{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:34:13Z","timestamp":1760236453528,"version":"build-2065373602"},"reference-count":44,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004061","name":"Oesterreichische Nationalbank","doi-asserted-by":"publisher","award":["15866"],"award-info":[{"award-number":["15866"]}],"id":[{"id":"10.13039\/501100004061","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Oncology"],"abstract":"<jats:p>Brain parenchyma infiltration with glioblastoma (GB) cannot be entirely visualized by conventional magnetic resonance imaging (MRI). The aim of this study was to investigate changes in the energy and membrane metabolism measured with phosphorous MR spectroscopy (31P-MRS) in the presumably \u201cnormal-appearing\u201d brain following chemoradiation therapy (CRT) in GB patients in comparison to healthy controls. Twenty (seven female, thirteen male) GB patients underwent a 31P-MRS scan prior to surgery (baseline) and after three months of standard CRT (follow-up examination. The regions of interest \u201ccontrast-enhancing (CE) tumor\u201d (if present), \u201cadjacent to the (former) tumor\u201d, \u201cipsilateral distant\u201d hemisphere, and \u201ccontralateral\u201d hemisphere were compared, differentiating between patients with stable (SD) and progressive disease (PD). Metabolite ratios PCr\/ATP, Pi\/ATP, PCr\/Pi, PME\/PDE, PME\/PCr, and PDE\/ATP were investigated. In PD, energy and membrane metabolism in CE tumor areas have a tendency to \u201cnormalize\u201d under therapy. In different \u201cnormal-appearing\u201d brain areas of GB patients, the energy and membrane metabolism either \u201cnormalized\u201d or were \u201cdisturbed\u201d, in comparison to baseline or controls. Differences were also detected between patients with SD and PD. 31P-MRS might contribute as an additional imaging biomarker for outcome measurement, which remains to be investigated in a larger cohort.<\/jats:p>","DOI":"10.3390\/curroncol28060424","type":"journal-article","created":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T01:43:22Z","timestamp":1638323002000},"page":"5041-5053","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Changes in Brain Energy and Membrane Metabolism in Glioblastoma following Chemoradiation"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2304-3946","authenticated-orcid":false,"given":"Astrid Ellen","family":"Grams","sequence":"first","affiliation":[{"name":"Department of Neuroradiology, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria"},{"name":"Neuroimaging Core Facility, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5790-2724","authenticated-orcid":false,"given":"Stephanie","family":"Mangesius","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria"},{"name":"Neuroimaging Core Facility, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruth","family":"Steiger","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria"},{"name":"Neuroimaging Core Facility, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivan","family":"Radovic","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria"},{"name":"Neuroimaging Core Facility, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0808-2667","authenticated-orcid":false,"given":"Andreas","family":"Rietzler","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria"},{"name":"Neuroimaging Core Facility, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa Maria","family":"Walchhofer","sequence":"additional","affiliation":[{"name":"Department of Radiology, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6577-0784","authenticated-orcid":false,"given":"Malik","family":"Galija\u0161evi\u0107","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria"},{"name":"Neuroimaging Core Facility, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0855-1870","authenticated-orcid":false,"given":"Julian","family":"Mangesius","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8068-315X","authenticated-orcid":false,"given":"Martha","family":"Nowosielski","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8228-8217","authenticated-orcid":false,"given":"Christian Franz","family":"Freyschlag","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johannes","family":"Kerschbaumer","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elke Ruth","family":"Gizewski","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria"},{"name":"Neuroimaging Core Facility, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1056\/NEJMoa043330","article-title":"Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma","volume":"352","author":"Stupp","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1227\/00006123-199604000-00026","article-title":"Migration of human glioma cells on myelin","volume":"38","author":"Giese","year":"1996","journal-title":"Neurosurgery"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1038\/nrn3765","article-title":"A neurocentric perspective on glioma invasion","volume":"15","author":"Cuddapah","year":"2014","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_4","first-page":"333","article-title":"Structural development in gliomas","volume":"34","author":"Scherer","year":"1938","journal-title":"Am. J. Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1001\/archneurol.2011.2910","article-title":"Addressing diffuse glioma as a systemic brain disease with single-cell analysis","volume":"69","author":"Sahm","year":"2012","journal-title":"Arch. Neurol."