scholarly journals Prospective Longitudinal Analysis of 2-Hydroxyglutarate Magnetic Resonance Spectroscopy Identifies Broad Clinical Utility for the Management of Patients With IDH-Mutant Glioma

2016 ◽  
Vol 34 (33) ◽  
pp. 4030-4039 ◽  
Author(s):  
Changho Choi ◽  
Jack M. Raisanen ◽  
Sandeep K. Ganji ◽  
Song Zhang ◽  
Sarah S. McNeil ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Time Course ◽  
Imaging Biomarker ◽  
Resonance Spectroscopy ◽  
Lower Grade ◽  
Clinical Magnetic Resonance Imaging ◽  
Treatment Type ◽  
Longitudinal Imaging ◽  
Prospective Longitudinal

Purpose Proton magnetic resonance spectroscopy (MRS) of the brain can detect 2-hydroxyglutarate (2HG), the oncometabolite produced in neoplasms harboring a mutation in the gene coding for isocitrate dehydrogenase ( IDH). We conducted a prospective longitudinal imaging study to determine whether quantitative assessment of 2HG by MRS could serve as a noninvasive clinical imaging biomarker for IDH-mutated gliomas. Patients and Methods 2HG MRS was performed in 136 patients using point-resolved spectroscopy at 3 T in parallel with standard clinical magnetic resonance imaging and assessment. Data were analyzed in patient cohorts representing the major phases of the glioma clinical course and were further subgrouped by histology and treatment type to evaluate 2HG. Histologic correlations were performed. Results Quantitative 2HG MRS was technically and biologically reproducible. 2HG concentration > 1 mM could be reliably detected with high confidence. During the period of indolent disease, 2HG concentration varied by less than ± 1 mM, and it increased sharply with tumor progression. 2HG concentration was positively correlated with tumor cellularity and significantly differed between high- and lower-grade gliomas. In response to cytotoxic therapy, 2HG concentration decreased rapidly in 1p/19q codeleted oligodendrogliomas and with a slower time course in astrocytomas and mixed gliomas. The magnitude and time course of the decrease in 2HG concentration and magnitude of the decrease in tumor volume did not differ between oligodendrogliomas treated with temozolomide or carmustine. Criteria for 2HG MRS were established to make a presumptive molecular diagnosis of an IDH mutation in gliomas technically unable to undergo a surgical procedure. Conclusion 2HG concentration as measured by MRS was reproducible and reliably reflected the disease state. These data provide a basis for incorporating 2HG MRS into clinical management of IDH-mutated gliomas.

scholarly journals Detection of 2-Hydroxyglutarate by 3.0-Tesla Magnetic Resonance Spectroscopy in Gliomas with Rare IDH Mutations: Making Sense of “False-Positive” Cases

Diagnostics ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 2129
Author(s):  
Manabu Natsumeda ◽  
Hironaka Igarashi ◽  
Ramil Gabdulkhaev ◽  
Haruhiko Takahashi ◽  
Kunio Motohashi ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Dna Analysis ◽  
Resonance Spectroscopy ◽  
Lower Grade ◽  
Short Article ◽  
High Accumulation ◽  
Idh1 R132h ◽  
Idh Mutations ◽  
Idh1 And Idh2 Mutations

We have previously published a study on the reliable detection of 2-hydroxyglutarate (2HG) in lower-grade gliomas by magnetic resonance spectroscopy (MRS). In this short article, we re-evaluated five glioma cases originally assessed as isocitrate dehydrogenase (IDH) wildtype, which showed a high accumulation of 2HG, and were thought to be false-positives. A new primer was used for the detection of IDH2 mutation by Sanger sequencing. Adequate tissue for DNA analysis was available in 4 out of 5 cases. We found rare IDH2 mutations in two cases, with IDH2 R172W mutation in one case and IDH2 R172K mutation in another case. Both cases had very small mutant peaks, suggesting that the tumor volume was low in the tumor samples. Thus, the specificity of MRS for detecting IDH1/2 mutations was higher (81.3%) than that originally reported (72.2%). The detection of 2HG by MRS can aid in the diagnosis of rare, non-IDH1-R132H IDH1 and IDH2 mutations in gliomas.

scholarly journals Investigating the Metabolic Changes due to Visual Stimulation using Functional Proton Magnetic Resonance Spectroscopy at 7 T

2012 ◽  
Vol 32 (8) ◽  
pp. 1484-1495 ◽  
Author(s):  
Yan Lin ◽  
Mary C Stephenson ◽  
Lijing Xin ◽  
Antonio Napolitano ◽  
Peter G Morris
Keyword(s):  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Proton Magnetic Resonance ◽  
Proton Magnetic Resonance Spectroscopy ◽  
Time Course ◽  
Visual Stimulation ◽  
Metabolic Changes ◽  
Resonance Spectroscopy ◽  
Functional Changes ◽  
Increased Activity

Proton magnetic resonance spectroscopy (1H-MRS) has been used to demonstrate metabolic changes in the visual cortex on visual stimulation. Small (2% to 11%) but significant stimulation induced increases in lactate, glutamate, and glutathione were observed along with decreases in aspartate, glutamine, and glycine, using 1H-MRS at 7 T during single and repeated visual stimulation. In addition, decreases in glucose and increases in γ-aminobutyric acid (GABA) were seen but did not reach significance. Changes in glutamate and aspartate are indicative of increased activity of the malate–aspartate shuttle, which taken together with the opposite changes in glucose and lactate, reflect the expected increase in brain energy metabolism. These results are in agreement with those of Mangia et al. In addition, increases in glutamate and GABA coupled with the decrease in glutamine can be interpreted in terms of increased activity of the neurotransmitter cycles. An entirely new observation is the increase of glutathione during prolonged visual stimuli. The similarity of its time course to that of glutamate suggests that it may be a response to the increased release of glutamate or to the increased production of reactive oxygen species. Together, these observations constitute the most detailed analysis to date of functional changes in human brain metabolites.

scholarly journals Magnetic Resonance Spectroscopy: An In Vivo Molecular Imaging Biomarker for Parkinson’s Disease?

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Rosella Ciurleo ◽  
Giuseppe Di Lorenzo ◽  
Placido Bramanti ◽  
Silvia Marino
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Molecular Imaging ◽  
Magnetic Resonance ◽  
Early Diagnosis ◽  
Magnetic Resonance Spectroscopy ◽  
Dopaminergic Neurons ◽  
Imaging Biomarker ◽  
Resonance Spectroscopy

Parkinson’s disease (PD) is a neurodegenerative disorder caused by selective loss of dopaminergic neurons in the substantia nigra pars compacta which leads to dysfunction of cerebral pathways critical for the control of movements. The diagnosis of PD is based on motor symptoms, such as bradykinesia, akinesia, muscular rigidity, postural instability, and resting tremor, which are evident only after the degeneration of a significant number of dopaminergic neurons. Currently, a marker for early diagnosis of PD is still not available. Consequently, also the development of disease-modifying therapies is a challenge. Magnetic resonance spectroscopy is a quantitative imaging technique that allows in vivo measurement of certain neurometabolites and may produce biomarkers that reflect metabolic dysfunctions and irreversible neuronal damage. This review summarizes the abnormalities of cerebral metabolites found in MRS studies performed in patients with PD and other forms of parkinsonism. In addition, we discuss the potential role of MRS as in vivo molecular imaging biomarker for early diagnosis of PD and for monitoring the efficacy of therapeutic interventions.

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