Influence of scan time point and volume of intravenous contrast administration on blood-pool and liver SUVmax and SUVmean in [18F] FDG PET/CT.

AIM: To investigate the influence of scan time point and volume of intravenous contrast material in 18F-FDG PET/CT on maximum and mean standardized uptake values (SUVmax/mean) in bloodpool and liver. METHODS: In 120 patients scheduled for routine whole-body 18F-FDG PET/CT the maximum and mean standardized uptake values (SUVmax/SUVmean) in the liver and blood pool were measured after varying scan time-point (delay 0 s-140 s post injectionem) and volume of contrast material (CM; 0 ml, 80 ml, 100 ml of 300 mg/ml of Iodine). Six groups of 20 patients were investigated: (1) without intravenous CM, (2-5) injection of 100 ml CM with a delay of 80 s (2), 100 s (3), 120 s (4), 140 s (5), and 80 ml CM and a delay of 100 s (6). SUVmax, SUVmean, maximum Hounsfield units (HUmax) and average Hounsfield units (HUav) were calculated with the use of manually drawn regions of interests (ROIs) over the aortic arch and healthy liver tissue. RESULTS: SUVmax in bloodpool was significantly higher in group 3, 4 and 6 compared to group 1. Groups 2 and 5 also showed higher mean values of SUVmax, but the difference was not significant. SUVmean in bloodpool was also higher in groups 2, 3, 4, 5 and 6 compared to group 1, but the differences were only statistically significant in group 3. Both SUVmax and SUVmean in healthy liver tissue did not show significant differences when compared to the non contrast-enhanced control group. CONCLUSION: SUVmax and to a lesser extent SUVmean measured in CM enhanced FDG PET/CT in blood pool could be significantly altered in high contrast CT examinations. This should be kept in mind in PET/CT protocols and evaluation relying on SUVmax and SUVmean, for example when used in the assessment of therapy response, especially in highly vascularized tumor lesions. ZIEL:: Das Ziel dieser Studie war den Einfluss von unterschiedlichen Messzeitpunkten und Volumina bei der Gabe von intravenösem Kontrastmittel in der 18F-FDG PET/CT auf SUVmax und SUVmean im Blutpool und Lebergewebe zu untersuchen. METHODEN: In 120 Patienten, geplant für eine Ganzkörper 18F-FDG -PET/CT, wurden die maximalen und durchschnittlichen standardisierten Aufnahmewerte (SUVmax/SUVmean) in der Leber und im Blutpool, jeweils nach unterschiedlichen Messzeitpunkten (Verzögerung 0 s-140 s post injectionem) und verschiedenen Volumina von Kontrastmittel (KM; 0 ml, 80 ml, 100 ml mit einer Konzentration von 300 mg/ml Jod) gemessen. Sechs Gruppen von je 20 Patienten wurden untersucht: (1) ohne intravenöses KM, (2-5) Injektion von 100 ml KM mit einer Verzögerung von 80 s (2), 100 s (3), 120 s (4), 140 s (5), und 80 ml KM mit einer Verzögerung von 100 s (6). Es wurden jeweils die SUVmax, SUVmean, die maximalen and die durchschnittlichen Hounsfield Einheiten (HUav, HUmax) anhand manuell gezeichneter Bereiche von Interesse (ROIs) im Aortenbogen und im gesunden Lebergewebe berechnet. ERGEBNISSE: Die SUVmax im Blutpool waren im Vergleich zur Gruppe 1 signifikant höher in Gruppe 3, 4 und 6. Die Gruppen 2 und 5 zeigten ebenfalls höhere Durchschnittswerte von SUVmax, der Unterschied war jedoch nicht signifikant. Die SUVmean im Blutpool waren im Vergleich zur Gruppe 1 ebenfalls höher in den Gruppen 2, 3, 4, 5 und 6, allerdings waren die Unterschiede nur in Gruppe 3 statistisch signifikant. Im Lebergewebe zeigten sowohl SUVmax, als auch SUVmean keine signifikanten Unterschiede im Vergleich zu der nativen Kontrollgruppe. SCHLUSSFOLGERUNGEN: In der Kontrastmittel-gestützten FDG PET/CT können die SUVmax und in geringerem Ausmaß auch SUVmean im Blutpool durch Hochkontrast-CT Untersuchungen signifikant beeinflusst werden. Dies sollte bei PET/CT Protokollen bzw. Auswertungen, die auf SUVmax und SUVmean beruhen, berücksichtigt werden, zum Beispiel bei der Beurteilung des Therapieansprechens insbesondere bei stark vaskularisiertem Tumorgewebe.

Erythropoietin improves functional and histological recovery of traumatized skeletal muscle tissue.

Apart from its hematopoietic effect, erythropoietin (EPO) is known as pleiotropic cytokine with anti-inflammatory and anti-apoptotic properties. Here, we evaluated for the first time the EPO-dependent regeneration capacity in an in vivo rat model of skeletal muscle trauma. A myoblast cell line was used to study the effect of EPO on serum deprivation-induced cell apoptosis in vitro. A crush injury was performed to the left soleus muscle in 80 rats treated with either EPO or saline. Muscle recovery was assessed by analysis of contraction capacities. Intravital microscopy, BrdU/laminin double immunohistochemistry and cleaved caspase-3 immunohistochemistry of muscle tissue on days 1, 7, 14, and 42 posttrauma served for assessment of local microcirculation, tissue integrity, and cell proliferation. Serum deprivation-induced myoblast apoptosis of 23.9 +/- 1.5% was reduced by EPO to 17.2 +/- 0.8%. Contraction force analysis in the EPO-treated animals revealed significantly improved muscle strength with 10-20% higher values of twitch and tetanic forces over the 42-day observation period. EPO-treated muscle tissue displayed improved functional capillary density as well as reduced leukocytic response and consecutively macromolecular leakage over day 14. Concomitantly, muscle histology showed significantly increased numbers of BrdU-positive satellite cells and interstitial cells as well as slightly lower counts of cleaved caspase-3-positive interstitial cells. EPO results in faster and better regeneration of skeletal muscle tissue after severe trauma and goes along with improved microcirculation. Thus, EPO, a compound established as clinically safe, may represent a promising therapeutic option to optimize the posttraumatic course of muscle tissue healing.

