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Within the bone marrow microenvironment, endothelial cells (EC) exert important functions. Arterial EC support hematopoiesis while H-type capillaries induce bone formation. Here, we show that BM sinusoidal EC (BM-SEC) actively control erythropoiesis. Mice with stabilized β-catenin in BM-SEC ( Ctnnb1 OE-SEC ) generated by using a BM-SEC-restricted Cre mouse line ( Stab2-iCreF3 ) develop fatal anemia. While activation of Wnt-signaling in BM-SEC causes an increase in erythroblast subsets (PII–PIV), mature erythroid cells (PV) are reduced indicating impairment of terminal erythroid differentiation/reticulocyte maturation. Transplantation of Ctnnb1 OE-SEC hematopoietic stem cells into wildtype recipients confirms lethal anemia to be caused by cell-extrinsic, endothelial-mediated effects. Ctnnb1 OE-SEC BM-SEC reveal aberrant sinusoidal differentiation with altered EC gene expression and perisinusoidal ECM deposition and angiocrine dysregulation with de novo endothelial expression of FGF23 and DKK2, elevated in anemia and involved in vascular stabilization, respectively. Our study demonstrates that BM-SEC play an important role in the bone marrow microenvironment in health and disease. Niche crosstalk with Haematopoietic cells underlies normal haematopoiesis and myeloid disorders. Here the authors report a Stabilin2-Cre driver mouse with Cre-activity restricted to bone marrow sinusoidal endothelial cells, and that Stabilin2-Cre driven overactivation of b-catenin leads to erythroid differentiation defects and anaemia.

Computer-assisted reporting (CAR) tools were suggested to improve radiology report quality by context-sensitively recommending key imaging biomarkers. However, studies evaluating machine learning (ML) algorithms on cross-lingual ontological (RadLex) mappings for developing embedded CAR algorithms are lacking. Therefore, we compared ML algorithms developed on human expert-annotated features against those developed on fully automated cross-lingual (German to English) RadLex mappings using 206 CT reports of suspected stroke. Target label was whether the Alberta Stroke Programme Early CT Score (ASPECTS) should have been provided (yes/no:154/52). We focused on probabilistic outputs of ML-algorithms including tree-based methods, elastic net, support vector machines (SVMs) and fastText (linear classifier), which were evaluated in the same 5 × fivefold nested cross-validation framework. This allowed for model stacking and classifier rankings. Performance was evaluated using calibration metrics (AUC, brier score, log loss) and -plots. Contextual ML-based assistance recommending ASPECTS was feasible. SVMs showed the highest accuracies both on human-extracted- (87%) and RadLex features (findings:82.5%; impressions:85.4%). FastText achieved the highest accuracy (89.3%) and AUC (92%) on impressions. Boosted trees fitted on findings had the best calibration profile. Our approach provides guidance for choosing ML classifiers for CAR tools in fully automated and language-agnostic fashion using bag-of-RadLex terms on limited expert-labelled training data.

Automated tools have been proposed to quantify brain volume for suspected dementia diagnoses. However, their robustness in longitudinal, real-life cohorts remains unexplored. This exploratory study examined if expert visual assessment (EVA) of atrophy progression is reflected by automated volumetric analyses (AVA) on sequential MR-imaging. We analyzed a random subset of 20 patients with two consecutive 3D T1-weighted examinations (median follow-up 4.0 years, LQ-UQ: 2.1–5.2, range: 0.2–10). Thirteen (65%) with cognitive decline, the remaining with other neuropsychiatric diseases. EVA was performed by two blinded neuroradiologists using a 3 or 5-point Likert scale for atrophy progression (scores ± 0–2: no, probable and certain progression or decrease, respectively) in dementia-relevant brain regions (frontal-, parietal-, temporal lobes, hippocampi, ventricles). Differences of AVA-volumes were normalized to baseline (delta). Inter-rater agreement of EVA scores was excellent (κ = 0.92). AVA-delta and EVA showed significant global associations for the right hippocampus (p KW  = 0.035), left temporal lobe (p KW  = 0.0092), ventricle volume (p KW  = 0.0091) and a weak association for the parietal lobe (p KW  = 0.067). Post hoc testing revealed additional significant link for the left hippocampus (p WSRT  = 0.039). In conclusion, the associations between volumetric deltas and EVA of atrophy progression showed promising results for certain brain regions. However, AVA-deltas exhibited unexpected variance, highlighting the need for caution and expert visual confirmation, particularly when scanners or acquisition protocols vary during follow-ups. Therefore, further validation, ideally in large prospective cohorts, is necessary before AVA can be recommended for routine clinical implementation in longitudinal follow-ups.

