Digital subtraction angiography (DSA) plays a central role in the diagnosis and treatment of cerebrovascular disease, yet its invasive nature and high acquisition cost severely limit large-scale data collection and public data sharing. Therefore, we developed a semantically conditioned latent diffusion model (LDM) that synthesizes arterial-phase cerebral DSA frames under explicit control of anatomical circulation (anterior vs. posterior) and canonical C-arm positions. We curated a large single-centre DSA dataset of 99,349 frames and trained a conditional LDM using text embeddings that encoded anatomy and acquisition geometry. To assess clinical realism, four medical experts, including two neuroradiologists, one neurosurgeon, and one internal medicine expert, systematically rated 400 synthetic DSA images using a 5-grade Likert scale for evaluating proximal large, medium, and small peripheral vessels. The generated images achieved image-wise overall Likert scores ranging from 3.1 to 3.3, with high inter-rater reliability (ICC(2,k) = 0.80–0.87). Distributional similarity to real DSA frames was supported by a low median Fréchet inception distance (FID) of 15.27. Our results indicate that semantically controlled LDMs can produce realistic synthetic DSAs suitable for downstream algorithm development, research, and training.

The climate crisis underscores the need for weather-based predictive analytics in healthcare, as weather factors contribute to ~11% of the global stroke burden. Therefore, we developed machine learning models using locoregional weather data to forecast daily acute ischemic stroke (AIS) admissions. An AIS cohort of 7914 patients admitted between 2015 and 2021 at the tertiary University Medical Center Mannheim, Germany, with a 600,000-population catchment area, was geospatially matched to German Weather Service data. Poisson regression, boosted generalized additive models, support vector machines, random forest, and extreme gradient boosting (XGB) were evaluated within a time-stratified nested cross-validation framework. XGB performed best (mean absolute error: 1.21 cases/day). Maximum air pressure was the top predictor, with temperature exhibiting a bimodal link. Cold and heat stressor days (Tmin_lag3 < −2 °C; Tperceived < −1.4 °C; Tmin_lag7 > 15 °C) and stormy conditions (wind gusts > 14 m/s) increased stroke admissions. This generalizable framework could aid real-time hospital planning, effective care and forecasting of various weather-related disease burdens.

Primary brain calcification (primary familial brain calcification in inherited cases) is an often-genetic condition characterized by symmetrical brain calcifications and neuropsychiatric symptoms. The calcifications can also occur without overt clinical symptoms. Identifying laboratory biomarkers in primary brain calcification and their association with imaging, genetic, and clinical data will be crucial for a deeper understanding of primary brain calcification causation and progression and the planning of therapeutic trials. The serum biomarkers for neuronal degeneration (phosphorylated tau, neuron-specific enolase, neurofilament light- and heavy chain) and glial activation (glial fibrillary acidic protein, S100 calcium-binding protein B) were measured in 101 probands (41 controls and 60 probands with primary brain calcification). The deep phenotyping protocol of the German Fahr-NET register included neurological and neuropsychological examination, routine laboratory workup, and whole exome sequencing. We also performed and analyzed 45 cranial CT scans using the total calcification score. While mild pallidal calcifications were observed early in young, asymptomatic primary brain calcification mutation carriers, individuals with calcifications extending beyond the pallidum were symptomatic. Individuals with primary brain calcification had elevated serum glial fibrillary acidic protein and neurofilament light chain levels. Serum biomarkers correlated with both the extent of calcifications and the clinical impairment. Elevated parathyroid hormone levels distinguished the primary brain calcification group without identified mutation from both genetic primary brain calcification and control groups. Our results define a practical imaging cut-off indicating the presence of primary brain calcification symptoms. Elevated parathyroid hormone levels in primary brain calcification without identified mutation, but not in primary brain calcification with a monogenic cause, suggest abortive calcium regulation defects as a pathogenic factor specifically for primary brain calcification without identified mutation. Elevated glial fibrillary acidic protein and neurofilament concentrations in individuals with primary brain calcification indicate early, chronic astrocytosis and neuronal impairment, respectively. The significant association of neurofilament light chain with clinical scores and brain imaging results will be relevant for future therapeutic studies.

