Magnetic resonance spectroscopic imaging in gliomas: clinical diagnosis and radiotherapy planning

Abstract

The reprogramming of cellular metabolism is a hallmark of cancer diagnosis and prognosis. Proton magnetic resonance spectroscopic imaging (MRSI) is a non-invasive diagnostic technique for investigating brain metabolism to establish cancer diagnosis and IDH gene mutation diagnosis as well as facilitate pre-operative planning and treatment response monitoring. By allowing tissue metabolism to be quantified, MRSI provides added value to conventional MRI. MRSI can generate metabolite maps from a single volume or multiple volume elements within the whole brain. Metabolites such as NAA, Cho and Cr, as well as their ratios Cho:NAA ratio and Cho:Cr ratio, have been used to provide tumor diagnosis and aid in radiation therapy planning as well as treatment assessment. In addition to these common metabolites, 2-hydroxygluterate (2HG) has also been quantified using MRSI following the recent discovery of IDH mutations in gliomas. This has opened up targeted drug development to inhibit the mutant IDH pathway. This review provides guidance on MRSI in brain gliomas, including its acquisition, analysis methods, and evolving clinical applications.

Diagnostic Accuracy of Magnetic Resonance Spectroscopy in Predicting the Grade of Glioma Keeping Histopathology as the Gold Standard

“…Non-invasive detection of changed isocitrate dehydrogenase gene status in gliomas, as well as cancer diagnosis and treatment response monitoring for therapeutic purposes, have been extensively researched. Radiation therapy planning can benefit from MRSI, but further research is needed to determine whether it has any real impact on clinical practice [23].…”

D-2-Hydroxyglutarate in Glioma Biology

“…Several recent studies discovered that non-invasive diagnostic approaches, such as magnetic resonance (MR)-based imaging (MRI) [ 43 ] and spectroscopy (MRS) [ 44 ] could be used to predict IDH mutations by measuring D-2-HG in gliomas with mM level sensitivity. Magnetic resonance spectroscopic imaging (MRSI) integrates the information of MRS and MRI, which can detect and quantify various metabolites, and generate the metabolite map from multiple lesions within the brain [ 45 ], which adds value to conventional MRI in pre-operation planning and post-treatment monitoring. MRS-based methods provide 88.6% accuracy in identifying the IDH mutational status, with 89.5% sensitivity and 81.3% specificity, suggesting that MR-based techniques are safe and promising approaches to support glioma diagnosis [ 46 ].…”

“…TET-mediated demethylation plays a critical role in regulation of gene expression [ 55 ], DNA base excision repair [ 56 ], and chromosome replication [ 57 ]. Experimental evidence shows that expression of IDH1mut R132H or IDH2mut R172K inhibits TET1/2 activity and decreases the level of 5-hmC [ 45 ]. Deficiency of TET2 catalytic function could lead to oncogenesis, through global hypermethylation and further enhanced cellular proliferation [ 58 ].…”

Establishing Imaging Biomarkers of Host Immune System Efficacy during Glioblastoma Therapy Response: Challenges, Obstacles and Future Perspectives

“…The acquisition of MRSI is indeed approached in some clinical centers, but most of them are academic hospitals involved in research with protocols that are not fully integrated into standard clinical practice pipelines and, in general, use quantification (or the generation of a metabolic image) of few metabolites or ratios, such as NAA, Cr, Cho, glx, m-Ino/gly, GABA, or 2HG [ 122 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 , 134 , 135 ]. Recent reviews suggest that 3D-1H MRSI sequences are useful in evaluating therapy response, since they are able to map metabolomic information from peritumoral regions [ 20 ], but these types of sequences are challenging and are not widely available in regular clinical centers.…”