title: MR spectroscopy using normalized and non-normalized metabolite ratios for differentiating recurrent brain tumor from radiation injury.
abstract: OBJECTIVE
  To compare the ability of normalized versus non-normalized metabolite ratios to differentiate recurrent brain tumor from radiation injury using magnetic resonance spectroscopy (MRS) in previously treated patients.
  
  
  METHODS
  Twenty-five patients with previous diagnosis of primary intracranial neoplasm confirmed with biopsy/resection, previously treated with radiation therapy (range, 54-70 Gy) with or without chemotherapy and new contrast enhancing lesion on a 1.5 T magnetic resonance imaging at the site of the primary neoplasm participated in this retrospective study. After MRS, clinical, radiological, and histopathology data were used to classify new contrast-enhancing lesions as either recurrent neoplasm or radiation injury. Volume of interest included both the lesion and normal-appearing brain on the contralateral side. Non-normalized metabolic ratios were calculated from choline (Cho), creatine (Cr), and N-acetylaspartate (NAA) spectroscopic values obtained within the contrast-enhancing lesion: Cho/Cr, NAA/Cr, and Cho/NAA. Normalized ratios were calculated using the metabolic values from the contralateral normal side: Cho/normal creatinine (nCr), Cho/normal N-acetylaspartate (nNAA), Cho/normal choline, NAA/nNAA, NAA/nCr, and Cr/nCr. Results were correlated with the final diagnosis by Wilcoxon rank-sum analysis.
  
  
  RESULTS
  Two of three non-normalized ratios, Cho/NAA (sensitivity 86%, specificity 90%) and NAA/Cr (sensitivity 93%, specificity 70%) significantly associated with tumor recurrence even after correcting for multiple comparisons. Of the six normalized ratios, only Cho/nNAA significantly correlated with tumor recurrence (sensitivity 73%, specificity 40%), but did not remain significant after correcting for multiple comparisons.
  
  
  CONCLUSIONS
  Cho/NAA and NAA/Cr were the two ratios with the best discriminating ability and both had better discriminating ability than their corresponding normalized ratios (Area under the curve = 0.92 versus 0.77, AUC= 0.85 vs. 0.66), respectively.
authors.affiliation: Department of Radiology, University of Michigan Health Systems, Ann Arbor, 48109, USA. aelias@med.umich.edu
authors.forename: Augusto E
authors.initials: AE
authors.lastname: Elias
authors.forename: Ruth C
authors.initials: RC
authors.lastname: Carlos
authors.forename: Ethan A
authors.initials: EA
authors.lastname: Smith
authors.forename: Dan
authors.initials: D
authors.lastname: Frechtling
authors.forename: Bekris
authors.initials: B
authors.lastname: George
authors.forename: Pavel
authors.initials: P
authors.lastname: Maly
authors.forename: Pia C
authors.initials: PC
authors.lastname: Sundgren
mesh_terms: D000293:Adolescent; D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism* / Q000532:radiotherapy*; D002648:Child; D002675:Child, Preschool; D002794:Choline / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000378:metabolism*; D012372:ROC Curve; D011832:Radiation Injuries / Q000175:diagnosis* / Q000378:metabolism*; D012189:Retrospective Studies; D018709:Statistics, Nonparametric
chemical_list: D001224:Aspartic Acid; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline