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  • 1
    Language: English
    In: Journal of neuro-oncology, 2016-02-13, Vol.127 (3), p.463-472
    Description: The ability to diagnose cancer rapidly with high sensitivity and specificity is essential to exploit advances in new treatments to lead significant reductions in mortality and morbidity. Current cancer diagnostic tests observing tissue architecture and specific protein expression for specific cancers suffer from inter-observer variability, poor detection rates and occur when the patient is symptomatic. A new method for the detection of cancer using 1 μl of human serum, attenuated total reflection—Fourier transform infrared spectroscopy and pattern recognition algorithms is reported using a 433 patient dataset (3897 spectra). To the best of our knowledge, we present the largest study on serum mid-infrared spectroscopy for cancer research. We achieve optimum sensitivities and specificities using a Radial Basis Function Support Vector Machine of between 80.0 and 100 % for all strata and identify the major spectral features, hence biochemical components, responsible for the discrimination within each stratum. We assess feature fed-SVM analysis for our cancer versus non-cancer model and achieve 91.5 and 83.0 % sensitivity and specificity respectively. We demonstrate the use of infrared light to provide a spectral signature from human serum to detect, for the first time, cancer versus non-cancer, metastatic cancer versus organ confined, brain cancer severity and the organ of origin of metastatic disease from the same sample enabling stratified diagnostics depending upon the clinical question asked.
    Subject(s): Adolescent ; Adult ; Aged ; Aged, 80 and over ; Algorithms ; Analysis ; ATR-FTIR ; Biomarkers, Tumor - blood ; Brain Neoplasms - blood ; Brain Neoplasms - diagnosis ; Brain tumors ; Cancer ; Case-Control Studies ; Cell Differentiation ; Diagnosis ; Diagnostics ; Early Detection of Cancer ; Female ; Follow-Up Studies ; Glioma ; Gliomas ; Health aspects ; Humans ; Infrared spectroscopy ; Laboratory Investigation ; Male ; Medicine ; Medicine & Public Health ; Metastasis ; Middle Aged ; Mortality ; Neoplasm Grading ; Neurology ; Oncology ; Prognosis ; Rapid ; Serum ; Spectroscopy ; Spectroscopy, Fourier Transform Infrared - methods ; Support Vector Machine ; Young Adult
    ISSN: 0167-594X
    E-ISSN: 1573-7373
    Source: Alma/SFX Local Collection
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  • 2
    Language: English
    In: Scientific reports, 2022-01-20, Vol.12 (1), p.1102-1102
    Description: Brain metastases comprise 40% of all metastatic tumours and breast tumours are among the tumours that most commonly metastasise to the brain, the role that epigenetic gene dysregulation plays in this process is not well understood. We carried out 450 K methylation array analysis to investigate epigenetically dysregulated genes in breast to brain metastases (BBM) compared to normal breast tissues (BN) and primary breast tumours (BP). For this, we referenced 450 K methylation data for BBM tumours prepared in our laboratory with BN and BP from The Cancer Genome Atlas. Experimental validation on our initially identified genes, in an independent cohort of BP and in BBM and their originating primary breast tumours using Combined Bisulphite and Restriction Analysis (CoBRA) and Methylation Specific PCR identified three genes (RP11-713P17.4, MIR124-2, NUS1P3) that are hypermethylated and three genes (MIR3193, CTD-2023M8.1 and MTND6P4) that are hypomethylated in breast to brain metastases. In addition, methylation differences in candidate genes between BBM tumours and originating primary tumours shows dysregulation of DNA methylation occurs either at an early stage of tumour evolution (in the primary tumour) or at a later evolutionary stage (where the epigenetic change is only observed in the brain metastasis). Epigentic changes identified could also be found when analysing tumour free circulating DNA (tfcDNA) in patient's serum taken during BBM biopsies. Epigenetic dysregulation of RP11-713P17.4, MIR3193, MTND6P4 are early events suggesting a potential use for these genes as prognostic markers.
    Subject(s): Biomarkers, Tumor - genetics ; Biopsy ; Brain - metabolism ; Brain Neoplasms - genetics ; Breast cancer ; Breast Neoplasms - genetics ; Breast Neoplasms - pathology ; Coding ; Databases, Genetic ; Deoxyribonucleic acid ; DNA ; DNA - genetics ; DNA methylation ; DNA Methylation - genetics ; Epigenesis, Genetic - genetics ; Epigenetics ; Epigenomics ; Female ; Gene Expression - genetics ; Gene Expression Profiling - methods ; Gene Expression Regulation, Neoplastic - genetics ; Genomes ; Humans ; Metastases ; Metastasis ; MicroRNAs ; Neoplasm Metastasis - genetics ; Prognosis ; Promoter Regions, Genetic - genetics ; Receptors, Cell Surface ; RNA, Untranslated - genetics ; Transcriptome - genetics ; Tumors
    E-ISSN: 2045-2322
    Source: Nature Open Access
    Source: Academic Search Ultimate
    Source: PubMed Central
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  • 3
    Language: English
    In: Analytical and bioanalytical chemistry, 2019-12-21, Vol.412 (5), p.1077-1086
    Description: Meningiomas are the commonest types of tumours in the central nervous system (CNS). It is a benign type of tumour divided into three WHO grades (I, II and III) associated with tumour growth rate and likelihood of recurrence, where surgical outcomes and patient treatments are dependent on the meningioma grade and histological subtype. The development of alternative approaches based on attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy could aid meningioma grade determination and its biospectrochemical profiling in an automated fashion. Herein, ATR-FTIR in combination with chemometric techniques is employed to distinguish grade I, grade II and grade I meningiomas that re-occurred. Ninety-nine patients were investigated in this study where their formalin-fixed paraffin-embedded (FFPE) brain tissue samples were analysed by ATR-FTIR spectroscopy. Subsequent classification was performed via principal component analysis plus linear discriminant analysis (PCA-LDA) and partial least squares plus discriminant analysis (PLS-DA). PLS-DA gave the best results where grade I and grade II meningiomas were discriminated with 79% accuracy, 80% sensitivity and 73% specificity, while grade I versus grade I recurrence and grade II versus grade I recurrence were discriminated with 94% accuracy (94% sensitivity and specificity) and 97% accuracy (97% sensitivity and 100% specificity), respectively. Several wavenumbers were identified as possible biomarkers towards tumour differentiation. The majority of these were associated with lipids, protein, DNA/RNA and carbohydrate alterations. These findings demonstrate the potential of ATR-FTIR spectroscopy towards meningioma grade discrimination as a fast, low-cost, non-destructive and sensitive tool for clinical settings. Graphical abstract Attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy was used to discriminate meningioma WHO grade I, grade II and grade I recurrence tumours.
    Subject(s): Accuracy ; Analysis ; Analytical Chemistry ; ATR-FTIR ; Biochemistry ; Biomarkers ; Carbohydrates ; Central nervous system ; Characterization and Evaluation of Materials ; Chemistry ; Chemistry and Materials Science ; Chemometrics ; Deoxyribonucleic acid ; Differentiation ; Discriminant Analysis ; DNA ; Food Science ; Fourier transform infrared spectroscopy ; Fourier transforms ; general ; Growth rate ; Humans ; Identification and classification ; Infrared reflection ; Infrared spectroscopy ; Laboratory Medicine ; Lipids ; Meningeal Neoplasms - chemistry ; Meningioma ; Meningioma - chemistry ; Methods ; Monitoring/Environmental Analysis ; Paraffin ; Paraffins ; Principal Component Analysis ; Principal components analysis ; Profiling ; Research Paper ; Ribonucleic acid ; RNA ; Sensitivity ; Sensitivity and Specificity ; Spectroscopy ; Spectroscopy, Fourier Transform Infrared - methods ; Spectrum analysis ; Tissue analysis ; Tumors ; Usage
    ISSN: 1618-2642
    E-ISSN: 1618-2650
    Source: Academic Search Ultimate
    Source: Alma/SFX Local Collection
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  • 4
    Language: English
    In: Cancers, 2020-06-27, Vol.12 (7), p.1710
    Description: Patients living with brain tumours have the highest average years of life lost of any cancer, ultimately reducing average life expectancy by 20 years. Diagnosis depends on brain imaging and most often confirmatory tissue biopsy for histology. The majority of patients experience non-specific symptoms, such as headache, and may be reviewed in primary care on multiple occasions before diagnosis is made. Sixty-two per cent of patients are diagnosed on brain imaging performed when they deteriorate and present to the emergency department. Histological diagnosis from invasive surgical biopsy is necessary prior to definitive treatment, because imaging techniques alone have difficulty in distinguishing between several types of brain cancer. However, surgery itself does not necessarily control tumour growth, and risks morbidity for the patient. Due to their similar features on brain scans, glioblastoma, primary central nervous system lymphoma and brain metastases have been known to cause radiological confusion. Non-invasive tests that support stratification of tumour subtype would enhance early personalisation of treatment selection and reduce the delay and risks associated with surgery for many patients. Techniques involving vibrational spectroscopy, such as attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy, have previously demonstrated analytical capabilities for cancer diagnostics. In this study, infrared spectra from 641 blood serum samples obtained from brain cancer and control patients have been collected. Firstly, we highlight the capability of ATR-FTIR to distinguish between healthy controls and brain cancer at sensitivities and specificities above 90%, before defining subtle differences in protein secondary structures between patient groups through Amide I deconvolution. We successfully differentiate several types of brain lesions (glioblastoma, meningioma, primary central nervous system lymphoma and metastasis) with balanced accuracies 〉80%. A reliable blood serum test capable of stratifying brain tumours in secondary care could potentially avoid surgery and speed up the time to definitive therapy, which would be of great value for both neurologists and patients.
