title: Post-WBRT cognitive impairment and hippocampal neuronal depletion measured by in vivo metabolic MR spectroscopy: Results of prospective investigational study.
abstract: The aim of this prospective study is to evaluate post-whole brain radiotherapy (WBRT) changes in hippocampal concentration of N-acetylaspartate (h-tNAA) as a marker of neuronal loss and to correlate those changes to neurocognitive function.
  
  
  
  Thirty-five patients with brain metastases underwent baseline single slice multi-voxel MR spectroscopy (MRS) examination for measurement of hippocampal h-tNAA together with baseline battery of neurocognitive tests focused on memory (Auditory Verbal Learning Test and Brief Visuospatial Memory Test - Revised) as well as quality of life questionnaires (EORTC QLQ-C30 a EORTC QLQ-BN20). Eighteen patients completed follow-up evaluation four months after standard WBRT (2 laterolateral fields, 10×3.0Gy, 6MV photons) and were included in this analysis. MRS and cognitive examinations were repeated and compared to baseline measurements.
  
  
  
  Statistically significant decreases in h-tNAA were observed in the right (8.52-7.42mM; -12.9%, 95%CI: -7.6 to -16.4%) as well as in the left hippocampus (8.64-7.60mM; -12%, 95%CI: -7.9 to -16.2%). Statistically significant decline was observed in all AVLT and BVMT-R subtests with exception of AVLT_Recognition. Quality of life declined after WBRT (mean Δ -14.1±20.3 points in transformed 0-100 point scale; p=0.018) with no correlation to changes in hippocampal metabolite concentrations. Moderate positive correlation was observed between left h-tNAA concentration decrease and AVLT_TR decline (r=+0.32; p=0.24) as well as with AVLT_DR (r=+0.33; p=0.22) decline. Changes in right h-tNAA/Cr negatively correlated with AVLT_DR (r=-0.48; p=0.061). No correlation between right hippocampus h-tNAA and memory decline (AVLT) was observed.
  
  
  
  Our results suggest hippocampal NAA concentrations decline after WBRT and MRS may be a useful biomarker for monitoring neuronal loss after radiotherapy.
authors.affiliation: Department of Radiation Oncology, Faculty of Medicine, Masaryk University, Brno, Czech Republic; Department of Radiation Oncology, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Pospisil
authors.affiliation: Department of Radiation Oncology, Faculty of Medicine, Masaryk University, Brno, Czech Republic; Department of Radiation Oncology, Masaryk Memorial Cancer Institute, Brno, Czech Republic; International Clinical Research Center, St. Anne's University Hospital Brno, Czech Republic.
authors.forename: Tomas
authors.initials: T
authors.lastname: Kazda
authors.affiliation: Department of Radiation Oncology, Faculty of Medicine, Masaryk University, Brno, Czech Republic; Department of Radiation Oncology, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
authors.forename: Ludmila
authors.initials: L
authors.lastname: Hynkova
authors.affiliation: Department of Diagnostic Imaging, St. Anne's University Hospital Brno, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Bulik
authors.affiliation: Department of Clinical Psychology, St. Anne's University Hospital Brno, Czech Republic.
authors.forename: Marie
authors.initials: M
authors.lastname: Dobiaskova
authors.affiliation: Department of Radiation Oncology, Faculty of Medicine, Masaryk University, Brno, Czech Republic; Department of Radiation Oncology, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Burkon
authors.affiliation: Department of Radiation Oncology, Mayo Clinic, Rochester, United States.
authors.forename: Nadia N
authors.initials: NN
authors.lastname: Laack
authors.affiliation: Department of Radiation Oncology, Faculty of Medicine, Masaryk University, Brno, Czech Republic; Department of Radiation Oncology, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Slampa
authors.affiliation: Department of Neurosurgery - St. Anne's University Hospital Brno, Faculty of Medicine, Masaryk University, Czech Republic; Department of Neurosurgery, St. Anne's University Hospital Brno, Czech Republic. Electronic address: radim.jancalek@fnusa.cz.
authors.forename: Radim
authors.initials: R
authors.lastname: Jancalek
mesh_terms: D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001932:Brain Neoplasms / Q000532:radiotherapy* / Q000556:secondary; D060825:Cognitive Dysfunction / Q000209:etiology* / Q000378:metabolism; D016371:Cranial Irradiation / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000378:metabolism / Q000528:radiation effects*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D008568:Memory / Q000528:radiation effects; D008875:Middle Aged; D009410:Nerve Degeneration / Q000209:etiology* / Q000378:metabolism; D009483:Neuropsychological Tests; D011446:Prospective Studies; D011788:Quality of Life; D011795:Surveys and Questionnaires
chemical_list: D015415:Biomarkers; D001224:Aspartic Acid; C000179:N-acetylaspartate
keywords: Hippocampus; Magnetic resonance spectroscopy; Neurocognitive function; Radiation injury