In Vivo Imaging of Local Inflammation: Monitoring LPS-Induced CD80/CD86 Upregulation by PET

Purpose

The co-stimulatory molecules CD80 and CD86 are upregulated on activated antigen-presenting cells (APC). We investigated whether local APC activation, induced by subcutaneous (s.c.) inoculation of lipopolysaccharides (LPS), can be imaged by positron emission tomography (PET) with CD80/CD86-targeting ⁶⁴Cu-labelled abatacept.

Procedures

Mice were inoculated s.c. with extracellular-matrix gel containing either LPS or vehicle (PBS). Immune cell populations were analysed by flow cytometry and marker expression by RT-qPCR. ⁶⁴Cu-NODAGA-abatacept distribution was analysed using PET/CT and ex vivo biodistribution.

Results

The number of CD80⁺ and CD86⁺ immune cells at the LPS inoculation site significantly increased a few days after inoculation. CD68 and CD86 expression were higher at the LPS than the PBS inoculation site, and CD80 was only increased at the LPS inoculation site. CTLA-4 was highest 10 days after LPS inoculation, when CD80/CD86 decreased again. A few days after inoculation, ⁶⁴Cu-NODAGA-abatacept distribution to the inoculation site was significantly higher for LPS than PBS (4.2-fold). Co-administration of unlabelled abatacept or human immunoglobulin reduced tracer uptake. The latter reduced the number of CD86⁺ immune cells at the LPS inoculation site.

Conclusions

CD80 and CD86 are upregulated in an LPS-induced local inflammation, indicating invasion of activated APCs. ⁶⁴Cu-NODAGA-abatacept PET allowed following APC activation over time.

     

Inappropriate emergency department visits

Guidelines adopted in 1982 by the American College of Emergency Physicians were used to determine appropriate and inappropriate emergency department (ED) utilization patterns at three community hospitals during a two-week period in August 1983. In all, 3,130 visits were examined. There was an overall inappropriate visit rate of 10.8%, although considerable variation was observed among the three hospitals. Subgroups with the highest inappropriate visit rates included the following: 1) persons with Medicaid as the primary payment source (17.3%); 2) children aged 5 years or younger (15.2%); 3) those unable to identify a personal physician (14.1%); 4) unemployed persons (13.1%); 5) patients making visits during regular office hours (12.6%); and 6) those failing to attempt to contact their personal physicians (12.4%). These variations in inappropriate usage were all statistically significant at the P less than .05 level or better. Inability to identify a personal physician emerged as the most pervasive influence on inappropriate ED visit rates (P less than .001).     

The no-reflow phenomenon in coronary arteries

No reflow occurs when there is inadequate myocardial perfusion of a given segment of the coronary circulation without evidence of epicardial vessel obstruction. It is a rare but clinically significant condition associated with myocardial infarction and coronary interventions. Diagnosis is usually based on clinical signs of myocardial ischemia (symptoms and/or ECG changes) combined with coronary angiography. Management can be difficult and primarily consists of intracoronary administration of vasodilators. One interesting etiology is thromboembolism and this has become the focus for new potential treatments, including distal embolic protection devices.     

Magnetic resonance imaging of multiple sclerosis: a study of pulse-technique efficacy

Forty-two patients with the clinical diagnosis of multiple sclerosis were examined by proton magnetic resonance imaging (MRI) at 0.5 T. An extensive protocol was used to facilitate a comparison of the efficacy of different pulse techniques. Results were also compared in 39 cases with high-resolution x-ray computed tomography (CT). MRI revealed characteristic abnormalities in each case, whereas CT was positive in only 15 of 33 patients. Milder grades 1 and 2 disease were usually undetected by CT, and in all cases, the abnormalities noted on MRI were much more extensive than on CT. Cerebral abnormalities were best shown with the T2-weighted spin-echo sequence (TE/TR = 120/1000); brainstem lesions were best defined on the inversion-recovery sequence (TE/TI/TR = 30/400/1250). Increasing TE to 120 msec and TR to 2000 msec heightened the contrast between normal and abnormal white matter. However, the signal intensity of cerebrospinal fluid with this pulse technique obscured some abnormalities.     