Filament perforation is a widely-used method to induce subarachnoid hemorrhage (SAH) in mice. Whereas the perforation site has been assumed to be in the branching of middle cerebral artery (MCA) and anterior cerebral artery (ACA), we recently observed more proximal perforations. Filament perforation was performed in CD1- (n = 10) and C57Bl/6N-mice (n = 9) ex vivo. The filament was left in place and the perforation site was microscopically assessed. Digital subtraction angiography (DSA) was performed in CD1- (n = 9) and C57Bl/6J-mice (n = 29) and anatomical differences of the internal carotid artery (ICA) were determined. Whereas in C57Bl/6N-mice perforation occurred in the proximal intracranial ICA in 89% (n = 8), in CD1-mice the perforation site was in the proximal ICA in 50% (n = 5), in the branching between MCA and ACA in 40% (n = 4), and in the proximal ACA in 10% (n = 1). DSA revealed a stronger angulation (p<0.001) of the ICA in CD1-mice (163.5±2.81°) compared to C57Bl/6J-mice (124.5±5.49°). Body weight and ICA-angle showed no significant correlation in C57Bl/6J- (r = -0.06, p.sub.weight/angle = 0.757) and CD1-mice (r = -0.468, p.sub.weight/angle = 0.242). Filament perforation in mice occurs not only at the hitherto presumed branching between MCA and ACA, but seems to depend on mouse strain and anatomy as the proximal intracranial ICA may also be perforated frequently.

This study provides an objective comparison of cranial computed tomography (CT) imaging quality and radiation dose between photon counting detectors (PCCTs) and energy-integrated detectors (EIDs). We retrospectively analyzed 158 CT scans from 76 patients, employing both detector types on the same individuals to ensure a consistent comparison. Our analysis focused on the Computed Tomography Dose Index and the Dose-Length Product together with the contrast-to-noise ratio and the signal-to-noise ratio for brain gray and white matter. We utilized standardized imaging protocols and consistent patient positioning to minimize variables. PCCT showed a potential for higher image quality and lower radiation doses, as highlighted by this study, thus achieving diagnostic clarity with reduced radiation exposure, underlining its significance in patient care, particularly for patients requiring multiple scans. The results demonstrated that while both systems were effective, PCCT offered enhanced imaging and patient safety in neuroradiological evaluations.

IgG4‐related disease (IgG4‐RD) is a fibroinflammatory disorder signified by aberrant infiltration of IgG4‐restricted plasma cells into a variety of organs. Clinical presentation is heterogeneous, and pathophysiological mechanisms of IgG4‐RD remain elusive. There are very few cases of IgG4‐RD with isolated central nervous system manifestation. By leveraging single‐cell sequencing of the cerebrospinal fluid (CSF) of a patient with an inflammatory intracranial pseudotumor, we provide novel insights into the immunopathophysiology of IgG4‐RD. Our data illustrate an IgG4‐RD‐associated polyclonal T‐cell response in the CSF and an oligoclonal T‐cell response in the parenchymal lesions, the latter being the result of a multifaceted cell–cell interaction between immune cell subsets and pathogenic B cells. We demonstrate that CD8 + T effector memory cells might drive and sustain autoimmunity via macrophage migration inhibitory factor (MIF)‐CD74 signaling to immature B cells and CC‐chemokine ligand 5 (CCL5)‐mediated recruitment of cytotoxic CD4 + T cells. These findings highlight the central role of T cells in sustaining IgG4‐RD and open novel avenues for targeted therapies. SYNOPSIS This translational study demonstrates the potential of single‐cell profiling technologies to support clinicians in the diagnosis of rare autoimmune disorders while shedding new light into potential molecular pathomechanisms of intercellular communication in IgG4‐related disease. T‐cell ‐ T‐cell crosstalk facilitates recruitment of helper and cytotoxic CD4 + T‐cells to manifestation sites of IgG4‐related disease. T‐cell‐derived CXCL13 might regulate pathogenic B cell migration into the CNS and promote intrathecal accumulation of B‐cells. Recurrent IgG4‐RD in three intracranial manifestation sites is driven by a clonal T‐cell response. Graphical Abstract This translational study demonstrates the potential of single‐cell profiling technologies to support clinicians in the diagnosis of rare autoimmune disorders while shedding new light into potential molecular pathomechanisms of intercellular communication in IgG4‐related disease.

Micro-CT imaging of liver disease in mice relies on high soft tissue contrast to detect small lesions like liver metastases. Purpose of this study was to characterize the localization and time course of contrast enhancement of a nanoparticular alkaline earth metal-based contrast agent (VISCOVER ExiTron nano) developed for small animal liver CT imaging. ExiTron nano 6000 and ExiTron nano 12000, formulated for liver/spleen imaging and angiography, respectively, were intravenously injected in C57BL/6J-mice. The distribution and time course of contrast enhancement were analysed by repeated micro-CT up to 6 months. Finally, mice developing liver metastases after intrasplenic injection of colon carcinoma cells underwent longitudinal micro-CT imaging after a single injection of ExiTron nano. After a single injection of ExiTron nano the contrast of liver and spleen peaked after 4-8 hours, lasted up to several months and was tolerated well by all mice. In addition, strong contrast enhancement of abdominal and mediastinal lymph nodes and the adrenal glands was observed. Within the first two hours after injection, particularly ExiTron nano 12000 provided pronounced contrast for imaging of vascular structures. ExiTron nano facilitated detection of liver metastases and provided sufficient contrast for longitudinal observation of tumor development over weeks. The nanoparticulate contrast agents ExiTron nano 6000 and 12000 provide strong contrast of the liver, spleen, lymph nodes and adrenal glands up to weeks, hereby allowing longitudinal monitoring of pathological processes of these organs in small animals, with ExiTron nano 12000 being particularly optimized for angiography due to its very high initial vessel contrast.

