Analyseverfahren der Resting-State-fMRT-Bildgebung zur funktionellen Konnektivität am Beispiel der Friedreich-Ataxie

Das menschliche Gehirn zeigt im Zustand ruhender Wachheit (Resting-State) kohärente Muster neuronaler Aktivität, die sich als niederfrequente Signalschwankungen mittels funktioneller Magnetresonanztomographie (fMRT) nachweisen lassen. Funktionelle Konnektivität (FC) beschreibt die Synchronität dieser Signalschwankungen in umschriebenen Hirnregionen, die dann als Ruhenetzwerke (RSNs) bezeichnet werden. Die Untersuchung dieser Netzwerke ist insbesondere im Kontext von ZNS-Erkrankungen interessant. Für die hier durchgeführte Studie konnten fMRT-Daten von 17 gesunden Probanden und 17 Patienten mit Friedreich-Ataxie erhoben werden. Bei dieser neurodegenerative Erkrankung handelt es sich um die häufigste Form einer erblichen Ataxie. Der klinische Zustand der Patienten wurde mit dem SARA-Score und PATA-Test bewertet. Für die Analyse der Resting-State-Aufnahmen wurde ein explorativer Ansatz mit der unabhängigen Komponentenanalyse (ICA) gewählt. Nach einer Vorverarbeitung zur Reduktion von Störeinflüssen wurden die fMRT-Daten in 75 unabhängigen Komponenten (ICs) zerlegt. Die Auswahl der RSNs repräsentierenden ICs erfolgte in einem mehrstufigen Prozedere, das sowohl räumliche Eigenschaften als auch Frequenz-Charakteristiken berücksichtigt. Neben dem direkten Vergleich der FC innerhalb der RSNs bei den Patienten und gesunden Probanden wurde auch die Korrelation der FC mit den klinischen Parametern (SARA- und PATA-Wert) untersucht. Es konnten alle bekannten Ruhenetzwerke (Basalganglien-, auditorisches, sensomotorisches, visuelles, Default-Mode-, Aufmerksamkeits- und frontales Netzwerk) identifiziert werden – sowie ein Sprachnetzwerk. Im Vergleich der Patienten mit den gesunden Probanden konnte eine verminderte FC der Patienten im rechten frontoinsulären Kortex (rFIC) des Salienznetzwerks (Teil des Aufmerksamkeitsnetzwerks) festgestellt werden. Eine positive Korrelation der FC mit dem PATA-Wert zeigte sich im anterioren zingulären Kortex und im Gyrus frontalis medius des Salienznetzwerks. Negative Korrelationen der FC mit dem SARA-Score fanden sich in mehreren RSNs, die die Basalganglien und Teile des auditorischen, sensomotorischen und visuellen Kortex mit einschließen. In einem Teil des Sprachnetzwerks im linken Gyrus temporalis superior, einer zuvor als „Area Spt“ bezeichneten Region, korrelierte die FC positiv mit dem SARA-Score. Die gefundenen Unterschiede in der FC und ihre Korrelationen mit dem klinischen Schweregrad lassen sich im Rahmen bestehender Kenntnisse über die betroffenen, funktionellen Hirnregionen interpretieren. So könnte bspw. die verminderte FC der Patienten im rFIC ein Hinweis auf eine gestörte Vermittlung im Informationsfluss zwischen Default-Mode- und zentralem Exekutivnetzwerk sein und sich somit auch auf die motorischen Handlungen der Patienten auswirken. Diese Arbeit demonstriert die weitreichenden Möglichkeiten einer hypothesenfreien Untersuchung des Gehirns im Ruhezustand

German public finances through the financial crisis

The German experience of the crisis was very different compared to those of most other countries in Europe. Germany was hit by a very strong shock which was relatively concentrated in the exporting, manufacturing industries. In addition, the German labour market was very resilient during the crisis due to earlier labour market reforms and policy instruments facilitating labour hoarding. As a consequence, public finances were only moderately affected and not many policy reforms had to be enacted. This chapter will present the German experience of the financial crisis. We start by presenting the macroeconomic situation and how the crisis unfolded in Germany, before focusing on the situation of public finances. Finally, we analyse the policy responses to the financial crisis

The EIVE CubeSat - Developing a Satellite Bus for a 71-76 GHz E-Band Transmitter Payload