    Subject(s): Biopsy ; Blood tests ; Brain Cancer ; Brain tumors ; Cancer ; Cancer therapies ; Central nervous system ; Data analysis ; Diagnosis ; Diagnostics ; Emergency medical care ; Fourier transforms ; Glioblastoma ; Headache ; Infrared ; Invasiveness ; Life span ; Lymphoma ; Meningioma ; Metastases ; Metastasis ; Morbidity ; Neuroimaging ; Patients ; Principal components analysis ; Radiation therapy ; Serum ; Spectroscopy ; Spectrum analysis ; Surgery ; Tumors ; Tumour Stratification
    ISSN: 2072-6694
    E-ISSN: 2072-6694
    Source: Academic Search Ultimate
    Source: PubMed Central
    Source: Alma/SFX Local Collection
    Source: DOAJ Directory of Open Access Journals - Not for CDI Discovery
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  • 5
    Language: English
    In: Biosensors (Basel), 2019-06-01, Vol.9 (2), p.49
    Description: 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 (kappa = 0.87). Similar results were observed when compared to the final formalin-fixed paraffin embedded tissue diagnosis (kappa = 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.
    Subject(s): Accuracy ; Algorithms ; Biopsy ; Brain ; Brain cancer ; Brain surgery ; Brain tumors ; brain tumour diagnosis ; Chemistry ; Chemistry, Analytical ; classification ; Diagnosis ; Feature extraction ; forward feature extraction algorithm ; Gold ; Instruments & Instrumentation ; intraoperative use ; Laboratories ; Lymphatic system ; Lymphoma ; Metastases ; Nanoparticles ; Nanoscience & Nanotechnology ; Neuropathology ; Paraffin ; Paraffins ; Physical Sciences ; Prediction models ; Principal components analysis ; Raman probe ; Raman spectra ; Raman spectroscopy ; Science & Technology ; Science & Technology - Other Topics ; Sensitivity ; Software ; Spectrochemical analysis ; Spectrum analysis ; Surgeons ; Technology ; Tissues ; Tumors
    ISSN: 2079-6374
    E-ISSN: 2079-6374
    Source: Web of Science - Science Citation Index Expanded - 2019〈img src="http://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" /〉
    Source: PubMed Central
    Source: DOAJ Directory of Open Access Journals - Not for CDI Discovery
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  • 6
    Language: English
    In: Journal of clinical pathology, 2012-12, Vol.65 (12), p.1138-1140
    Description: Introduction Giant cell arteritis (GCA) has been successfully treated with steroids for many years and temporal artery biopsy (TAB) is regarded as the gold standard diagnostic test. The primary aim of this study was to determine whether steroid pretreatment abrogates histological features of GCA reducing diagnostic return, as suspected on the basis of anecdotal evidence. This impacts upon patients suspected of having GCA and the need for prompt treatment balanced with the diagnostic need for TAB. Methods A 6-year single-centre retrospective study of biopsies (2005–2011) was performed with interrogation of the medical notes for information regarding steroid use. The null hypothesis considered there was no association between steroid use and biopsy outcome. Results No significant difference was found between steroid use and biopsy outcome, with biopsies still producing positive results after weeks of steroid treatment. Conclusions TAB is still useful in the diagnosis of GCA, even after commencing steroid treatment.
