PURPOSE: The aim of this study is to design a method of myocardial T1 quantification in small laboratory animals and to investigate the effects of spatiotemporal regularization and the needed acquisition duration. METHODS: We propose a compressed-sensing approach to T1 quantification based on self-gated inversion-recovery radial two/three-dimensional (2D/3D) golden-angle stack-of-stars acquisition with image reconstruction performed using total-variation spatiotemporal regularization. The method was tested on a phantom and on a healthy rat, as well as on rats in a small myocardium-remodeling study. RESULTS: The results showed a good match of the T1 estimates with the results obtained using the ground-truth method on a phantom and with the literature values for rats myocardium. The proposed 2D and 3D methods showed significant differences between normal and remodeling myocardium groups for acquisition lengths down to approximately 5 and 15 min, respectively. CONCLUSIONS: A new 2D and 3D method for quantification of myocardial T1 in rats was proposed. We have shown the capability of both techniques to distinguish between normal and remodeling myocardial tissue. We have shown the effects of image-reconstruction regularization weights and acquisition length on the T1 estimates.
- MeSH
- fantomy radiodiagnostické MeSH
- krysa rodu rattus MeSH
- magnetická rezonanční tomografie metody MeSH
- myokard * MeSH
- počítačové zpracování obrazu metody MeSH
- reprodukovatelnost výsledků MeSH
- zobrazování trojrozměrné * metody MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: High-grade serous ovarian carcinoma (HGSOC) is the most common and aggressive subtype of epithelial ovarian carcinoma. It is primarily diagnosed at stage III or IV when the 5-year survival rate ranges between 20% and 40%. Here, we aimed to validate the hypothesis, based on HGSOC cell lines, that proposed the existence of two distinct groups of HGSOC cells with high and low oxidative phosphorylation (OXPHOS) metabolism, respectively, which are associated with their responses to glucose and glutamine withdrawal. METHODS: We isolated and cultivated primary cancer cell cultures from HGSOC and nontransformed ovarian fibroblasts from the surrounding ovarium of 45 HGSOC patients. We tested the metabolic flexibility of the primary cells, particularly in response to glucose and glutamine depletion, analyzed and modulated endoplasmic reticulum stress, and searched for indices of the existence of previously reported groups of HGSOC cells with high and low OXPHOS metabolism. RESULTS: The primary HGSOC cells did not form two groups with high and low OXPHOS that responded differently to glucose and glutamine availabilities in the cell culture medium. Instead, they exhibited a continuum of OXPHOS phenotypes. In most tumor cell isolates, the responses to glucose or glutamine withdrawal were mild and surprisingly correlated with those of nontransformed ovarian fibroblasts from the same patients. The growth of tumor-derived cells in the absence of glucose was positively correlated with the lipid trafficking regulator FABP4 and was negatively correlated with the expression levels of HK2 and HK1. The correlations between the expression of electron transport chain (ETC) proteins and the oxygen consumption rates or extracellular acidification rates were weak. ER stress markers were strongly expressed in all the analyzed tumors. ER stress was further potentiated by tunicamycin but not by the recently proposed ER stress inducers based on copper(II)-phenanthroline complexes. ER stress modulation increased autophagy in tumor cell isolates but not in nontransformed ovarian fibroblasts. CONCLUSIONS: Analysis of the metabolism of primary HGSOC cells rejects the previously proposed hypothesis that there are distinct groups of HGSOC cells with high and low OXPHOS metabolism that respond differently to glutamine or glucose withdrawal and are characterized by ETC protein levels.
- Publikační typ
- časopisecké články MeSH
Pátá edice klasifikace WHO nádorů centrálního nervového systému rozděluje difuzní gliomy do dvou hlavních skupin dle typického věku výskytu: dětský typ, který postihuje především dětské pacienty, a dospělý typ, který se dominantně vyskytuje u pacientů v dospělém věku. Do skupiny difuzních gliomů dětského typu byly recentně zařazeny nové jednotky poprvé definované dle klasifikace WHO 2021. Současně i etablované gliomy prodělaly změny v diagnostických kritériích na podkladě recentních poznatků molekulárně-genetického podkladu. Tato druhá část přehledové práce předkládá souhrn jednotek zařazených do skupiny difuzních gliomů dětského typu dle 5. edice klasifikace WHO nádorů centrálního nervového systému z roku 2021.
