Noninvasive Magnetic Resonance Spectroscopic Imaging Biomarkers to Predict the Clinical Grade of Pediatric Brain Tumors

Abstract

The diagnosis and therapy of childhood brain tumors, most of which are low grade, can be complicated because of their frequent adjacent location to crucial structures, which limits diagnostic biopsy. Also, although new prognostic biomarkers identified by molecular analysis or DNA microarray gene profiling are promising, they too depend on invasive biopsy. Here, we test the hypothesis that combining information from biologically important intracellular molecules (biomarkers), noninvasively obtained by proton magnetic resonance spectroscopic imaging, will increase the diagnostic accuracy in determining the clinical grade of pediatric brain tumors. We evaluate the proton magnetic resonance spectroscopic imaging exams for 66 children with brain tumors. The intracellular biomarkers for choline-containing compounds (Cho), N-acetylaspartate, total creatine, and lipids and/or lactate were measured at the highest Cho region and normalized to the surrounding healthy tissue total creatine. Neuropathological grading was done with WHO criteria. Normalized Cho and lipids and/or lactate were elevated in high-grade (n ‫؍‬ 23) versus low-grade (n ‫؍‬ 43) tumors, which multiple logistic regression confirmed are independent predictors of tumor grade (for Cho, odds ratio 24.8, P < 0.001; and for lipids and/or lactate, odds ratio 4.4, P < 0.001). A linear combination of normalized Cho and lipids and/or lactate that maximizes diagnostic accuracy was calculated by maximizing the area under the receiver operating characteristic curve. Proton magnetic resonance spectroscopic imaging, although not a proxy for histology, provides noninvasive, in vivo biomarkers for predicting clinical grades of pediatric brain tumors.

Comparative metabolic profiling of paediatric ependymoma, medulloblastoma and pilocytic astrocytoma

“…This possibly hampers the detection of statistical correlations in these metabolites. Our findings support the previous ex vivo and in vivo results reported at short echo times regarding levels of taurine as the most discriminant metabolite of medulloblastoma (11,32). Overall, the HR-MAS profile of paediatric medulloblastomas provides important metabolic information including an increased membrane turnover, low neuronal viability and glycolysis alterations.…”

“…Many medulloblastomas appear on MRI images as solid, contrast-enhancing masses dropping from the vermis into the ventricular cavity of the fourth ventricle (2). Their metabolic profiles have been characterized mostly by in vivo spectroscopy in 1.5 T clinical scanners (6)(7)(8)(9)(10)(11). The predominant and most characteristic metabolic feature of medulloblastoma with respect to other types of tumours is higher levels of taurine.…”

“…Cellular and anaplastic ependymoma are WHO grades II and III, respectively (12). Despite in vivo MRS spectra from both cellular and anaplastic ependymomas exhibiting considerable heterogeneity, their metabolic common profile include lower relative levels of N-acetyl-aspartate (NAA) in comparison to other tumours (6)(7)(8)(9)(10)(11). Prognosis, treatment strategy and survival rates in cases of medulloblastoma and ependymoma depend on many factors.…”

“…Low levels of creatine, myo-inositol and taurine are the most relevant features of the in vivo MRS metabolic profile of pylocytic astrocytoma (6)(7)(8)(9)(10)(11)14). Overall, in vivo MRS biomarkers may help in the non-invasive diagnosis of paediatric brain tumours (6)(7)(8)(9)(10)(11)15). However, in vivo MRS of paediatric brain tumours still exhibits some limitations.…”

Clinical decision support systems for brain tumor characterization using advanced magnetic resonance imaging techniques

“…If coupled with the morphological features provided by MRI techniques, it can provide accurate identification and quantification of biologically important chemical compounds in soft tissue, thus increasing the understanding of the underlying pathologies. There have been numerous studies that indicate the significant contribution of 1 H-MRS for the characterization of brain tumors [6][7][8] , and fewer studies have concentrated on pediatric tumors [9,10] .…”