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 (pKW = 0.035), left temporal lobe (pKW = 0.0092), ventricle volume (pKW = 0.0091) and a weak association for the parietal lobe (pKW = 0.067). Post hoc testing revealed additional significant link for the left hippocampus (pWSRT = 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.

BACKGROUND/AIM:The current study was designed to evaluate the etiologies of hypernatremic episodes in patients with severe burn injuries in comparison to critically ill non-burn patients.PATIENTS AND METHODS:The retrospective data acquisition was limited to the first 14 days and to patients with at least 20% total body surface area (TBSA) 2nd degree burn injuries or more than 10% TBSA when including areas of 3rd degree burn injuries. The results were compared to the results of a previously published study that analyzed the risk factors for hypernatremia in 390 non-burn intensive care unit patients.RESULTS:In total, 120 patients with a total of 50 hypernatremic episodes were included. Compared to non-burn injury patients, no significant differences were detectable except for a lower rate of hypokalemia and a higher rate of mechanical ventilation. The main trigger for hypernatremic episodes was the loss of free water, while 24% of the hypernatremic episodes seemed to be at least partly triggered by a surplus sodium influx. Patients with hypernatremic episodes had a significantly higher mortality rate. However, in none of the cases was hypernatremia the decisive cause of death.CONCLUSION:Besides the unique phenomenon of high volume internal and external volume shifts, the overall risk factors and etiologies of hypernatremia in patients with severe burn injury do not seem to significantly differ from other ICU patient collectives. Remarkably, a surplus of sodium influx and therefore a modifiable factor besides the specific burn injury volume resuscitation had an impact on the hypernatremic episodes in 24% of cases.

Automated tools have been proposed to quantify brain volume for suspected dementia diagnoses. However, their robustness in longitudinal, real-life cohorts remains unexplored. We investigated 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=0.035), left temporal lobe (p=0.0092), ventricle volume (p=0.0091) and a weak association for the parietal lobe (p=0.067). Post hoc testing revealed a significant link for the left hippocampus (p=0.039). In conclusion, the associations between volumetric deltas and EVA of atrophy progression were robust for certain brain regions. However, AVA-deltas showed unexpected variance, and therefore should be used with caution in individual cases, especially when acquisition protocols vary.### Competing Interest StatementM.E.M. and H.W. report consultancy for Siemens Healthineers GmbH. M.E.M. unrelated consultancy for EppData GmbH. The remaining authors have no conflicts of interest to declare.### Funding StatementM.E.M. and N.S. reports funding from the German Ministry for Education and Research (BMBF) within the framework of the Medical Informatics Initiative (MII) MIRACUM Consortium (Medical Informatics for Holistic Disease Models in Personalized and Preventive Medicine, MIDorAI; 01ZZ2020). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.### Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:The study was approved by the Medical Ethics Commission II of Medical Faculty Mannheim, University of Heidelberg (approval nr.: 2017-825R-MA and 2017-828R-MA). The need for informed consent was waived because of the retrospective nature of the study. All procedures were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.YesAll data produced in the present study are available upon reasonable request to the authors.

ObjectiveAlthough sepsis and delayed cerebral ischemia (DCI) are severe complications in patients with aneurysmal subarachnoid hemorrhage (aSAH) and share pathophysiological features, their interrelation and additive effect on functional outcome is uncertain. We investigated the association between sepsis and DCI and their cumulative effect on functional outcome in patients with aSAH using current sepsis-3 definition.MethodsPatients admitted to our hospital between 11/2014 and 11/2018 for aSAH were retrospectively analyzed. The main explanatory variable was sepsis, diagnosed using sepsis-3 criteria. Endpoints were DCI and functional outcome at hospital discharge (modified Rankin Scale (mRS) 0–3 vs. 4–6). Propensity score matching (PSM) and multivariable logistic regressions were performed.ResultsOf 238 patients with aSAH, 55 (23.1%) developed sepsis and 74 (31.1%) DCI. After PSM, aSAH patients with sepsis displayed significantly worse functional outcome (p < 0.01) and longer ICU stay (p = 0.046). Sepsis was independently associated with DCI (OR = 2.46, 95%CI: 1.28–4.72, p < 0.01). However, after exclusion of patients who developed sepsis before (OR = 1.59, 95%CI: 0.78–3.24, p = 0.21) or after DCI (OR = 0.85, 95%CI: 0.37–1.95, p = 0.70) this statistical association did not remain. Good functional outcome gradually decreased from 56.3% (76/135) in patients with neither sepsis nor DCI, to 43.8% (21/48) in those with no sepsis but DCI, to 34.5% (10/29) with sepsis but no DCI and to 7.7% (2/26) in patients with both sepsis and DCI.ConclusionOur study demonstrates a strong association between sepsis, DCI and functional outcome in patients with aSAH and suggests a complex interplay resulting in a cumulative effect towards poor functional outcome, which warrants further studies.

