservation, which almost invariably leads to delayed graft function after transplantation. More importantly, up to 15-25% of these kidneys will never regain function, unnecessarily exposing recipients to the risks of major surgery and immunological sensitization (43).Adequate reperfusion is essential for functional recovery of donor kidneys and prevents ongoing ischemic tissue injury after revascularization. In rodent models of ischemic acute kidney injury, it has been demonstrated that the peritubular microcirculation suffers endothelial injury and functional impairment after reperfusion (5, 44), which has recently been observed in humans as well (13,21,31). The endothelium is covered by the glycocalyx, a dynamic network of proteoglycans and glycoproteins that determines vascular permeability, transduces shear stress to the endothelium, and prevents interaction of leukocytes and platelets with the vascular wall (29). Loss of endothel...

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Background— 18 F-fluorocholine ( 18 F-FCH) uptake is associated with cell proliferation and activity in tumor patients. We hypothesized that 18 F-FCH could similarly be a valuable imaging tool to identify vulnerable plaques and associated intraplaque inflammation and atheroma cell proliferation. Methods and Results— Ten consecutive stroke patients (90% men, median age 66.5 years, range, 59.4–69.7) with ipsilateral >70% carotid artery stenosis and who underwent carotid endarterectomy were included in the study. Before carotid endarterectomy, all patients underwent positron emission tomography to assess maximum 18 F-FCH uptake in ipsilateral symptomatic carotid plaques and contralateral asymptomatic carotid arteries, which was corrected for background activity, resulting in a maximum target-to-background ratio (TBRmax). Macrophage content was assessed in all carotid endarterectomy specimens as a percentage of CD68 + -staining per whole plaque area (plaqueCD68 + ) and as a maximum CD68 + percentage (maxCD68 + ) in the most inflamed section/plaque. Dynamic positron emission tomography imaging demonstrated that an interval of 10 minutes between 18 F-FCH injection and positron emission tomography acquisition is appropriate for carotid plaque imaging. TBRmax in ipsilateral symptomatic carotid plaques correlated significantly with plaqueCD68 + (Spearman’s ρ=0.648, P =0.043) and maxCD68 + (ρ=0.721, P =0.019) in the 10 corresponding carotid endarterectomy specimens. TBRmax was significantly higher ( P =0.047) in ipsilateral symptomatic carotid plaques (median: 2.0; interquartile range [Q1–Q3], 1.5–2.5) compared with the contralateral asymptomatic carotid arteries (median: 1.4; Q1–Q3, 1.3–1.6). TBRmax was not significantly correlated to carotid artery stenosis (ρ=0.506, P =0.135). Conclusions— In vivo uptake of 18 F-FCH in human carotid atherosclerotic plaques correlated strongly with degree of macrophage infiltration and recent symptoms, thus 18 F-FCH positron emission tomography is a promising tool for the evaluation of vulnerable plaques. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01899014.