To characterize the non-Gaussian diffusion patterns of cerebral glioma microstructure with respect to the different glioma grades by using a new method called diffusional kurtosis (DK) imaging.
In ...this study with institutional review board approval and patient consent, diffusional measures of mean kurtosis (MK), fractional anisotropy (FA), and apparent diffusion coefficient (ADC) were compared prospectively. Data were normalized to the contralateral white matter. A Mann-Whitney test was used to compare each histologic glioma subtype regarding the diffusion measurements. Receiver operating characteristic curves were used to test for the parameter with the best sensitivity and specificity for glioma grade discrimination.
In 34 patients with cerebral gliomas (five World Health Organization WHO grade II astrocytomas, 13 WHO grade III astrocytomas, and 16 WHO grade IV glioblastomas multiforme), significantly different diffusion patterns were found among the three glioma groups. MK values increased with higher glioma malignancy, whereas ADCs tended to decrease with higher malignancy; FA values did not differ significantly among tumor groups. Significant differences between astrocytoma grades WHO II and WHO III were demonstrated only by DK values. Area under the receiver operating characteristic curve was highest for normalized MK (0.972) during testing to discriminate between low- and high-grade gliomas.
This study demonstrates specific diffusion patterns for low- and high-grade gliomas, showing that DK imaging is able to depict microstructural changes within glioma tissue and is able to help differentiate among glioma grades. (c) RSNA, 2010.
In addition to necrosis and apoptosis, the two forms of cell death that have been known for many decades, other non-apoptotic forms of cell death have been discovered, many of which also play a role ...in tumors. Starting with the description of autophagy more than 60 years ago, newer forms of cell death have become important for the biology of tumors, such as ferroptosis, pyroptosis, necroptosis, and paraptosis. In this review, all non-apoptotic and oncologically relevant forms of programmed cell death are presented, starting with their first descriptions, their molecular characteristics, and their role and their interactions in cell physiology and pathophysiology. Based on these descriptions, the current state of knowledge about their alterations and their role in gliomas will be presented. In addition, current efforts to therapeutically influence the molecular components of these forms of cell death will be discussed. Although research into their exact role in gliomas is still at a rather early stage, our review clarifies that all these non-apoptotic forms of cell death show significant alterations in gliomas and that important insight into understanding them has already been gained.
During the last 20 years, molecular alterations have gained increasing significance in the diagnosis and biological assessment of tumors. Gliomas represent the largest group of tumors of the central ...nervous system, and the main aim of this review is to present the current knowledge on molecular pathways and their alterations in gliomas. A wide range of new insights has been gained, including evidence for the involvement of the WNT pathway or the hippo pathway in the pathobiology of gliomas, indicating a broad involvement of different pathways formerly not considered to play a central role in gliomas. Even new aspects of angiogenic, apoptotic, and metabolic pathways are presented, as well as the rapidly growing field of epigenetic processes, including non-coding RNAs. The two major conclusions drawn from the present review are the distinct interconnectivity of the whole spectrum of molecular pathways and the prominent role of non-coding RNAs, especially circular RNAs, in the regulation of specific targets. All these new insights are discussed, even considering the topic of the resistance to therapy of gliomas, along with aspects that are still incompletely understood, like the role of hydroxymethylation, or even ferroptosis, in the pathobiology of gliomas.
A generation ago, the molecular properties of tumor cells were the focus of scientific interest in oncology research. Since then, it has become increasingly apparent that the tumor environment (TEM), ...whose major components are non-neoplastic cell types, is also of utmost importance for our understanding of tumor growth, maintenance and resistance. In this review, we present the current knowledge concerning all cellular components within the TEM in gliomas, focusing on their molecular properties, expression patterns and influence on the biological behavior of gliomas. Insight into the TEM of gliomas has expanded considerably in recent years, including many aspects that previously received only marginal attention, such as the phenomenon of phagocytosis of glioma cells by macrophages and the role of the thyroid-stimulating hormone on glioma growth. We also discuss other topics such as the migration of lymphocytes into the tumor, phenotypic similarities between chemoresistant glioma cells and stem cells, and new clinical approaches with immunotherapies involving the cells of TEM.
