Publications

17 Apr 2023

Advanced MR Techniques for Preoperative Glioma Characterization: Part 1

Preoperative clinical magnetic resonance imaging (MRI) protocols for gliomas, brain tumors with dismal outcomes due to their infiltrative properties, still rely on conventional structural MRI, which does not deliver information on tumor genotype and is limited in the delineation of diffuse gliomas. The GliMR COST action wants to raise awareness about the state of the art of advanced MRI techniques in gliomas and their possible clinical translation or lack thereof. This review describes current methods, limits, and applications of advanced MRI for the preoperative assessment of glioma, summarizing the level of clinical validation of different techniques. In this first part, we discuss dynamic susceptibility contrast and dynamic contrast-enhanced MRI, arterial spin labeling, diffusion-weighted MRI, vessel imaging, and magnetic resonance fingerprinting. The second part of this review addresses magnetic resonance spectroscopy, chemical exchange saturation transfer, susceptibility-weighted imaging, MRI-PET, MR elastography, and MR-based radiomics applications.

17 Apr 2023

Molecular Biomarkers of Neuronal Injury in Epilepsy Shared with Neurodegenerative Diseases

In neurodegenerative diseases, changes in neuronal proteins in the cerebrospinal fluid and blood are viewed as potential biomarkers of the primary pathology in the central nervous system (CNS). Recent reports suggest, however, that level of neuronal proteins in fluids also alters in several types of epilepsy in various age groups, including children. With increasing evidence supporting clinical and sub-clinical seizures in Alzheimer's disease, Lewy body dementia, Parkinson's disease, and in other less common neurodegenerative conditions, these findings call into question the specificity of neuronal protein response to neurodegenerative process and urge analysis of the effects of concomitant epilepsy and other comorbidities. In this article, we revisit the evidence for alterations in neuronal proteins in the blood and cerebrospinal fluid associated with epilepsy with and without neurodegenerative diseases.

17 Apr 2023

Advanced MR Techniques for Preoperative Glioma Characterization: Part 2

Preoperative clinical MRI protocols for gliomas, brain tumors with dismal outcomes due to their infiltrative properties, still rely on conventional structural MRI, which does not deliver information on tumor genotype and is limited in the delineation of diffuse gliomas. The GliMR COST action wants to raise awareness about the state of the art of advanced MRI techniques in gliomas and their possible clinical translation. This review describes current methods, limits, and applications of advanced MRI for the preoperative assessment of glioma, summarizing the level of clinical validation of different techniques. In this second part, we review magnetic resonance spectroscopy (MRS), chemical exchange saturation transfer (CEST), susceptibility-weighted imaging (SWI), MRI-PET, MR elastography (MRE), and MR-based radiomics applications. The first part of this review addresses dynamic susceptibility contrast (DSC) and dynamic contrast-enhanced (DCE) MRI, arterial spin labeling (ASL), diffusion-weighted MRI, vessel imaging, and magnetic resonance fingerprinting (MRF).

5 Apr 2023

MicroRNA Profiling of Self-Renewing Human Neural Stem Cells Reveals Novel Sets of Differentially Expressed microRNAs During Neural Differentiation In Vitro

The involvement of microRNAs (miRNAs) in orchestrating self-renewal and differentiation of stem cells has been revealed in a number of recent studies. And while in human pluripotent stem cells, miRNAs have been directly linked to the core pluripotency network, including the cell cycle regulation and the maintenance of the self-renewing capacity, their role in the onset of differentiation in other contexts, such as determination of neural cell fate, remains poorly described. To bridge this gap, we used three model cell types to study miRNA expression patterns: human embryonic stem cells (hESCs), hESCs-derived self-renewing neural stem cells (NSCs), and differentiating NSCs. The comprehensive miRNA profiling presented here reveals novel sets of miRNAs differentially expressed during human neural cell fate determination in vitro. 

