Clinical Investigative Study Role of Proton Magnetic Resonance Spectroscopy in Differentiating Oligodendrogliomas from Astrocytomas Sanjeev Chawla, PhD, Laura Oleaga, MD, Sumei Wang, MD, Jaroslaw Krejza, MD, PhD, Ronald L. Wolf, MD, PhD, John H. Woo, MD, Donald M. O’Rourke, MD, Kevin D. Judy, MD, Michael S. Grady, MD, Elias R. Melhem, MD, PhD, Harish Poptani, PhD From the Departments of Radiology (SC, SW, JK, RLW, JHW, ERM, HP) and Neurosurgery (DMO, KDJ, MSG), University of Pennsylvania, Philadelphia, Pennsylvania; Department of Radiology, Hospital Cl´ ınico, Barcelona, Spain (LO); Department of Nuclear Medicine, Medical University of Gdansk, Gdansk, Poland. [Correction added after online publication 15-December-2009: Received date has been corrected.] Keywords: Gliomas, astrocytomas, oligodendrogliomas, proton magnetic resonance spectroscopy, myo-inositol. Acceptance: Received March 31, 2008, and in revised form July 7, 2008. Ac- cepted for publication August 19, 2008. Correspondence: Address correspon- dence to Harish Poptani, PhD, University of Pennsylvania, B6 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104, E-mail: poptanih@uphs.upenn.edu. J Neuroimaging 2010;20:3-8. DOI: 10.1111/j.1552-6569.2008.00307.x ABSTRACT BACKGROUND AND PURPOSE Preoperative differentiation of astrocytomas from oligodendrogliomas is clinically im- portant, as oligodendrogliomas are more sensitive to chemotherapy. The purpose of this study was to assess the role of proton magnetic resonance spectroscopy in distinguishing astrocytomas from oligodendrogliomas. METHODS Forty-six patients [astrocytomas (n = 17) and oligodendrogliomas (n = 29)] underwent magnetic resonance imaging and multi voxel proton magnetic resonance spectroscopic imaging before treatment. Peak areas for N-acetylaspartate (NAA), creatine (Cr), choline (Cho), myo-inositol (mI), glutamate/glutamine (Glx), and lipids + lactate (Lip+Lac) were analyzed from voxels that exhibited hyperintensity on fluid-attenuated inversion recovery images and were normalized to Cr from each voxel. The average metabolite/Cr ratios from these voxels were then compared between astrocytomas and oligodendrogliomas. Receiver-operating curve analyses were used as measures of differentiation accuracy of metabolite ratios. A threshold value for a metabolite ratio was estimated by maximizing the sum of sensitivity and specificity. RESULTS A significant difference in mI/Cr was observed between astrocytomas and oligoden- drogliomas (.50 ± .18 vs. 0.66 ± 0.20, P < .05). Using a threshold value of .56 for mI/Cr ratio, it was possible to differentiate oligodendrogliomas from astrocytomas with a sensitivity of 72.4% and specificity of 76.4%. CONCLUSION These results suggest that mI/Cr might aid in distinguishing oligodendrogliomas from astrocytomas. Introduction Gliomas comprise of a heterogeneous group of neoplasms, and the two most common histologic subtypes are astrocytomas and oligodendrogliomas. 1 Identification of histologic subtypes of gliomas is important for the determination of therapeutic re- sponse and prognosis. Since both pure oligodendrogliomas and mixed oligoastrocytomas are uniquely sensitive to chemother- apy, in contrast to astrocytomas that are substantially more resis- tant to chemotherapeutic agents, 2 it is important to distinguish these histological subtypes of primary intracranial neoplasms. While histopathologic evaluation remains the gold standard for predicting accurate subtype of gliomas, outcome is lim- ited by subjective criteria and tissue sampling error. 3 Based on clinical presentation and magnetic resonance (MR) imag- ing characteristics, it has been reported that oligodendroglial neoplasms may not be easily distinguished from other primary brain neoplasms, especially astrocytomas. 4 Anecdotal proton magnetic resonance spectroscopic ( 1 H MRS) studies have dealt with preoperative differential diagnosis of oligodendrogliomas from astrocytomas. 5-7 These studies have reported significantly higher glutamate/glutamine (Glx) in oligodendrogliomas com- pared to astrocytomas. However, lower signal intensities of Glx multiplet in the 2.1-2.5 ppm region along with overlapping res- onances from N- acetyl aspartate (NAA), gamma aminobutyric acid (GABA), and mobile lipids (Lip) complicates the specific identification of signal contributions from Glx on in vivo 1 H MRS, unless some type of editing or homonuclear decoupling scheme is used. 8,9 With this limitation in mind, the present study was performed to ascertain more reliable and easily quan- tifiable metabolites, such as NAA, creatine (Cr), choline (Cho), Copyright ◦ C 2008 by the American Society of Neuroimaging 3