Quantitative MRI (qMRI) techniques allow assessing cerebral tissue properties. However, previous studies on the accuracy of quantitative T1 and T2 mapping reported a scanner model bias of up to 10% ...for T1 and up to 23% for T2. Such differences would render multi-centre qMRI studies difficult and raise fundamental questions about the general precision of qMRI. A problem in previous studies was that different methods were used for qMRI parameter mapping or for measuring the transmitted radio frequency field B1 which is critical for qMRI techniques requiring corrections for B1 non-uniformities.
The goal was to assess the intra- and inter-scanner reproducibility of qMRI data at 3 T, using two different scanner models from the same vendor with exactly the same multiparametric acquisition protocol.
Proton density (PD), T1, T2* and T2 mapping was performed on healthy subjects and on a phantom, performing each measurement twice for each of two scanner models. Although the scanners had different hardware and software versions, identical imaging sequences were used for PD, T1 and T2* mapping, adapting the codes of an existing protocol on the older system line by line to match the software version of the newer scanner. For T2-mapping, the respective manufacturer’s sequence was used which depended on the software version. However, system-dependent corrections were carried out in this case. Reproducibility was assessed by average values in regions of interest.
Mean scan-rescan variations were not exceeding 2.14%, with average values of 1.23% and 1.56% for the new and old system, respectively. Inter-scanner model deviations were not exceeding 5.21% with average values of about 2.2–3.8% for PD, 2.5–3.0% for T2*, 1.6–3.1% for T1 and 3.3–5.2% for T2.
Provided that identical acquisition sequences are used, discrepancies between qMRI data acquired with different scanner models are low. The level of systematic differences reported in this work may help to interpret multi-centre data.
•The goal was to assess the intra- and inter-scanner reproducibility of qMRI data.•Mean scan-rescan variations were not exceeding 2.14%.•Mean inter-scanner model deviations were not exceeding 5.21%.•Provided that identical acquisition sequences are used, discrepancies between qMRI data acquired with different scanner models are low.
Dysphagia is common in patients with middle cerebral artery (MCA) infarctions and associated with malnutrition, pneumonia, and mortality. Besides bedside screening tools, brain imaging findings may ...help to timely identify patients with swallowing disorders. We investigated whether the
Alberta stroke program early CT score
(ASPECTS) allows for the correlation of distinct ischemic lesion patterns with dysphagia. We prospectively examined 113 consecutive patients with acute MCA infarctions. Fiberoptic endoscopic evaluation of swallowing (FEES) was performed within 24 h after admission for validation of dysphagia. Brain imaging (CT or MRI) was rated for ischemic changes according to the ASPECT score. 62 patients (54.9%) had FEES-proven dysphagia. In left hemispheric strokes, the strongest associations between the ASPECTS sectors and dysphagia were found for the lentiform nucleus (odds ratio 0.113 CI 0.028–0.433;
p
= 0.001), the insula (0.275 0.102–0.742;
p
= 0.011), and the frontal operculum (0.280 CI 0.094–0.834;
p
= 0.022). A combination of two or even all three of these sectors together increased relative dysphagia frequency up to 100%. For right hemispheric strokes, only non-significant associations were found which were strongest for the insula region. The distribution of early ischemic changes in the MCA territory according to ASPECTS may be used as risk indicator of neurogenic dysphagia in MCA infarction, particularly when the left hemisphere is affected. However, due to the exploratory nature of this research, external validation studies of these findings are warranted in future.
Even in the presence of oxygen, malignant cells often highly depend on glycolysis for energy generation, a phenomenon known as the Warburg effect. One strategy targeting this metabolic phenotype is ...glucose restriction by administration of a high-fat, low-carbohydrate (ketogenic) diet. Under these conditions, ketone bodies are generated serving as an important energy source at least for non-transformed cells.
To investigate whether a ketogenic diet might selectively impair energy metabolism in tumor cells, we characterized in vitro effects of the principle ketone body 3-hydroxybutyrate in rat hippocampal neurons and five glioma cell lines. In vivo, a non-calorie-restricted ketogenic diet was examined in an orthotopic xenograft glioma mouse model.
The ketone body metabolizing enzymes 3-hydroxybutyrate dehydrogenase 1 and 2 (BDH1 and 2), 3-oxoacid-CoA transferase 1 (OXCT1) and acetyl-CoA acetyltransferase 1 (ACAT1) were expressed at the mRNA and protein level in all glioma cell lines. However, no activation of the hypoxia-inducible factor-1α (HIF-1α) pathway was observed in glioma cells, consistent with the absence of substantial 3-hydroxybutyrate metabolism and subsequent accumulation of succinate. Further, 3-hydroxybutyrate rescued hippocampal neurons from glucose withdrawal-induced cell death but did not protect glioma cell lines. In hypoxia, mRNA expression of OXCT1, ACAT1, BDH1 and 2 was downregulated. In vivo, the ketogenic diet led to a robust increase of blood 3-hydroxybutyrate, but did not alter blood glucose levels or improve survival.
