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

Publication date: Available online 4 January 2017
Source:Radiotherapy and Oncology
Author(s): Petr Pospisil, Tomas Kazda, Ludmila Hynkova, Martin Bulik, Marie Dobiaskova, Petr Burkon, Nadia N. Laack, Pavel Slampa, Radim Jancalek
Background and purposeThe 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 methodsThirty-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.ResultsStatistically 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.ConclusionsOur results suggest hippocampal NAA concentrations decline after WBRT and MRS may be a useful biomarker for monitoring neuronal loss after radiotherapy.



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