Mononuclear cell composition and activation in blood and mucosal tissue of eosinophilic esophagitis.

Introduction: Eosinophilic esophagitis (EoE) is a chronic, inflammatory, antigen-driven disease of the esophagus. Tissue EoE pathology has previously been extensively characterized by novel transcriptomics and proteomic platforms, however the majority of surface marker determination and screening has been performed in blood due to mucosal tissue size limitations. While eosinophils, CD4+ T cells, mast cells and natural killer (NK) T cells were previously investigated in the context of EoE, an accurate picture of the composition of peripheral blood mononuclear cells (PBMC) and their activation is missing. Methods: In this study, we aimed to comprehensively analyze the composition of peripheral blood mononuclear cells and their activation using surface marker measurements with multicolor flow cytometry simultaneously in both blood and mucosal tissue of patients with active EoE, inactive EoE, patients with gastroesophageal reflux disease (GERD) and controls. Moreover, we set out to validate our data in co-cultures of PBMC with human primary esophageal epithelial cells and in a novel inducible mouse model of eosinophilic esophagitis, characterized by extensive IL-33 secretion in the esophagus. Results: Our results indicate that specific PBMC populations are enriched, and that they alter their surface expression of activation markers in mucosal tissue of active EoE. In particular, we observed upregulation of the immunomodulatory molecule CD38 on CD4+ T cells and on myeloid cells in biopsies of active EoE. Moreover, we observed significant upregulation of PD-1 on CD4+ and myeloid cells, which was even more prominent after corticosteroid treatment. With co-culture experiments we could demonstrate that direct cell contact is needed for PD-1 upregulation on CD4+ T cells. Finally, we validated our findings of PD-1 and CD38 upregulation in an inducible mouse model of EoE. Discussion: Herein we show significant alterations in the PBMC activation profile of patients with active EoE in comparison to inactive EoE, GERD and controls, which could have potential implications for treatment. To our knowledge, this study is the first of its kind expanding the multi-color flow cytometry approach in different patient groups using in vitro and in vivo translational models.

Tumor microenvironment-derived monoacylglycerol lipase provokes tumor-specific immune responses and lipid profiles.

We recently described that monoacylglycerol lipase (MGL) is present in the tumor microenvironment (TME), increasing tumor growth. In this study we compare the implications of MGL deficiency in the TME in different tumor types. We show that subcutaneous injection of KP (KrasLSL-G12D/p53fl/fl, mouse lung adenocarcinoma) or B16-F10 cells (mouse melanoma) induced tumor growth in MGL wild type (WT) and knockout (KO) mice. MGL deficiency in the TME attenuated the growth of KP cell tumors whereas tumors from B16-F10 cells increased in size. Opposite immune cell profiles were detected between the two tumor types in MGL KO mice. In line with their anti-tumorigenic function, the number of CD8+ effector T cells and eosinophils increased in KP cell tumors of MGL KO vs. WT mice whereas their presence was reduced in B16-F10 cell tumors of MGL KO mice. Differences were seen in lipid profiles between the investigated tumor types. 2-arachidonoylglycerol (2-AG) content significantly increased in KP, but not B16-F10 cell tumors of MGL KO vs. WT mice while other endocannabinoid-related lipids remained unchanged. However, profiles of phospho- and lysophospholipids, sphingomyelins and fatty acids in KP cell tumors were clearly distinct to those measured in B16-F10 cell tumors. Our data indicate that TME-localized MGL impacts tumor growth, as well as levels of 2-AG and other lipids in a tumor specific manner.

Velocity-selective arterial spin labeling perfusion MRI: A review of the state of the art and recommendations for clinical implementation.

