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A prominent trend in spatial audio research is the realization of virtual acoustic environments based on binaural technology. This study estimates the perceptual influence of system errors on the binaural reproduction of spherical microphone array data for room simulation applications. Specifically, the impact of spatial aliasing, system noise, and microphone positioning errors is perceptually analyzed in a listening experiment using an auditory model. Perceptual and technical data are related by various predictive modeling techniques, which enable estimating the perceptual strength of system errors. The experimental data comprises spherical array simulations under free-field conditions and in two reflective environments, a dry and a reverberant shoebox-shaped room, using five different audio signals for auralization. Results show that error prediction is possible with high accuracy and low errors using nonlinear modeling techniques such as artificial neural networks.

The current high mortality of human lung cancer stems largely from the lack of feasible, early disease detection tools. An effective test with serum metabolomics predictive models able to suggest patients harboring disease could expedite triage patient to specialized imaging assessment. Here, using a training-validation-testing-cohort design, we establish our high-resolution magic angle spinning (HRMAS) magnetic resonance spectroscopy (MRS)-based metabolomics predictive models to indicate lung cancer presence and patient survival using serum samples collected prior to their disease diagnoses. Studied serum samples were collected from 79 patients before (within 5.0 y) and at lung cancer diagnosis. Disease predictive models were established by comparing serum metabolomic patterns between our training cohorts: patients with lung cancer at time of diagnosis, and matched healthy controls. These predictive models were then applied to evaluate serum samples of our validation and testing cohorts, all collected from patients before their lung cancer diagnosis. Our study found that the predictive model yielded values for prior-to-detection serum samples to be intermediate between values for patients at time of diagnosis and for healthy controls; these intermediate values significantly differed from both groups, with an F1 score = 0.628 for cancer prediction. Furthermore, values from metabolomics predictive model measured from prior-to-diagnosis sera could significantly predict 5-y survival for patients with localized disease.

Purpose Recent research identified histone H3 K27M mutations to be associated with a dismal prognosis in pediatric diffuse midline glioma (pDMG); however, data on detailed MRI characteristics with respect to H3 K27 mutation status and molecular subgroups (H3.1 and H3.3 K27M mutations) are limited. Methods Standardized magnetic resonance imaging (MRI) parameters and epidemiologic data of 68 pDMG patients (age Results Intracranial gliomas (n = 58) showed heterogeneous phenotypes with isointense to hyperintense signal in T2-weighted images and frequent contrast enhancement. Hemorrhage and necrosis may be present. Comparing H3 K27M mutant to WT tumors, there were significant differences in the following parameters: i) tumor localization (p = 0.001), ii) T2 signal intensity (p = 0.021), and iii) T1 signal homogeneity (p = 0.02). No significant imaging differences were found in any parameter between H3.1 and H3.3 K27M mutant tumors; however, H3.1 mutant tumors occurred at a younger age (p = 0.004). Considering spinal gliomas (n = 10) there were no significant imaging differences between the analyzed molecular groups. Conclusion With this study, we are the first to provide detailed MR imaging data on H3 K27M mutant pDMG with respect to molecular subgroup status in a large patient cohort. Our findings may support diagnosis and future targeted therapeutic trials of pDMG within the framework of the radiogenomics concept.

Urinary tests have been used as noninvasive, cost-effective tools for screening, diagnosis and monitoring of diseases since ancient times. As we progress through the 21st century, modern analytical platforms have enabled effective measurement of metabolites, with promising results for both a deeper understanding of cancer pathophysiology and, ultimately, clinical translation. The first study to measure metabolomic urinary cancer biomarkers using NMR and mass spectrometry (MS) was published in 2006 and, since then, these techniques have been used to detect cancers of the urological system (kidney, prostate and bladder) and nonurological tumours including those of the breast, ovary, lung, liver, gastrointestinal tract, pancreas, bone and blood. This growing field warrants an assessment of the current status of research developments and recommendations to help systematize future research. Urinalysis has long been used as a tool for managing diseases, but 21st century techniques have enabled measurement of metabolomic urinary cancer biomarkers using NMR and mass spectrometry. In this Review, the authors discuss the current status of research developments and offer recommendations to help systematize future research in the field.

