title: Proton magnetic resonance spectroscopy in immunocompetent patients with primary central nervous system lymphoma.
abstract: BACKGROUND
  Magnetic resonance spectroscopy imaging (MRSI) non-invasively evaluates the metabolic profile of normal and abnormal brain tissue. Primary central nervous system lymphoma (PCNSL) is a highly aggressive tumor responsive to high-dose methotrexate based regimens. Patients often have complete responses but relapses are common. We characterized the MR spectra of PCNSL patients, correlated MRSI with MRI and evaluated whether early recurrence could be detected by MRSI.
  
  
  METHODS
  Patients with PCNSL had multi-voxel MRSI before, during, and after treatment. The region of interest was defined using axial FLAIR images. Metabolites assessed were N-acetyl-aspartate (NAA), choline (Cho), creatine (Cr), lipid, and lactate. Ratios of Cho/Cr, NAA/Cho, and NAA/Cr were calculated and correlated with MRI. Overall survival (OS), progression free survival (PFS), and relative risks of each of the ratios were determined.
  
  
  RESULTS
  MRSI was performed on 11 men and seven women; median age of 59. Sixty-seven MRSI studies were performed, 17 baseline and 48 follow-up studies. Median ratios in 16 pretreated patients were Cho/Cr-1.90, NAA/Cho-0.39, and NAA/Cr-1.27. Two patients had lipid at baseline, five had lactate and two had both. MRSI correlated with tumor response or progression on MRI; in three patients MRSI suggested disease progression prior to changes on MRI. Univariate analysis of metabolite ratios, lipid, and lactate revealed that none significantly affected PFS or OS. Kaplan-Meier analysis of the presence or absence of lipid, lactate or both revealed a trend for increased PFS.
  
  
  CONCLUSIONS
  MRSI and MRI correlate with tumor response or progression and may allow early detection of disease recurrence. The presence or absence of lipid and/or lactate may have prognostic significance. Further research using MRSI needs to be done to validate our findings and determine the role of MRSI in PCNSL.
authors.affiliation: Department of Neurology, Feinberg School of Medicine, Northwestern University, Abbott Hall, Room 1123, 710 North Lake Shore Drive, Chicago, IL 60611, USA. jraizer@nmff.org
authors.forename: J J
authors.initials: JJ
authors.lastname: Raizer
authors.forename: J A
authors.initials: JA
authors.lastname: Koutcher
authors.forename: L E
authors.initials: LE
authors.lastname: Abrey
authors.forename: K S
authors.initials: KS
authors.lastname: Panageas
authors.forename: L M
authors.initials: LM
authors.lastname: DeAngelis
authors.forename: E
authors.initials: E
authors.lastname: Lis
authors.forename: S
authors.initials: S
authors.lastname: Xu
authors.forename: K L
authors.initials: KL
authors.lastname: Zakian
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D016543:Central Nervous System Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D002794:Choline / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007121:Immunocompetence; D019344:Lactic Acid / Q000378:metabolism; D050356:Lipid Metabolism; D008223:Lymphoma / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy / Q000592:standards; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000627:therapeutic use; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis; D011522:Protons; D016019:Survival Analysis
chemical_list: D000964:Antimetabolites, Antineoplastic; D011522:Protons; D001224:Aspartic Acid; D019344:Lactic Acid; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline; D008727:Methotrexate