This review article provides an overview of the current status of velocity-selective arterial spin labeling (VSASL) perfusion MRI and is part of a wider effort arising from the International Society for Magnetic Resonance in Medicine (ISMRM) Perfusion Study Group. Since publication of the 2015 consensus paper on arterial spin labeling (ASL) for cerebral perfusion imaging, important advancements have been made in the field. The ASL community has, therefore, decided to provide an extended perspective on various aspects of technical development and application. Because VSASL has the potential to become a principal ASL method because of its unique advantages over traditional approaches, an in-depth discussion was warranted. VSASL labels blood based on its velocity and creates a magnetic bolus immediately proximal to the microvasculature within the imaging volume. VSASL is, therefore, insensitive to transit delay effects, in contrast to spatially selective pulsed and (pseudo-) continuous ASL approaches. Recent technical developments have improved the robustness and the labeling efficiency of VSASL, making it a potentially more favorable ASL approach in a wide range of applications where transit delay effects are of concern. In this review article, we (1) describe the concepts and theoretical basis of VSASL; (2) describe different variants of VSASL and their implementation; (3) provide recommended parameters and practices for clinical adoption; (4) describe challenges in developing and implementing VSASL; and (5) describe its current applications. As VSASL continues to undergo rapid development, the focus of this review is to summarize the fundamental concepts of VSASL, describe existing VSASL techniques and applications, and provide recommendations to help the clinical community adopt VSASL.

Validation of the estimation of the macrovascular contribution in multi-timepoint arterial spin labeling MRI using a 2-component kinetic model.

PURPOSE: In this paper, the ability to quantify cerebral blood flow by arterial spin labeling (ASL) was studied by investigating the separation of the macrovascular and tissue component using a 2-component model. Underlying assumptions of this model, especially the inclusion of dispersion in the analysis, were studied, as well as the temporal resolution of the ASL datasets. METHODS: Four different datasets were acquired: (1) 4D ASL angiography to characterize the macrovascular component and to study dispersion modeling within this component, (2) high temporal resolution ASL data to investigate the separation of the 2 components and the effect of dispersion modelling on this separation, (3) low temporal resolution ASL dataset to study the effect of the temporal resolution on the separation of the 2 components, and (4) low temporal resolution ASL data with vascular crushing. RESULTS: The model that included a gamma dispersion kernel had the best fit to the 4D ASL angiography. For the high temporal resolution ASL dataset, inclusion of the gamma dispersion kernel led to more signal included in the arterial blood volume map, which resulted in decreased cerebral blood flow values. The arterial blood volume and cerebral blood flow maps showed overall higher arterial blood volume values and lower cerebral blood flow values for the high temporal resolution dataset compared to the low temporal resolution dataset. CONCLUSION: Inclusion of a gamma dispersion kernel resulted in better fitting of the model to the data. The separation of the macrovascular and tissue component is affected by the inclusion of a gamma dispersion kernel and the temporal resolution of the ASL dataset.

Time-encoded golden angle radial arterial spin labeling: Simultaneous acquisition of angiography and perfusion data.

The objective of the current study was to combine a time-encoded pseudocontinuous arterial spin labeling (te-pCASL) scheme with a golden angle radial readout for simultaneous acquisition of angiography and perfusion images from one single dataset, both in a highly flexible single-slice approach as well as within a multislice setting. A te-pCASL preparation and the golden angle radial readout were both used as a temporal resolution tool to retrospectively choose the temporal window for the reconstruction of both angiography and perfusion images from a single-slice dataset. The temporal window could be chosen retrospectively and adjusted to the hemodynamics of the volunteer on the scanner for the single-slice dataset. Angiographic images were reconstructed at a minimum temporal resolution of 69 ms. For the perfusion phase, only the densely sampled center of k-space was included in the reconstruction. For a multislice acquisition, the golden angle radial readout allowed reconstruction of images with different spatial resolutions to provide angiographic and perfusion information over 10 slices. The te-pCASL preparation was used as the only source for dynamic information. The multislice acquisition shows the ability of the golden angle radial readout to display the inflow of the labeled blood into the arteries as well as the perfusion in the tissue with full brain coverage. By combining a te-pCASL preparation with a golden angle radial readout, single-slice high temporal resolution angiography and good quality perfusion images were reconstructed in a flexible manner from a single dataset. Optimizing the golden angle radial readout for reconstructions at multiple spatial resolutions allows for multislice acquisition.