A high-speed data downlink system provides many challenges for a CubeSat design. Two major aspect are an adequate power management as well as the thermal implications of the dissipated power. The goal of the 6U CubeSat EIVE is to prove the feasibility of an E-band link at 71-76 GHz and explore the influence of different atmospheric conditions on the link quality. The requirements of the E-band transmitter in terms of mass, volume, power and pointing accuracy outline the specific constraints imposed on the design of the satellite bus. The major design drivers of the system are the peak power demand of 60 W for the payload itself and the required pointing accuracy of less than 1◦. To cope with these demands, general design considerations, the choice of the orbit and the operation of the satellite are discussed. A special focus is the power generation and consumptions by means of a dynamic attitude and power simulation. The thermal simulation is verified by building a detailed structural and thermal replica of the satellite to investigate the heat dissipation. An overview of the current EIVE CubeSat platform design concludes this paper

Level-Specific Volumetric BMD Threshold Values for the Prediction of Incident Vertebral Fractures Using Opportunistic QCT: A Case-Control Study

Purpose: To establish and evaluate the diagnostic accuracy of volumetric bone mineral density (vBMD) threshold values at different spinal levels, derived from opportunistic quantitative computed tomography (QCT), for the prediction of incident vertebral fractures (VF). Materials and Methods: In this case-control study, 35 incident VF cases (23 women, 12 men; mean age: 67 years) and 70 sex- and age-matched controls were included, based on routine multi detector CT (MDCT) scans of the thoracolumbar spine. Trabecular vBMD was measured from routine baseline CT scans of the thoracolumbar spine using an automated pipeline including vertebral segmentation, asynchronous calibration for HU-to-vBMD conversion, and correction of intravenous contrast medium (https://anduin.bonescreen.de). Threshold values at T1-L5 were calculated for the optimal operating point according to the Youden index and for fixed sensitivities (60 – 85%) in receiver operating characteristic (ROC) curves. Results: vBMD at each single level of the thoracolumbar spine was significantly associated with incident VFs (odds ratio per SD decrease [OR], 95% confidence interval [CI] at T1-T4: 3.28, 1.66–6.49; at T5-T8: 3.28, 1.72–6.26; at T9-T12: 3.37, 1.78–6.36; and at L1-L4: 3.98, 1.97–8.06), independent of adjustment for age, sex, and prevalent VF. AUC showed no significant difference between vertebral levels and was highest at the thoracolumbar junction (AUC = 0.75, 95%-CI = 0.63 - 0.85 for T11-L2). Optimal threshold values increased from lumbar (L1-L4: 52.0 mg/cm³) to upper thoracic spine (T1-T4: 69.3 mg/cm³). At T11-L2, T12-L3 and L1-L4, a threshold of 80.0 mg/cm³ showed sensitivities of 85 - 88%, and specificities of 41 - 49%. To achieve comparable sensitivity (85%) at more superior spinal levels, resulting thresholds were higher: 114.1 mg/cm³ (T1-T4), 92.0 mg/cm³ (T5-T8), 88.2 mg/cm³ (T9-T12). Conclusions: At all levels of the thoracolumbar spine, lower vBMD was associated with incident VFs in an elderly, predominantly oncologic patient population. Automated opportunistic osteoporosis screening of vBMD along the entire thoracolumbar spine allows for risk assessment of imminent VFs. We propose level-specific vBMD threshold at the thoracolumbar spine to identify individuals at high fracture risk

A Guide for Publishing, Using, and Licensing Research Software in Germany

Research software has become a central asset in academic research. In Germany, the German Research Foundation (DFG, Deutsche Forschungsgemeinschaft) recently updated the Guidelines for Safeguarding Good Research Practice. Research software is now valued similarly to classic publications and data with implications for research software sustainability and legal aspects. In this document, we present four decision trees and corresponding legal documentation tables to aid researchers. The decision trees should ease to identify i) the software policy of your institution, ii) restrictions imposed by contributors and the environment, iii) licensing collisions if 3rd party software is included, and iv) problems in licensing (existing) research software

Proposed diagnostic volumetric bone mineral density thresholds for osteoporosis and osteopenia at the cervicothoracic spine in correlation to the lumbar spine