The advent of prostate specific antigen (PSA) testing led to increased early prostate cancer (PCa) detection and has decreased PCa-related death. However, PSA is not cancer-specific, and the challenge persists of differentiating those PCa patients with indolent tumors from those requiring definitive therapy. Metabolomic profiles have the potential to capture molecular dynamics of disease and to reflect disease status before cellular manifestations become observable by histopathology. With clinical, multiparametric magnetic resonance imaging (mpMRI)-positive, fusion biopsy-targeted tissue cores and mpMRI-negative controls in a training-testing cohort design, we studied the potential of magnetic resonance spectroscopy (MRS) to yield cancer metabolomic profiles that could help discriminate likely indolent from clinically significant disease. Using MRS-based PCa metabolomic analyses, performed prior to histology, our approach is able to: determine metabolomic relevations identified in fusion biopsy targets, estimate the scale of PCa metabolomic fields, and detect clinically significant disease in tissues deemed benign or low-risk PCa by pathology and imaging. Our intact tissue MRS metabolomics evaluations indicated significant differences in individual prostate tissue metabolites based on Target-Contralateral (Contral) paired comparisons for both Training and Testing cohorts. We identified metabolomic differences among Target prostate biopsy cores obtained from mpMRI lesions of different PI-RADS scores, and between Target and non-target Contral cores. As a retrospective study, we also analyzed data collected at the time of the initial prostate biopsy alongside patient status across follow up. By introducing metabolomics, as compared with using PSAd or PI-RADS alone, the sensitivity predictions increased by 80.0% and 25.0%, respectively; NPV increased by 18.1% and 8.0%; and accuracy for PSAd increased by 13.0%. PI-RADS accuracy stayed the same Our results show that tissue metabolomic profiles could augment current MR-based imaging findings and histopathological evaluations of fusion biopsies for certain patient populations by more accurately characterizing them into clinically significant or insignificant subgroups. In our analyses, tissue metabolomics alone, or its combination with other clinical parameters, improved sensitivity and negative predictive values, as well as overall accuracy, for our testing cohort. This method, which relies on performing tissue MRS of needle biopsy cores prior to histopathologic analysis, causes no interruption to patient care. Findings from our study demonstrate the utility and translational potential of cancer metabolomics in personalized treatment for PCa and encourages the development of in vivo PCa metabolomic imaging to enhance the diagnostic utility of mpMRI. Citation Format: Leo L. Cheng, Adam S. Feldman, Lindsey A. Vandergrift, Isabella H. Muti, Florian Rumpf, Andrew Gusev, Yannick Berker, Marcella R. Cardoso, Taylor L. Fuss, Emily D. Negroponte, Shulin Wu, Felix Ehret, Christopher A. Dietz, Sarah S. Dinges, Thitinan Chulroek, Edouard Nicaise, Piet Habbel, Martin Ayree, Johannes Nowak, Douglas M. Dahl, Chin-Lee Wu, Mukesh Harisinghani. Detecting clinically significant prostate cancers: Tissue metabolomics refines multiparametric MRI-ultrasound fusion prostate biopsy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2222.

Rhabdoid tumors (RT) are embryonal neoplasms occurring most frequently in the central nervous system where they are termed atypical teratoid rhabdoid tumor (ATRT). A common hallmark of RT is homozygous loss of the BAF complex subunit SMARCB1. RT patients have a poor prognosis with an overall survival time of 17 months and >60% of patients suffer from relapses. The lack of an optimal treatment strategy could be attributed to the heterogeneity within and between different subgroups of ATRT. Despite the recent advancements in characterizing RT at a molecular level, the cellular origin of RT remains elusive. Thus, this study focused on the identification of the cellular origin of MYC-RT and underlying epigenetic deregulations which account for the cellular heterogeneity in these tumors. We showed that Smarcb1 abrogation in Sox2-positive progenitor cells at E6.5 give rise to RT of the MYC and SHH subgroup in genetically engineered mouse models (GEMM). To uncover distinct cells of origin (COO) for the SHH and MYC subgroups, unbiased computational approaches were used to compare single-cell transcriptomes of GEMMs with single-cell reference maps of murine early embryogenesis. While SHH tumors arise from mid/hindbrain progenitor cells, primordial germ cells (PGCs) emerge as COO of both intracranial and extracranial MYC tumors. PGCs as COO of MYC-RT were validated in vivo by using PGC-specific Smarcb1 knockout mouse model. We further characterized a deregulated transcriptome in MYC-RT compared to PGCs, which is sustained by a subset of epigenetically driven tumor cells. Deregulated expression of genes driving methylation/demethylation processes in MYC tumors and regression of these tumors upon treatment with decitabine in vitro and in vivo, indicates that DNA methylation plays a key role in cellular transformation and development of MYC-RT.