The fifth edition of the WHO Classification of Tumors of the Central Nervous System categorizes diffuse gliomas into the pediatric type, which mainly affects children, and into the adult type of diffuse gliomas occurring dominantly in adult patients. Recently characterized tumors, defined for the first time according to the 2021 WHO classification, have been included in the group of diffuse gliomas of the pediatric type. At the same time, established gliomas have undergone changes in their diagnostic criteria, reflecting the latest insights from molecular-genetic research. This second part of the review presents a comprehensive summary of tumors classified into the pediatric-type diffuse gliomas group according to the fifth edition of the WHO Classification of Tumors of the Central Nervous System published in 2021.
- Klíčová slova
- difúzní gliomy dětského typu,
- MeSH
- dítě MeSH
- gliom * diagnóza klasifikace patologie MeSH
- lidé MeSH
- nádory nervového systému * diagnóza klasifikace patologie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
OBJECTIVE: Focal cortical dysplasia (FCD), hippocampal sclerosis (HS), nonspecific gliosis (NG), and normal tissue (NT) comprise the majority of histopathological results of surgically treated drug-resistant epilepsy patients. Epileptic spikes, high-frequency oscillations (HFOs), and connectivity measures are valuable biomarkers of epileptogenicity. The question remains whether they could also be utilized for preresective differentiation of the underlying brain pathology. This study explored spikes and HFOs together with functional connectivity in various epileptogenic pathologies. METHODS: Interictal awake stereoelectroencephalographic recordings of 33 patients with focal drug-resistant epilepsy with seizure-free postoperative outcomes were analyzed (15 FCD, 8 HS, 6 NT, and 4 NG). Interictal spikes and HFOs were automatically identified in the channels contained in the overlap of seizure onset zone and resected tissue. Functional connectivity measures (relative entropy, linear correlation, cross-correlation, and phase consistency) were computed for neighboring electrode pairs. RESULTS: Statistically significant differences were found between the individual pathologies in HFO rates, spikes, and their characteristics, together with functional connectivity measures, with the highest values in the case of HS and NG/NT. A model to predict brain pathology based on all interictal measures achieved up to 84.0% prediction accuracy. SIGNIFICANCE: The electrophysiological profile of the various epileptogenic lesions in epilepsy surgery patients was analyzed. Based on this profile, a predictive model was developed. This model offers excellent potential to identify the nature of the underlying lesion prior to resection. If validated, this model may be particularly valuable for counseling patients, as depending on the lesion type, different outcomes are achieved after epilepsy surgery.
- MeSH
- elektroencefalografie metody MeSH
- epilepsie * diagnóza chirurgie MeSH
- lidé MeSH
- mozek diagnostické zobrazování chirurgie MeSH
- refrakterní epilepsie * diagnostické zobrazování chirurgie MeSH
- stereotaktické techniky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Diffusion-weighted imaging (DWI) and its numerical expression via apparent diffusion coefficient (ADC) values are commonly utilized in non-invasive assessment of various brain pathologies. Although numerous studies have confirmed that ADC values could be pathognomic for various ring-enhancing lesions (RELs), their true potential is yet to be exploited in full. The article was designed to introduce an image analysis method allowing REL recognition independently of either absolute ADC values or specifically defined regions of interest within the evaluated image. For this purpose, the line of interest (LOI) was marked on each ADC map to cross all of the RELs' compartments. Using a machine learning approach, we analyzed the LOI between two representatives of the RELs, namely, brain abscess and glioblastoma (GBM). The diagnostic ability of the selected parameters as predictors for the machine learning algorithms was assessed using two models, the k-NN model and the SVM model with a Gaussian kernel. With the k-NN machine learning method, 80% of the abscesses and 100% of the GBM were classified correctly at high accuracy. Similar results were obtained via the SVM method. The proposed assessment of the LOI offers a new approach for evaluating ADC maps obtained from different RELs and contributing to the standardization of the ADC map assessment.