Objectives: To determine the correlation between cervicothoracic and lumbar volumetric bone mineral density (vBMD) in an average cohort of adults and to identify specific diagnostic thresholds for the cervicothoracic spine on the individual subject level. Methods: In this HIPPA–compliant study, we retrospectively included 260 patients (59.7 ± 18.3 years, 105 women), who received a contrast-enhanced or non-contrast-enhanced CT scan. vBMD was extracted using an automated pipeline (https://anduin.bonescreen.de). The association of vBMD between each vertebra spanning C2–T12 and the averaged values at the lumbar spine (L1–L3) was analyzed before and after semiquantitative assessment of fracture status and degeneration, and respective vertebra-specific cut-off values for osteoporosis were calculated using linear regression. Results: In both women and men, trabecular vBMD decreased with age in the cervical, thoracic, and lumbar regions. vBMD values of cervicothoracic vertebrae showed strong correlations with lumbar vertebrae (L1–L3), with a median Pearson value of r = 0.87 (range: r$_{C2}$ = 0.76 to r$_{T12}$ = 0.96). The correlation coefficients were significantly lower (p < 0.0001) without excluding fractured and degenerated vertebrae, median r = 0.82 (range: r$_{C2}$ = 0.69 to r$_{T12}$ = 0.93). Respective cut-off values for osteoporosis peaked at C4 (209.2 mg/ml) and decreased to 83.8 mg/ml at T12. Conclusion: Our data show a high correlation between clinically used mean L1–L3 values and vBMD values elsewhere in the spine, independent of age. The proposed cut-off values for the cervicothoracic spine therefore may allow the determination of low bone mass even in clinical cases where only parts of the spine are imaged. Key Points: vBMD of all cervicothoracic vertebrae showed strong correlation with lumbar vertebrae (L1–L3), with a median Pearson’s correlation coefficient of r = 0.87 (range: r$_{C2}$ = 0.76 to r$_{T12}$ = 0.96). The correlation coefficients were significantly lower (p < 0.0001) without excluding fractured and moderate to severely degenerated vertebrae, median r = 0.82 (range: r$_{C2}$ = 0.69 to r$_{T12}$ = 0.93). We postulate that trabecular vBMD < 200 mg/ml for the cervical spine and < 100 mg/ml for the thoracic spine are strong indicators of osteoporosis, similar to < 80 mg/ml at the lumbar spine

Incidental vertebral fracture prediction using neuronal network-based automatic spine segmentation and volumetric bone mineral density extraction from routine clinical CT scans.

OBJECTIVES To investigate vertebral osteoporotic fracture (VF) prediction by automatically extracted trabecular volumetric bone mineral density (vBMD) from routine CT, and to compare the model with fracture prevalence-based prediction models. METHODS This single-center retrospective study included patients who underwent two thoraco-abdominal CT scans during clinical routine with an average inter-scan interval of 21.7 ± 13.1 months (range 5-52 months). Automatic spine segmentation and vBMD extraction was performed by a convolutional neural network framework (anduin.bonescreen.de). Mean vBMD was calculated for levels T5-8, T9-12, and L1-5. VFs were identified by an expert in spine imaging. Odds ratios (ORs) for prevalent and incident VFs were calculated for vBMD (per standard deviation decrease) at each level, for baseline VF prevalence (yes/no), and for baseline VF count (n) using logistic regression models, adjusted for age and sex. Models were compared using Akaike's and Bayesian information criteria (AIC & BIC). RESULTS 420 patients (mean age, 63 years ± 9, 276 males) were included in this study. 40 (25 female) had prevalent and 24 (13 female) had incident VFs. Individuals with lower vBMD at any spine level had higher odds for VFs (L1-5, prevalent VF: OR,95%-CI,p: 2.2, 1.4-3.5,p=0.001; incident VF: 3.5, 1.8-6.9,p<0.001). In contrast, VF status (2.15, 0.72-6.43,p=0.170) and count (1.38, 0.89-2.12,p=0.147) performed worse in incident VF prediction. Information criteria revealed best fit for vBMD-based models (AIC vBMD=165.2; VF status=181.0; count=180.7). CONCLUSIONS VF prediction based on automatically extracted vBMD from routine clinical MDCT outperforms prediction models based on VF status and count. These findings underline the importance of opportunistic quantitative osteoporosis screening in clinical routine MDCT data

Automated Opportunistic Osteoporosis Screening in Routine Computed Tomography of the Spine: Comparison With Dedicated Quantitative CT