Given the particular relevance of arousal and alerting in panic disorder (PD), here the alerting network was investigated (1) contrasting patients with PD and healthy controls, (2) as a function of anxiety sensitivity constituting a dimensional measure of panic-related anxiety, and (3) as a possible correlate of treatment response. Using functional magnetic resonance imaging (fMRI), 45 out-patients with PD (f = 34) and 51 matched healthy controls were investigated for brain activation patterns and effective connectivity (Dynamic Causal Modeling, DCM) while performing the Attention Network Task (ANT). Anxiety sensitivity was ascertained by the Anxiety Sensitivity Index (ASI). Forty patients and 48 controls were re-scanned after a 6 weeks cognitive-behavioral treatment (CBT) or an equivalent waiting time, respectively. In the alerting condition, patients showed decreased activation in fronto-parietal pathways including the middle frontal gyrus and the superior parietal lobule (MFG, SPL). In addition, ASI scores were negatively correlated with connectivity emerging from the SPL, the SFB and the LC and going to the MFG in patients but not in healthy controls. CBT resulted in an increase in middle frontal and parietal activation along with increased connectivity going from the MFG to the SPL. This change in connectivity was positively correlated with reduction in ASI scores. There were no changes in controls. The present findings point to a pathological disintegration of the MFG in a fronto-parietal pathway in the alerting network in PD which was observed to be reversible by a successful CBT intervention.

Epigenetic profiling has recently identified clinically and molecularly distinct subgroups of ependymoma. The 2016 World Health Organization (WHO) classification recognized supratentorial ependymomas (ST-EPN) with REL-associated protein/p65 (RELA) fusion as a clinicopathological entity. These tumors represent 70% of pediatric ST-EPN characterized by recurrent C11orf95-RELA fusion transcripts, which lead to pathological activation of the nuclear factor ‘kappa-light-chain-enhancer’ of activated B-cells (NF-κB) signaling pathway. Cyclin-dependent kinase inhibitor 2A (CDKN2A) inactivation has also been reported to correlate with poor prognosis. Here, we systematically describe magnetic resonance imaging (MRI) characteristics of RELA-fused ST-EPN, with respect to CDKN2A deletion status. Our cohort of patients with ST-EPN (n = 57) was obtained from the database of the German Brain Tumor Reference Center of the German Society for Neuropathology and Neuroanatomy (DGNN), and tumors were diagnosed according to the 2016 WHO classification. Molecular characterization identified 47 RELA-fused tumors. We analyzed the preoperative MRI according to standardized criteria, and comparison was performed between CDKN2A altered (n = 21) and CDKN2A wild type (n = 26) tumors. The RELA-fused ST-EPN showed a spectrum of predominantly hemispheric tumors with cysts and necrosis. Statistical analysis on CDKN2A status revealed significant differences in terms of younger manifestation age (p =0.002) and more intratumoral hemorrhage in T2-weighted imaging (T2WI) (p =0.010) in wild type tumors; however, the location was not a parameter for differentiation. This study first provides comprehensive MRI data for RELA-fused ST-EPN as a distinct entity, with further interest on CDKN2A genomic status. Patient stratification by morphological MRI alone seems difficult at present. The results may support ongoing research in ST-EPN within the framework of the radiogenomics concept.

Soft elastic composite materials containing particulate rigid inclusions in a soft elastic matrix are candidates for developing soft actuators or tunable damping devices. The possibility to reversibly drive the rigid inclusions within such a composite together to a close-to-touching state by an external stimulus would offer important benefits. Then, a significant tuning of the mechanical properties could be achieved due to the resulting mechanical hardening. For a long time, it has been argued whether a virtual touching of the embedded magnetic particles with subsequent detachment can actually be observed in real materials, and if so, whether the process is reversible. Here, we present experimental results that demonstrate this phenomenon in reality. Our system consists of two paramagnetic nickel particles embedded at finite initial distance in a soft elastic polymeric gel matrix. Magnetization in an external magnetic field tunes the magnetic attraction between the particles and drives the process. We quantify the scenario by different theoretical tools, i.e., explicit analytical calculations in the framework of linear elasticity theory, a projection onto simplified dipole-spring models, as well as detailed finite-element simulations. From these different approaches, we conclude that in our case the cycle of virtual touching and detachment shows hysteretic behavior due to the mutual magnetization between the paramagnetic particles. Our results are important for the design and construction of reversibly tunable mechanical damping devices. Moreover, our projection on dipole-spring models allows the formal connection of our description to various related systems, e.g., magnetosome filaments in magnetotactic bacteria., Comment: 14 pages, 7 figures