Exploring label dynamics of velocity-selective arterial spin labeling in the kidney.

PURPOSE: Velocity-selective arterial spin labeling (VSASL) has been proposed for renal perfusion imaging to mitigate planning challenges and effects of arterial transit time (ATT) uncertainties. In VSASL, label generation may shift in the vascular tree as a function of cutoff velocity. Here, we investigate label dynamics and especially the ATT of renal VSASL and compared it with a spatially selective pulsed arterial spin labeling technique, flow alternating inversion recovery (FAIR). METHODS: Arterial spin labeling data were acquired in 7 subjects, using free-breathing dual VSASL and FAIR with five postlabeling delays: 400, 800, 1200, 2000, and 2600 ms. The VSASL measurements were acquired with cutoff velocities of 5, 10, and 15 cm/s, with anterior-posterior velocity-encoding direction. Cortical perfusion-weighted signal, temporal SNR, quantified renal blood flow, and arterial transit time were reported. RESULTS: In contrast to FAIR, renal VSASL already showed fairly high signal at the earliest postlabeling delays, for all cutoff velocities. The highest VSASL signal and temporal SNR was obtained with a cutoff velocity of 10 cm/s at postlabeling delay = 800 ms, which was earlier than for FAIR at 1200 ms. Fitted ATT on VSASL was ≤ 0 ms, indicating ATT insensitivity, which was shorter than for FAIR (189 ± 79 ms, P < .05). Finally, the average cortical renal blood flow measured with cutoff velocities of 5 cm/s (398 ± 84 mL/min/100 g) and 10 cm/s (472 ± 160 mL/min/100 g) were similar to renal blood flow measured with FAIR (441 ± 84 mL/min/100 g) (P > .05) with good correlations on subject level. CONCLUSION: Velocity-selective arterial spin labeling in the kidney reduces ATT sensitivity compared with the recommended pulsed arterial spin labeling method, as well as if cutoff velocity is increased to reduce spurious labeling due to motion. Thus, VSASL has potential as a method for time-efficient, single-time-point, free-breathing renal perfusion measurements, despite lower tSNR than FAIR.

Multi-organ comparison of flow-based arterial spin labeling techniques: Spatially non-selective labeling for cerebral and renal perfusion imaging.

PURPOSE: Flow-based arterial spin labeling (ASL) techniques provide a transit-time insensitive alternative to the more conventional spatially selective ASL techniques. However, it is not clear which flow-based ASL technique performs best and also, how these techniques perform outside the brain (taking into account eg, flow-dynamics, field-inhomogeneity, and organ motion). In the current study we aimed to compare 4 flow-based ASL techniques (ie, velocity selective ASL, acceleration selective ASL, multiple velocity selective saturation ASL, and velocity selective inversion prepared ASL [VSI-ASL]) to the current spatially selective reference techniques in brain (ie, pseudo-continuous ASL [pCASL]) and kidney (ie, pCASL and flow alternating inversion recovery [FAIR]). METHODS: Brain (n = 5) and kidney (n = 6) scans were performed in healthy subjects at 3T. Perfusion-weighted signal (PWS) maps were generated and ASL techniques were compared based on temporal SNR (tSNR), sensitivity to perfusion changes using a visual stimulus (brain) and robustness to respiratory motion by comparing scans acquired in paced-breathing and free-breathing (kidney). RESULTS: In brain, all flow-based ASL techniques showed similar tSNR as pCASL, but only VSI-ASL showed similar sensitivity to perfusion changes. In kidney, all flow-based ASL techniques had comparable tSNR, although all lower than FAIR. In addition, VSI-ASL showed a sensitivity to B1 -inhomogeneity. All ASL techniques were relatively robust to respiratory motion. CONCLUSION: In both brain and kidney, flow-based ASL techniques provide a planning-free and transit-time insensitive alternative to spatially selective ASL techniques. VSI-ASL shows the most potential overall, showing similar performance as the golden standard pCASL in brain. However, in kidney, a reduction of B1 -sensitivity of VSI-ASL is necessary to match the performance of FAIR.