5 Apr 2023

Predictors of age at diagnosis in autism spectrum disorders: the use of multiple regression analyses and a classification tree on a clinical sample

The increasing prevalence of autism spectrum disorders (ASD) has led to worldwide interest in factors influencing the age of ASD diagnosis. Parents or caregivers of 237 ASD children (193 boys, 44 girls) diagnosed using the Autism Diagnostic Observation Schedule (ADOS) completed a simple descriptive questionnaire. The data were analyzed using the variable-centered multiple regression analysis and the person-centered classification tree method. We believed that the concurrent use of these two methods could produce robust results. The mean age at diagnosis was 5.8 ± 2.2 years (median 5.3 years). Younger ages for ASD diagnosis were predicted (using multiple regression analysis) by higher scores in the ADOS social domain, higher scores in ADOS restrictive and repetitive behaviors and interest domain, higher maternal education, and the shared household of parents.

4 Apr 2023

Infant attachment in the Czech Republic: Categorical and dimensional findings from a post-communist country

Infant attachment remains virtually unexplored in former Eastern Bloc countries. The dimensional approach to infant attachment, which could ease common obstacles in cross-cultural attachment research, necessitates more empirical support. This study explores infant attachment in the Czech Republic, a post-communist country with a unique family policy, using both the categorical and the dimensional models. It also compares the Czech infant attachment distribution to infant attachment distributions in other countries and compares infant attachment distributions in European countries to the Baltimore study sample. In the Strange Situation Procedure, forty-nine (74 %) out of sixty-six mother-infant dyads (35 boys, M = 13.8, SD = 0.9) received the B classification. Despite the generous family policy and cultural emphasis on close mother-infant relationships, the Czech distribution of insecure categories did not differ from the Baltimore study sample. 

4 Apr 2023

Utility of quantitative MRI metrics in brain ageing research

The advent of new, advanced quantitative MRI metrics allows for in vivo evaluation of multiple biological processes highly relevant for ageing. The presented study combines several MRI parameters hypothesised to detect distinct biological characteristics as myelin density, cellularity, cellular membrane integrity and iron concentration. 116 healthy volunteers, continuously distributed over the whole adult age span, underwent a multi-modal MRI protocol acquisition.

Scatterplots of individual MRI metrics revealed that certain MRI protocols offer much higher sensitivity to early adulthood changes while plateauing in higher age (e.g., global functional connectivity in cerebral cortex or orientation dispersion index in white matter), while other MRI metrics provided reverse ability-stable levels in young adulthood with sharp changes with rising age (e.g., T1ρ and T2ρ). 

4 Apr 2023

Language impairment in Parkinson's disease: fMRI study of sentence reading comprehension

Parkinson's disease (PD) affects the language processes, with a significant impact on the patients' daily communication. We aimed to describe specific alterations in the comprehension of syntactically complex sentences in patients with PD (PwPD) as compared to healthy controls (HC) and to identify the neural underpinnings of these deficits using a functional connectivity analysis of the striatum. A total of 20 patients PwPD and 15 HC participated in the fMRI study. We analyzed their performance of a Test of sentence comprehension (ToSC) adjusted for fMRI. A task-dependent functional connectivity analysis of the striatum was conducted using the psychophysiological interaction method (PPI). On the behavioral level, the PwPD scored significantly lower (mean ± sd: 77.3 ± 12.6) in the total ToSC score than the HC did (mean ± sd: 86.6 ± 8.0), p = 0.02, and the difference was also significant specifically for sentences with a non-canonical word order (PD-mean ± sd: 69.9 ± 14.1, HC-mean ± sd: 80.2 ± 11.5, p = 0.04).

4 Apr 2023

A color-tunable single-benzene fluorophore-based sensor for sensitive detection of palladium in solution and living cells

Single-benzene fluorophores are bright and the smallest fluorochromes known so far. In single-benzene fluorophores, the fluorescence is mediated by the push/pull effect of substituting groups. Despite a plethora of advantageous properties, this group of molecules has not been extensively studied for design of high-performance fluorescent sensors of catalytic or enzymatic activities. Thus, herein, new fluorescent probes based on the Tsuji-Trost reaction were developed for the selective detection of palladium and other transition metals (platinum and gold) in an aqueous/organic mixed solvent with the sensitivity down to 2.5 nM (for palladium). The relative flexibility in the synthesis of these probes allows for facile color tuning of the emitted fluorescence. In this study, we have successfully utilized a yellow emission variant for sensitive detection of palladium under cell-free conditions and in living cells, validating its possible applicability for high-throughput optical sensing of catalysts for bioorthogonal chemistry under physiological conditions.

