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Article ; Online: DUSP15 expression is reduced in the hippocampus of Myrf knock-out mice but attention and object recognition memory remain intact.

Rawlings-Mortimer, Florence / Gullino, L Sophie / Rühling, Sebastian / Ashton, Anna / Barkus, Chris / Johansen-Berg, Heidi

PloS one

2023 Volume 18, Issue 2, Page(s) e0281264

Abstract: The atypical protein tyrosine phosphatase enzyme, dual-specificity phosphate 15 (DUSP15) is thought to be activated by myelin regulatory factor (MyRF) and to have a role in oligodendrocyte differentiation. Here, we assess whether Dusp15 is reduced in the ...

Abstract	The atypical protein tyrosine phosphatase enzyme, dual-specificity phosphate 15 (DUSP15) is thought to be activated by myelin regulatory factor (MyRF) and to have a role in oligodendrocyte differentiation. Here, we assess whether Dusp15 is reduced in the hippocampus of mice with conditional knock-out of Myrf in oligodendrocyte precursor cells. Using quantitative polymerase chain reaction (qPCR) we found that Dusp15 expression was indeed lower in these mice. Alterations in myelin have been associated with Alzheimer's disease (AD), autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD). Symptoms of these disorders can include impairments of object recognition and attention. We, therefore tested the mice in the object recognition task (ORT) and 5-choice serial reaction time task (5CSRTT). However, we did not find behavioural impairments indicating that attentional abilities and object recognition are not impacted by reduced oligodendrogenesis and hippocampal Dusp15 expression. Gaining insight into the role of newly formed oligodendrocytes and Dusp15 expression is helpful for the development of well targeted treatments for myelin dysregulation.
MeSH term(s)	Mice ; Animals ; Mice, Knockout ; Autism Spectrum Disorder/metabolism ; Phosphates/metabolism ; Myelin Sheath/metabolism ; Hippocampus ; Attention Deficit Disorder with Hyperactivity/metabolism
Chemical Substances	Phosphates
Language	English
Publishing date	2023-02-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0281264
Database	MEDical Literature Analysis and Retrieval System OnLINE

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

Rühling, Sebastian / Dittmann, Jonas / Müller, Tobias / Husseini, Malek El / Bodden, Jannis / Hernandez Petzsche, Moritz R / Löffler, Maximilian T / Sollmann, Nico / Baum, Thomas / Seifert-Klauss, Vanadin / Wostrack, Maria / Zimmer, Claus / Kirschke, Jan S

Frontiers in endocrinology

2024 Volume 15, Page(s) 1352048

Abstract: Objectives: To 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.: Methods: We retrospectively included 168 ... ...

Abstract	Objectives: To 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. Methods: We 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. Results: In the 40-60 years age group, women had a significantly higher trabecular vBMD than men at all thoracolumbar levels (p<0.05 to p<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<0.01 to p<0.0001). Between baseline and last follow-up examinations, the vertebral body volume slightly increased in women (T1-12: 1.1 ± 1.0 cm Conclusion: Sex 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.
MeSH term(s)	Adult ; Female ; Humans ; Male ; Middle Aged ; Aged ; Vertebral Body ; Sex Characteristics ; Bone Density ; Retrospective Studies ; Spine
Language	English
Publishing date	2024-02-15
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2024.1352048
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Book ; Online ; Thesis: Neurodegeneration in multiple sclerosis mouse models

Rühling, Sebastian [Verfasser] / Kipp, Markus [Akademischer Betreuer]

2021

Author's details	Sebastian Rühling ; Betreuer: Markus Kipp
Keywords	Medizin, Gesundheit ; Medicine, Health
Subject code	sg610
Language	English
Publisher	Universitätsbibliothek der Ludwig-Maximilians-Universität
Publishing place	München
Document type	Book ; Online ; Thesis
Database	Digital theses on the web

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Article: Endovascular thrombectomy is cost-effective in acute basilar artery occlusion stroke.

Schwarting, Julian / Rühling, Sebastian / Bodden, Jannis / Schwarting, Stéphanie K / Zimmer, Claus / Mehrens, Dirk / Kirschke, Jan S / Kunz, Wolfgang G / Boeckh-Behrens, Tobias / Froelich, Matthias F

Frontiers in neurology

2023 Volume 14, Page(s) 1185304

Abstract: Objective: Endovascular thrombectomy is a long-established therapy for acute basilar artery occlusion (aBAO). Unlike for anterior circulation stroke, cost-effectiveness of endovascular treatment has not been evaluated and is urgently needed to calculate ...