Background: Although sepsis and delayed cerebral ischemia (DCI) are severe complications in patients with aneurysmal subarachnoid hemorrhage (aSAH) and share pathophysiological features, their interrelation and additive effect on functional outcome is uncertain. We investigated the association of sepsis with DCI and their cumulative effect on functional outcome in patients with aSAH using current sepsis-3 definition. Methods: Patients admitted to our hospital between 11/2014-11/2018 for aSAH were retrospectively analyzed. The main explanatory variable was sepsis, diagnosed using sepsis-3 criteria. Endpoints were DCI and functional outcome at hospital discharge (modified Rankin Scale (mRS) 0-3 vs. 4-6). Propensity score matching (PSM) and multivariable logistic regressions were performed. Results: Of 238 patients with aSAH, 55 (23%) developed sepsis and 74 (31%) DCI. After PSM, aSAH patients with sepsis displayed significantly worse functional outcome (p<0.01) and longer ICU stay (p=0.046). Sepsis was independently associated with DCI (OR=2.46, 95%CI: 1.28-4.72, p<0.01). However, after exclusion of patients who developed sepsis before (OR=1.59, 95%CI: 0.78-3.24, p=0.21) or after DCI (OR=0.85, 95%CI: 0.37-1.95, p=0.70) this statistical association did not remain. Good functional outcome gradually decreased from 56% (76/135) in patients with neither sepsis nor DCI, to 43% (21/48) in those with no sepsis but DCI, to 34% (10/29) with sepsis but no DCI and to 8% (2/26) in patients with both sepsis and DCI. Conclusions: Our study demonstrates a strong association between sepsis, DCI and functional outcome in patients with aSAH and suggests a complex interplay resulting in a cumulative effect towards poor functional outcome, which warrants further studies. ### Competing Interest Statement Dr. Centner, Dr. Schoettler and Prof. Dr. Thiel report funding from the Klaus Tschira Stiftung, grant number 00.277.2015. Dr. Maros reports funding from the German Ministry for Education and Research (BMBF) within the framework of the Medical Informatics Initiative (MII) MIRACUM Consortium (Medical Informatics for Holistic Disease Models in Personalized and Preventive Medicine, MIDorAI; 01ZZ2020) and unrelated consultancy for Siemens Healthineers GmbH and EppData GmbH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The remaining authors have no conflicts of interest to declare. ### Clinical Protocols ### Funding Statement Dr. Centner, Dr. Schoettler and Prof. Dr. Thiel report funding from the Klaus Tschira Stiftung, grant number 00.277.2015. Dr. Maros reports funding from the German Ministry for Education and Research (BMBF) within the framework of the Medical Informatics Initiative (MII) MIRACUM Consortium (Medical Informatics for Holistic Disease Models in Personalized and Preventive Medicine, MIDorAI; 01ZZ2020). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Medical Ethics Commission II of Medical Faculty Mannheim, University of Heidelberg, approved the study design as well as reanalysis of neuroradiological reports and imaging data (reference nr.: 2019-1096R, 2017-825R-MA and 2017-828R-MA; date of approval: 01/10/2019). The need for informed consent was waived because of the retrospective nature of the study. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Study design and reporting adhered to the STROBE guidelines. All data produced in the present study are available upon reasonable request to the authors.