21 Feb 2023

Relative Entropy is an easy-to-use invasive EEG Biomarker of the Epileptogenic Zone

Objective: High-frequency oscillations are considered among the most promising interictal biomarkers of the epileptogenic zone in patients suffering from pharmaco-resistant focal epilepsy. However, there is no clear definition of pathological High-frequency oscillations and the existing detectors vary in methodology, performance, and computational costs. This study proposes Relative Entropy as an easy-to-use novel interictal biomarker of the epileptic tissue.

Methods: We evaluated Relative Entropy and High-frequency oscillations biomarkers on intracranial EEG data from 39 patients with seizure-free postoperative outcome (Engel Ia) from three Institutions. We tested their capability to localize the epileptogenic zone, defined as resected contacts located in seizure-onset zone. The performance was compared using areas under the receiver operating curves [AUROC] and precision-recall curves [AUPRC]. 

21 Feb 2023

Basilar artery occlusion management: Specialist perspectives from an international survey

Background and purpose: Two early basilar artery occlusion (BAO) randomized controlled trials did not establish the superiority of endovascular thrombectomy (EVT) over medical management. While many providers continue to recommend EVT for acute BAO, perceptions of equipoise in randomizing patients with BAO to EVT versus medical management may differ between clinician specialties.

Methods: We conducted an international survey (January 18, 2022 to March 31, 2022) regarding management strategies in acute BAO prior to the announcement of two trials indicating the superiority of EVT, and compared responses between interventionalists (INTs) and non-interventionalists (nINTs). Selection practices for routine EVT and perceptions of equipoise regarding randomizing to medical management based on neuroimaging and clinical features were compared between the two groups using descriptive statistics.

21 Feb 2023

Parental education, cognition and functional connectivity of the salience network

The aim was to investigate the association of parental education at birth with cognitive ability in childhood and young adulthood and determine, whether functional connectivity of the salience network underlies this association. We studied participants of the Czech arm of the European Longitudinal Study of Pregnancy and Childhood who underwent assessment of their cognitive ability at age 8 (Wechsler Intelligence Scale for Children) and 28/29 years (Wechsler Adult Intelligence Scale) and measurement with resting state functional MRI at age 23/24. We estimated the associations of parental education with cognitive ability and functional connectivity between the seeds in the salience network and other voxels in the brain. We found that lower education of both mothers and fathers was associated with lower verbal IQ, performance IQ and full-scale IQ of the offspring at age 8. Only mother´s education was associated with performance IQ at age 28/29.

9 Feb 2023

Association of statin pre-treatment with baseline stroke severity and outcome in patients with acute ischemic stroke and received reperfusion treatment: An observational study

Background: Statins have an important role in stroke prevention, especially in high-risk populations and may also affect the initial stroke severity and outcomes in patients taking them before an ischemic stroke.

Aims: Our aim was to evaluate the association of statin pre-treatment with the severity in acute ischemic stroke (AIS).

Methods: We analyzed AIS patients received intravenous thrombolysis (IVT) and/or endovascular thrombectomy (EVT) and recorded in the SITS International Thrombolysis and Thrombectomy Registry from 2011 to 2017. We identified patients with statin information at baseline. The primary outcome was baseline National Institutes of Health Stroke Scale (NIHSS) score. 

9 Feb 2023

Stroke Learning Health Systems: A Topical Narrative Review With Case Examples

To our knowledge, the adoption of Learning Health System (LHS) concepts or approaches for improving stroke care, patient outcomes, and value have not previously been summarized. This topical review provides a summary of the published evidence about LHSs applied to stroke, and case examples applied to different aspects of stroke care from high and low-to-middle income countries. Our attempt to systematically identify the relevant literature and obtain real-world examples demonstrated the dissemination gaps, the lack of learning and action for many of the related LHS concepts across the continuum of care but also elucidated the opportunity for continued dialogue on how to study and scale LHS advances. In the field of stroke, we found only a few published examples of LHSs and health systems globally implementing some selected LHS concepts, but the term is not common. A major barrier to identifying relevant LHS examples in stroke may be the lack of an agreed taxonomy or terminology for classification.

