MMCA heatmaps based on datasets from astrocytomas, meningiomas, oligodendrogliomas and metastases.

<p>The heatmaps are normalized and filtered using a p-value cut-off of 0.001 coupled to a bootstrap confidence interval of level 0.999. Metabolites are arranged according to the main biochemical modules.</p

Average HRMAS ¹H NMR spectra from the five tumour types.

<p>From bottom and upwards: glioblastomas (black, n = 132), astrocytomas (blue, n = 101), meningiomas (red, n = 75), oligodendrogliomas (brown, n = 37) and metastases (pink, n = 33).</p

Correlation coefficients of metabolite pairs across the five tumour types.

<p>Correlation coefficients of metabolite pairs across the five tumour types.</p

MR images and corresponding H&E sections from five types of brain tumours.

<p>The five tumour types illustrated are a glioblastoma (GBM), an astrocytoma (AST), a meningioma (MN), an oligodendroglioma (ODG) and a metastasis (MET) from a mammary carcinoma.</p

Metabolic interactions between brain tumour cells and host cells.

<p>The lactate from tumour cell is transported to glial cells, where it is used a fuel to produce ATP. ATP and PCr are connected via the creatine-kinase reaction. PCr, phosphocreatine; Cr, creatine; TCA, tricarboxylic acid cycle.</p

Diagrams illustrating biochemical mechanisms that could give rise to the observed correlations between metabolites.

<p>(A) Glycolytic products. The enzymes driving relevant reactions are: 1, lactate dehydrogenase; 2, alanine aminotransferase; 3, glutamine synthetase; 4, glutaminase. (B) Glutaminolysis pathway to bypass PKM2 inhibition. Active enzymes are: 1, glutaminase; 2, aspartate aminotransferase; 3, malate dehydrogenase; 4, malate decarboxylase. (C) Correlations involving the creatine pool. Dashed boxes indicate pools of metabolites: tCr, total creatines (creatine + phosphocreatine); tCho, total cholines (choline + phosphocholine + glycerophosphocholine). The enzyme creatine kinase is marked by the number 1. (D) Correlations involving the choline pool. Dashed boxes indicate pools of metabolites: tCr, total creatines (creatine + phosphocreatine); tCho, total cholines (choline + phosphocholine + glycerophosphocholine); tGlut, glutamate + glutamine pool; PtdCho, phosphatidylcholine. The enzymes marked are: 1, choline kinase; 2, CTP:phosphocholine cytidylyltransferase and choline phosphotransferase; 3, phospholipase Al; phospholipase A2, and lysophospholipase; 4, GPC:choline phosphodiesterase. Metabolites that were not detected by the ¹H HR-MAS NMR are shown in grey. Positive correlations are shown in red while negative correlations are in blue.</p

Correlation heatmap and selected metabolite distribution summaries based on glioblastoma datasets.

<p>The correlation heatmap shown is normalized and filtered using a p-value cut-off of 0.001 coupled to a bootstrap confidence interval of level 0.999. Metabolites are arranged according to the main biochemical modules. The highlighted squares in the heatmap show the correlations between lactate (Lac) and alanine (Ala), glutamate (Glu) and glutamine (Gln), as well as between tGlut (Glu+Gln) and lipid signals at 1.3ppm (Lip 13a+Lip13b).</p