scholarly journals Ex Vivo Raman Spectrochemical Analysis Using a Handheld Probe Demonstrates High Predictive Capability of Brain Tumour Status

Biosensors ◽  
2019 ◽  
Vol 9 (2) ◽  
pp. 49 ◽  
Author(s):  
Danielle Bury ◽  
Camilo Morais ◽  
Katherine Ashton ◽  
Timothy Dawson ◽  
Francis Martin
Keyword(s):  
Gold Nanoparticles ◽  
Brain Tissue ◽  
Brain Tumour ◽  
Sensitivity And Specificity ◽  
Brain Tumours ◽  
Ex Vivo ◽  
Diagnostic Tools ◽  
Low Grade ◽  
Normal Brain ◽  
Raman Probe

With brain tumour incidence increasing, there is an urgent need for better diagnostic tools. Intraoperatively, brain tumours are diagnosed using a smear preparation reported by a neuropathologist. These have many limitations, including the time taken for the specimen to reach the pathology department and for results to be communicated to the surgeon. There is also a need to assist with resection rates and identifying infiltrative tumour edges intraoperatively to improve clearance. We present a novel study using a handheld Raman probe in conjunction with gold nanoparticles, to detect primary and metastatic brain tumours from fresh brain tissue sent for intraoperative smear diagnosis. Fresh brain tissue samples sent for intraoperative smear diagnosis were tested using the handheld Raman probe after application of gold nanoparticles. Derived Raman spectra were inputted into forward feature extraction algorithms to build a predictive model for sensitivity and specificity of outcome. These results demonstrate an ability to detect primary from metastatic tumours (especially for normal and low grade lesions), in which accuracy, sensitivity and specificity were respectively equal to 98.6%, 94.4% and 99.5% for normal brain tissue; 96.1%, 92.2% and 97.0% for low grade glial tumours; 90.3%, 89.7% and 90.6% for high grade glial tumours; 94.8%, 63.9% and 97.1% for meningiomas; 95.4%, 79.2% and 98.8% for metastases; and 99.6%, 88.9% and 100% for lymphoma, based on smear samples (κ = 0.87). Similar results were observed when compared to the final formalin-fixed paraffin embedded tissue diagnosis (κ = 0.85). Overall, our results have demonstrated the ability of Raman spectroscopy to match results provided by intraoperative smear diagnosis and raise the possibility of use intraoperatively to aid surgeons by providing faster diagnosis. Moving this technology into theatre will allow it to develop further and thus reach its potential in the clinical arena.

scholarly journals Determination of SOX9 Gene Expression In Brain Tumours Among East Coast Malaysia Population

2020 ◽  
Vol 18 (2) ◽  
Author(s):  
Md Dzali NB ◽  
Wan Taib WR ◽  
Zahary MN ◽  
Abu Bakar NH ◽  
Abd Latif AZ ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Brain Tumour ◽  
Brain Tumours ◽  
East Coast ◽  
Rna Extraction ◽  
Slight Modification ◽  
Low Grade ◽  
Normal Brain ◽  
Sox9 Expression ◽  
Sox9 Gene

Introduction: SOX9, a members of SOX family, plays a significant roles in developmental processes during embryogenesis, including brain tissue. Few studies have shown that SOX9 has been involved in tumourigenesis of several types of cancer including brain tumour. However, such studies are still lacking in the Malaysian population. The aim of this study was to determine SOX9 expression level in several types of brain tumours in East Coast Malaysia. Materials and Methods: Five formalin-fixed pariffin-embedded brain tumour samples of Malay descendants were sectioned by using microtome. RNA extraction was performed with slight modification by adding Trizol during tissue lysis. The RNA was converted to cDNA using reverse transcription technique before SOX9 expression was detected using RT q-PCR assay in brain tumours normalized to non-neoplastic brain tissues. Results: Overall results displayed that SOX9 gene in all samples were up-regulated. SOX9 overexpression was found in both high and low grade glioma (anaplastic and pilocytic astrocytoma respectively). This is consistence with both low grade (benign) and atypical meningioma. Secondary brain tumour also showed up-regulation when compared to normal brain tissue. Conclusion: Up-regulation in SOX9 expression in selected brain tumours in Malay patients revealed its significant roles in brain tumourigenesis. Functional studies should be carried out to observe the SOX9 functions and mechanism whether they should reflect their diverse roles in Malaysia population.

