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The eTUMOUR (eT) multi-centre project gathered in vivo and ex vivo magnetic resonance (MR) data, as well as transcriptomic and clinical information from brain tumour patients, with the purpose of improving the diagnostic and prognostic evaluation of future patients. In order to carry this out, among other work, a database--the eTDB--was developed. In addition to complex permission rules and software and management quality control (QC), it was necessary to develop anonymization, processing and data visualization tools for the data uploaded. It was also necessary to develop sophisticated curation strategies that involved on one hand, dedicated fields for QC-generated meta-data and specialized queries and global permissions for senior curators and on the other, to establish a set of metrics to quantify its contents. The indispensable dataset (ID), completeness and pairedness indices were set. The database contains 1317 cases created as a result of the eT project and 304 from a previous project, INTERPRET. The number of cases fulfilling the ID was 656. Completeness and pairedness were heterogeneous, depending on the data type involved.

Altres ajuts: INTERPRET (EU-IST1999-10310). This work was also partially funded by the Centro de Investigación Biomédica en Red - Bioingeniería, Biomateriales y Nanomedicina, which is an initiative of the Instituto de Salud Carlos III (Spain) co-funded by EU FEDER funds. MRI and MRS are established methodologies for evaluating intracranial lesions. One MR spectral feature suggested for in vivo grading of astrocytic tumours is the apparent myo-Inositol (mI) intensity (ca 3.55ppm) at short echo times, although glycine (gly) may also contribute in vivo to this resonance. The purpose of this study was to quantitatively evaluate the mI + gly contribution to the recorded spectral pattern in vivo and correlate it with in vitro data obtained from perchloric acid extraction of tumour biopsies. Patient spectra (n = 95) at 1.5T at short (20-31 ms) and long (135-136 ms) echo times were obtained from the INTERPRET MRS database (http://gabrmn.uab.es/interpretvalidateddb/). Phantom spectra were acquired with a comparable protocol. Spectra were automatically processed and the ratios of the (mI + gly) to Cr peak heights ((mI + gly)/Cr) calculated. Perchloric acid extracts of brain tumour biopsies were analysed by high-resolution NMR at 9.4T. The ratio (mI + gly)/Cr decreased significantly with astrocytic grade in vivo between low-grade astrocytoma (A2) and glioblastoma multiforme (GBM). In vitro results displayed a somewhat different tendency, with anaplastic astrocytomas having significantly higher (mI + gly)/Cr than A2 and GBM. The discrepancy between in vivo and in vitro data suggests that the NMR visibility of glycine in glial brain tumours is restricted in vivo.

BACKGROUND AND PURPOSE: Different TE can be used for obtaining MR spectra of brain tumors. The purpose of this study was to determine the influence of the TE used in brain tumor classification by comparing the performance of spectra obtained at two different TE (30 ms and 136 ms). METHODS: One hundred fifty-one studies of patients with brain tumors (37 meningiomas, 12 low grade astrocytomas, 16 anaplastic astrocytomas, 54 glioblastomas, and 32 metastases) were retrospectively selected from a series of 378 consecutive examinations of brain masses. Single voxel proton MR spectroscopy at TE 30 ms and 136 ms was performed with point-resolved spectroscopy in all cases. Fitted areas of nine resonances of interest were normalized to water. Tumors were classified into four groups (meningioma, low grade astrocytoma, anaplastic astrocytoma, and glioblastoma-metastases) by means of linear discriminant analysis. The performance of linear discriminant analysis at each TE was assessed by using the leave-one-out method. RESULTS: Tumor classification was slightly better at short TE (123 [81%] of 151 cases correctly classified) than at long TE (118 [78%] of 151 cases correctly classified). Meningioma was the only group that showed higher sensitivity and specificity at long TE. Improved results were obtained when both TE were considered simultaneously: the suggested diagnosis was correct in 105 (94%) of 112 cases when both TE agreed, whereas the correct diagnosis was suggested by at least one TE in 136 (90%) of 151 cases. CONCLUSION: Short TE provides slightly better tumor classification, and results improve when both TE are considered simultaneously. Meningioma was the only tumor group in which long TE performed better than short TE.

Machine learning has provided, over the last decades, tools for knowledge extraction in complex medical domains. Most of these tools, though, are ad hoc solutions and lack the systematic approach that would be required to become mainstream in medical practice. In this brief paper, we define a machine learning-based analysis pipeline for helping in a difficult problem in the field of neuro-oncology, namely the discrimination of brain glioblastomas from single brain metastases. This pipeline involves source extraction using k-Meansinitialized Convex Non-negative Matrix Factorization and a collection of classifiers, including Logistic Regression, Linear Discriminant Analysis, AdaBoost, and Random Forests.

Mobile lipids have been detected by proton nuclear magnetic resonance (NMR) in animal and human tumors (cultured cells, biopsies, and in vivo), but their origin and subcellular location are still unclear. They have been associated with malignancy, metastatic ability, drug resistance, and necrosis. We wanted to determine whether these lipids are located within plasma membrane microdomains or in lipid droplets for a C6 cell-induced rat glioma. NMR-visible mobile lipids were found in all subcellular fractions isolated from the rat tumor, except in the cytosolic supernatants. Transmission electron microscopy showed that lipid droplets were present in all subcellular fractions containing NMR-visible lipids and in the necrotic and perinecrotic areas of the tumor. The mean diameter of droplets isolated by flotation in the subcellular fractionation protocol was 0.97 microm (n = 682; droplet profile diameter range between 0.2 and 5.0 microm). The apparent diffusion coefficient for these lipids (46 +/- 17 microm2 s(-1) measured in vivo by proton spectroscopy was four orders of magnitude higher than would be expected if mobile lipids were inside plasma membrane microdomains. The combined results demonstrated that mobile lipids detected in vivo by proton NMR in the C6 rat glioma are located in large lipid droplets, associated with the necrotic process.