},{"key":"ref_6","first-page":"2137","article-title":"Whole-brain N-acetylaspartate spectroscopy and diffusion tensor imaging in patients with newly diagnosed gliomas: A preliminary study","volume":"27","author":"Inglese","year":"2006","journal-title":"AJNR Am. J. Neuroradiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"439","DOI":"10.3174\/ajnr.A3702","article-title":"Utility of diffusion tensor imaging in evaluation of the peritumoral region in patients with primary and metastatic brain tumors","volume":"35","author":"Sternberg","year":"2014","journal-title":"AJNR Am. J. Neuroradiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.neuroimage.2005.12.052","article-title":"Diffusion tensor imaging in primary brain tumors: Reproducible quantitative analysis of corpus callosum infiltration and contralateral involvement using a probabilistic mixture model","volume":"31","author":"Stieltjes","year":"2006","journal-title":"Neuroimage"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1016\/S0735-1097(02)02160-5","article-title":"Absolute concentrations of high-energy phosphate metabolites in normal, hypertrophied, and failing human myocardium measured noninvasively with (31)P-SLOOP magnetic resonance spectroscopy","volume":"40","author":"Beer","year":"2002","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1038\/jcbfm.1987.106","article-title":"Effects of traumatic brain injury on cerebral high-energy phosphates and pH: A 31P magnetic resonance spectroscopy study","volume":"7","author":"Vink","year":"1987","journal-title":"J. Cereb. Blood Flow Metab. Off. J. Int. Soc. Cereb. Blood Flow Metab."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1002\/nbm.1109","article-title":"Skeletal muscle energetics with PNMR: Personal views and historic perspectives","volume":"19","author":"Chance","year":"2006","journal-title":"NMR Biomed."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1002\/jmri.25278","article-title":"MRI assessment of regional differences in phosphorus-31 metabolism and morphological abnormalities of the foot muscles in diabetes","volume":"44","author":"Lin","year":"2016","journal-title":"J. Magn. Reson. Imaging JMRI"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1212\/WNL.39.4.538","article-title":"Preliminary observations on brain energy metabolism in migraine studied by in vivo phosphorus 31 NMR spectroscopy","volume":"39","author":"Welch","year":"1989","journal-title":"Neurology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1159\/000017471","article-title":"Non-invasive methods for studying brain energy metabolism: What they show and what it means","volume":"22","author":"Kemp","year":"2000","journal-title":"Dev. Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1002\/mrm.20312","article-title":"Proton-decoupled 31P MRS in untreated pediatric brain tumors","volume":"53","author":"Albers","year":"2005","journal-title":"Magn. Reson. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"14875","DOI":"10.1016\/S0021-9258(18)48107-0","article-title":"Phospholipid metabolism in cancer cells monitored by 31P NMR spectroscopy","volume":"262","author":"Daly","year":"1987","journal-title":"J. Biol. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1002\/nbm.1940050506","article-title":"Phospholipid metabolites as indicators of cancer cell function","volume":"5","author":"Cohen","year":"1992","journal-title":"NMR Biomed."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1111\/bdi.12339","article-title":"Decreased brain PME\/PDE ratio in bipolar disorder: A preliminary (31) P magnetic resonance spectroscopy study","volume":"17","author":"Shi","year":"2015","journal-title":"Bipolar Disord."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"477","DOI":"10.3348\/kjr.2013.14.3.477","article-title":"Application of 31P MR spectroscopy to the brain tumors","volume":"14","author":"Ha","year":"2013","journal-title":"Korean J. Radiol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Hattingen, E., Bahr, O., Rieger, J., Blasel, S., Steinbach, J., and Pilatus, U. (2013). Phospholipid metabolites in recurrent glioblastoma: In vivo markers detect different tumor phenotypes before and under antiangiogenic therapy. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0056439"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1002\/nbm.735","article-title":"Phosphorus-31 MR spectroscopy of normal adult human brain and brain tumours","volume":"15","author":"Maintz","year":"2002","journal-title":"NMR Biomed."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1177\/197140090702000608","article-title":"Efficacy of in vivo 31Phosphorus Magnetic Resonance Spectroscopy in Differentiation and Staging of Adult Human Brain Tumors","volume":"20","author":"Bulakbasi","year":"2007","journal-title":"Neuroradiol. J."},{"key":"ref_23","first-page":"Rc05","article-title":"Energy status and metabolism in intracranial space occupying lesions: A prospective 31p spectroscopic study","volume":"8","author":"Kamble","year":"2014","journal-title":"J. Clin. Diagn. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1002\/jmri.25619","article-title":"Intracellular pH measured by (31) P-MR-spectroscopy might predict site of progression in recurrent glioblastoma under antiangiogenic therapy","volume":"46","author":"Wenger","year":"2017","journal-title":"J. Magn. Reson. Imaging JMRI"},{"key":"ref_25","first-page":"488","article-title":"Noninvasive study of brain tumours metabolism using phosphorus-31 magnetic resonance spectroscopy","volume":"121","author":"Hnilicova","year":"2020","journal-title":"Bratisl. Lek. Listy"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1093\/neuonc\/nor132","article-title":"Bevacizumab impairs oxidative energy metabolism and shows antitumoral effects in recurrent glioblastomas: A 31P\/1H MRSI and quantitative magnetic resonance imaging study","volume":"13","author":"Hattingen","year":"2011","journal-title":"Neuro-Oncology"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Walchhofer, L.M., Steiger, R., Rietzler, A., Kerschbaumer, J., Freyschlag, C.F., Stockhammer, G., Gizewski, E.R., and