scholarly journals Segmentation of Brain Images by Optimizing Clustering of Convolution Based Features

2021 ◽  
Vol 229 ◽  
pp. 01034
Author(s):  
Vikas Kumar
Keyword(s):  
Brain Tumour ◽  
Brain Tumours ◽  
Normal Brain ◽  
Resonance Imaging ◽  
Comprehensive Overview ◽  
Brain Images ◽  
Non Invasive ◽  
Tumour Segmentation ◽  
Tissue Contrast ◽  
Brain Tumour Segmentation

Brain tumour segmentation aims to separate the various types of tumour tissues like active cells, necrotic core, and edema from normal brain tissues of substantia alba (WM), grey matter (GM), and spinal fluid (CSF). Magnetic Resonance Imaging based brain tumour segmentation studies are attracting more and more attention in recent years thanks to non-invasive imaging and good soft tissue contrast of resonance Imaging (MRI) images. With the event of just about two decades, the ingenious approaches applying computer-aided techniques for segmenting brain tumour are getting more and more mature and coming closer to routine clinical applications. the aim of this paper is to supply a comprehensive overview for MRIbased brain tumour segmentation methods. Firstly, a quick introduction to brain tumours and imaging modalities of brain tumours is given in this proposed research, convolution based optimization. These stepwise step refine the segmentation and improve the classification parameter with the assistance of particle swarmoptimization.

scholarly journals P11.57 A 3D brain organoid coculture system delineates the invasive cell components in glioblastoma

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii56-iii57
Author(s):  
W Zhou ◽  
B Klink ◽  
G Dittmar ◽  
P Nazarov ◽  
E M Garcia ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Cell Invasion ◽  
Ex Vivo ◽  
Normal Brain ◽  
Rna Seq ◽  
Normal Brain Tissue ◽  
Coculture System ◽  
Mature Brain ◽  
Brain Organoid ◽  
The Brain

Abstract BACKGROUND Glioblastoma (GBM) cell infiltration into the surrounding normal brain tissue where the blood brain barrier is intact, represents a major problem for clinical management and therapy. There is a vital need to understand the molecular mechanism that drives tumor cell invasion into the surrounding brain. We have previously developed a 3D coculture model where mature brain organoids are confronted with patient-derived glioblastoma stem-like cells (GSCs). In such a coculture system, single cell invasion into the normal brain tissue can be studied in detail. Here, we first describe in detail, by RNA-seq and proteomics, the differentiation of various neural cell lineages into mature brain organoids as well as their cellular organization. By real-time confocal microscopy and imaging analyses we also determine the speed of tumor cell invasion into the brain. Finally, we used this coculture system to delineate in detail the cellular heterogeneity within the invasive compartment and their gene expression. MATERIAL AND METHODS Immunohistochemistry and immunofluorescence were used to determine the expression and distribution of mature neurons, astrocytes, oligodendrocytes, and microglia within the brain organoids. Proteomics and RNA-seq were used to determine brain development ex-vivo. To assess the clonal composition of the GBM-invasive compartment, we used cellular (RGB) barcoding technology. By advanced imaging, we tracked in real time the invasion of barcoded cells into the brain organoids. Finally, we isolated invasive cells and non-invasive cells from our coculture system and used single cell sequencing to analyze their gene expression profiles and molecular phenotypes. RESULTS Immunohistochemistry and immunofluorescence showed that brain organoids, after 21 days of differentiation, display a highly cellular and structural organization. RNA-seq and proteomics, performed at different time points of organoid differentiation, revealed that the brain organoids develop into mature brain structures after 21 days as verified by a comparative analysis to normal rat brain development in vivo. Imaging analyses showed that multiple clones within the GBMs have the capacity to invade into the brain tissue with an average speed of ~ 20 μm/h. RNA-sec analysis of the invasive compartment revealed a strong up-regulation of genes and pathways associated with anaerobic respiration (glycolysis). CONCLUSION We describe a highly standardized brain organoid coculture system that can be used to delineate GBM invasion ex-vivo. We demonstrate that this platform can be used to unravel the mechanisms that drive GBM invasion into the normal brain.

scholarly journals Single-cell resolution in high-resolution synchrotron X-ray CT imaging with gold nanoparticles