Abstract	Objective: Endovascular thrombectomy is a long-established therapy for acute basilar artery occlusion (aBAO). Unlike for anterior circulation stroke, cost-effectiveness of endovascular treatment has not been evaluated and is urgently needed to calculate expected health benefits and financial rewards. The aim of this study was therefore to simulate patient-level costs, analyze the economic potential of endovascular thrombectomy in patients with acute basilar artery occlusion (aBAO), and identify major determinants of cost-effectiveness. Methods: A Markov model was developed to compare outcome and cost parameters between patients treated by endovascular thrombectomy and patients treated by best medical care, based on four recent prospective clinical trials (ATTENTION, BAOCHE, BASICS, and BEST). Treatment outcomes were derived from the most recent literature. Uncertainty was addressed by deterministic and probabilistic sensitivity analyses. Willingness to pay per QALY thresholds were set at 1x gross domestic product Results: Endovascular treatment of acute aBAO stroke yielded an incremental gain of 1.71 quality-adjusted life-years per procedure with an incremental cost-effectiveness ratio of $7,596 per QALY. This was substantially lower than the Willingness to pay of $63,593 per QALY. Lifetime costs were most sensitive to costs of the endovascular procedure. Conclusion: Endovascular treatment is cost-effective in patients with aBAO stroke.
Language	English
Publishing date	2023-04-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564214-5
ISSN	1664-2295
ISSN	1664-2295
DOI	10.3389/fneur.2023.1185304
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Article: Long-term reproducibility of opportunistically assessed vertebral bone mineral density and texture features in routine clinical multi-detector computed tomography using an automated segmentation framework.

Bodden, Jannis / Dieckmeyer, Michael / Sollmann, Nico / Rühling, Sebastian / Prucker, Philipp / Löffler, Maximilian T / Burian, Egon / Subburaj, Karupppasamy / Zimmer, Claus / Kirschke, Jan S / Baum, Thomas

Quantitative imaging in medicine and surgery

2023 Volume 13, Issue 9, Page(s) 5472–5482

Abstract: Background: To investigate reproducibility of texture features and volumetric bone mineral density (vBMD) extracted from trabecular bone in the thoracolumbar spine in routine clinical multi-detector computed tomography (MDCT) data in a single scanner ... ...

Abstract	Background: To investigate reproducibility of texture features and volumetric bone mineral density (vBMD) extracted from trabecular bone in the thoracolumbar spine in routine clinical multi-detector computed tomography (MDCT) data in a single scanner environment. Methods: Patients who underwent two routine clinical thoraco-abdominal MDCT exams at a single scanner with a time interval of 6 to 26 months (n=203, 131 males; time interval mean, 13 months; median, 12 months) were included in this observational study. Exclusion criteria were metabolic and hematological disorders, bone metastases, use of bone-active medications, and history of osteoporotic vertebral fractures (VFs) or prior diagnosis of osteoporosis. A convolutional neural network (CNN)-based framework was used for automated spine labeling and segmentation (T5-L5), asynchronous Hounsfield unit (HU)-to-BMD calibration, and correction for the intravenous contrast medium phase. Vertebral vBMD and six texture features [variance Results: SRE, LRE, RLN, and RP exhibited substantial reproducibility with RMSCV-values below 2%, for both sexes and at all spine levels, while vBMD was less reproducible (RMSCV =11.9-16.2%). Entropy showed highest variability (RMSCV =4.34-7.69%) due to statistically significant increases [range, mean ± standard deviation: (4.40±5.78)% to (8.36±8.66)%, P<0.001]. RMSCV of variance Conclusions: Opportunistic assessment of texture features in a single scanner environment using the presented CNN-based framework yields substantial reproducibility, outperforming vBMD reproducibility. Lowest scan-rescan variability was found for higher-order texture features. Further studies are warranted to determine, whether microarchitectural changes to the trabecular bone may be assessed through texture features.
Language	English
Publishing date	2023-08-09
Publishing country	China
Document type	Journal Article
ZDB-ID	2653586-5
ISSN	2223-4306 ; 2223-4292
ISSN (online)	2223-4306
ISSN	2223-4292
DOI	10.21037/qims-23-19
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Article: Incidental vertebral fracture prediction using neuronal network-based automatic spine segmentation and volumetric bone mineral density extraction from routine clinical CT scans.

Bodden, Jannis / Dieckmeyer, Michael / Sollmann, Nico / Burian, Egon / Rühling, Sebastian / Löffler, Maximilian T / Sekuboyina, Anjany / El Husseini, Malek / Zimmer, Claus / Kirschke, Jan S / Baum, Thomas

Frontiers in endocrinology

2023 Volume 14, Page(s) 1207949

Abstract: 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.: ... ...