Combining T2 measurements and crusher gradients into a single ASL sequence for comparison of the measurement of water transport across the blood-brain barrier.

PURPOSE: Arterial spin labeling can be used to assess the transition time of water molecules across the blood-brain barrier when combined with sequence modules, which allow a separation of intravascular from tissue signal. The bipolar gradient technique measures the intravascular fraction by removing flowing spins. The T2 -relaxation-under-spin-tagging (TRUST) technique modulates the TE to differentiate between intravascular and extravascular spins based on T2 . These modules were combined into a single time-encoded pseudo-continuous arterial spin labeling sequence to compare their mechanisms of action as well as their assessment of water transition across the blood-brain barrier. METHODS: This protocol was acquired on a scanner with 9 healthy volunteers who provided written, informed consent. The sequence consisted of a Hadamard-encoded pseudo-continuous arterial spin labeling module, followed by the TRUST module (effective TEs of 0, 40, and 80 ms) and bipolar flow-crushing gradients (2, 4, and ∞ cm/s). An additional experiment was performed with TRUST and a 3D gradient and spin-echo readout. RESULTS: Gradients imperfectly canceled the intravascular signal, as evidenced by the presence of residual signal in the arteries at early postlabeling delays as well as the underestimation of the intravascular fraction as compared with the TRUST method. The TRUST module allowed us to detect the transport of water deeper into the vascular tree through changes in T2 than the used crusher gradients could, with their limited b-value. CONCLUSION: Of the implemented techniques, TRUST allowed us to follow intravascular signal deeper into the vascular tree than the approach with (relatively weak) crusher gradients when quantifying the transport time of water across the blood-brain barrier.

Influence of the cardiac cycle on velocity selective and acceleration selective arterial spin labeling.

PURPOSE: In this study, the influence of the cardiac cycle on the amount of label produced by a velocity-selective (VSASL) and acceleration-selective arterial spin labeling (AccASL) module was investigated. METHODS: A short-PLD sequence was developed where a single VSASL- or AccASL-module was preceded by pCASL labeling to isolate the arterial blood pool. ASL subtraction was performed with label/control images with similar cardiac phase and time-of-measurement, followed by retrospective binning in 10 cardiac phase bins. ASL signal variation over the heart cycle was evaluated and tested for significance using a permutation test. RESULTS: VSASL and AccASL showed significant arterial signal fluctuations over the cardiac cycle of up to ~36% and ~64%, respectively, mainly in areas containing large arteries. pCASL also showed significant signal fluctuations, of up to ~25% in arteries. Raw label/control images confirmed that the observed signal fluctuations were caused by the amount of label produced during the cardiac cycle, rather than inflow-effects, because the raw images did not all show equal cardiac phase dependence. No significant effects of the cardiac cycle were found on the gray matter ASL-signal. CONCLUSION: Significant influence of the cardiac cycle on the generated label was found for spatially nonselective ASL-sequences. Hence, to become independent of the cardiac cycle, sufficient averages need to be taken. Alternatively, these findings could be highly interesting for the purpose of quantifying pulsatility more distally in the vascular tree.

High temporal resolution arterial spin labeling MRI with whole-brain coverage by combining time-encoding with Look-Locker and simultaneous multi-slice imaging.

PURPOSE: The goal of this study was to achieve high temporal resolution, multi-time point pseudo-continuous arterial spin labeling (pCASL) MRI in a time-efficient manner, while maintaining whole-brain coverage. METHODS: A Hadamard 8-matrix was used to dynamically encode the pCASL labeling train, thereby providing the first source of temporal information. The second method for obtaining dynamic arterial spin labeling (ASL) signal consisted of a Look-Locker (LL) readout of 4 phases that are acquired with a flip-angle sweep to maintain constant sensitivity over the phases. To obtain whole-brain coverage in the short LL interval, 4 slices were excited simultaneously by multi-banded radiofrequency pulses. After subtraction according to the Hadamard scheme, the ASL signal was corrected for the use of the flip-angle sweep and background suppression pulses. The BASIL toolkit of the Oxford Centre for FMRIB was used to quantify the ASL signal. RESULTS: By combining a time-encoded pCASL labeling scheme with an LL readout and simultaneous multi-slice acquisition, 28 time points of 16 slices with a 75- or 150-ms time resolution were acquired in a total scan time of 10 minutes 20 seconds, from which cerebral blood flow (CBF) maps, arterial transit time maps, and arterial blood volume could be determined. CONCLUSION: Whole-brain ASL images were acquired with a 75-ms time resolution for the angiography and 150-ms resolution for the perfusion phase by combining the proposed techniques. Reducing the total scan time to 1 minute 18 seconds still resulted in reasonable CBF maps, which demonstrates the feasibility of this approach for practical studies on brain hemodynamics.