Our objective is to develop a decision support system that improves the accuracy of non-invasive brain tumour diagnosis and grading by enabling radiologists to use data from Magnetic Resonance Spectroscopy (MRS). The system, which uses pattern recognition techniques, is trained on a validated database of spectra and associated clinical information to provide automated classification of spectra from brain tumours. An innovative user-interface presents classification results as a two-dimensional overview plot in which points representing cases of different diseases form distinct clusters. Users can inspect any cases in these plots and compare them with the new, unknown spectrum. Hence, the overview plot can both communicate the classification of a case and help provide explanation for that classification in part by supporting human case-based reasoning. This paper describes the development of a prototype system implemented in JAVA.

There is an ongoing controversy about the subcellular origin of the fatty acyl chains that give rise to the NMR visible mobile lipids (MLs) resonance at approximately 1.24 ppm in the 1H spectra of cells and solid tumors. Some groups have been supporting the hypothesis that triglycerides originating MLs are isotropically tumbling in small membrane microdomains, whereas other authors back the proposal that they are inside cytosolic or extracellular (necrotic areas) lipid droplets. Furthermore, MLs are frequently present in in vivo spectra recorded from human brain tumors, but the meaning of this detection is not fully clear. We have addressed the possible contribution of intracellular droplets to the ML pattern recorded from human brain tumors in vivo by studying cultured C6 rat glioma cells as a model system for astrocytic tumors. We show here that cultured C6 cells display ML resonances in high field (9.4 T) 1H NMR spectra recorded at 136 ms echo time when grown at saturation density conditions, but no MLs are visible for log-phase cells. Fluorescence microscopy analysis of cells stained with the lipophylic dye Nile red shows intracellular spherical yellow-gold droplets containing neutral lipids; cells at saturation density present lipid droplets of diameters about 1.6 microm in most cells (85%), whereas they are almost absent in log-phase cells (only 6% of the cells contain them). Furthermore, log-phase cells can be induced to display MLs and accumulate Nile red-positive droplets by culturing them for 24 h at pH 6.2. This acid pH effect can be fully reversed by 24 h of standard media incubation. Lipid droplet volume calculated from fluorescence microscopy preparations in an average cell is different for both culture conditions (2.2 times higher volume for saturation density than for pH-stressed cells). This difference in lipid droplet volume is reflected by a different ML peak height at 1.24 ppm (about 2 times higher for saturation density than for pH-stressed cells). Flow cytometry analysis shows that both culture conditions result in a slowing down of the proliferation rate of the cells. The fact that MLs are found to originate in lipid droplets inside cells that are growth compromised but still viable suggests that changes in the proliferative state of tumor cells, in the absence of necrosis, may be detected non invasively by in vivo NMR spectroscopy.

The 31P NMR spectra of germinating maize seeds showed a single broad resonance that shifted its position as germination proceeded (studied between 0 and 10 days). The resonance was shown to originate from the phosphate groups of phytine (Mg2+, Ca2+ and K+ salt of myoinositol hexakisphosphate) in a subcellular compartment of the embryo scutellar cells. A series of calibration curves for the chemical shift dependence of the phytate resonance in the presence of Mg2+ and Ca2+ were constructed. These calibration curves allowed us to determine that an acidification of the phytate containing compartment in the seed embryo takes place, reaching a minimum at about pH 4 after three days of germination. This acidification could be important in allowing phytate solubilization for export to growing parts of the maize seedling.

Characterization of glioblastoma (GB) response to treatment is a key factor for improving patients' survival and prognosis. MRI and magnetic resonance spectroscopic imaging (MRSI) provide morphologic and metabolic profiles of GB but usually fail to produce unequivocal biomarkers of response. The purpose of this work is to provide proof of concept of the ability of a semi-supervised signal source extraction methodology to produce images with robust recognition of response to temozolomide (TMZ) in a preclinical GB model. A total of 38 female C57BL/6 mice were used in this study. The semi-supervised methodology extracted the required sources from a training set consisting of MRSI grids from eight GL261 GBs treated with TMZ, and six control untreated GBs. Three different sources (normal brain parenchyma, actively proliferating GB and GB responding to treatment) were extracted and used for calculating nosologic maps representing the spatial response to treatment. These results were validated with an independent test set (7 control and 17 treated cases) and correlated with histopathology. Major differences between the responder and non-responder sources were mainly related to the resonances of mobile lipids (MLs) and polyunsaturated fatty acids in MLs (0.9, 1.3 and 2.8 ppm). Responding tumors showed significantly lower mitotic (3.3 ± 2.9 versus 14.1 ± 4.2 mitoses/field) and proliferation rates (29.8 ± 10.3 versus 57.8 ± 5.4%) than control untreated cases. The methodology described in this work is able to produce nosological images of response to TMZ in GL261 preclinical GBs and suitably correlates with the histopathological analysis of tumors. A similar strategy could be devised for monitoring response to treatment in patients. Copyright © 2016 John Wiley & Sons, Ltd.