2013 ◽  
Vol 21 (1) ◽  
pp. 242-250 ◽  
Author(s):  
Elisabeth Schültke ◽  
Ralf Menk ◽  
Bernd Pinzer ◽  
Alberto Astolfo ◽  
Marco Stampanoni ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Single Cell ◽  
Brain Tumour ◽  
Ex Vivo ◽  
Small Animal ◽  
C6 Glioma Cells ◽  
X Ray ◽  
Local Tomography ◽  
The Brain

Gold nanoparticles are excellent intracellular markers in X-ray imaging. Having shown previously the suitability of gold nanoparticles to detect small groups of cells with the synchrotron-based computed tomography (CT) technique bothex vivoandin vivo, it is now demonstrated that even single-cell resolution can be obtained in the brain at leastex vivo. Working in a small animal model of malignant brain tumour, the image quality obtained with different imaging modalities was compared. To generate the brain tumour, 1 × 105C6 glioma cells were loaded with gold nanoparticles and implanted in the right cerebral hemisphere of an adult rat. Raw data were acquired with absorption X-ray CT followed by a local tomography technique based on synchrotron X-ray absorption yielding single-cell resolution. The reconstructed synchrotron X-ray images were compared with images obtained by small animal magnetic resonance imaging. The presence of gold nanoparticles in the tumour tissue was verified in histological sections.

scholarly journals Quantitative fluorescence in intracranial tumor: implications for ALA-induced PpIX as an intraoperative biomarker

2011 ◽  
Vol 115 (1) ◽  
pp. 11-17 ◽  
Author(s):  
Pablo A. Valdés ◽  
Frederic Leblond ◽  
Anthony Kim ◽  
Brent T. Harris ◽  
Brian C. Wilson ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Fluorescence Imaging ◽  
Low Grade ◽  
Normal Brain ◽  
Intracranial Tumors ◽  
Neoplastic Tissue ◽  
Fluorescence Measurements ◽  
Significant Difference ◽  
Quantitative Fluorescence

Object Accurate discrimination between tumor and normal tissue is crucial for optimal tumor resection. Qualitative fluorescence of protoporphyrin IX (PpIX), synthesized endogenously following δ-aminolevulinic acid (ALA) administration, has been used for this purpose in high-grade glioma (HGG). The authors show that diagnostically significant but visually imperceptible concentrations of PpIX can be quantitatively measured in vivo and used to discriminate normal from neoplastic brain tissue across a range of tumor histologies. Methods The authors studied 14 patients with diagnoses of low-grade glioma (LGG), HGG, meningioma, and metastasis under an institutional review board–approved protocol for fluorescence-guided resection. The primary aim of the study was to compare the diagnostic capabilities of a highly sensitive, spectrally resolved quantitative fluorescence approach to conventional fluorescence imaging for detection of neoplastic tissue in vivo. Results A significant difference in the quantitative measurements of PpIX concentration occurred in all tumor groups compared with normal brain tissue. Receiver operating characteristic (ROC) curve analysis of PpIX concentration as a diagnostic variable for detection of neoplastic tissue yielded a classification efficiency of 87% (AUC = 0.95, specificity = 92%, sensitivity = 84%) compared with 66% (AUC = 0.73, specificity = 100%, sensitivity = 47%) for conventional fluorescence imaging (p < 0.0001). More than 81% (57 of 70) of the quantitative fluorescence measurements that were below the threshold of the surgeon's visual perception were classified correctly in an analysis of all tumors. Conclusions These findings are clinically profound because they demonstrate that ALA-induced PpIX is a targeting biomarker for a variety of intracranial tumors beyond HGGs. This study is the first to measure quantitative ALA-induced PpIX concentrations in vivo, and the results have broad implications for guidance during resection of intracranial tumors.

scholarly journals Developing guidelines for the management of brain tumour related epilepsy

2021 ◽  
Vol 23 (Supplement_4) ◽  
pp. iv3-iv4
Author(s):  
Elizabeth Vacher ◽  
Miguel Rodriguez Ruiz ◽  
Jeremy Rees
Keyword(s):  
Quality Of Life ◽  
Risk Factors ◽  
Brain Tumour ◽  
Brain Tumours ◽  
Current Evidence ◽  
Low Grade ◽  
Clinical Nurse Specialists ◽  
Primary Brain Tumours ◽  
Low Incidence