Suspensions of magnetic nanoparticles in suitable carrier liquids, denoted as ferrofluids, are in the focus of current research in the biomedical area. Those fluids can be potentially used for the treatment of cancer by coupling chemotherapeutic agents and accumulating them in the diseased region with the help of external magnetic fields or by artificially local induced heating. Those applications rely on the help of external magnetic fields, which are well known to drastically influence the physical behaviour of ferrofluids. This study investigates the changing viscosity of a biocompatible ferrofluid in a flow situation close to the situation found in a biomedical application. For this purpose blood as diluting agent and thin capillaries have been utilised. The strong magnetoviscous effects found lead to the assumption of quite big changes of the microstructure due to the external magnetic fields, which was investigated and quantified using a microscopic setup. In the result an increases of the structure size as well as faster structure formation in the stronger magnetic fields were observed. Moreover, with increasing duration of the applied magnetic field the size of the structures increases too. The observed process of the structure formation is reversible.

Blood serum MRS metabolomics screening of human lung cancer prior to disease diagnosis Lung cancer (LuCa), the leading cause of cancer deaths, is often diagnosed late. Low-dose spiral CT can detect small and early stage LuCa lesions, but cannot be used widely as an annual LuCa screening tool. Metabolomics detects global metabolite variations under physiology and pathology. Metabolomic profiles measured from blood may reveal LuCa at early stages as a screening tool to triage suspicious patients to CT tests. Blood sera obtained from LuCa patients prior to their diagnosis were studied with MRS to establish LuCa screening metabolomic profiles.Samples. Sera from non-small cell LuCa (NSCLC) patients and their age, gender and smoking habit matched healthy controls were grouped according to the design of training-testing-validation cohorts in this study. The training cohort included 25 NSCLC sera from patients at the time of diagnosis (TOD) and controls (Ctrl); the testing cohort consisted 25 sera collected 0.5 to 5 yrs prior to diagnosis (PTD) from the 25 NSCLC patients in the training cohort; and the validation cohort recruited sera collected less than 2 yrs PTD from additional 54 NSCLC patients and controls. MR Spectroscopy. High resolution magic angle spinning (HRMAS) MRS analysis of serum samples are performed at 4°C by a 600MHz Bruker spectrometer at 3,600Hz spinning rate. Spectra are analyzed with a MatLab-based curve fitting program. Data Analysis. 57 spectral regions were selected based on the training and testing cohorts. Following selections of these regions, all data analytical procedures, including principal component and canonical analyses, were performed on the training cohort and followed by the testing and validation cohorts. Analyses of native sera HRMAS MRS of the training cohort selected 57 spectral regions for statistical analyses, and PCA and canonical analysis were conducted to differentiate TOD from Ctrl groups, with the testing and validation cohorts passively followed the calculations to produce scores within each case.Using the mean plus one standard error (M+SE) as the threshold, calculated from the canonical score differences between TOD and PTD for each case, i.e. the difference of the two scores for each patient, a Kaplan-Meier survival analysis indicates better survival rate from their time of NSCLC diagnoses for patients with score differences higher than the threshold (p=0.031). Furthermore, for Stage I and IIA patients, survivals can be predicted (p=0.027) from their PTD samples, if their score values are higher than the M+SE threshold. Since neither testing nor validation cohorts were involved in the determination of values of the canonical score, by collectively examining all Stage I and IIA in both cohorts, the resulting Kaplan-Meier survival predicting capability by the threshold (established by the testing cohort) was enhanced significantly (p=0.0044). For 5-year survival, our data showed Sen=0.63, Spe=1.00, PPV=1.00, NPV=0.21, ACC=0.67, and F1=0.78. Thus, serum metabolomics may be a screening candidate for early detections with the potential to further probe into all the related metabolic pathways for better understanding of disease. Citation Format: Tjada Schult, Mara Lauer, Yannick Berker, Marcella Cardoso, Lindsey Vandergrift, Piet Habbel, Johannes Nowak, Martin Aryee, Mari Mino-Kenudson, David Christiani, Leo Cheng. Blood serum MRS metabolomics screening of human lung cancer prior to disease diagnosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB209.

Embryonal tumors with multilayered rosettes (ETMRs) have recently been described as a new entity of rare pediatric brain tumors with a fatal outcome. We show here that ETMRs are characterized by a parallel activation of Shh and Wnt signaling. Co-activation of these pathways in mouse neural precursors is sufficient to induce ETMR-like tumors in vivo that resemble their human counterparts on the basis of histology and global gene-expression analyses, and that point to apical radial glia cells as the possible tumor cell of origin. Overexpression of LIN28A, which is a hallmark of human ETMRs, augments Sonic-hedgehog (Shh) and Wnt signaling in these precursor cells through the downregulation of let7-miRNA, and LIN28A/let7a interaction with the Shh pathway was detected at the level of Gli mRNA. Finally, human ETMR cells that were transplanted into immunocompromised host mice were responsive to the SHH inhibitor arsenic trioxide (ATO). Our work provides a novel mouse model in which to study this tumor type, demonstrates the driving role of Wnt and Shh activation in the growth of ETMRs and proposes downstream inhibition of Shh signaling as a therapeutic option for patients with ETMRs.