Abstract	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.
MeSH term(s)	Male ; Humans ; Female ; Middle Aged ; Bone Density/physiology ; Spinal Fractures/diagnostic imaging ; Spinal Fractures/epidemiology ; Retrospective Studies ; Osteoporotic Fractures/diagnostic imaging ; Osteoporotic Fractures/epidemiology ; Osteoporotic Fractures/etiology ; Bayes Theorem ; Tomography, X-Ray Computed/methods ; Prevalence
Language	English
Publishing date	2023-07-17
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2023.1207949
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Article ; Online: Do pre-clinical multiple sclerosis models allow us to measure neurodegeneration and clinical progression?

Hochstrasser, Tanja / Jiangshan, Zhan / Rühling, Sebastian / Schmitz, Christoph / Kipp, Markus

Expert review of neurotherapeutics

2018 , Page(s) 1–3

Language	English
Publishing date	2018-04-04
Publishing country	England
Document type	Journal Article
ZDB-ID	2112534-X
ISSN	1744-8360 ; 1473-7175
ISSN (online)	1744-8360
ISSN	1473-7175
DOI	10.1080/14737175.2018.1459190
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Article ; Online: Automated detection of the contrast phase in MDCT by an artificial neural network improves the accuracy of opportunistic bone mineral density measurements.

Rühling, Sebastian / Navarro, Fernando / Sekuboyina, Anjany / El Husseini, Malek / Baum, Thomas / Menze, Bjoern / Braren, Rickmer / Zimmer, Claus / Kirschke, Jan S

European radiology

2021 Volume 32, Issue 3, Page(s) 1465–1474

Abstract: Objectives: To determine the accuracy of an artificial neural network (ANN) for fully automated detection of the presence and phase of iodinated contrast agent in routine abdominal multidetector computed tomography (MDCT) scans and evaluate the effect ... ...

Abstract	Objectives: To determine the accuracy of an artificial neural network (ANN) for fully automated detection of the presence and phase of iodinated contrast agent in routine abdominal multidetector computed tomography (MDCT) scans and evaluate the effect of contrast correction for osteoporosis screening. Methods: This HIPPA-compliant study retrospectively included 579 MDCT scans in 193 patients (62.4 ± 14.6 years, 48 women). Three different ANN models (2D DenseNet with random slice selection, 2D DenseNet with anatomy-guided slice selection, 3D DenseNet) were trained in 462 MDCT scans of 154 patients (threefold cross-validation), who underwent triphasic CT. All ANN models were tested in 117 unseen triphasic scans of 39 patients, as well as in a public MDCT dataset containing 311 patients. In the triphasic test scans, trabecular volumetric bone mineral density (BMD) was calculated using a fully automated pipeline. Root-mean-square errors (RMSE) of BMD measurements with and without correction for contrast application were calculated in comparison to nonenhanced (NE) scans. Results: The 2D DenseNet with anatomy-guided slice selection outperformed the competing models and achieved an F1 score of 0.98 and an accuracy of 98.3% in the test set (public dataset: F1 score 0.93; accuracy 94.2%). Application of contrast agent resulted in significant BMD biases (all p < .001; portal-venous (PV): RMSE 18.7 mg/ml, mean difference 17.5 mg/ml; arterial (AR): RMSE 6.92 mg/ml, mean difference 5.68 mg/ml). After the fully automated correction, this bias was no longer significant (p > .05; PV: RMSE 9.45 mg/ml, mean difference 1.28 mg/ml; AR: RMSE 3.98 mg/ml, mean difference 0.94 mg/ml). Conclusion: Automatic detection of the contrast phase in multicenter CT data was achieved with high accuracy, minimizing the contrast-induced error in BMD measurements. Key points: • A 2D DenseNet with anatomy-guided slice selection achieved an F1 score of 0.98 and an accuracy of 98.3% in the test set. In a public dataset, an F1 score of 0.93 and an accuracy of 94.2% were obtained. • Automated adjustment for contrast injection improved the accuracy of lumbar bone mineral density measurements (RMSE 18.7 mg/ml vs. 9.45 mg/ml respectively, in the portal-venous phase). • An artificial neural network can reliably reveal the presence and phase of iodinated contrast agent in multidetector CT scans ( https://github.com/ferchonavarro/anatomy_guided_contrast_c ). This allows minimizing the contrast-induced error in opportunistic bone mineral density measurements.
MeSH term(s)	Bone Density ; Female ; Humans ; Multidetector Computed Tomography ; Neural Networks, Computer ; Osteoporosis/diagnostic imaging ; Retrospective Studies
Language	English
Publishing date	2021-10-23
Publishing country	Germany
Document type	Journal Article ; Multicenter Study
ZDB-ID	1085366-2
ISSN	1432-1084 ; 0938-7994 ; 1613-3749
ISSN (online)	1432-1084
ISSN	0938-7994 ; 1613-3749
DOI	10.1007/s00330-021-08284-z
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Article: Cost-effectiveness of opportunistic QCT-based osteoporosis screening for the prediction of incident vertebral fractures.