Opportunistic osteoporosis screening in nondedicated routine computed tomography (CT) is of increasing importance. The purpose of this study was to compare lumbar volumetric bone mineral density (vBMD) assessed by a convolutional neural network (CNN)-based framework in routine CT to vBMD from dedicated quantitative CT (QCT), and to evaluate the ability of vBMD and surrogate measurements of Hounsfield units (HU) to distinguish between patients with and without osteoporotic vertebral fractures (VFs). A total of 144 patients (median age: 70.7 years, 93 females) with clinical routine CT (eight different CT scanners, 120 kVp or 140 kVp, with and without intravenous contrast medium) and dedicated QCT acquired within ≤30 days were included. Vertebral measurements included (i) vBMD from the CNN-based approach including automated vertebral body labeling, segmentation, and correction of the contrast media phase for routine CT data (vBMD_OPP), (ii) vBMD from dedicated QCT (vBMD_QCT), and (iii) noncalibrated HU from vertebral bodies of routine CT data as previously proposed for immanent opportunistic osteoporosis screening based on CT attenuation. The intraclass correlation coefficient (ICC) for vBMD_QCT versus vBMD_OPP indicated better agreement (ICC = 0.913) than the ICC for vBMD_QCT versus noncalibrated HU (ICC = 0.704). Bland-Altman analysis showed data points from 137 patients (95.1%) within the limits of agreement (LOA) of -23.2 to 25.0 mg/cm3 for vBMD_QCT versus vBMD_OPP. Osteoporosis (vBMD <80 mg/cm3 ) was detected in 89 patients (vBMD_QCT) and 88 patients (vBMD_OPP), whereas no patient crossed the diagnostic thresholds from normal vBMD to osteoporosis or vice versa. In a subcohort of 88 patients (thoracolumbar spine covered by imaging for VF reading), 69 patients showed one or more prevalent VFs, and the performance for discrimination between patients with and without VFs was best for vBMD_OPP (area under the curve [AUC] = 0.862; 95% confidence interval [CI], 0.771-0.953). In conclusion, automated opportunistic osteoporosis screening in routine CT of various scanner setups is feasible and may demonstrate high diagnostic accuracy for prevalent VFs. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)

Sex differences and age-related changes in vertebral body volume and volumetric bone mineral density at the thoracolumbar spine using opportunistic QCT

ObjectivesTo quantitatively investigate the age- and sex-related longitudinal changes in trabecular volumetric bone mineral density (vBMD) and vertebral body volume at the thoracolumbar spine in adults.MethodsWe retrospectively included 168 adults (mean age 58.7 ± 9.8 years, 51 women) who received ≥7 MDCT scans over a period of ≥6.5 years (mean follow-up 9.0 ± 2.1 years) for clinical reasons. Level-wise vBMD and vertebral body volume were extracted from 22720 thoracolumbar vertebrae using a convolutional neural network (CNN)-based framework with asynchronous calibration and correction of the contrast media phase. Human readers conducted semiquantitative assessment of fracture status and bony degenerations.ResultsIn the 40-60 years age group, women had a significantly higher trabecular vBMD than men at all thoracolumbar levels (p&lt;0.05 to p&lt;0.001). Conversely, men, on average, had larger vertebrae with lower vBMD. This sex difference in vBMD did not persist in the 60-80 years age group. While the lumbar (T12-L5) vBMD slopes in women only showed a non-significant trend of accelerated decline with age, vertebrae T1-11 displayed a distinct pattern, with women demonstrating a significantly accelerated decline compared to men (p&lt;0.01 to p&lt;0.0001). Between baseline and last follow-up examinations, the vertebral body volume slightly increased in women (T1-12: 1.1 ± 1.0 cm3; L1-5: 1.0 ± 1.4 cm3) and men (T1-12: 1.2 ± 1.3 cm3; L1-5: 1.5 ± 1.6 cm3). After excluding vertebrae with bony degenerations, the residual increase was only small in women (T1-12: 0.6 ± 0.6 cm3; L1-5: 0.7 ± 0.7 cm3) and men (T1-12: 0.7 ± 0.6 cm3; L1-5: 1.2 ± 0.8 cm3). In non-degenerated vertebrae, the mean change in volume was &lt;5% of the respective vertebral body volumes.ConclusionSex differences in thoracolumbar vBMD were apparent before menopause, and disappeared after menopause, likely attributable to an accelerated and more profound vBMD decline in women at the thoracic spine. In patients without advanced spine degeneration, the overall volumetric changes in the vertebral body appeared subtle