This article deals with the assessment and prediction of the reproduction quality when binaurally auralizing spherical microphone array data for room simulation applications. The auralization is perceptually assessed in a listening experiment using the two attributes, apparent source width (ASW) and listener envelopment (LEV), for spatial quality description, whereas the technical analysis employs a psychoacoustically motivated model for room acoustical perception (RAP) which is specifically designed to estimate ASW and LEV. Both analyses focus on the array configuration in terms of varying modal resolutions and its influence on the spatial reproduction quality. The auralizations comprise three simulated environments, i.e., free-field sound fields as well as a dry and a reverberant room. Ten different audio signals are used as test material. Perceptual results show that the array configuration strongly influences the perception of ASW and LEV which also depends on the reflection properties of the simulated room. The ASW and LEV predictions by the RAP model correlate well with the results from the listening experiment.

Immunoproteasomes (IP) are the main type of protein degrading proteasomes in immune cells. They can be induced in non-parenchymal cells upon inflammatory activation. Our recent analysis identified markedly induced expression of IPs in parenchymal cells in idiopathic pulmonary fibrosis (IPF). We here investigate the role of IP in fibrotic remodeling and fibroblast activation. IP expression was elevated in bleomycin-induced lung fibrosis and oxalate-induced kidney fibrosis in mice as demonstrated by Western blotting of fibrotic tissue. Interestingly, the profibrotic cytokine TGFs decreased the amount of immunoproteasomes in primary human lung fibroblasts (phLF), both on RNA and protein level and also reduced IP activity in myodifferentiated phLF. Specific inhibition of the immunoproteasome, however, did not alter fibrotic marker gene expression in vitro. Similarly, deficiency of the single immunosubunit LMP2 did not significantly influence TGFs–induced myofibroblast differentiation in primary murine lung fibroblasts (pmLF) compared to wildtype littermates. In a next step, we will perform bleomycin challenge on LMP2-/- and LMP7-/- mice as a causal approach to investigate the role of immunoproteasomes in fibrotic lung remodeling. In conclusion, immunoproteasomes are activated upon fibrotic tissue remodeling but downregulated by TGFs in isolated lung fibroblasts suggesting that other stimuli promote immunoproteasome activation in fibrosis. The use of specific immunoproteasome inhibitors in the model of bleomycin-induced lung fibrosis will help to identify the role of immunoproteasomes in pulmonary fibrosis and may identify immunoproteasomes as a potential therapeutic target in chronic lung disease.

Suspensions of magnetic nanoparticles are receiving a growing interest in biomedical research. These ferrofluids can, e.g., be used for the treatment of cancer, making use of the drug targeting principle or using an artificially induced heating. To enable a safe application the basic properties of the ferrofluids have to be well understood, including the viscosity of the fluids if an external magnetic field is applied. It is well known that the viscosity of ferrofluids rises if a magnetic field is applied, where the rise depends on shear rate and magnetic field strength. In case of biocompatible ferrofluids such investigations proved to be rather complicated as the experimental setup should be close to the actual application to allow justified predictions of the effects which have to be expected. Thus a capillary viscometer, providing a flow situation comparable to the flow in a blood vessel, has been designed. The glass capillary is exchangeable and different inner diameters can be used. The range of the shear rates has been adapted to the range found in the human organism. The application of an external magnetic field is enabled with two different coil setups covering the ranges of magnetic field strengths required on the one hand for a theoretical understanding of particle interaction and resulting changes in viscosity and on the other hand for values necessary for a potential biomedical application. The results show that the newly designed capillary viscometer is suitable to measure the magnetoviscous effect in biocompatible ferrofluids and that the results appear to be consistent with data measured with rotational rheometry. In addition, a strong change of the flow behaviour of a biocompatible ferrofluid was proven for ranges of the shear rate and the magnetic field strength expected for a potential biomedical application.

