Background-Atherosclerotic plaque rupture is usually a consequence of inflammatory cell activity within the plaque.Current imaging techniques provide anatomic data but no indication of plaque inflammation. The current "gold standard" imaging technique for atherosclerosis is x-ray contrast angiography, which provides high-resolution definition of the site and severity of luminal stenoses, but no information about plaque inflammation.There is a need to quantify plaque inflammation to predict the risk of plaque rupture and to monitor the effects of atheroma-modifying therapies. This is important because recent experimental and clinical studies strongly suggest that hepatic hydroxymethyl glutaryl coenzyme A reductase inhibitors (statins) promote plaque stability by decreasing plaque macrophage content and activity without substantially reducing plaque size and therefore angiographic appearance. 4 [ 18 F]-fluorodeoxyglucose ( 18 FDG) is a glucose analogue that is taken up by cells in proportion to their metabolic activity. 5 We tested the hypothesis that plaque inflammation could be visualized and quantified non-invasively using 18 FDG-PET in patients with symptomatic carotid artery disease. Methods Patient RecruitmentWe recruited 8 patients who had experienced a recent carotidterritory transient ischemic attack and had an internal carotid artery stenosis of at least 70%. Patients were excluded if they had either carotid artery occlusion or diabetes. The study protocol was approved by the local ethics committee and the UK Administration of Radioactive Substances Advisory Committee. All patients gave written informed consent. PET ProtocolPET was carried out using a GE Advance PET scanner (GE Medical Systems). We administered 370 MBq 18 FDG intravenously over 60 seconds. PET images (as 4ϫ5 minute frames) were acquired in 3D mode, at 190 (Ϯ6) minutes after 18 FDG administration. This timepoint was chosen after preliminary dynamic studies indicated that late imaging provided optimal contrast between the 18 FDG concentration in plaque and the main background region, namely blood.A stiff cervical collar was worn to minimize patient movement. PET images were reconstructed using the 3D reprojection algorithm, 6 with corrections applied for attenuation, dead time, scatter, and random coincidences. Rigid body co-registration with CT was performed, using a combination of fiducial markers and internal anatomical landmarks (spinal cord and muscles of the jaw and neck). This resulted in co-registration typically to within 1 mm in each dimension around the stenosis. To estimate plaque 18 FDG concentration, three-dimensional volumes of interest (VOI) were drawn CT ProtocolUsing a GE Hispeed Advantage CT scanner (GE Medical Systems), helical contrast CT angiograms were acquired from skull base to 3 cm below the level of the carotid bifurcation. Plaque HistologyAfter imaging, carotid endarterectomy samples from all 8 patients imaged were fixed and stained with hematoxylin and eosin. Immunohistochemistry was performed using anti-macr...

Increased diffusion barriers may reduce cellular oxygen delivery following head injury and attenuate the ability of the brain to increase oxygen extraction in response to hypoperfusion. Global or regional OEF underestimates tissue hypoxia due to such mechanisms.

Background— The pathophysiology of aortic stenosis is incompletely understood, and the relative contributions of valvular calcification and inflammation to disease progression are unknown. Methods and Results— Patients with aortic sclerosis and mild, moderate, and severe stenosis were compared prospectively with age- and sex-matched control subjects. Aortic valve severity was determined by echocardiography. Calcification and inflammation in the aortic valve were assessed by 18F-sodium fluoride (18F-NaF) and 18F-fluorodeoxyglucose (18F-FDG) uptake with the use of positron emission tomography. One hundred twenty-one subjects (20 controls; 20 aortic sclerosis; 25 mild, 33 moderate, and 23 severe aortic stenosis) were administered both 18F-NaF and 18F-FDG. Quantification of tracer uptake within the valve demonstrated excellent interobserver repeatability with no fixed or proportional biases and limits of agreement of ±0.21 (18F-NaF) and ±0.13 (18F-FDG) for maximum tissue-to-background ratios. Activity of both tracers was higher in patients with aortic stenosis than in control subjects (18F-NaF: 2.87±0.82 versus 1.55±0.17; 18F-FDG: 1.58±0.21 versus 1.30±0.13; both P <0.001). 18F-NaF uptake displayed a progressive rise with valve severity ( r 2 =0.540, P <0.001), with a more modest increase observed for 18F-FDG ( r 2 =0.218, P <0.001). Among patients with aortic stenosis, 91% had increased 18F-NaF uptake (>1.97), and 35% had increased 18F-FDG uptake (>1.63). A weak correlation between the activities of these tracers was observed ( r 2 =0.174, P <0.001). Conclusions— Positron emission tomography is a novel, feasible, and repeatable approach to the evaluation of valvular calcification and inflammation in patients with aortic stenosis. The frequency and magnitude of increased tracer activity correlate with disease severity and are strongest for 18F-NaF. Clinical Trial Registration— http://www.clinicaltrials.gov . Unique identifier: NCT01358513.