OBJECTIVE: We analyzed trends in patients' characteristics, outcomes, and waiting times over the last 25 years at our epilepsy surgery center situated in Central Europe to highlight possible areas of improvement in our care for patients with drug-resistant epilepsy. METHODS: A total of 704 patients who underwent surgery at the Brno Epilepsy Center were included in the study, 71 of those were children. Patients were separated into three time periods, 1996-2000 (n = 95), 2001-2010 (n = 295) and 2011-2022 (n = 314) based on first evaluation at the center. RESULTS: The average duration of epilepsy before surgery in adults remained high over the last 25 years (20.1 years from 1996 to 2000, 21.3 from 2001 to 2010, and 21.3 from 2011 to 2020, P = 0.718). There has been a decrease in rate of surgeries for temporal lobe epilepsy in the most recent time period (67%-70%-52%, P < 0.001). Correspondingly, extratemporal resections have become more frequent with a significant increase in surgeries for focal cortical dysplasia (2%-8%-19%, P < 0.001). For resections, better outcomes (ILAE scores 1a-2) have been achieved in extratemporal lesional (0%-21%-61%, P = 0.01, at least 2-year follow-up) patients. In temporal lesional patients, outcomes remained unchanged (at least 77% success rate). A longer duration of epilepsy predicted a less favorable outcome for resective procedures (P = 0.024) in patients with disease duration of less than 25 years. SIGNIFICANCE: The spectrum of epilepsy surgery is shifting toward nonlesional and extratemporal cases. While success rates of extratemporal resections at our center are getting better, the average duration of epilepsy before surgical intervention is still very long and is not improving. This underscores the need for stronger collaboration between epileptologists and outpatient neurologists to ensure prompt and effective treatment for patients with drug-resistant epilepsy.
- MeSH
- dítě MeSH
- dospělí MeSH
- epilepsie temporálního laloku * chirurgie MeSH
- epilepsie * chirurgie MeSH
- lidé MeSH
- neurochirurgické výkony metody MeSH
- refrakterní epilepsie * chirurgie MeSH
- výsledek terapie MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND/AIM: Brain metastases (BMs) are the most frequent intracranial tumors in adults and one of the greatest challenges for modern oncology. Most are derived from lung, breast, renal cell, and colorectal carcinomas and melanomas. Up to 14% of patients are diagnosed with BMs of unknown primary, which are commonly characterized by an early and aggressive metastatic spread. It is important to discover novel biomarkers for early identification of BM origin, allowing better management of patients with this disease. Our study focused on microRNAs (miRNAs), which are very stable in frozen native and FFPE tissues and have been shown to be sensitive and specific diagnostic biomarkers of cancer. We aimed to identify miRNAs with significantly different expression in the five most frequent groups of BMs and develop a diagnostic classifier capable of sensitive and specific classification of BMs. MATERIALS AND METHODS: Total RNA enriched for miRNAs was isolated using the mirVana miRNA Isolation Kit from 71 fresh-frozen histopathologically confirmed BM tissues originating in 5 cancer types. Sequencing libraries were prepared using the QIAseq miRNA Library Kit and sequenced on the NextSeq 500 platform. MiRNA expression was further validated by RT-qPCR. RESULTS: Differential analysis identified 373 miRNAs with significantly different expression between 5 BM groups (p<0.001). A classifier model was developed based on the expression of 6 miRNAs (hsa-miR-141-3p, hsa-miR-141-5p, hsa-miR-146a-5p, hsa-miR-194-5p, hsa-miR-200b-3p and hsa-miR-365b-5p) with the ability to correctly classify 91.5% of samples. Subsequent validation confirmed both significantly different expression of selected miRNAs in 5 BM groups as well as their diagnostic potential. CONCLUSION: To date, our study is the first to analyze miRNA expression in various types of BMs using small RNA sequencing to develop a diagnostic classifier and, thus, to help stratify BMs of unknown primary. The presented results confirm the importance of studying the dysregulated expression of miRNAs in BMs and the diagnostic potential of the validated 6-miRNA signature.
