Human primary brain tumour metabolism in vivo: a phosphorus magnetic resonance spectroscopy study

Abstract

Summary Magnetic resonance spectroscopy was used to study intracellular pH and compounds which contain phosphorus in normal human brain and primary brain tumours non-invasively. In normal subjects (n=7) intracellular pH (pHi) of the brain was 7.03+0.02 (mean±s.e.m.). The pHi did not vary between superficial (2cm, majority grey matter) and deep brain (5cm, majority white matter). The relative concentrations of phosphocreatine (PCr) and phosphomonoesters (PME) to ATP were also constant with depth. The relative concentration of phosphodiesters (PDE) increased from superficial to deep in normal brain. The astrocytomas (n = 7, grade II-IV) were significantly more alkaline (pHi = 7.08 + 0.03), and contained more PCr and PME, with respect to ATP, than normal brain at similar depth. The meningiomas (n = 4) were also more alkaline (pHi = 7.19 + 0.02) with a raised PME level but reduced PCr. The reduction in meningioma PCr may be due to the significant necrosis (>20 %) seen in the surgical biopsies. No significant necrosis was seen in the gliomas. Previous in vitro studies suggest that increased PME may be due to accumulation of phosphoethanolamine (PE), a phospholipid precursor. These results suggest that human primary brain tumours characteristically are more alkaline with increased PME than normal brain.Magnetic resonance spectroscopy (MRS) offers a noninvasive, non-disruptive method of studying intra-cellular metabolism in vivo. The development of wide bore magnets has allowed 31P MRS to be applied to the study of tumours in humans. Differences between the biochemistry of normal and neoplastic tissues have been used to design optimum forms of chemotherapy. This technique gives information on phosphocreatine (PCr), ATP, inorganic phosphate (Pi) levels and phosphomonester (PME) and phosphodiester (PDE) containing compounds within the cell, and on intracellular pH (pHi) (Radda, 1986).PCr, ATP and Pi are compounds involved in energy transfer within the cell. The intracellular levels of these compounds are determined in part by the balance between substrate supply and energy demand. PME and PDE peaks contain signal derived from compounds which are involved in phospholipid synthesis and degradation . Relative levels of PME and PDE may reflect differing rates of cell turnover. Animal and tissue culture tumour models have been studied using phosphorus MRS (Daly et al., 1987;Miceli et al., 1988). These studies have shown a consistently raised PME peak within the neoplastic cell. The PME peak was mainly composed of phosphoethanolamine (PE), a precursor in phospholipid synthesis. Human studies of neuroblastoma and other tumours in vivo have also found a raised PME peak (Maris et al., 1985) and alkaline pHi relative to normal tissue in some brain tumours (Oberhaensli et al., 1986).The aim of this study was to investigate the phosphorus metabolism of normal brain and primary brain tumours and relate biochemical differences to histological features seen in the tumour biopsies taken within 24h of the MRS study. The phase modulated r...

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