Untreated Glioblastoma Multiforme: Increased<i>Myo</i>-inositol and Glutamine Levels in the Contralateral Cerebral Hemisphere at Proton MR Spectroscopy

Kallenberg, Kai; Bock, Hans; Helms, Gunther; Jung, Klaus; Wrede, Arne; Buhk, Jan‐Hendrik; Giese, Alf; Frahm, Jens; Strik, Herwig; Dechent, Peter; Knauth, Michael

doi:10.1148/radiol.2533071654

Cited by 75 publications

(65 citation statements)

References 34 publications

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“…The results in this study may, to some extent, also be attributed to diaschisis, which refers to metabolic and functional changes remote from the origin but communicating with the damaged focus via anatomical structures [36]. However, previous MRS findings in normal appearing white matter in tumor patients indicate the presence of proliferative processes [18].…”

Section: Discussionmentioning

confidence: 77%

“…Several studies have reported the infiltrative growth of glioblastoma multiforme (GBM) cells in apparently unaffected brain regions remote from the confirmed primary lesion [5,17,24,32] without correlating changes on computed tomographic or MR images [20,38]. Diffusion tensor imaging (DTI) [2,14,34] and localized proton MRS provided subtle hints towards remote infiltration of GBM cells [4,14,18]. This work investigated the use of DTI and corresponding metrics as putative indicators of the invasiveness of malignant brain tumors.…”

Section: Communicating Authormentioning

confidence: 99%

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Original article Abnormalities in the normal appearing white matter of the cerebral hemisphere contralateral to a malignant brain tumor detected by diffusion tensor imaging

Kallenberg¹,

Goldmann²,

Menke³

et al. 2014

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Section: Discussionmentioning

confidence: 77%

Section: Communicating Authormentioning

confidence: 99%

Original article Abnormalities in the normal appearing white matter of the cerebral hemisphere contralateral to a malignant brain tumor detected by diffusion tensor imaging

Kallenberg¹,

Goldmann²,

Menke³

et al. 2014

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“…We found that the CSF myo-inositol levels decrease, whereas cholesteryl sulfate level increases linearly respect to tumor size as measured by Tgad and FLAIR according to the Macdonald's criteria. Myo-inositol is a cerebral osmolyte found to be significantly lowered in glioblastomas and anaplastic astrocytomas than in low-grade gliomas and normal brain tissue as detected by magnetic resonance spectroscopy (MRS) (46,47). Consistent with the previous MRS findings that decreasing myo-inositol level was associated with increasing aggressiveness of the glioma phenotype, our data also showed that the tumor size in our cohort negatively correlated with myo-inositol levels in the CSF.…”

Section: Discussionmentioning

confidence: 99%

Metabolomics of Human Cerebrospinal Fluid Identifies Signatures of Malignant Glioma

Locasale

Melman

Song

et al. 2012

Molecular & Cellular Proteomics

100

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Cerebrospinal fluid is routinely collected for the diagnosis and monitoring of patients with neurological malignancies. However, little is known as to how its constituents may change in a patient when presented with a malignant glioma. Here, we used a targeted mass-spectrometry based metabolomics platform using selected reaction monitoring with positive/negative switching and profiled the relative levels of over 124 polar metabolites present in patient cerebrospinal fluid. We analyzed the metabolic profiles from 10 patients presenting malignant gliomas and seven control patients that did not present malignancy to test whether a small sample size could provide statistically significant signatures. We carried out multiple unbiased forms of classification using a series of unsupervised techniques and identified metabolic signatures that distinguish malignant glioma patients from the control patients. One subtype identified contained metabolites enriched in citric acid cycle components. Newly diagnosed patients segregated into a different subtype and exhibited low levels of metabolites involved in tryptophan metabolism, which may indicate the absence of an inflammatory signature. Together our results provide the first global assessment of the polar metabolic composition in cerebrospinal fluid that accompanies malignancy, and demonstrate that data obtained from high throughput mass spectrometry technology may have suitable predictive capabilities for the

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“…More recent studies have shown that the spectroscopic abnormality is 20% larger than the volume of increased T 2 signal and biopsies of this region show evidence of tumour invasion [67]. Other studies have detected increases in myoinositol (a spectroscopic marker of glia) and glutamate (implicated with anabolic pathways upregulated in tumours) in the contralateral hemisphere of glioblastomas [68]. This change was not seen in either low-grade gliomas or normal controls.…”

Section: Tumour Metabolismmentioning

confidence: 98%

Imaging biomarkers of brain tumour margin and tumour invasion

Price

Gillard²

2011

BJR

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ABSTRACT. Invasion of tumour cells into the normal brain is one of the major reasons of treatment failure for gliomas. Although there is a good understanding of the molecular and cellular processes that occur during this invasion, it is not possible to detect the extent of the tumour with conventional imaging. However, there is an understanding that the degree of invasion differs with individual tumours, and yet they are all treated the same. Newer imaging techniques that probe the pathological changes within tumours may be suitable biomarkers for invasion. Imaging methods are now available that can detect subtle changes in white matter organisation (diffusion tensor imaging), tumour metabolism and cellular proliferation (using MR spectroscopy and positron emission tomography) occurring in regions of tumour that cannot be detected by conventional imaging. The role of such biomarkers of invasion should allow better delineation of tumour margins, which should improve treatment planning (especially surgery and radiotherapy) and provide information on the invasiveness of an individual tumour to help select the most appropriate therapy and help stratify patients for clinical trials.

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Untreated Glioblastoma Multiforme: IncreasedMyo-inositol and Glutamine Levels in the Contralateral Cerebral Hemisphere at Proton MR Spectroscopy

Abstract: Increased concentrations of myo-inositol and glutamine in the contralateral normal-appearing white matter of GBM patients are consistent with mild astrocytosis and suggest the detectability of early neoplastic infiltration by using proton MR spectroscopy in vivo.

Cited by 75 publications

References 34 publications

Original article Abnormalities in the normal appearing white matter of the cerebral hemisphere contralateral to a malignant brain tumor detected by diffusion tensor imaging

Original article Abnormalities in the normal appearing white matter of the cerebral hemisphere contralateral to a malignant brain tumor detected by diffusion tensor imaging

Metabolomics of Human Cerebrospinal Fluid Identifies Signatures of Malignant Glioma

Imaging biomarkers of brain tumour margin and tumour invasion

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