Structure and function of complex brain networks

An increasing number of theoretical and empirical studies approach the function of the human brain from a network perspective. The analysis of brain networks is made feasible by the development of new imaging acquisition methods as well as new tools from graph theory and dynamical systems. This review surveys some of these methodological advances and summarizes recent findings on the architecture of structural and functional brain networks. Studies of the structural connectome reveal several modules or network communities that are interlinked by hub regions mediating communication processes between modules. Recent network analyses have shown that network hubs form a densely linked collective called a “rich club,” centrally positioned for attracting and dispersing signal traffic. In parallel, recordings of resting and task-evoked neural activity have revealed distinct resting-state networks that contribute to functions in distinct cognitive domains. Network methods are increasingly applied in a clinical context, and their promise for elucidating neural substrates of brain and mental disorders is discussed.     

Reverse Engineering of Biochemical Reaction Networks Using Co-evolution with Eng-Genes

A major challenge when attempting to model biochemical reaction networks within the cell is that the dimensionality can become huge, where a large number of molecular species can be involved even in relatively small networks. This investigation attempts to infer models of these networks using a co-evolutionary algorithm that reverse engineers differential equation models of the target system from time-series data. The algorithm not only estimates the system parameters, but also the symbolic structure of the network. To reduce the problem of dimensionality, the algorithm uses a partitioning method while integrating candidate models in order to decouple system equations. In addition, the conventional evolutionary algorithm has been modified and extended to include a technique called ‘eng-genes’, where candidate models are built up from fundamental mathematical terms derived from knowledge about the target system a priori. This technique essentially focuses the search on more biologically plausible models. The approach is demonstrated on several example reaction networks. The results show that the eng-genes method of limiting the term pool using a priori knowledge improves the convergence of the reverse engineering process compared with the conventional method, resulting in more accurate and transparent models.     

Characterization of 18F-FDG uptake in human endothelial cells in vitro.

The contribution of (18)F-FDG uptake by endothelial cells to uptake values measured by PET in various tissues is as yet unclear. We therefore sought to characterize (18)F-FDG uptake in an in vitro model of human endothelial cells. METHODS: Commercially obtained human umbilical vein endothelial cells (HUVECs) were seeded in 6-multiwell plates 48-96 h before incubation with 1-2 MBq (18)F-FDG per well. Radioactivity measurements were performed after washing and mechanical dissolvation of the cellular monolayers. Cellular (18)F-FDG uptake was referred to protein concentration. This experimental protocol was subsequently varied to study the effect of different parameters of interest. Furthermore, radio-thin-layer chromatography was used to identify intracellular (18)F-FDG metabolites. (18)F-FDG uptake in HUVECs was compared with that by a human monocyte-macrophage (HMM) preparation and by glioblastoma cells (GLIOs) under identical experimental conditions. RESULTS: (18)F-FDG accumulated in HUVECs in a time-dependent manner and was trapped mainly as (18)F-FDG-6-phosphate and (18)F-FDG-1,6-diphosphate. Unlabeled glucose and cytochalasin B competitively inhibited (18)F-FDG uptake, whereas phlorizin had no significant effect. Glucose deprivation significantly enhanced (18)F-FDG uptake by a factor of 2.7, whereas sodium depletion had no significant influence. HUVECs treated with vascular endothelial growth factor (VEGF) showed a significant 82% increase in (18)F-FDG accumulation after a 2-h exposure to 50 ng/mL VEGF. (18)F-FDG uptake in HUVECs was significantly higher than that in HMMs and in the range of the uptake values measured in GLIOs. CONCLUSION: (18)F-FDG accumulates in HUVECs by mechanisms analogous to those in neoplastic cells or neurons. VEGF significantly stimulates endothelial (18)F-FDG uptake. The observed differences in (18)F-FDG uptake between HUVECs, HMMs, and GLIOs are difficult to extrapolate to in vivo conditions but stimulate further studies on the contribution of endothelial (18)F-FDG uptake to the overall uptake of that tracer in neoplastic or vascular lesions.     