Advances in arterial spin labelling MRI methods for measuring perfusion and collateral flow.

With the publication in 2015 of the consensus statement by the perfusion study group of the International Society for Magnetic Resonance in Medicine (ISMRM) and the EU-COST action 'ASL in dementia' on the implementation of arterial spin labelling MRI (ASL) in a clinical setting, the development of ASL can be considered to have become mature and ready for clinical prime-time. In this review article new developments and remaining issues will be discussed, especially focusing on quantification of ASL as well as on new technological developments of ASL for perfusion imaging and flow territory mapping. Uncertainty of the achieved labelling efficiency in pseudo-continuous ASL (pCASL) as well as the presence of arterial transit time artefacts, can be considered the main remaining challenges for the use of quantitative cerebral blood flow (CBF) values. New developments in ASL centre around time-efficient acquisition of dynamic ASL-images by means of time-encoded pCASL and diversification of information content, for example by combined 4D-angiography with perfusion imaging. Current vessel-encoded and super-selective pCASL-methodology have developed into easily applied flow-territory mapping methods providing relevant clinical information with highly similar information content as digital subtraction angiography (DSA), the current clinical standard. Both approaches seem therefore to be ready for clinical use.

Cerebral magnetic resonance imaging in quiescent Crohn's disease patients with fatigue.

AIM: To evaluate brain involvement in quiescent Crohn's disease (CD) patients with fatigue using quantitative magnetic resonance imaging (MRI). METHODS: Multiple MRI techniques were used to assess cerebral changes in 20 quiescent CD patients with fatigue (defined with at least 6 points out of an 11-point numeric rating scale compared with 17 healthy age and gender matched controls without fatigue. Furthermore, mental status was assessed by cognitive functioning, based on the neuropsychological inventory including the different domains global cognitive functioning, memory and executive functioning and in addition mood and quality of life scores. Cognitive functioning and mood status were correlated with MRI findings in the both study groups. RESULTS: Reduced glutamate + glutamine (Glx = Glu + Gln) concentrations (P = 0.02) and ratios to total creatine (P = 0.02) were found in CD patients compared with controls. Significant increased Cerebral Blood Flow (P = 0.05) was found in CD patients (53.08 ± 6.14 mL/100 g/min) compared with controls (47.60 ± 8.62 mL/100 g/min). CD patients encountered significantly more depressive symptoms (P < 0.001). Cognitive functioning scores related to memory (P = 0.007) and executive functioning (P = 0.02) were lower in CD patients and both scores showed correlation with depression and anxiety. No correlation was found subcortical volumes between CD patients and controls in the T1-weighted analysis. In addition, no correlation was found between mental status and MRI findings. CONCLUSION: This work shows evidence for perfusion, neurochemical and mental differences in the brain of CD patients with fatigue compared with healthy controls.

Decreased cerebral perfusion in Duchenne muscular dystrophy patients.

