Magnetic resonance spectroscopy metabolite profiles predict survival in paediatric brain tumours

Abstract

BackgroundBrain tumours cause the highest mortality and morbidity rate of all childhood tumour groups and new methods are required to improve clinical management. 1H magnetic resonance spectroscopy (MRS) allows non-invasive concentration measurements of small molecules present in tumour tissue, providing clinically useful imaging biomarkers. The primary aim of this study was to investigate whether MRS detectable molecules can predict the survival of paediatric brain tumour patients.Patients and methodsShort echo time (30 ms) single voxel 1H MRS was performed on children attending Birmingham Children’s Hospital with a suspected brain tumour and 115 patients were included in the survival analysis. Patients were followed-up for a median period of 35 months and Cox-Regression was used to establish the prognostic value of individual MRS detectable molecules. A multivariate model of survival was also investigated to improve prognostic power.ResultsLipids and scyllo-inositol predicted poor survival whilst glutamine and N-acetyl aspartate predicted improved survival (p < 0.05). A multivariate model of survival based on three MRS biomarkers predicted survival with a similar accuracy to histologic grading (p < 5e–5). A negative correlation between lipids and glutamine was found, suggesting a functional link between these molecules.ConclusionsMRS detectable biomolecules have been identified that predict survival of paediatric brain tumour patients across a range of tumour types. The evaluation of these biomarkers in large prospective studies of specific tumour types should be undertaken. The correlation between lipids and glutamine provides new insight into paediatric brain tumour metabolism that may present novel targets for therapy.

Clinical Proton MR Spectroscopy in Central Nervous System Disorders

“…A tCho/tNAA peak amplitude ratio of at least 2.1 (either at single-voxel spectroscopy with a TE of 144 or 270 msec or at MR spectroscopic imaging with a TE of 280 msec) was found prognostic of unfavorable outcome in pediatric diffuse pontine gliomas (61). Prognostic MR spectroscopy markers are important for treatment stratification and can help identify patients who need more intensive treatment from the outset for some tumor types (47,62,63). These include the detection of 2-hydroxyglutarate in isocitrate dehydrogenase-1 mutated gliomas (47), citrate in proliferating pediatric astrocytomas (62), and highly MR spectroscopy-visible saturated lipids with elevated scylloinositol and low glutamine in high-risk pediatric brain tumors (64).…”

Immunohistochemical staining of lipid droplets with adipophilin in paraffin-embedded glioma tissue identifies an association between lipid droplets and tumour grade

“…As lipids are a marker of poor prognosis in gliomas [10][11][12] the ability to detect them in diagnostic biopsies is likely to be of clinical relevance. Interestingly, there were fewer adipophilin positive tumour cells in all three cases of giant cell glioblastoma when compared to grade four glioblastoma.…”

“…Lipid accumulation has been detected in high grade gliomas using ex-vivo nuclear magnetic resonance (NMR) techniques and evidence from electron microscopy and fluorescent labelling with Nile Red has determined that cytoplasmic lipid droplets are the major contributor to this lipid [8,9]. In addition in-vivo magnetic resonance spectroscopy studies of both paediatric and adult brain tumours have reported increased lipids at diagnosis as a marker of poor prognostic outcome [10][11][12].…”

“…As intracellular lipids are a marker of both prognosis and treatment response in brain tumours [10,12,17], the ability to routinely detect lipid droplets in FFPE biopsies taken from tumours at diagnosis may allow their detection to be more readily translated into clinical practice. As such, we have investigated adipophilin expression using immunohistochemistry in a series of tissue microarrays (TMAs) containing glioma tissue of varying grade and tumour type.…”

Metabolite Levels in Paediatric Brain Tumours Correlate with Histological Features

“…A growing number of studies are investigating the value of MRS for both diagnostic classification and post-treatment monitoring in brain tumours [4,[13][14][15][16]. However, whilst some studies have correlated clinical information such as tumour grade with MRS features, there are relatively few studies that have directly examined the relationship between in vivo metabolite markers and traditional histopathological measures [17][18][19][20][21].…”