Clearance of iron oxide particles in rat liver: effect of hydrated particle size and coating material on liver metabolism

OBJECTIVES: We sought to evaluate the effect of the particle size and coating material of various iron oxide preparations on the rate of rat liver clearance. MATERIALS AND METHODS: The following iron oxide formulations were used in this study: dextran-coated ferumoxide (size = 97 nm) and ferumoxtran-10 (size = 21 nm), carboxydextran-coated SHU555A (size = 69 nm) and fractionated SHU555A (size = 12 nm), and oxidized-starch coated materials either unformulated NC100150 (size = 15 nm) or formulated NC100150 injection (size = 12 nm). All formulations were administered to 165 rats at 2 dose levels. Quantitative liver R2* values were obtained during a 63-day time period. The concentration of iron oxide particles in the liver was determined by relaxometry, and these values were used to calculate the particle half-lives in the liver. RESULTS: After the administration of a high dose of iron oxide, the half-life of iron oxide particles in rat liver was 8 days for dextran-coated materials, 10 days for carboxydextran materials, 14 days for unformulated oxidized-starch, and 29 days for formulated oxidized-starch. CONCLUSIONS: The results of the study indicate that materials with similar coating but different sizes exhibited similar rates of liver clearance. It was, therefore, concluded that the coating material significantly influences the rate of iron oxide clearance in rat liver.     

Cardiac steady-state free precession CINE magnetic resonance imaging at 3.0 tesla: impact of parallel imaging acceleration on volumetric accuracy and signal parameters

OBJECTIVES: We sought to evaluate the impact of 3.0 T on accelerated CINE steady-state free precession (SSFP) regarding signal parameters and its volumetric accuracy. MATERIAL AND METHODS: Ten individuals underwent cardiac CINE imaging at 1.5 T and 3.0 T using standard single-slice CINE and multislice TSENSE-accelerated CINE (5 slices/breath-hold) with 4-fold acceleration. Data were evaluated for left ventricular volumetric parameters (EDV, ESV, and EF) as well as for SNR and CNR. Phantom based data allowed for g-factor evaluation for estimation of noise levels for accelerated data sets. Volumetric results and signal parameters were compared with results of single-slice CINE SSFP at 1.5 T as standard of reference (SOR). RESULTS: Single-slice CINE at 3.0 T showed a approximately 90% increase in CNR compared with the SOR (P < 0.001). At 3.0 T, TSENSE CINE showed a less pronounced estimated loss in CNR (-58 +/- 6%) compared with single-slice CINE than at 1.5 T (-71 +/- 2%). 3.0 T TSENSE CINE showed a 21 +/- 18% lower CNR than the nonaccelerated 1.5 T CINE (P < 0.05). EF results for all data sets did not show any significant error while for EDV some errors have been encountered. CONCLUSION: 3.0 T permits compensation for the high CNR loss, which accompanies the 4-fold TSENSE acceleration at 1.5 T and shows volumetric accuracy. The use of parallel imaging may help to alleviate SAR limitations at higher field strength.     

Morphologic and functional changes in nontumorous liver tissue after radiofrequency ablation in an in vivo model: comparison of 18F-FDG PET/CT, MRI, ultrasound, and CT.

Rimlike contrast enhancement on morphologic imaging and increased tracer uptake on (18)F-FDG PET in the periphery of the necrosis can hamper differentiation of residual tumor from regenerative tissue after radiofrequency ablation of liver lesions. This study used MRI, CT, ultrasound, and (18)F-FDG PET/CT to assess the typical appearance of lesions in nontumorous animal liver tissue after radiofrequency ablation. METHODS: Lesions were created by radiofrequency ablation of normal liver parenchyma in 21 minipigs. Follow-up was performed by 3 contrast-enhanced morphologic modalities-MRI, CT, and ultrasound-and by (18)F-FDG PET/CT immediately, 3 and 10 d, and 1, 2, 3, and 6 mo after radiofrequency ablation. Images were evaluated qualitatively for areas of increased enhancement and regions of elevated tracer uptake. Furthermore, all images were assessed quantitatively by determination of ratios comparing enhancement/tracer uptake in the periphery of the necrosis with enhancement/tracer uptake in normal liver parenchyma. Imaging findings were compared with histopathology findings. RESULTS: Immediately after radiofrequency ablation, no increase in (18)F-FDG uptake was visible, whereas elevated enhancement was noticed in the periphery of the necrosis on all morphologic imaging procedures. At further follow-up, an area of rimlike increase in (18)F-FDG uptake surrounding the necrosis was detected on PET/CT. The rimlike pattern of increased enhancement in the arterial phase was present for all liver lesions on CT, MRI, and ultrasound, especially between day 3 and month 1 after the radiofrequency ablation. Both elevated glucose metabolism and enhancement persisted for 6 mo postinterventionally. Histologic examination showed a hemorrhagic border converting into a regeneration capsule. CONCLUSION: If performed immediately after radiofrequency ablation, (18)F-FDG PET/CT probably has benefits over those of morphologic imaging procedures when assessing liver tissue for residual tumor. Later follow-up may be hampered by visualization of peripheral hyperperfusion and tissue regeneration. Further studies on a patient population are essential.     

Multi-slice echo-planar spectroscopic MR imaging provides both global and local metabolite measures in multiple sclerosis.