Duchenne muscular dystrophy is caused by dystrophin gene mutations which lead to the absence of the protein dystrophin. A significant proportion of patients suffer from learning and behavioural disabilities, in addition to muscle weakness. We have previously shown that these patients have a smaller total brain and grey matter volume, and altered white matter microstructure compared to healthy controls. Patients with more distal gene mutations, predicted to affect dystrophin isoforms Dp140 and Dp427, showed greater grey matter reduction. Now, we studied if cerebral blood flow in Duchenne muscular dystrophy patients is altered, since cerebral expression of dystrophin also occurs in vascular endothelial cells and astrocytes associated with cerebral vasculature. T1-weighted anatomical and pseudo-continuous arterial spin labeling cerebral blood flow images were obtained from 26 patients and 19 age-matched controls (ages 8-18 years) on a 3 tesla MRI scanner. Group comparisons of cerebral blood flow were made with and without correcting for grey matter volume using partial volume correction. Results showed that patients had a lower cerebral blood flow than controls (40.0 ± 6.4 and 47.8 ± 6.3 mL/100 g/min respectively, p = 0.0002). This reduction was independent of grey matter volume, suggesting that they are two different aspects of the pathophysiology. Cerebral blood flow was lowest in patients lacking Dp140. There was no difference in CBF between ambulant and non-ambulant patients. Only three patients showed a reduced left ventricular ejection fraction. No correlation between cerebral blood flow and age was found. Our results indicate that cerebral perfusion is reduced in Duchenne muscular dystrophy patients independent of the reduced grey matter volume.

Insight into the labeling mechanism of acceleration selective arterial spin labeling.

OBJECTIVES: Acceleration selective arterial spin labeling (AccASL) is a spatially non-selective labeling technique, used in traditional ASL methods, which labels spins based on their flow acceleration rather than spatial localization. The exact origin of the AccASL signal within the vasculature is not completely understood. To obtain more insight into this, the acceleration selective module was performed followed by a velocity selective module, which is used in velocity selective arterial spin labeling (VS-ASL). MATERIALS AND METHODS: Nine healthy volunteers were scanned with various combinations of the control and label conditions in both the acceleration and velocity selective module. The cut-off acceleration (0.59 m/s2) or velocity (2 cm/s) was kept constant in one module, while it was varied over a large range in the other module. With the right subtractions this resulted in AccASL, VS-ASL, combined AccASL and VS-ASL signal, and signal from one module with crushing from the other. RESULTS: The label created with AccASL has an overlap of approximately 50% in the vascular region with VS-ASL, but also originates from smaller vessels closer to the capillaries. CONCLUSION: AccASL is able to label spins both in the macro- and meso-vasculature, as well as in the microvasculature.

Time-efficient determination of spin compartments by time-encoded pCASL T2-relaxation-under-spin-tagging and its application in hemodynamic characterization of the cerebral border zones.

Information on water-transport across the blood-brain barrier can be determined from the T2 of the arterial spin labeling (ASL) signal. However, the current approach of using separate acquisitions of multiple inversion times is too time-consuming for clinical (research) applications. The aim of this study was to improve the time-efficiency of this method by combining it with time-encoded pseudo-continuous ASL (te-pCASL). Furthermore, the hemodynamic properties of the border zone regions in the brains of healthy, young volunteers were characterized as an example application. The use of te-pCASL instead of multi-TI pCASL significantly reduced the total scan duration, while providing a higher temporal resolution. A significantly lower cerebral blood flow (CBF) was found in the border zone regions compared with the central regions in both the posterior and the middle cerebral artery (MCA) flow territory. The arterial transit time (ATT) was almost two times longer in the border zone regions than in the central regions (p<0.05), with an average delay in ATT of 382ms in the posterior and 539ms in the MCA flow territory. When corrected for the ATT, the change in T2 over time was not significantly different for the border zones as compared to the central regions. In conclusion, te-pCASL-TRUST provided a time-efficient method to distinguish spin compartments based on their T2. The ATT in the border zone is significantly longer than in the central region. However, the exchange of the label from the arterial to the tissue compartment appears to be at a similar rate.

Comparison of velocity- and acceleration-selective arterial spin labeling with [15O]H2O positron emission tomography.