Crossed cerebellar diaschisis (CCD) is a state of neural depression caused by loss of connections to injured neural structures remote from the cerebellum usually evaluated by positron emission tomography. Recently it has been shown that dynamic susceptibility contrast perfusion weighted MRI (PWI) may also be feasible to detect the phenomenon. In this study we aimed to assess the frequency of CCD on PWI in patients with acute thalamic infarction. From a MRI report database we identified patients with acute isolated thalamic infarction. Contralateral cerebellar hypoperfusion was identified by inspection of time to peak (TTP) maps and evaluated quantitatively on TTP, mean transit time (MTT), cerebral blood flow and volume (CBF, CBV) maps. A competing cerebellar pathology or an underlying vascular pathology were excluded. A total of 39 patients was included. Common symptoms were hemiparesis (53.8%), hemihypaesthesia (38.5%), dysarthria (30.8%), aphasia (17.9%), and ataxia (15.4%). In 9 patients (23.1%) PWI showed hypoperfusion in the contralateral cerebellar hemisphere. All of these had lesions in the territory of the tuberothalamic, paramedian, or inferolateral arteries. Dysarthria was observed more frequently in patients with CCD (6/9 vs. 6/30; OR 8.00; 95%CI 1.54-41.64, p = 0.01). In patients with CCD, the median ischemic lesion volume on DWI (0.91 cm³), IQR 0.49-1.54 cm³) was larger compared to patients with unremarkable PWI (0.51 cm³, IQR 0.32-0.74, p = 0.05). The most pronounced changes were found in CBF (0.94±0.11) and MTT (1.06±0.13) signal ratios, followed by TTP (1.05±0.02). Multimodal MRI demonstrates CCD in about 20% of acute isolated thalamic infarction patients. Lesion size seems to be a relevant factor in its pathophysiology.

Various neurological disorders are associated with lesions predominantly or exclusively affecting the splenium of the corpus callosum (CC), such as Marchiafava-Bignami syndrome (MBS), reversible splenium lesion (RSL), and ischemic stroke (IS). The spectrum of symptoms is broad and clinical presentations may be indistinguishable. Therefore, we aimed to investigate the additional value of diffusion-weighted imaging (DWI) findings of splenial lesions in patients with MBS, RSL, and IS. Overall, 23 patients (4 patients with MBS, 10 patients with RSL, and 9 patients with isolated IS in the splenium) were identified from a magnetic resonance imaging report database and analyzed with focus on lesion localization, shape, and size on DWI, as well as relative apparent diffusion coefficient (ADC). A focal hyperintensity in the splenium was observed on DWI in all patients. In MBS symmetrical boomerang-shaped lesions, in RSL central oval or round lesions, and in IS eccentric irregular lesions in the splenium were found. The median lesion size in MBS [6.25 (IQR=2.04-8.62) ml] was significantly larger than that in RSL [0.38 (IQR=0.09-0.92) ml, p=0.01], and in IS [0.09 (IQR=0.05-0.94) ml; p=0.01]. Regarding relative ADC values, no significant differences between MBS [0.32 (IQR=0.19-0.62)], RSL [0.22 (IQR=0.14-0.30)], and IS [0.27 (IQR=0.20-1.19)] were found. Diffusion restricted lesions in the splenium of the CC are best classified by localization, shape, and size, whereas relative ADC values are of limited value for differentiation of different neurological disorders.

Background: Recent advancements in computed tomography (CT), notably in photon-counting CT (PCCT), are revolutionizing the medical imaging field. PCCT’s spectral imaging can better visualize tissues based on their material properties. This research aims to establish a fundamental approach for the in vivo visualization of intracranial cerebrospinal fluid (CSF) using PCCT. Methods: PCCT was integrated to distinguish the CSF within the intracranial space with spectral imaging. In this study, we analyzed monoenergetic +67 keV reconstructions alongside virtual non-contrast and iodine phase images. This approach facilitated the assessment of the spectral characteristics of CSF in patients who did not present with intra-axial pathology or inflamation. Results: Our findings illustrate PCCT’s effectiveness in providing distinct and clear visualizations of intracranial CSF structures, building a foundation. The signal-to-noise ratio was quantified across all measurements, to check in image quality. Conclusions: PCCT serves as a robust, non-invasive platform for the detailed visualization of intracranial CSF. This technology is promising in enhancing diagnostic accuracy through different conditions.