- MeSH
- biologické markery MeSH
- dospělí MeSH
- lidé MeSH
- melanom * MeSH
- mikro RNA * genetika metabolismus MeSH
- nádory mozku * genetika MeSH
- nádory neznámé primární lokalizace * MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Publikační typ
- abstrakt z konference MeSH
Cannabidiol (CBD) and cannabigerol (CBG) are the two main non-psychotropic phytocannabinoids with high application potential in drug development. Both substances are redox-active and are intensively investigated for their cytoprotective and antioxidant action in vitro. In this study, we focused on an in vivo safety evaluation and the effect of CBD and CBG on the redox status in rats in a 90-d experiment. The substances were administered orogastrically in a dose of 0.66 mg synthetic CBD or 0.66 mg/1.33 mg CBG/kg/day. CBD produced no changes in the red or white blood count or biochemical blood parameters in comparison to the control. No deviations in the morphology or histology of the gastrointestinal tract and liver were observed. After 90 d of CBD exposure, a significant improvement in redox status was found in the blood plasma and liver. The concentration of malondialdehyde and carbonylated proteins was reduced compared to the control. In contrast to CBD, total oxidative stress was significantly increased and this was accompanied by an elevated level of malondialdehyde and carbonylated proteins in CBG-treated animals. Hepatotoxic (regressive changes) manifestations, disruption in white cell count, and alterations in the ALT activity, level of creatinine and ionized calcium were also found in CBG-treated animals. Based on liquid chromatography-mass spectrometry analysis, CBD/CBG accumulated in rat tissues (in the liver, brain, muscle, heart, kidney and skin) at a low ng level per gram. Both CBD and CBG molecular structures include a resorcinol moiety. In CBG, there is an extra dimethyloctadienyl structural pattern, which is most likely responsible for the disruption to the redox status and hepatic environment. The results are valuable to further investigation of the effects of CBD on redox status and should contribute towards opening up critical discussion on the applicability of other non-psychotropic cannabinoids.
- MeSH
- kanabidiol * toxicita MeSH
- kanabinoidy * toxicita MeSH
- krysa rodu rattus MeSH
- oxidace-redukce MeSH
- vápník MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Recentní poznatky na poli molekulárně genetických změn difuzních gliomů u dospělých a dětských pacientů iniciovaly významné změny v jejich klasifikaci a diagnostice. Tyto změny předkládá 5. edice klasifikace WHO nádorů centrálního nervového systému zdůrazňující odsun od tradiční kategorizace tumorů na podkladu morfologie k integrované diagnostice inkorporující charakteristické molekulárně-genetické a epigenetické změny s tradičními morfologickými znaky. Tato první část přehledové práce předkládá souhrn jednotek, které jsou zařazeny do skupiny difuzních gliomů dospělého typu, s důrazem na diagnostická kritéria a grading dle 5. edice klasifikace WHO nádorů centrálního nervového systému z roku 2021.
Recent findings in the field of molecular-genetic alterations in diffuse gliomas, encompassing both adult and pediatric types, have initiated significant changes in their classification and diagnostics. These changes are presented in the fifth edition of the WHO Classification of Tumors of the Central Nervous System emphasizing a pivotal shift from the conventional categorization of tumors based on morphology to an integrated diagnostic approach, which incorporates characteristic molecular-genetic and epigenetic alterations alongside traditional morphological features. This review presents a summary of the units that are included in the group of diffuse gliomas of the adult type, with an emphasis on diagnostic criteria and grading according to the fifth edition of the WHO Classification of Tumors of the Central Nervous System, published in 2021.
- MeSH
- astrocytom diagnóza patologie MeSH
- glioblastom patologie MeSH
- gliom * diagnóza genetika klasifikace patologie MeSH
- imunohistochemie MeSH
- lidé MeSH
- mutace MeSH
- oligodendrogliom patologie MeSH
- stupeň závažnosti nemoci MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