    Subject(s): Abridged Index Medicus ; Adult ; Age ; Aged ; Aged, 80 and over ; Biological and medical sciences ; Biopsy ; Care and treatment ; Dosage and administration ; Female ; Giant cell arteritis ; Giant Cell Arteritis - drug therapy ; Giant Cell Arteritis - pathology ; Glucocorticoids - pharmacology ; Glucocorticoids - therapeutic use ; Health aspects ; Histology ; Humans ; Hypotheses ; Investigative techniques, diagnostic techniques (general aspects) ; Male ; Medical sciences ; Middle Aged ; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques ; Research ; Retrospective Studies ; Rheumatology ; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis ; Steroids ; Steroids (Drugs) ; Temporal Arteries - drug effects ; Temporal Arteries - pathology
    ISSN: 0021-9746
    E-ISSN: 1472-4146
    Source: Hellenic Academic Libraries Link
    Source: BMJ Journals - NESLi2
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  • 7
    Language: English
    In: Journal of biophotonics, 2020-09, Vol.13 (9), p.e202000118-n/a
    Description: In recent years, the diagnosis of brain tumors has been investigated with attenuated total reflection‐Fourier transform infrared (ATR‐FTIR) spectroscopy on dried human serum samples to eliminate spectral interferences of the water component, with promising results. This research evaluates ATR‐FTIR on both liquid and air‐dried samples to investigate “digital drying” as an alternative approach for the analysis of spectra obtained from liquid samples. Digital drying approaches, consisting of water subtraction and least‐squares method, have demonstrated a greater random forest (RF) classification performance than the air‐dried spectra approach when discriminating cancer vs control samples, reaching sensitivity values higher than 93.0% and specificity values higher than 83.0%. Moreover, quantum cascade laser infrared (QCL‐IR) based spectroscopic imaging is utilized on liquid samples to assess the implications of a deep‐penetration light source on disease classification. The RF classification of QCL‐IR data has provided sensitivity and specificity amounting to 85.1% and 75.3% respectively. Early diagnosis of cancer represents a primary step in increasing survival rates and quality of life in cancer patients. Research on liquid serum samples analysis by ATR‐FTIR and QCL‐FTIR coupled with “digital drying” shows great classification values when distinguishing brain tumor samples vs healthy control samples. The use of digital drying improves times of acquisition and sample preparation, reducing the barriers through clinical translation.
    Subject(s): ATR‐FTIR ; Brain tumors ; cancer ; Classification ; digital drying ; Drying ; Fourier transforms ; Infrared analysis ; Infrared lasers ; Infrared reflection ; Infrared spectroscopy ; Light sources ; Neuroimaging ; Quantum cascade lasers ; Sensitivity ; serum ; Spectra ; Spectrum analysis ; Subtraction
    ISSN: 1864-063X
    E-ISSN: 1864-0648
    Source: Get It Now
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  • 8
    Language: English
    In: Molecular carcinogenesis, 2016-03, Vol.55 (3), p.268-279
    Description: Cyclic nucleotides (cAMP & cGMP) are critical intracellular second messengers involved in the transduction of a diverse array of stimuli and their catabolism is mediated by phosphodiesterases (PDEs). We previously detected focal genomic amplification of PDE1C in 〉90 glioblastoma multiforme (GBM) cells suggesting a potential as a novel therapeutic target in these cells. In this report, we show that genomic gain of PDE1C was associated with increased expression in low passage GBM‐derived cell cultures. We demonstrate that PDE1C is essential in driving cell proliferation, migration and invasion in GBM cultures since silencing of this gene significantly mitigates these functions. We also define the mechanistic basis of this functional effect through whole genome expression analysis by identifying down‐stream gene effectors of PDE1C which are involved in cell cycle and cell adhesion regulation. In addition, we also demonstrate that Vinpocetine, a general PDE1 inhibitor, can also attenuate proliferation with no effect on invasion/migration. Up‐regulation of at least one of this gene set (IL8, CXCL2, FOSB, NFE2L3, SUB1, SORBS2, WNT5A, and MMP1) in TCGA GBM cohorts is associated with worse outcome and PDE1C silencing down‐regulated their expression, thus also indicating potential to influence patient survival. Therefore we conclude that proliferation, migration, and invasion of GBM cells could also be regulated downstream of PDE1C. © 2015 Wiley Periodicals, Inc.