Facilitated processing of interoceptive and exteroceptive information in the salience network is suggested to promote the development of anxiety and anxiety disorders. Here, it was investigated whether the adenosine 2 A receptor gene (ADORA2A) 1976T/C (rs5751876) variant – previously associated with anxiety disorders and anxiety-related phenotypes as well as general attentional efficiency –was involved in the regulation of this network. In detail, fMRI recordings of 65 healthy participants (female=35) were analyzed regarding ADORA2A genotype effects on brain connectivity related to (1) interoceptive processing in terms of functional connectivity resting-state fMRI, and (2) exteroceptive processing using dynamic causal modeling in task-based fMRI. In a subsample, cardiac interoceptive accuracy was furthermore measured via the Mental Tracking Task. ADORA2A genotype was found to modulate a fronto-insular network at rest (interoceptive processing) and while performing an executive control task (exteroceptive processing). Across both modalities, the ADORA2A TT risk genotype was associated with increased connectivity between the insula and the prefrontal cortex. The strength in connectivity correlated with interoceptive accuracy. It is concluded that alterations in fronto-insular connectivity are modulated by both the adenosinergic system and interoceptive accuracy. Thus, fronto-insular connectivity in synopsis with ADORA2A genotypic information could serve as combined biomarkers for personalized treatment approaches in anxiety disorders targeting exteroceptive and interoceptive dysfunction.

Low-dose CT has shown promise in detecting early stage lung cancer. However, concerns about the adverse health effects of radiation and high cost prevent its use as a population-wide screening tool. Effective and feasible screening methods to triage suspicious patients to CT are needed. We investigated human lung cancer metabolomics from 93 paired tissue-serum samples with magnetic resonance spectroscopy and identified tissue and serum metabolomic markers that can differentiate cancer types and stages. Most interestingly, we identified serum metabolomic profiles that can predict patient overall survival for all cases (p = 0.0076), and more importantly for Stage I cases alone (n = 58, p = 0.0100), a prediction which is significant for treatment strategies but currently cannot be achieved by any clinical method. Prolonged survival is associated with relative overexpression of glutamine, valine, and glycine, and relative suppression of glutamate and lipids in serum.

BACKGROUND: Recently, 3 molecular subgroups of atypical teratoid/rhabdoid tumor (ATRT) were identified, but little is known of their clinical and magnetic resonance imaging (MRI) characteristics. METHODS: A total of 43 patients with known molecular subgroup status (ATRT–sonic hedgehog [SHH], n = 17; ATRT-tyrosine [TYR], n = 16; ATRT–myelocytomatosis oncogene [MYC], n = 10) were retrieved from the EU-RHAB Registry and analyzed for clinical and MRI features. RESULTS: On MRI review, differences in preferential tumor location were confirmed, with ATRT-TYR being predominantly located infratentorially (P < 0.05). Peritumoral edema was more pronounced in ATRT-MYC compared with ATRT-SHH (P < 0.05) and ATRT-TYR (P < 0.05). Conversely, peripheral tumor cysts were found more frequently in ATRT-SHH (71%) and ATRT-TYR (94%) compared with ATRT-MYC (40%, P < 0.05). Contrast enhancement was absent in 29% of ATRT-SHH (0% of ATRT-TYR; 10% of ATRT-MYC; P < 0.05), and there was a trend toward strong contrast enhancement in ATRT-TYR and ATRT-MYC. We found the characteristic (bandlike) enhancement in 28% of ATRT as well as restricted diffusion in the majority of tumors. A midline/off-midline location in the posterior fossa was also not subgroup specific. Visible meningeal spread (M2) at diagnosis was rare throughout all subgroups. CONCLUSION: These exploratory findings suggest that MRI features vary across the 3 molecular subgroups of ATRT. Within future prospective trials, MRI may aid diagnosis and treatment stratification.

This paper evaluates the application of three methods for Sound Source Separation (SSS) in industrial acoustic condition monitoring scenarios. To evaluate the impact of SSS, we use a machine learning approach where a classifier is trained to detect a specific operating machine. The evaluation procedure is based on simulated and measured data, comprising three different machine sounds as targets and 10 interfering signals. Various intermixing levels of target and interfering signal are taken into account, using three different signal-to-interference ratios. Results show that the chosen source separation methods, originally developed for music analysis, work well for industrial signals, significantly improving the classification accuracy.

Insbesondere bei kleineren sozialen Organisationen ist das Gebäudemanagement oft eine lästige Nebenaufgabe der Leitung. Doch der Aufbau eines funktionierenden Systems der Bewirtschaftung genutzter Räumlichkeiten lohnt sich auch finanziell, meint Johannes Nowak vom Beratungsbüro Meerbusch.