Purpose: Detection of ischemic lesions in patients with transient neurovascular symptoms is relevant for the estimation of the risk of a subsequent stroke and etiological classification. To improve detection rates, different technical approaches have been used, such as diffusion-weighted imaging (DWI) with high b-values or higher magnetic field strength. Here, we sought to investigate the value of computed DWI (cDWI) with high b-values in these patients. Methods: From an MRI report database we identified patients with transient neurovascular symptoms who underwent repeated MRI including DWI. cDWI was calculated with a monoexponential model with high bvalues (2000, 3000, and 4000 s/mm2) and compared to the routinely used standard DWI with regard to presence of ischemic lesions and lesion detectability. Result: Overall 33 patients with transient neurovascular symptoms (71 [IQR 57-83.5] years; 21 [63.6%] male) were included. On DWI, acute ischemic lesions were observed in 22 (78.6%). Acute ischemic lesions were observed in 17 (51.5%) patients on initial DWI, and in 26 (78.8%) patients on follow-up DWI. Lesion detectability was rated significantly better on cDWI at 2000s/mm2 compared to standard DWI. In 2 (9.1%) patients, cDWI at 2000s/mm2 revealed an acute ischemic lesion proven on follow-up standard DWI which was not detected with certainty on the initial standard DWI. Conclusion: cDWI might be a valuable addition to routinely acquired standard DWI in patients with transient neurovascular symptoms since its use might result in improved ischemic lesion detection. A b-value of 2000s/mm2 seems most promising for clinical practice. (c) 2023 Elsevier Masson SAS. All rights reserved.

AbstractBackgroundIn the midst of the emerging climate crisis, healthcare providers lack locally validated, disease-specific surveillance models. Stroke, a significant contributor to the global disease burden, has been linked to climate change. Therefore, we developed and benchmarked machine learning (ML) models based on locoregional weather systems to forecast the number of daily acute ischemic stroke (AIS) admissions.MethodsAIS patients diagnosed between 2015 and 2021 at the tertiary University Medical Center (UMC) Mannheim, Germany were extracted from the local data integration center and geospatially matched to weather data from the German Weather Service (DWD) based on the clinic’s, patients’ home and closest tower’s locations at the time of admission. Statistical- (Poisson), boosted generalized additive model (GAM), support vector machines (SVR), and tree-based models including random forest (RF) and extreme gradient boosting (XGB) were evaluated in regression settings within time-stratified nested cross-validation setup (training-validation: 2015-2020, test set: 2021) to predict the number of daily AIS admissions.FindingsThe cohort included 7,914 AIS patients (4,244 male, 53·6%). XGB showed the best test performance with lowest mean absolute error (MAE) of 1·21 cases/day. Maximum air pressure was identified as the top predictive variable. Shapley additive explanations analyses revealed that temperature extremes of extended cold-(lag-3 minimum temperature <-2 °C; minimum perceived temperature <-1·4 °C) and hot stressors (lag-7 minimum temperature >15 °C), as well as stormy conditions (lag-1 and lag-2 maximum wind gust >14 m/s and speed >10·4 m/s), increased stroke incidences substantially with distinct seasonal associations.InterpretationML models can sufficiently forecast AIS admissions based on weather patterns allowing for improved resource allocation and preparedness.

Rosette-forming glioneuronal tumors (RGNT) are extremely rare mostly benign tumors of the central nervous system, which are often studied for its histological aspects despite relatively small numbers of clinical especially radiological knowledge.Despite the increasing number of publications on different localizations and treatment protocols, the morphologic and temporal development process of this rare tumor entity is not clear. We were able to coincidentally observe the entire course of the tumor growth of a RGNT on subsequent MRI examinations in a typical case with mild clinical symptoms and no other neurological illnesses, thus possible clinical complications were prevented.

