P05.03 Post-radiation cognitive inpairment and hippocampal neuronal depletion measured by in-vivo metabolic MR spectroscopy: Results of prospective investigational study

Abstract

Introduction: Hippocampal radioinjury-mediated cognitive impairment is currently widely investigated in many preclinical and clinical trials. Further studying of hippocampal pathophysiological changes after radiation and its relation to memory alteration are still needed to enable critical evidence for introduction hippocampal sparing and/or drug intervention for preserving memory function. For confirmation of this concept, a deeper understanding of the correlations of imaging and functional changes is needed. 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 it to neurocognitive dysfunction. Materials And Methods: Thirty-five patients with brain metastases underwent baseline single slice multi-voxel MR spectroscopy examination for measurement of hippocampal h-tNAA together with baseline battery of neurocognitive tests focused on memory as well as quality of life questionnaires (EORTC QLQ-C30 a EORTC QLQ-BN20). Hippocampal spectroscopy was performed using GE Medical Systems Discovery MR 750 3T. Region of interest was placed through the whole temporal lobi with the voxel layer position adjusted based on the localization of hippocampi. Specialized software was utilized for measurement of absolute NAA concentration in voxels within right, left and both hippocampi. 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 four months after standard WBRT (2 laterolateral fields, 10x3.0 Gy, delivered by linear accelerator, 6MV photons) and compared on the case by case basis. The h-tNAA and memory changes were correlated. Results: The statistically significant decrease of h-tNAA was observed in the right (from 8.52 to 7.42 mM; -12%, 95%CI: -7.6 to -16.4%) as well as in the left hippocampus (from 8.64 to 7.60 mM; -12%, 95%CI: -7.9 to -16.2%). Statistically significant decline was observed in all AVLT and BVMT subtests with exception of AVLT-R. For left h-tNAA concentration decrease, positive moderate correlation was among others with AVLT-TR (r=+0.32; p=0.24) as well as with AVLT-DR (r=+0.33; p=0.22) decline. Changes in normalized right h-tNAA/Creatinin negatively correlated with AVLT-DR (r=-0.48; p=0.061). No positive correlation between right hippocampus changes and memory decline was observed. Conclusions: Our results prompt investigational of laterality in hippocampal radio-injury as well as the need of robust analysis of pre-irradiation imaging studies as possible predictive biomarkers for decision making for the best radiotherapy approach in the treatment of brain metastases.