Abstract Aims Brain Tumour Related Epilepsy (BTRE) has a significant impact on Quality of Life with implications for driving, employment and social and domestic activities. Management of BTRE is complex due to the higher incidence of pharmacoresistance and the potential for interaction between anti-cancer therapy and anti-epileptic drugs (AEDs). Neurologists, oncologists, palliative care physicians and clinical nurse specialists treating these patients would benefit from up-to-date clinical guidelines. We aim to review the current evidence to adapt current NICE guidelines for Epilepsy and to outline specific recommendations for the optimal treatment of BTRE, encompassing both primary and metastatic brain tumours. Method A comprehensive search of the literature from the past 20 years on BTRE was carried out in three databases: Embase, Medline and EMCARE. A broad search strategy was used and the evidence was evaluated and graded based on the Oxford Centre for Evidence-Based Medicine Levels of Evidence. Results All patients with BTRE should be treated with AEDs. There is no proven benefit for the use of prophylactic AEDs, although there are no randomised trials testing newer agents. Seizure frequency varies between 10-40% (Class 2a evidence) in patients with Brain Metastases (BM) and from 30% (high-grade gliomas) to 90% (low-grade gliomas) (Class 2a evidence) in patients with Primary Brain Tumours (PBT). In patients with BM, risk factors include number of BM and melanoma histology (Class 2b evidence). In patients with PBT, risk factors include frontal and temporal location, oligodendroglial histology, IDH mutation and cortical infiltration (Class 2b evidence). There is a low incidence of seizures (13%) after stereotactic radiosurgery for BM (Class 2b evidence). Non-enzyme inducing AEDs are recommended as first line treatment for BTRE, but up to 50% of patients with BTRE due to PBT remain resistant (Class 2b evidence). Conclusion The review has highlighted the relative dearth of high quality evidence for the management of BTRE, and provides a framework for further studies aiming to improve seizure control, quality of life, and indications for AEDs.

scholarly journals Multiple Irradiation Affects Cellular and Extracellular Components of the Mouse Brain Tissue and Adhesion and Proliferation of Glioblastoma Cells in Experimental System In Vivo

2021 ◽  
Vol 22 (24) ◽  
pp. 13350
Author(s):  
Maxim O. Politko ◽  
Alexandra Y. Tsidulko ◽  
Oxana A. Pashkovskaya ◽  
Konstantin E. Kuper ◽  
Anastasia V. Suhovskih ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Mouse Brain ◽  
Glial Cells ◽  
Ex Vivo ◽  
Experimental System ◽  
Normal Brain ◽  
Biosynthetic Activity ◽  
Normal Brain Tissue

Intensive adjuvant radiotherapy (RT) is a standard treatment for glioblastoma multiforme (GBM) patients; however, its effect on the normal brain tissue remains unclear. Here, we investigated the short-term effects of multiple irradiation on the cellular and extracellular glycosylated components of normal brain tissue and their functional significance. Triple irradiation (7 Gy*3 days) of C57Bl/6 mouse brain inhibited the viability, proliferation and biosynthetic activity of normal glial cells, resulting in a fast brain-zone-dependent deregulation of the expression of proteoglycans (PGs) (decorin, biglycan, versican, brevican and CD44). Complex time-point-specific (24–72 h) changes in decorin and brevican protein and chondroitin sulfate (CS) and heparan sulfate (HS) content suggested deterioration of the PGs glycosylation in irradiated brain tissue, while the transcriptional activity of HS-biosynthetic system remained unchanged. The primary glial cultures and organotypic slices from triple-irradiated brain tissue were more susceptible to GBM U87 cells’ adhesion and proliferation in co-culture systems in vitro and ex vivo. In summary, multiple irradiation affects glycosylated components of normal brain extracellular matrix (ECM) through inhibition of the functional activity of normal glial cells. The changed content and pattern of PGs and GAGs in irradiated brain tissues are accompanied by the increased adhesion and proliferation of GBM cells, suggesting a novel molecular mechanism of negative side-effects of anti-GBM radiotherapy.

scholarly journals Association of Angiogenic Cells in the Tumour Microenvironment and the Circulating Matured Endothelial Cells in Astrocytic Glioma

