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

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.

Hippocampal proton MR spectroscopy as a novel approach in the assessment of radiation injury and the correlation to neurocognitive function impairment: initial experiences.

BACKGROUND: The hippocampus is considered as the main radiosensitive brain structure responsible for postradiotherapy cognitive decline. We prospectively assessed correlation of memory change to hippocampal N-acetylaspartate (h-tNAA) concentration, a neuronal density and viability marker, by (1)H-MR spectroscopy focused on the hippocampus. METHODS: Patients with brain metastases underwent whole brain radiotherapy (WBRT) to a dose of 30 Gy in ten fractions daily. Pre-radiotherapy (1)H-MR spectroscopy focused on the h-tNAA concentration and memory testing was performed. Memory was evaluated by Auditory Verbal Learning Test (AVLT) and Brief Visuospatial Memory Test-Revised (BVMT-R). Total recall, recognition and delayed recall were reported. The both investigation procedures were repeated 4 months after WBRT and the h-tNAA and memory changes were correlated. RESULTS: Of the 20 patients, ten passed whole protocol. The h-tNAA concentration significantly decreased from pre-WBRT 8.9, 8.86 and 8.88 [mM] in the right, left and both hippocampi to 7.16, 7.65 and 7.4 after WBRT, respectively. In the memory tests a significant decrease was observed in AVLT total-recall, BVMT-R total-recall and BVMT-R delayed-recall. Weak to moderate correlations were observed between left h-tNAA and AVLT recognition and all BVMT-R subtests and between the right h-tNAA and AVLT total-recall. CONCLUSIONS: A significant decrease in h-tNAA after WBRT was proven by (1)H-MR spectroscopy as a feasible method for the in vivo investigation of radiation injury. Continuing patient recruitment focusing on other cognitive tests and metabolites is needed.