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Despite following recommended safe-handling practices, workplace contamination with antineoplastic drugs in pharmacy and nursing areas continues at these locations.

SUMMARY1. Positron emission tomographic imaging of brain blood flow was used to identify areas of motor activation associated with volitional inspiration in six normal male subjects.2. Scans were performed using intravenous infusion of H2150 during voluntary targeted breathing and positive pressure passive ventilation at the same level.3. Regional increases in brain blood flow, due to active inspiration, were derived using a pixel by pixel comparison of images obtained during the voluntary and passive ventilation phases.4. Pooling data from all subjects revealed statistically significant increases in blood flow bilaterally in the primary motor cortex (left, 54%; right, 4 3%), in the right pre-motor cortex (7-6 %), in the supplementary motor area (SMA; 341 %) and in the cerebellum (4-9%).5. The site of increased neural activation in the motor cortex, associated with volitional inspiration, is consistent with an area which when stimulated, either directly during neurosurgery or transcranially with a magnetic stimulus, results in activation of the diaphragm.6. The presence of additional sites of neural activation in the pre-motor cortex and SMA appears analogous to the results of studies on voluntary limb movement. The site of the increase in the SMA was posterior to that previously reported for arm movements. These areas are believed to have a role 'upstream ' of the motor cortex in the planning and organization of movement.7. This technique provides a means of studying the volitional motor control of respiratory related tasks in man.

Background and Purpose-Carotid endarterectomy is currently guided by angiographic appearance on the assumption that the most stenotic lesion visible at angiography is likely to be the lesion from which future embolic events will arise. However, risk of plaque rupture, the most common cause of atherosclerosis-related thromboembolism, is dictated by the composition of the plaque, in particular the degree of inflammation. Angiography may, therefore, be an unreliable method of identifying vulnerable plaques. In this study, plaque inflammation was quantified before endarterectomy using the combination of 18 F fluorodeoxyglucose positron (FDG)-emission tomography (PET) and high-resolution MRI (HRMRI). Methods-Twelve patients, all of whom had suffered a recent transient ischemic attack, had a severe stenosis in the ipsilateral carotid artery, and were awaiting carotid endarterectomy underwent FDG-PET and HRMRI scanning. A semiquantitative estimate of plaque inflammation was calculated for all of the lesions identified on HRMRI. Results-In 7 of 12 patients (58%), high FDG uptake was seen in the lesion targeted for endarterectomy. In the remaining 5 patients, FDG uptake in the targeted lesion was low. In these 5 patients, 3 had nonstenotic lesions identified on HRMRI that exhibited a high level of FDG uptake. All 3 of the highly inflamed nonstenotic lesions were located in a vascular territory compatible with the patients' presenting symptoms. Conclusions-Our data suggest that angiography may not always identify the culprit lesion. Combined FDG-PET and HRMRI can assess the degree of inflammation in stenotic and nonstenotic plaques and could potentially be used to identify lesions responsible for embolic events.

Summary: Antemortem demonstration of ischemia has proved elusive in head injury because regional CBF reductions may represent hypoperfusion appropriately coupled to hypometabolism. Fifteen patients underwent positron emission tomography within 24 hours of head injury to map cerebral blood flow (CBF), cerebral oxygen metabolism (CMRO2), and oxygen extraction fraction (OEF). We estimated the volume of ischemic brain (IBV) and used the standard deviation of the OEF distribution to estimate the efficiency of coupling between CBF and CMRO2. The IBV in patients was significantly higher than controls (67 ± 69 vs. 2 ± 3 mL; P < 0.01). The coexistence of relative ischemia and hyperemia in some patients implies mismatching of perfusion to oxygen use. Whereas the saturation of jugular bulb blood (SjO 2 ) correlated with the IBV (r ‫ס‬ 0.8, P < 0.01), SjO 2 values of 50% were only achieved at an IBV of 170 ± 63 mL (mean ± 95% CI), which equates to 13 ± 5% of the brain. Increases in IBV correlated with a poor Glasgow Outcome Score 6 months after injury ( ‫ס‬ −0.6, P < 0.05). These results suggest significant ischemia within the first day after head injury. The ischemic burden represented by this "traumatic penumbra" is poorly detected by bedside clinical monitors and has significant associations with outcome.