In the last decade spatially nonselective arterial spin labeling (SNS-ASL) methods such as velocity-selective ASL (VS-ASL) and acceleration-selective ASL have been introduced, which label spins based on their flow velocity or acceleration rather than spatial localization. Since labeling also occurs within the imaging plane, these methods suffer less from transit delay effects than traditional ASL methods. However, there is a need for validation of these techniques. In this study, a comparison was made between these SNS-ASL techniques with [(15)O]H2O positron emission tomography (PET), which is regarded as gold standard to measure quantitatively cerebral blood flow (CBF) in humans. In addition, the question of whether these techniques suffered from sensitivity to arterial cerebral blood volume (aCBV), as opposed to producing pure CBF contrast, was investigated. The results show high voxelwise intracranial correlation (0.72 to 0.89) between the spatial distribution of the perfusion signal from the SNS-ASL methods and the PET CBF maps. A similar gray matter (GM) CBF was measured by dual VS-ASL compared with PET (46.7 ± 4.1 versus 47.1 ± 6.5 mL/100 g/min, respectively). Finally, only minor contribution of aCBV patterns in GM to all SNS-ASL methods was found compared with pseudo-continuous ASL. In conclusion, VS-ASL provides a similar quantitative CBF, and all SNS-ASL methods provide qualitatively similar CBF maps as [(15)O]H2O PET.

Thrombosis as a complication of central venous access in pediatric patients with malignancies: a 5-year single-center experience.

BACKGROUND: Reliable central venous access (CVC) is essential for hematology-oncology patients since frequent puncture of peripheral veins-e.g., for chemotherapy, antibiotic administration, repeated blood sampling, and monitoring-can cause unacceptable pain and psychological trauma, as well as severe side effects in cases of extravasation of chemotherapy drugs. However, CVC lines still carry major risk factors, including thrombosis, infection (e.g., entry site, tunnel, and luminal infections), and catheter dislocation, leakage, or breakage. METHODS: Here we performed a retrospective database analysis to determine the incidence of CVC-associated thrombosis in a single-center cohort of 448 pediatric oncologic patients, and to analyze whether any subgroup of patients was at increased risk and thus might benefit from prophylactic anticoagulation. RESULTS: Of the 448 patients, 269 consecutive patients received a CVC, and 55 of these 269 patients (20%) also had a thrombosis. Of these 55 patients, 43 had at least one CVC-associated thrombosis (total number of CVC-associated thrombosis: n = 52). Among all patients, the median duration of CVC exposure was 464 days. Regarding exposure time, no significant difference was found between patients with and without CVC-associated thrombosis. Subclavia catheters and advanced tumor stages seem to be the main risk factors for the development of CVC-associated thrombosis, whereas pharmacologic prophylaxis did not seem to have a relevant impact on the rate of thrombosis. CONCLUSIONS: We conclude that pediatric surgeons and oncologists should pay close attention to ensuring optimal and accurate CVC placement, as this appears the most effective tool to minimize CVC-associated complications.

Effects of background suppression on the sensitivity of dual-echo arterial spin labeling MRI for BOLD and CBF signal changes.

Dual-echo arterial spin labeling (DE-ASL) enables the simultaneous acquisition of BOLD and CBF fMRI data and is often used for calibrated BOLD and cerebrovascular CO2 reactivity measurements. DE-ASL, like all ASL techniques, suffers from a low intrinsic CBF SNR, which can be improved by suppressing the background signal via the inclusion of additional inversion pulses. However, until now this approach has been considered to be undesirable for DE-ASL, because the BOLD signal is extracted from the background signal and attenuating the background signal could decrease the sensitivity of DE-ASL scans for BOLD changes. In this study, the effect of background suppression on the sensitivity of DE-ASL MRI for BOLD and CBF signal changes with a visual stimulation paradigm was studied. Results showed that with an average background suppression level of 70% the BOLD sensitivity of DE-ASL MRI decreases slightly (15%), while the CBF sensitivity of the scans increased by almost a factor-of-two (81%). These findings support the conclusion that the gains in CBF sensitivity of DE-ASL MRI due to background suppression outweigh the slight decrease in sensitivity of these scans for BOLD changes, and thus that background suppression is highly recommended for DE-ASL.