    Subject(s): 3',5'-Cyclic-nucleotide phosphodiesterase ; Analysis ; Brain - metabolism ; Brain - pathology ; Brain cancer ; Brain Neoplasms - genetics ; Brain Neoplasms - metabolism ; Brain Neoplasms - pathology ; Ca2+/calmodulin-dependent phosphodiesterase ; cAMP ; Catabolism ; Cell adhesion ; Cell adhesion & migration ; Cell cycle ; Cell growth ; Cell migration ; Cell Movement ; Cell Proliferation ; Cell survival ; cGMP ; Cyclic AMP - metabolism ; Cyclic GMP ; Cyclic GMP - metabolism ; Cyclic Nucleotide Phosphodiesterases, Type 1 - genetics ; Cyclic Nucleotide Phosphodiesterases, Type 1 - metabolism ; Cyclic nucleotides ; Enzymes ; FosB protein ; Gene expression ; Gene Expression Regulation, Neoplastic ; Genomes ; Genomics ; Glioblastoma ; Glioblastoma - genetics ; Glioblastoma - metabolism ; Glioblastoma - pathology ; Glioblastoma multiforme ; Humans ; Interleukin 8 ; Neoplasm Invasiveness - genetics ; Neoplasm Invasiveness - pathology ; Nucleotides ; PDE1C signalling ; Phosphodiesterase ; Second messengers ; Therapeutic applications ; Up-Regulation ; Vinpocetine ; Wnt protein
    ISSN: 0899-1987
    E-ISSN: 1098-2744
    Source: Hellenic Academic Libraries Link
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  • 9
    Language: English
    In: Analytical letters, 2019-03-04, Vol.52 (4), p.575-587
    Description: Metastatic brain tumors represent a significant proportion of tumors identified intraoperatively. A rapid diagnostic method, circumventing the need for histopathology studies, could prove clinically useful. As many spectroscopic studies have shown ability to differentitate between different tumor types, this technique was evaluated for use within metastatic brain tumors. Spectrochemical approaches [Raman and attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR) spectroscopy] were applied to determine how readily they may identify the primary site for the metastatic tumor. Metastases were from primary adenocarcinomas of lung (n = 7) and colorectum (n = 7), and for comparison, metastatic melanoma (n = 7). The objective was to determine if Raman or ATR-FTIR spectroscopy could delineate the origin of the primary tumor. The results demonstrate that there are marked similarities between the two adenocarcinoma groups and whilst Raman and ATR-FTIR can distinguish the three groups with limited success, classification accuracy is greatly improved when combining the adenocarcinoma groups. The use of such techniques in the clinical setting is more likely to be found intraoperatively, determining the presence of a tumor and suggesting the tumor class; however, traditional histopathology would still be needed to identify the primary origin of the tumor.
    Subject(s): Attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy ; Brain ; Brain cancer ; Chemistry ; Chemistry, Analytical ; classification ; Diagnostic systems ; Fourier transforms ; Histopathology ; Infrared reflection ; Infrared spectroscopy ; linear discrimination analysis (LDA) ; Metastasis ; metastatic brain tumor ; neuro-oncology ; Physical Sciences ; Raman spectroscopy ; Science & Technology ; Spectrum analysis ; Tumors
    ISSN: 0003-2719
    E-ISSN: 1532-236X
    Source: Academic Search Ultimate
    Source: Web of Science - Science Citation Index Expanded - 2019〈img src="http://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" /〉
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  • 10
    Language: English
    In: British journal of neurosurgery, 2020-01-02, Vol.34 (1), p.40-45
    Description: Introduction: In order for brain tumours to be successfully treated, maximal resection is beneficial. A method to detect infiltrative tumour edges intraoperatively, improving on current methods would be clinically useful. Vibrational spectroscopy offers the potential to provide a handheld, reagent-free method for tumour detection. Purpose: This study was designed to determine the ability of both Raman and Fourier-transform infrared (FTIR) spectroscopy towards differentiating between normal brain tissue, glioma or meningioma. Method: Unfixed brain tissue, which had previously only been frozen, comprising normal, glioma or meningioma tissue was placed onto calcium fluoride slides for analysis using Raman and attenuated total reflection (ATR)-FTIR spectroscopy. Matched haematoxylin and eosin slides were used to confirm tumour areas. Analyses were then conducted to generate a classification model. Results: This study demonstrates the ability of both Raman and ATR-FTIR spectroscopy to discriminate tumour from non-tumour fresh frozen brain tissue with 94% and 97.2% of cases correctly classified, with sensitivities of 98.8% and 100%, respectively. This decreases when spectroscopy is used to determine tumour type. Conclusion: The study demonstrates the ability of both Raman and ATR-FTIR spectroscopy to detect tumour tissue from non-tumour brain tissue with a high degree of accuracy. This demonstrates the ability of spectroscopy when targeted for a cancer diagnosis. However, further improvement would be required for a classification model to determine tumour type using this technology, in order to make this tool clinically viable.
    Subject(s): Brain cancer ; Brain tumours ; classification model ; intraoperative diagnosis ; neurosurgery ; spectrochemical analyses ; Spectrum analysis
    ISSN: 0268-8697
    E-ISSN: 1360-046X
    Source: Academic Search Ultimate
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