MR spectroscopy (MRS) provides information about neuronal loss or dysfunction by measuring decreases in N-acetyl aspartate (NAA), a metabolite widely believed to be a marker of neuronal viability. In multiple sclerosis (MS), whole-brain NAA (WBNAA) has been suggested as a marker of disease progression and treatment efficacy in treatment trials, and the ability to measure NAA loss in specific brain regions early in the evolution of this disease may have prognostic value. Most spectroscopic studies to date have been limited to single voxels or nonlocalized measurements of WBNAA only, and longitudinal studies have often been hampered by standardization and reproducibility problems. Multi-slice echo-planar spectroscopic imaging (EPSI) is presented as a promising alternative to single-voxel or nonlocalized spectroscopy for obtaining global metabolite estimates in MS. In the same session, measurements of metabolites in specific brain areas chosen after image acquisition (e.g., normal-appearing white matter (NAWM), gray matter (GM), and lesions) can be obtained. The identification and exclusion of regions that are inadequate for spectroscopic evaluation in global assessments can significantly improve quality and reproducibility, as demonstrated by a low within-subject variance in healthy controls. The reproducibility of the technique makes it a promising tool for future longitudinal spectroscopic studies of MS.     

The TIM-1:TIM-4 pathway enhances renal ischemia-reperfusion injury

CD4+ T cells contribute to the pathogenesis of ischemia-reperfusion injury, which is the primary cause of delayed graft failure after kidney transplantation. The TIM-1:TIM-4 pathway participates in the activation/differentiation of CD4+ T cells, suggesting that it may modulate ischemia-reperfusion injury. Here, we studied the role of TIM-1 in a murine uninephrectomized renal ischemia-reperfusion injury model. Blocking the TIM-1:TIM-4 pathway with an antagonistic monoclonal antibody protected renal function and diminished reperfusion injury resulting from 30 minutes of ischemia. Histologic examination showed significantly less evidence of renal damage as evidenced by diminished tubular necrosis, preservation of the brush border, fewer cast formations, and less tubular dilation. Blocking TIM-1 also reduced the number of apoptotic cells and diminished local inflammation within ischemic kidneys, the latter shown by decreased recruitment of macrophages, neutrophils, and CD4+ T cells and by reduced local production of proinflammatory cytokines. Furthermore, TIM-1 blockade significantly improved survival after ischemia-reperfusion injury. Taken together, these data suggest that the TIM-1:TIM-4 pathway enhances injury after renal ischemia-reperfusion injury and may be a therapeutic target.     

Study on the clinical application of pulsed DC magnetic technology for tracking of intraoperative head motion during frameless stereotaxy

Background

Tracking of post-registration head motion is one of the major problems in frameless stereotaxy. Various attempts in detecting and compensating for this phenomenon rely on a fixed reference device rigidly attached to the patient's head. However, most of such reference tools are either based on an invasive fixation technique or have physical limitations which allow mobility of the head only in a restricted range of motion after completion of the registration procedure.

Methods

A new sensor-based reference tool, the so-called Dynamic Reference Frame (DRF) which is designed to allow an unrestricted, 360° range of motion for the intraoperative use in pulsed DC magnetic navigation was tested in 40 patients. Different methods of non-invasive attachment dependent on the clinical need and type of procedure, as well as the resulting accuracies in the clinical application have been analyzed.

Results

Apart from conventional, completely rigid immobilization of the head (type A), four additional modes of head fixation and attachment of the DRF were distinguished on clinical grounds: type B1 = pin fixation plus oral DRF attachment; type B2 = pin fixation plus retroauricular DRF attachment; type C1 = free head positioning with oral DRF; and type C2 = free head positioning with retroauricular DRF. Mean fiducial registration errors (FRE) were as follows: type A interventions = 1.51 mm, B1 = 1.56 mm, B2 = 1.54 mm, C1 = 1.73 mm, and C2 = 1.75 mm. The mean position errors determined at the end of the intervention as a measure of application accuracy were: 1.45 mm in type A interventions, 1.26 mm in type B1, 1.44 mm in type B2, 1.86 mm in type C1, and 1.68 mm in type C2.

Conclusion

Rigid head immobilization guarantees most reliable accuracy in various types of frameless stereotaxy. The use of an additional DRF, however, increases the application scope of frameless stereotaxy to include e.g. procedures in which rigid pin fixation of the cranium is not required or desired. Thus, continuous tracking of head motion allows highly flexible variation of the surgical strategy including intraoperative repositioning of the patient without impairment of navigational accuracy as it ensures automatic correction of spatial distortion. With a dental cast for oral attachment and the alternative option of non-invasive retroauricular attachment, flexibility in the clinical use of the DRF is ensured.