Primary familial brain calcification (PFBC; formerly Fahr's disease) and early-onset Alzheimer's disease (EOAD) may share partially overlapping pathogenic principles. Although the heterozygous loss-of-function mutation c.1523 + 1G > T in the PFBC-linked gene SLC20A2 was detected in a patient with asymmetric tremor, early-onset dementia, and brain calcifications, CSF β-amyloid parameters and FBB-PET suggested cortical β-amyloid pathology. Genetic re-analysis of exome sequences revealed the probably pathogenic missense mutation c.235G > A/p.A79T in PSEN1. The SLC20A2 mutation segregated with mild calcifications in two children younger than 30 years. We thus describe the stochastically extremely unlikely co-morbidity of genetic PFBC and genetic EOAD. The clinical syndromes pointed to additive rather than synergistic effects of the two mutations. MRI data revealed the formation of PFBC calcifications decades before the probable onset of the disease. Our report furthermore exemplifies the value of neuropsychology and amyloid PET for differential diagnosis.

Data on sepsis in patients with a subarachnoid hemorrhage (SAH) are scarce. We assessed the impact of different sepsis criteria on the outcome in an SAH cohort. Adult patients admitted to our ICU with a spontaneous SAH between 11/2014 and 11/2018 were retrospectively included. In patients developing an infection, different criteria for sepsis diagnosis (Sepsis-1, Sepsis-3_original, Sepsis-3_modified accounting for SAH-specific therapy, alternative sepsis criteria compiled of consensus conferences) were applied and their impact on functional outcome using the modified Rankin Scale (mRS) on hospital discharge and in-hospital mortality was evaluated. Of 270 SAH patients, 129 (48%) developed an infection. Depending on the underlying criteria, the incidence of sepsis and septic shock ranged between 21–46% and 9–39%. In multivariate logistic regression, the Sepsis-1 criteria were not associated with the outcome. The Sepsis-3 criteria were not associated with the functional outcome, but in shock with mortality. Alternative sepsis criteria were associated with mortality for sepsis and in shock with mortality and the functional outcome. While Sepsis-1 criteria were irrelevant for the outcome in SAH patients, septic shock, according to the Sepsis-3 criteria, adversely impacted survival. This impact was higher for the modified Sepsis-3 criteria, accounting for SAH-specific treatment. Modified Sepsis-3 and alternative sepsis criteria diagnosed septic conditions of a higher relevance for outcomes in patients with an SAH.

BACKGROUND/AIM: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.PATIENTS AND METHODS: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).RESULTS: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.CONCLUSION: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.

Pharmaceutical and medical technology companies accessing real-world medical data are not interested in personally identifiable data but rather in cohort data such as statistical aggregates, patterns, and trends. These companies cooperate with medical institutions that collect medical data and want to share it but they need to protect the privacy of individuals on the shared data. We present PyDPLib, a Python Differential Privacy library for private medical data analytics. We illustrate an application of differential privacy using PyDPLib in our platform for visualizing private statistics on a database of prostate cancer patients. Our experimental results show that PyDPLib allows creating statistical data plots without compromising patients’ privacy while preserving underlying data distributions. Even though PyDPLib has been developed to be used in our platform for reporting the radiological examinations and procedures, it is general enough to be used to provide differential privacy on data in any data analytics and visualization platform, service or application.

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.

Background: Crossed cerebellar diaschisis (CCD) is a phenomenon with depressed metabolism and hypoperfusion in the cerebellum. Using arterial spin-labelling perfusion weighted magnetic resonance imaging (ASL PWI), we investigated the frequency of CCD in patients with Alzheimer’s disease (AD) and differences between patients with and without CCD. Patients and Methods: In patients with AD who underwent a standardized magnetic resonance imaging including ASL PWI cerebral blood flow was evaluated in the cerebellum, and brain segmentation/volumetry was performed using mdbrain (mediaire GmbH, Berlin, Germany) and FSL FIRST (Functional Magnetic Resonance Imaging of the Brain Software Library). Results: In total, 65 patients were included, and 22 (33.8%) patients were assessed as being CCD-positive. Patients with CCD had a significantly smaller whole brain volume (862.8±49.9 vs. 893.7±62.7 ml, p=0.049) as well as white matter volume (352.9±28.0 vs. 374.3±30.7, p=0.008) in comparison to patients without CCD. Conclusion: It was possible to detect CCD by ASL PWI in approximately one-third of patients with AD and was associated with smaller whole brain and white matter volume.