Rühling, Sebastian / Schwarting, Julian / Froelich, Matthias F / Löffler, Maximilian T / Bodden, Jannis / Hernandez Petzsche, Moritz R / Baum, Thomas / Wostrack, Maria / Aftahy, A Kaywan / Seifert-Klauss, Vanadin / Sollmann, Nico / Zimmer, Claus / Kirschke, Jan S / Tollens, Fabian

Frontiers in endocrinology

2023 Volume 14, Page(s) 1222041

Abstract: Objectives: Opportunistic quantitative computed tomography (oQCT) derived from non-dedicated routine CT has demonstrated high accuracy in diagnosing osteoporosis and predicting incident vertebral fractures (VFs). We aimed to investigate the cost- ... ...

Abstract	Objectives: Opportunistic quantitative computed tomography (oQCT) derived from non-dedicated routine CT has demonstrated high accuracy in diagnosing osteoporosis and predicting incident vertebral fractures (VFs). We aimed to investigate the cost-effectiveness of oQCT screening compared to dual-energy X-ray absorptiometry (DXA) as the standard of care for osteoporosis screening. Methods: Three screening strategies ("no osteoporosis screening", "oQCT screening", and "DXA screening") after routine CT were simulated in a state-transition model for hypothetical cohorts of 1,000 patients (women and men aged 65 years) over a follow-up period of 5 years (base case). The primary outcomes were the cumulative costs and the quality-adjusted life years (QALYs) estimated from a U.S. health care perspective for the year 2022. Cost-effectiveness was assessed based on a willingness-to-pay (WTP) threshold of $70,249 per QALY. The secondary outcome was the number of prevented VFs. Deterministic and probabilistic sensitivity analyses were conducted to test the models' robustness. Results: Compared to DXA screening, oQCT screening increased QALYs in both sexes (additional 2.40 per 1,000 women and 1.44 per 1,000 men) and resulted in total costs of $3,199,016 and $950,359 vs. $3,262,934 and $933,077 for women and men, respectively. As a secondary outcome, oQCT screening prevented 2.6 and 2.0 additional VFs per 1,000 women and men, respectively. In the probabilistic sensitivity analysis, oQCT screening remained cost-effective in 88.3% (women) and 90.0% (men) of iterations. Conclusion: oQCT screening is a cost-effective ancillary approach for osteoporosis screening and has the potential to prevent a substantial number of VFs if considered in daily clinical practice.
MeSH term(s)	Male ; Humans ; Female ; Cost-Benefit Analysis ; Bone Density ; Osteoporosis/diagnostic imaging ; Osteoporosis/epidemiology ; Mass Screening/methods ; Spinal Fractures/diagnostic imaging ; Spinal Fractures/epidemiology
Language	English
Publishing date	2023-07-31
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2023.1222041
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Article ; Online: Proposed diagnostic volumetric bone mineral density thresholds for osteoporosis and osteopenia at the cervicothoracic spine in correlation to the lumbar spine.

Rühling, Sebastian / Scharr, Andreas / Sollmann, Nico / Wostrack, Maria / Löffler, Maximilian T / Menze, Bjoern / Sekuboyina, Anjany / El Husseini, Malek / Braren, Rickmer / Zimmer, Claus / Kirschke, Jan S

European radiology

2022 Volume 32, Issue 9, Page(s) 6207–6214

Abstract: 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 ... ...

Abstract	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 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
MeSH term(s)	Absorptiometry, Photon/methods ; Adult ; Bone Density ; Bone Diseases, Metabolic/diagnostic imaging ; Female ; Fractures, Bone ; Humans ; Lumbar Vertebrae/diagnostic imaging ; Lumbosacral Region ; Male ; Osteoporosis/diagnostic imaging ; Retrospective Studies ; Tomography, X-Ray Computed/methods
Language	English
Publishing date	2022-04-06
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1085366-2
ISSN	1432-1084 ; 0938-7994 ; 1613-3749
ISSN (online)	1432-1084
ISSN	0938-7994 ; 1613-3749
DOI	10.1007/s00330-022-08721-7
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