MR evaluation of neurovascular lesions after endovascular occlusion with detachable balloons

Three patients with surgically inaccessible giant carotid aneurysms/pseudoaneurysms and one patient with carotid cavernous fistula had endovascular occlusion with detachable silicone balloons filled with Cholografin. MR was performed before the procedures in three cases and again 18 hr to 44 days after embolization in all four cases. The age-related changes of arterial thrombi, as well as the optimal timing and value of different pulse sequences in the noninvasive follow-up, were evaluated. Arterial thrombi have some characteristics in common with intracerebral hematomas, being isointense on T1-weighted spin-echo images during acute phase and subsequently acquiring hyperintense signals on both T1- and T2-weighted spin-echo images during the subacute and chronic phases. Additional observations are that (1) hyperacute (less than 24 hr old) thrombus is hyperintense on T2-weighted spin-echo sequences; (2) hemosiderin is less conspicuous in chronic intraluminal thrombi than in intracerebral hematomas of comparable size; and (3) thrombosis is initiated at a site remote from the apex of the aneurysm and then progresses centripetally. The Cholografin-filled balloon is hypointense to gray matter on T1-weighted spin-echo images and isointense to both hyperacute and chronic thrombus on T2-weighted spin-echo images. The optimal timing and sequence for MR follow-up of a thrombosed aneurysm with conventional spin-echo technique is beyond 7 days on T1-weighted spin-echo images. The in vivo appearance of Cholografin-filled silicone balloons does not change appreciably on T1- and T2-weighted spin-echo sequences up to 6 weeks if filled according to the manufacturer's specification.     

Evaluation of myocardial metabolism with microdialysis after protection with cold blood- or cold crystalloid cardioplegia. A porcine model

OBJECTIVES: There has been a considerable change in the patient population referred for cardiac surgery in the last decade. More complex and marginal patients require optimized myocardial protection. An insufficient cardioplegic procedure results in anaerobic metabolism during cardiac arrest with subsequent lactate accumulation. Increased lactate level is regarded as a predictor for low cardiac output syndrome. In an acute porcine model we examined two standard cardioplegic methods. Myocardial microdialysis was used to investigate the metabolism during cardioplegic arrest and in the reperfusion period. METHODS: Twelve domestic pigs were randomly chosen to receive either cold blood-or cold crystalloid cardioplegia. After midline sternotomy two microdialysis probes were implanted in two different regions of the heart. Cardiopulmonary bypass was initiated, aorta was clamped, and antegrade cardioplegia was delivered. These conditions were maintained for 90 min. Subsequent to myocardial reperfusion the animals were observed for 180 min. Microdialysis and plasma markers to characterize myocardial metabolism, and plasma markers for myocardial failure and necrosis were obtained every 30 min. RESULTS: Lactate concentrations were significantly increased in the cold crystalloid cardioplegia group compared to the cold blood cardioplegia group, in tissue dialysate (p < 0.001) as well as in serum (p = 0.018). Pyruvate concentrations in the dialysate were significantly increased in the cold crystalloid cardioplegia group compared to the cold blood cardioplegia group (p = 0.008). There were no significant differences in dialysate concentrations of glycerol. Plasma markers for myocardial failure (Brain Natriuretic Peptide) and for myocardial necrosis (Cardiac Troponin T) showed no differences between the groups. CONCLUSION: The results indicate that cold blood cardioplegia offers superior protection of the heart, in terms of more rapid normalization of myocardial metabolism. The microdialysis technique seems to have a high sensitivity and ability to detect even minor metabolic changes. This enhances the possibility of designing a myocardial protection, which might lower morbidity and mortality risk.     

Deep brain stimulation of the ventral intermediate nucleus in patients with essential tremor: stimulation below intercommissural line is more efficient but equally effective as stimulation above

Background

The posterior subthalamic area (PSA), ventral to the intercommissural line (ICL) and the ventral intermediate nucleus (VIM), has been suggested as a promising target for deep brain stimulation (DBS) in patients suffering from essential tremor (ET). In this study the clinical benefit of VIM and PSA DBS on postural tremor suppression was systematically evaluated in a two step approach with a 3D ultrasound kinematic analysis tool.

Methods

We defined the exact position of 40 VIM-DBS-electrodes from 21 ET patients. In a first experiment with a subgroup of electrodes we subsequently activated a thalamic and a contact below ICL (sub-ICL) with equal parameter settings for within subject comparison. In a second step, we divided all electrodes into two groups, i.e. one group with activated thalamic and the other group with activated contacts below ICL and performed a group comparison under patients' individual stimulation parameters. Here, the corrected amplitude required for tremor suppression was analyzed separately for both groups.

Results

Within subject comparison with equal parameter settings revealed a significant improvement of sub-ICL compared to thalamic stimulation. In contrast, group comparison under patients' individual stimulation did not show any significant difference in tremor suppression between VIM and PSA DBS. Although higher corrected stimulation amplitude was needed in the thalamic group this difference was not significant.

Conclusion

The data suggest that sub-ICL stimulation may be more efficient compared to thalamic stimulation but equally effective when patients' individual stimulation parameters are used.