Glioblastoma may appear similar to cerebral metastasis on conventional MRI in some cases, but their therapies differ significantly. This prospective feasibility study was aimed at differentiating them by applying the quantitative susceptibility mapping and quantitative blood-oxygen-level-dependent (QSM + qBOLD) model to these entities for the first time. We prospectively included 15 untreated patients with glioblastoma (n = 7, median age: 68 years, range: 54–84 years) or brain metastasis (n = 8, median age 66 years, range: 50–78 years) who underwent preoperative MRI including multi-gradient echo and arterial spin labeling sequences. Oxygen extraction fraction (OEF), cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) were calculated in the contrast-enhancing tumor (CET) and peritumoral non-enhancing T2 hyperintense region (NET2), using an artificial neural network. We demonstrated that OEF in CET was significantly lower (p = 0.03) for glioblastomas than metastases, all features were significantly higher (p = 0.01) in CET than in NET2 for metastasis patients only, and the ratios of CET/NET2 for CBF (p = 0.04) and CMRO2 (p = 0.01) were significantly higher in metastasis patients than in glioblastoma patients. Discriminative power of a support-vector machine classifier was highest with a combination of two features, yielding an area under the receiver operating characteristic curve of 0.94 with 93% diagnostic accuracy. QSM + qBOLD allows for robust differentiation of glioblastoma and cerebral metastasis while yielding insights into tumor oxygenation.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a neuroinflammatory condition mediated by autoantibodies against the GluN1 subunit of the receptor. Clinically, it is characterized by a complex neuropsychiatric presentation with rapidly progressive psychiatric symptoms, cognitive deficits, seizures, and abnormal movements. Isolated psychiatric manifestations of anti-NMDAR encephalitis are rare and usually dominated by psychotic symptoms. We present a case of an 18-year-old female high school student—without a previous history of psychiatric disorders—with a rapid onset severe depressive syndrome. Surprisingly, we found pleocytosis and anti-NMDAR autoantibodies in the cerebrospinal fluid (CSF), despite an otherwise unremarkable diagnostic workup, including blood test, clinical examination, and cranial magnetic resonance imaging (MRI). After intravenous immunoglobulins treatment, a complete remission of the initial symptoms was observed. In a follow-up 5 years later, the young woman did not experience any relapse or sequelae. Anti-NMDAR encephalitis can present in rare cases as an organic disorder with major depressive symptoms without distinct concomitant psychotic or neurological symptoms. A clinical presentation such as a rapid onset of symptoms, distinct disturbance in the thought process, restlessness, and cognitive deficits should prompt screening for NMDAR- and other neural autoantibodies to rule out this rare but debilitating pathology.

Cells of the monocyte macrophage lineage form multinucleated giant cells (GCs) by fusion, which may express some cell cycle markers. By using a comprehensive marker set, here we looked for potential replication activities in GCs, and investigated whether these have diagnostic or clinical relevance in giant cell tumor of bone (GCTB). GC rich regions of 10 primary and 10 first recurrence GCTB cases were tested using immunohistochemistry in tissue microarrays. The nuclear positivity rate of the general proliferation marker, replication licensing, G1/S-phase, S/G2/M-phase, mitosis promoter, and cyclin dependent kinase (CDK) inhibitor reactions was analyzed in GCs. Concerning Ki67, moderate SP6 reaction was seen in many GC nuclei, while B56 and Mib1 positivity was rare, but the latter could be linked to more aggressive (p = 0.012) phenotype. Regular MCM6 reaction, as opposed to uncommon MCM2, suggested an initial DNA unwinding. Early replication course in GCs was also supported by widely detecting CDK4 and cyclin E, for the first time, and confirming cyclin D1 upregulation. However, post-G1-phase markers CDK2, cyclin A, geminin, topoisomerase-2a, aurora kinase A, and phospho-histone H3 were rare or missing. These were likely silenced by upregulated CDK inhibitors p15INK4b, p16INK4a, p27KIP1, p53 through its effector p21WAF1 and possibly cyclin G1, consistent with the prevention of DNA replication. In conclusion, the upregulation of known and several novel cell cycle progression markers detected here clearly verify early replication activities in GCs, which are controlled by cell cycle arresting CDK inhibitors at G1 phase, and support the functional maturation of GCs in GCTB.