Characterization of metabolites in infiltrating gliomas using ex vivo ¹ H high‐resolution magic angle spinning spectroscopy

Abstract

Gliomas are routinely graded according to histopathologic criteria established by the World Health Organization (WHO). Although this classification can be used to understand some of the variance in the clinical outcome of patients, there is still substantial heterogeneity within and between lesions of the same grade. This study evaluated image-guided tissue samples acquired from a large cohort of patients presenting with either new or recurrent gliomas of grades II-IV using ex vivo proton high-resolution magic-angle spinning (1H HR-MAS) spectroscopy. Quantification of metabolite levels revealed several discrete profiles associated with primary glioma subtypes, as well as secondary subtypes that had undergone transformation to a higher grade at the time of recurrence. Statistical modeling further demonstrated that these metabolomic profiles could be differentially classified with respect to pathologic grading and inter-grade conversions. Importantly, the myo-inositol-to-total-choline index (MCI) allowed for a separation of recurrent low-grade gliomas on different pathologic trajectories; the heightened ratio of PC/GPC uniformly characterized several forms of glioblastoma multiforme (GBM); and onco-metabolite D-2-hydroxyglutarate (2HG) was shown to help distinguish secondary from primary grade IV glioma, as well as grade II and III from grade IV glioma. These data provide evidence that metabolite levels are of interest for assessing both intra-grade and intra-lesional malignancy. Such information could be used to enhance the diagnostic specificity of in vivo spectroscopy and to aid in selecting the most appropriate therapy for individual patients.

Targeting Phospholipid Metabolism in Cancer

“…An increased total choline (tCho) signal, which consists of signals from phosphocholine (PC), glycerophosphocholine (GPC), and free choline (Cho), and whose chemical structures are shown in Figure 1, has been detected by 1 H MRS in all cancers tested so far (7). High-resolution 1 H MRS, which can resolve the signals from the individual components of the tCho signal, confirmed the increase of PC in breast (8–12), prostate (13, 14), ovarian (15), endometrial (16), cervical (15), and brain cancers (17–19). In some cancer cell types such as isolated breast and ovarian cancer cells, a relative decrease of GPC was observed as well, which led to the suggestion to use a higher ratio of PC/GPC as a marker of tumor progression (20, 21).…”

MR Molecular Imaging of Brain Cancer Metabolism Using Hyperpolarized 13C Magnetic Resonance Spectroscopy

“…However, although they provide crucial information on the structure and perfusion of the tumor as well as the integrity of the blood-brain barrier (BBB), these methods do not provide metabolic information on the lesions. 1 H magnetic resonance spectroscopy (MRS) in vivo or in biopsy samples allows probing steady-state metabolite levels, and several studies have demonstrated the potential of 1 H MRS to differentiate tumors from normal brain and non-neoplastic lesions 13,15–19 . Tumors are usually associated with high levels of choline-containing metabolites (comprised of choline, phosphocholine (PC) and glycerophosphocholine (GPC)) and low levels of N-acetyl-aspartate as well as an increase in lactate level in high-grade tumors 13,17 .…”

Nuclear Magnetic Resonance metabolomics reveals an excretory metabolic signature of renal cell carcinoma

“…In this context, metabolomics has been increasingly pursued in relation to cancer, either entailing the analysis of tumor tissue (e.g. melanoma5, breast67, ovarian8, colorectal9, brain101112) or of biofluids. The use of biofluid metabolomics in cancer research has consistently increased13, minimally invasive samples (plasma/serum and urine) having been used to study ovarian1415, colorectal16, kidney171819, breast1520, lung2122 and liver232425 cancers, either using Nuclear Magnetic Resonance (NMR) spectroscopy or Mass Spectrometry (MS).…”