Evidence has accumulated for a dysfunction of arousal and executive attention in anxiety. The neuropeptide S (NPS) system has been shown to play a pivotal role in the mediation of arousal and to be associated with anxiety/panic disorder. The present study aims at investigating the impact of functional neuropeptide S receptor ( NPSR1 ) gene variation on neural attention patterns applying an imaging genetics approach. In an event-related functional magnetic resonance imaging (fMRI) setting, 47 healthy subjects (f = 23) evenly pre-stratified for NPSR1 rs324981 A/T genotype were investigated for brain activation patterns while performing the Attention Network Task (ANT), simultaneously probing alerting and executive control functions. Anxiety sensitivity was ascertained by the Anxiety Sensitivity Index (ASI). In the alerting condition, NPSR1 TT homozygotes showed higher activations in the right prefrontal cortex and the locus coeruleus region as compared to A allele carriers. In the executive control condition, TT homozygotes displayed increased activations in fronto-parietal regions. Genotype-driven activation differences in the prefrontal cortex correlated with anxiety sensitivity, in both the alerting and the executive control system. The present results for the first time suggest NPSR1 gene variation to be associated with alterations of prefrontal functioning in the attentional functions alerting and executive control partly modulated by anxiety sensitivity. These findings may aid in unraveling the neurobiological underpinnings of distorted arousal and attention in anxiety and thereby possibly in the biomarker-guided development of preventive/therapeutic strategies targeting attention processes in anxiety disorders.

Magnetic targeting is considered a promising method to accumulate the nanoparticles at the sites of atherosclerotic lesions, but little is known about the biological effects of magnetic nanoparticles on the vascular wall. Here, we investigated endothelial cell growth and vitality upon treatment with SPION (0–60 mg/mL) using two complementing methods: real-time cell analysis and live-cell microscopy. Moreover, the uptake of circulating superparamagnetic iron oxide nanoparticles (SPIONs) was assessed in an in vitro model of arterial bifurcations. At the tested concentrations, SPIONs were well tolerated and had no major influence on endothelial cell growth. Our results further showed a uniform distribution of endothelial SPION uptake independent of channel geometry or hemodynamic conditions: In the absence of magnetic force, no increase in accumulation of SPIONs at non-uniform shear stress region at the outer walls of bifurcation was observed. Application of external magnet allowed enhanced accumulation of SPIONs at the regions of non-uniform shear stress. Increased uptake of SPIONs at non-uniform shear stress region was well tolerated by endothelial cells (ECs) and did not affect endothelial cell viability or attachment. These findings indicate that magnetic targeting can constitute a promising and safe technique for the delivery of imaging and therapeutic nanoparticles to atherosclerotic lesions.

High-resolution magic angle spinning (HRMAS) magnetic resonance spectroscopy (MRS) is a powerful method for gaining insight into the physiological and pathological processes of cellular metabolism. Given its ability to obtain high resolution spectra of non-liquid biological samples, while preserving tissue architecture for subsequent histopathological analysis, the technique has become invaluable for biochemical and biomedical studies. Using HRMAS MRS, alterations in measured metabolites, metabolic ratios, and metabolomic profiles present the possibility to improve identification and prognostication of various diseases and decipher the metabolomic impact of drug therapies. In this review, we evaluate HRMAS MRS results on human tissue specimens from malignancies and non-localized diseases reported in the literature since the inception of the technique in 1996. We present the diverse applications of the technique in understanding pathological processes of different anatomical origins, correlations with in vivo imaging, effectiveness of therapies, and progress in the HRMAS methodology.

BACKGROUND AND PURPOSE: Ependymoblastoma is a malignant embryonal tumor that develops in early childhood and has a dismal prognosis. Categorized by the World Health Organization as a subgroup of CNS-primitive neuroectodermal tumor, ependymoblastoma is histologically defined by “ependymoblastic rosettes.” Because it is so rare, little is known about specific MR imaging characteristics of ependymoblastoma. We systematically analyzed and discussed MR imaging features of ependymoblastoma in a series of 22 consecutive patients. MATERIALS AND METHODS: Ependymoblastoma cases were obtained from the database of the German multicenter HIT trials between 2002 and 2013. All cases within this study were centrally reviewed for histopathology, MR imaging findings, and multimodal therapy. For systematic analysis of initial MR imaging scans at diagnosis, we applied standardized criteria for reference image evaluation of pediatric brain tumors. RESULTS: Ependymoblastomas are large tumors with well-defined tumor margins, iso- to hyperintense signal on T2WI, and diffusion restriction. Contrast enhancement is variable, with a tendency to mild or moderate enhancement. Subarachnoid spread is common in ependymoblastoma but can be absent initially. There was a male preponderance (1.75:1 ratio) for ependymoblastoma in our cohort. Mean age at diagnosis was 2.1 years. CONCLUSIONS: With this study, we add the largest case collection to the limited published database of MR imaging findings in ependymoblastoma, together with epidemiologic data. However, future studies are needed to systematically compare MR imaging findings of ependymoblastoma with other CNS-primitive neuroectodermal tumors and ependymoma, to delineate imaging criteria that might help distinguish these pediatric brain tumor entities.