Grams, A.E. (2021). Phosphorous Magnetic Resonance Spectroscopy to Detect Regional Differences of Energy and Membrane Metabolism in Naive Glioblastoma Multiforme. Cancers, 13.","DOI":"10.3390\/cancers13112598"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Galijasevic, M., Steiger, R., Radovic, I., Birkl-Toeglhofer, A.M., Birkl, C., Deeg, L., Mangesius, S., Rietzler, A., Regodic, M., and Stockhammer, G. (2021). Phosphorous Magnetic Resonance Spectroscopy and Molecular Markers in IDH1 Wild Type Glioblastoma. Cancers, 13.","DOI":"10.3390\/cancers13143569"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e106","DOI":"10.1016\/j.ejrad.2013.11.009","article-title":"Clinical protocols for (3)(1)P MRS of the brain and their use in evaluating optic pathway gliomas in children","volume":"83","author":"Novak","year":"2014","journal-title":"Eur. J. Radiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1215\/S1152851703000620","article-title":"Prognostic factors for survival of patients with glioblastoma: Recursive partitioning analysis","volume":"6","author":"Lamborn","year":"2004","journal-title":"Neuro. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/S0167-8140(02)00078-6","article-title":"Radiotherapy for newly diagnosed malignant glioma in adults: A systematic review","volume":"64","author":"Laperriere","year":"2002","journal-title":"Radiother. Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1016\/j.clineuro.2012.01.026","article-title":"Glioblastoma: Clinical characteristics, prognostic factors and survival in 492 patients","volume":"114","author":"Stark","year":"2012","journal-title":"Clin. Neurol. Neurosurg."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1963","DOI":"10.1200\/JCO.2009.26.3541","article-title":"Updated response assessment criteria for high-grade gliomas: Response assessment in neuro-oncology working group","volume":"28","author":"Wen","year":"2010","journal-title":"J. Clin. Oncol."},{"key":"ref_34","first-page":"7806395","article-title":"Cerebral Phosphorus Magnetic Resonance Spectroscopy in a Patient with Giant Cell Arteritis and Endovascular Therapy","volume":"2018","author":"Steiger","year":"2018","journal-title":"Case Rep. Radiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/s10334-008-0148-9","article-title":"Combined 1H and 31P MR spectroscopic imaging: Impaired energy metabolism in severe carotid stenosis and changes upon treatment","volume":"22","author":"Hattingen","year":"2009","journal-title":"MAGMA"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1002\/nbm.1621","article-title":"Combined (1)H and (31)P spectroscopy provides new insights into the pathobiochemistry of brain damage in multiple sclerosis","volume":"24","author":"Hattingen","year":"2011","journal-title":"NMR Biomed."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3285","DOI":"10.1093\/brain\/awp293","article-title":"Phosphorus and proton magnetic resonance spectroscopy demonstrates mitochondrial dysfunction in early and advanced Parkinson\u2019s disease","volume":"132","author":"Hattingen","year":"2009","journal-title":"Brain A J. Neurol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s00062-017-0630-8","article-title":"In vivo Metabolic Profiles as Determined by (31)P and short TE (1)H MR-Spectroscopy: No Difference Between Patients with IDH Wildtype and IDH Mutant Gliomas","volume":"29","author":"Wenger","year":"2019","journal-title":"Clin. Neuroradiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1006\/jmre.1997.1244","article-title":"Improved method for accurate and efficient quantification of MRS data with use of prior knowledge","volume":"129","author":"Vanhamme","year":"1997","journal-title":"J. Magn. Reson."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1002\/nbm.891","article-title":"Issues of spectral quality in clinical 1H-magnetic resonance spectroscopy and a gallery of artifacts","volume":"17","author":"Kreis","year":"2004","journal-title":"NMR Biomed."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.molcel.2013.01.018","article-title":"Understanding metabolic regulation and its influence on cell physiology","volume":"49","author":"Metallo","year":"2013","journal-title":"Mol. Cell"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/0014-4827(82)90063-5","article-title":"Energy metabolism and ATP turnover time during the cell cycle of Ehrlich ascites tumour cells","volume":"141","author":"Skog","year":"1982","journal-title":"Exp. Cell Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4803","DOI":"10.1158\/1538-7445.AM2020-4803","article-title":"Mitochondrial response to temozolomide treatment in glioma cells","volume":"80","author":"Lenz","year":"2020","journal-title":"Cancer Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"567","DOI":"10.2174\/1570159X14666160121115641","article-title":"Mitochondrial Dysfunction in Gliomas: Pharmacotherapeutic Potential of Natural Compounds","volume":"14","author":"Guntuku","year":"2016","journal-title":"Curr. Neuropharmacol."}],"container-title":["Current Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1718-7729\/28\/6\/424\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:38:17Z","timestamp":1760168297000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1718-7729\/28\/6\/424"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,1]]},"references-count":44,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["curroncol28060424"],"URL":"https:\/\/doi.org\/10.3390\/curroncol28060424","relation":{},"ISSN":["1718-7729"],"issn-type":[{"type":"electronic","value":"1718-7729"}],"subject":[],"published":{"date-parts":[[2021,12,1]]}}}