Post-WBRT cognitive impairment and hippocampal neuronal depletion measured by in vivo metabolic MR spectroscopy: Results of prospective investigational study

Radiother Oncol. 2017 Mar;122(3):373-379. doi: 10.1016/j.radonc.2016.12.013. Epub 2017 Jan 4.

Abstract

Background and purpose: 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.

Material and methods: 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.

Results: 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.

Conclusions: Our results suggest hippocampal NAA concentrations decline after WBRT and MRS may be a useful biomarker for monitoring neuronal loss after radiotherapy.

Keywords: Hippocampus; Magnetic resonance spectroscopy; Neurocognitive function; Radiation injury.

MeSH terms

  • Aspartic Acid / analogs & derivatives
  • Aspartic Acid / metabolism
  • Biomarkers / metabolism
  • Brain Neoplasms / radiotherapy*
  • Brain Neoplasms / secondary
  • Cognitive Dysfunction / etiology*
  • Cognitive Dysfunction / metabolism
  • Cranial Irradiation / adverse effects*
  • Female
  • Follow-Up Studies
  • Hippocampus / diagnostic imaging
  • Hippocampus / metabolism
  • Hippocampus / radiation effects*
  • Humans
  • Magnetic Resonance Spectroscopy / methods*
  • Male
  • Memory / radiation effects
  • Middle Aged
  • Nerve Degeneration / etiology*
  • Nerve Degeneration / metabolism
  • Neuropsychological Tests
  • Prospective Studies
  • Quality of Life
  • Surveys and Questionnaires

Substances

  • Biomarkers
  • Aspartic Acid
  • N-acetylaspartate