Endolymphatic sac tumors (ELSTs) are rare, slow-growing tumors of the petrous bone. Despite the typical localisation, their radiological diagnosis can be challenging due to the variety of other tumors potentially showing similar features. We present a 16-year-old child with progressive hearing loss, vertigo, and tinnitus who had a large petrous bone lesion showing imaging features of both ELSTs and aneurysmal bone cysts (ABCs). The patient underwent preoperative embolization of the tumor-supplying vessels and subsequently a subtotal resection. Histological examination revealed an ELST. Despite the rarity of petrous bone ABCs, they should be considered as a differential diagnostic alternative of ELSTs due to their similar imaging appearance.

There is an increasing interest in suspensions of magnetic nanoparticles in the biomedical area. Those ferrofluids are e.g. used for magnetic resonance imaging and emerging research focuses on employing the fluids for magnetic drug targeting or magnetic particle heating as a potential treatment for cancer. For these applications the knowledge of the suspensions' thermophysical properties is of major interest to guarantee a safe and effective application. Therefore the flow behavior cannot be neglected as it might significantly influence the execution of the aforementioned applications. In this experimental study two biocompatible ferrofluids were investigated. Rheological measurements were carried out using rotational rheometry. To allow an interpretation of the fluids' behavior the microscopic make-up was investigated using dynamic light scattering and transmission electron microscopy. Measurements of diluted ferrofluids were carried out as a first step to simulate the rheological behavior reflecting the concentration of magnetic nanoparticles found in blood flow for most biomedical applications of such fluids. The detected strong effects show the potential to significantly influence application and handling of the biocompatible ferrofluids in the medical area and should therefore be taken into account for further research as well as for the application of such fluids.

The integration of renewable energy into the existing energy supply system is a core challenge regarding the successful realization of the German “Energiewende”. One concept to integrate decentralized regenerative power generators is a virtual power plant that operates many small facilities as one power plant. Essential parts of the concept are controllable loads and generators to reduce the impact of volatile energy resource – like wind power stations – on operational planning. Power-to-Heat-Systems (P2H) are one possible technology that can be used to a limited extent as a controllable load. The P2H-system as a component of virtual power plants is capable of supplying flexibility due to various possible operation strategies. This flexibility can either be used for ancillary services (primary, secondary and tertiary ancillary services), to provide schedule energy or for balancing group management. This paper presents a modeling approach for P2H systems as a component of virtual power plants with a high share of renewable energies. The operation strategies are evaluated with respect to economic and technical aspects and uncertainties in generation and load. The operation strategies of P2H systems are shown with regard to market integration of renewable energies within a virtual power plant and the provision of ancillary services.

Hypertrophic olivary degeneration (HOD) is a rare transsynaptic form of degeneration occurring secondary to the disruption of the dentato-rubro-olivary pathway ("Guillain-Mollaret triangle"). HOD can be caused by ischemic, hemorrhagic, traumatic, or neoplastic lesions, and it can also occur following posterior fossa surgery. MRI characteristics of HOD include T2 signal increase and hypertrophy. To date, blood–brain barrier disruption has not been reported in HOD. Here, we present the first case of HOD with temporary gadolinium enhancement in a 10-year-old child 7 months after resection of a posterior fossa medulloblastoma. The recognition of gadolinium enhancement as a radiological feature of HOD may help to distinguish between this benign secondary condition and tumor recurrence.

The advancing development in biomedical applications of magnetic nanoparticles leads to an increasing demand for reliable data concerning the thermophysical properties of the ferrofluids used. For applications with a relation to the flow behavior of the nanoparticle suspensions-like, e.g., magnetic drug targeting-the understanding of the basic rheological properties of the fluids under the influence of magnetic fields is of general importance. In the ongoing work presented here a magnetite-based commercial ferrofluid featuring multi-domain cores with dextran as surfactant was investigated using rotational rheometry. The analysis includes flow curve as well as yield stress measurements and reveals the magnetoviscous effect of the fluid. It has been found that significant changes of viscosity and of the overall flow behavior are induced even at low magnetic field strengths. The detected effects and therefore the changing rheological behavior of the fluid under investigation should be taken into account for further improvement of biomedical applications as well as for the synthesis of biocompatible ferrofluids.