Introduction of a new interlocked intramedullary nailing device for stabilization of critically sized femoral defects in the rat: A combined biomechanical and animal experimental study.

The goals of this study were to develop a new intramedullary, rotation-stable locking device and evaluate it biomechanically and in vivo for maintenance of a critical size osteotomy gap in a model of conscious pseudarthrosis. In standardized osteotomized rat femora (5 mm osteotomy gap) two different rotation- and axial-stable locking devices (group pS + cS) were tested in vitro with respect to biomechanics and compared to a control group without an additional locking device (K; n = 6 for each group). For in vivo studies, 27 male Sprague Dawley rats (250-300 g) underwent a femoral defect osteotomy of critical size and were stabilized by one of the three methods (n = 9 for each group). All groups were examined radiologically postoperatively, after 14 days, and after 12 weeks. In vitro testing revealed higher compression and torsional rigidities for the two locking devices (p < 0.05) compared to the control group (compression rigidity: pS = 103.6 +/- 13.2; cS = 91.3 +/- 10.9; K = 52.8 +/- 8.4 N/mm; torsional rigidity: pS = 5.9 +/- 0.9; cS = 4.3 +/- 1.4; K = 0.4 +/- 0.1 Nmm/ degrees ). In vivo, group K and pS exhibited up to two thirds wire dislocation and reduction of the osteotomy gap, while dislocation was less frequent in the cS group. Thus, the locking device with compression of the wire showed advantages in rotational and axial stability for a critically sized defect, though the osteotomy gap could not be maintained in all cases over the 12-week period. Nevertheless, our data corroborate the necessity of an internal fixation device with sufficient axial and rotational stability.

Ischemic preconditioning prevents skeletal muscle tissue injury, but not nerve lesion upon tourniquet-induced ischemia.

BACKGROUND: Prolonged ischemia followed by reperfusion (I/R) of skeletal muscle results in significant tissue injury. Ischemic preconditioning (IPC), achieved by brief periods of ischemia before sustained ischemia, has been shown to ameliorate I/R injury in a variety of tissues. We demonstrate that tourniquet hind limb ischemia-induced injury of the muscle benefits from IPC, whereas the peripheral nerve suffers from prolonged ischemia time and mechanical deterioration on IPC. METHODS: In anesthetized rats, hind limb ischemia was induced by tourniquet for 3 hours followed by 24 hours of reperfusion. In an additional series of experiments, IPC (three cycles of 10 minutes I/10 minutes R) preceded hind limb ischemia. Sham-operated animals without ischemia served as controls. Skeletal muscle tissue injury was assessed with respect to microcirculation, inflammatory cell response, and cell integrity using intravital fluorescence microscopy, Western blot protein analysis, and tissue histochemistry. Analysis of tactile and thermal allodynia served as indicators for postischemic pain. In addition, motor nerve conduction velocity and transmission electron microscopy allowed assessing postischemic nerve lesion. RESULTS: Tourniquet of the hind limb caused marked perfusion failure, enhanced leukocyte-endothelial cell interaction, and apoptotic cell death. IPC was able to improve microvascular perfusion and to reduce inflammatory cell response. Of interest, apoptotic cell death, assessed by cell nuclear morphology in vivo as well as Western blot and immunohistochemical analysis of caspase-3 cleavage, can be substantially reduced by IPC in tourniquet ischemia of the hind limb. Application of the tourniquet abolished nerve conduction in all animals. Non-IPC-treated animals still showed tactile allodynia, whereas IPC further caused loss of pain sensation and motor function of the postischemic hind limb. CONCLUSIONS: High susceptibility of the peripheral nerve to compression-induced ischemic injury disproves IPC in its clinical application for surgical procedures requiring prolonged tourniquet ischemia.

Migration of Salmonella typhimurium --harboring bone marrow--derived dendritic cells towards the chemokines CCL19 and CCL21.

Macrophages are considered as main cellular target encountered by the facultative intracellular bacterium Salmonella typhimurium. However, in orally infected mice these pathogens are first internalized by dendritic cells (DCs) that are located in the subepithelial dome of Peyer's patches. Moreover, DCs can penetrate the intestinal epithelium to sample bacteria. Here, we examined the interaction of Salmonella with bone marrow-derived DCs (BM-DCs). In order to study the role of DCs as vehicles for the dissemination of Salmonella, an in vitro model was established. In this model, Salmonella -activated BM-DCs enhanced surface expression of MHC class II and co-stimulatory molecules. We found that, upon maturation, BM-DCs upregulated chemokine receptor 7 (CCR7) mRNA and surface molecule expression. Salmonella -exposed DCs as well as mature DCs, but not immature DCs, were recruited towards the CC chemokines CCL19 and CCL21, two ligands of CCR7. The maturation process of DCs did neither require bacterial internalization nor viability. About one third of the migrated BM-DCs harbored intracellular bacteria, whereas the remaining two third did not contain bacteria. Salmonella, but not an apathogenic E. coli laboratory strain was capable to survive within BM-DCs. Taken together, our data implicate that DCs are first activated and subsequently utilized as carriers by Salmonella.