2020 ◽  
Vol 17 (2) ◽  
Author(s):  
Priscilla Das ◽  
Nyi Nyi Naing ◽  
Nadiah Wan Arfah ◽  
KON Noorjan ◽  
Yee Cheng Kueh ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Brain Tissue ◽  
Brain Tumour ◽  
Pearson Correlation ◽  
Circulating Endothelial Cells ◽  
Normal Brain ◽  
Normal Brain Tissue ◽  
Correlation Test ◽  
Astrocytic Glioma ◽  
Pearson Correlation Test

Introduction: Astrocytic gliomas are the most common and lethal intracranial brain tumours and rely on angiogenesis for the tumour development. Endothelial progenitor cells (EPCs) contribute to the angiogenesis of glioma tumour. Objectives: The study aimed to investigate the matured circulating endothelial cells population in the peripheral blood mononuclear cells (PBMCs) and its associations with tissue resident angiogenic cells in astrocytic glioma patients. Methods: A total of 22 astrocytic glioma patients were recruited from Hospital Universiti Sains Malaysia. Tumour were sliced and stained with CD133+ and VEGFA+ for angiogenic cells (n=22). The circulating (CD133-/VEGFR2+) matured endothelial cells in PBMCs (n=22) were quantified using FACS. The paired t-test and Pearson correlation test were used for the data analysis. Results: The angiogenic cells in brain tumour tissue were significantly higher compared to adjacent normal brain tissue (median 1.07±0.96% vs. median 0.69±0.68%; Wilcoxon signed rank test Z=-3.100; p=0.002). Positive correlation was found between the angiogenic cells of brain tumour tissue and adjacent normal brain tissue (Spearman’s rho correlation test, r=0.56; p=0.007). Significant positive correlation was found between matured endothelial cells in peripheral circulating systems and angiogenic cells in tumour of astrocytic glioma patients (Pearson correlation test, r=0.60, p=0.003).Conclusion:The findings of the study give support to the possible roles of EPCs in astrocytic glioma patients. Thus targeting tissue resident angiogenic cells and matured circulating endothelial cells by antiangiogenic treatment might be useful to prevent the tumour growth.

scholarly journals Enrichment of Aldolase C Correlates with Low Non-Mutated IDH1 Expression and Predicts a Favorable Prognosis in Glioblastomas

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1238 ◽  
Author(s):  
Chang ◽  
Tsai ◽  
Huang ◽  
Chen ◽  
Hsiao ◽  
...  
Keyword(s):  
Protein Expression ◽  
Mrna Expression ◽  
Brain Tissue ◽  
Low Grade ◽  
Normal Brain ◽  
Normal Brain Tissue ◽  
Expression Levels ◽  
Glioblastoma Patient ◽  
Favorable Prognosis ◽  
Aldolase C

The aldolases family is one of the main enzymes involved in the process of glycolysis. Aldolase C (ALDOC), which belongs to the aldolase family, is found in normal brain tissue and is responsible for the repair of injured tissue. However, the role of ALDOC in glioblastoma remains unclear. In this study, we data-mined in silico databases to evaluate aldolase family members’ mRNA expression in glioblastoma patient cohorts for determining its prognostic values. After that, we also performed immunohistochemical stain (IHC) analysis to evaluate protein expression levels of ALDOC in glioblastoma tissues. From The Cancer Genome Atlas (TCGA) database analyses, higher mRNA expression levels in normal brain tissue compared to glioblastoma was observed. In addition, compared to low-grade glioma, ALDOC expression was significantly downregulated in high-grade glioblastoma. Besides, the expression level of ALDOC was associated with molecular subtypes of glioblastomas and recurrent status in several data sets. In contrast, aldolase A (ALDOA) and aldolase B (ALDOB) revealed no significant prognostic impacts in the glioblastoma cohorts. Furthermore, we also proved that ALDOC mRNA and protein expression inversely correlated with non-mutated IDH1 expressions in glioblastoma patient cohorts. Additionally, the concordance of low ALDOC and high non-mutated IDH1 expressions predicted a stronger poor prognosis in glioblastoma patients compared to each of above tests presented alone. The plausible ALDOC and IDH1 regulatory mechanism was further elucidated. Our results support high ALDOC expression in glioblastomas that might imply the mutated status of IDH1, less possibility of mesenchymal subtype, and predict a favorable prognosis.

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