In summary, glioma cells are incapable of compensating for glucose restriction by metabolizing ketone bodies in vitro, suggesting a potential disadvantage of tumor cells compared to normal cells under a carbohydrate-restricted ketogenic diet. Further investigations are necessary to identify co-treatment modalities, e.g. glycolysis inhibitors or antiangiogenic agents that efficiently target non-oxidative pathways.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Patient care in a neurointensive care unit (neuro-ICU) is challenging. Multidrug-resistant organisms (MDROs) are increasingly common in the routine clinical practice. We evaluated the impact of ...infection with MDROs on outcomes in patients with subarachnoid hemorrhage (SAH). A single-center retrospective analysis of SAH cases involving patients treated in the neuro-ICU was performed. The outcome was assessed 6 months after SAH using the modified Rankin Scale mRS, favorable (0-2) and unfavorable (3-6). Data were compared by matched-pair analysis. Patient characteristics were well matched in the MDRO (n = 61) and control (n = 61) groups. In this center, one nurse was assigned to a two-bed room. If a MDRO was detected, the patient was isolated, and the nurse was assigned to the patient infected with the MDRO. In the MDRO group, 29 patients (48%) had a favorable outcome, while 25 patients (41%) in the control group had a favorable outcome; the difference was not significant (p > 0.05). Independent prognostic factors for unfavorable outcomes were worse status at admission (OR = 3.1), concomitant intracerebral hematoma (ICH) (OR = 3.7), and delayed cerebral ischemia (DCI) (OR = 6.8). Infection with MRDOs did not have a negative impact on the outcome in SAH patients. Slightly better outcomes were observed in SAH patients infected with MDROs, suggesting the benefit of individual care.
Purpose
Perfusion-weighted MRI (PWI) and O-(2-
18
Ffluoroethyl-)-
l
-tyrosine (
18
FFET) PET are both applied to discriminate tumor progression (TP) from treatment-related changes (TRC) in patients ...with suspected recurrent glioma. While the combination of both methods has been reported to improve the diagnostic accuracy, the performance of a sequential implementation has not been further investigated. Therefore, we retrospectively analyzed the diagnostic value of consecutive PWI and
18
FFET PET.
Methods
We evaluated 104 patients with WHO grade II–IV glioma and suspected TP on conventional MRI using PWI and dynamic
18
FFET PET. Leakage corrected maximum relative cerebral blood volumes (rCBV
max
) were obtained from dynamic susceptibility contrast PWI. Furthermore, we calculated static (i.e., maximum tumor to brain ratios; TBR
max
) and dynamic
18
FFET PET parameters (i.e., Slope). Definitive diagnoses were based on histopathology (
n
= 42) or clinico-radiological follow-up (
n
= 62). The diagnostic performance of PWI and
18
FFET PET parameters to differentiate TP from TRC was evaluated by analyzing receiver operating characteristic and area under the curve (AUC).
Results
Across all patients, the differentiation of TP from TRC using rCBV
max
or
18
FFET PET parameters was moderate (AUC = 0.69–0.75;
p
< 0.01). A rCBV
max
cutoff > 2.85 had a positive predictive value for TP of 100%, enabling a correct TP diagnosis in 44 patients. In the remaining 60 patients, combined static and dynamic
18
FFET PET parameters (TBR
max
, Slope) correctly discriminated TP and TRC in a significant 78% of patients, increasing the overall accuracy to 87%. A subgroup analysis of isocitrate dehydrogenase (IDH) mutant tumors indicated a superior performance of PWI to
18
FFET PET (AUC = 0.8/< 0.62,
p
< 0.01/≥ 0.3).
Conclusion
While marked hyperperfusion on PWI indicated TP,
18
FFET PET proved beneficial to discriminate TP from TRC when PWI remained inconclusive. Thus, our results highlight the clinical value of sequential use of PWI and
18
FFET PET, allowing an economical use of diagnostic methods. The impact of an
IDH
mutation needs further investigation.
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