9 Feb 2023

Single Cerebral Organoid Mass Spectrometry of Cell-Specific Protein and Glycosphingolipid Traits

Cerebral organoids are a prolific research topic and an emerging model system for neurological diseases in human neurobiology. However, the batch-to-batch reproducibility of current cultivation protocols is challenging and thus requires a high-throughput methodology to comprehensively characterize cerebral organoid cytoarchitecture and neural development. We report a mass spectrometry-based protocol to quantify neural tissue cell markers, cell surface lipids, and housekeeping proteins in a single organoid. Profiled traits probe the development of neural stem cells, radial glial cells, neurons, and astrocytes. We assessed the cell population heterogeneity in individually profiled organoids in the early and late neurogenesis stages. Here, we present a unifying view of cell-type specificity of profiled protein and lipid traits in neural tissue. Our workflow characterizes the cytoarchitecture, differentiation stage, and batch cultivation variation on an individual cerebral organoid level.

9 Feb 2023

International study: Global impact of COVID-19 on stroke care - the Polish contribution

The most severe consequences of the COVID-19 pandemic were reported during its first wave in 2019. Although airway inflammation is part of the main clinical picture of COVID-19, the consequences of a SARS-Cov2 infection can also include coagulation disorders, cardiomyopathy and endotheliopathy, which lead to stroke in 1.5% of patients.
With the global reach of the pandemic came collaboration between scientists and clinicians from around the world.
This transfer of knowledge between various medical centres contributed to greatly improved understanding of the mechanisms of transmission and the different manifestations of infection.
To assess the global impact of the pandemic on stroke hospitalisations and outcomes, Prof. Nogueira inspired the international community of neurologists and neurointerventionalists from six continents, 70 countries and almost 500 hospital stroke centres to participate in large, cross-sectional, observational, retrospective studies

9 Feb 2023

A preliminary choroid plexus volumetric study in individuals with psychosis

The choroid plexus (ChP) is part of the blood-cerebrospinal fluid barrier, regulating brain homeostasis and the brain's response to peripheral events. Its upregulation and enlargement are considered essential in psychosis. However, the timing of the ChP enlargement has not been established. This study introduces a novel magnetic resonance imaging-based segmentation method to examine ChP volumes in two cohorts of individuals with psychosis. The first sample consists of 41 individuals with early course psychosis (mean duration of illness = 1.78 years) and 30 healthy individuals. The second sample consists of 30 individuals with chronic psychosis (mean duration of illness = 7.96 years) and 34 healthy individuals. We utilized manual segmentation to measure ChP volumes. We applied ANCOVAs to compare normalized ChP volumes between groups and partial correlations to investigate the relationship between ChP, LV volumes, and clinical characteristics. Our segmentation demonstrated good reliability (.87).

9 Feb 2023

Glioblastoma and cerebral organoids: development and analysis of an in vitro model for glioblastoma migration

It is currently challenging to adequately model the growth and migration of glioblastoma using two-dimensional (2D) in vitro culture systems as they quickly lose the original, patient-specific identity and heterogeneity. However, with the advent of three-dimensional (3D) cell cultures and human induced pluripotent stem cell (iPSC)-derived cerebral organoids (COs), studies demonstrate that the glioblastoma-CO (GLICO) co-culture model helps to preserve the phenotype of the patient-specific tissue. Here, we aimed to set up such a model using mature COs and develop a pipeline for subsequent analysis of co-cultured glioblastoma. Our data demonstrates that the growth and migration of the glioblastoma cell line within the mature COs are significantly increased in the presence of extracellular matrix proteins, shortening the time needed for glioblastoma to initiate migration. We also describe in detail the method for the visualization and quantification of these migrating cells within the GLICO model.