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

Petr Pospisil, Tomas Kazda, Ludmila Hynkova, Martin Bulik, Marie Dobiaskova, Petr Burkon, Nadia N Laack, Pavel Slampa, Radim Jancalek

Research output: Contribution to journalArticle

16 Citations (Scopus)

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. ×. 3.0. Gy, 6. MV 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 (8.52-7.42. mM; -12.9%, 95%CI: -7.6 to -16.4%) as well as in the left hippocampus (8.64-7.60. mM; -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.

Original languageEnglish (US)
JournalRadiotherapy and Oncology
DOIs
StateAccepted/In press - Feb 14 2016

Fingerprint

Magnetic Resonance Spectroscopy
Radiotherapy
Prospective Studies
Brain
Hippocampus
Quality of Life
Verbal Learning
Cognitive Dysfunction
Photons
N-acetylaspartate
Biomarkers
Neoplasm Metastasis

Keywords

  • Hippocampus
  • Magnetic resonance spectroscopy
  • Neurocognitive function
  • Radiation injury

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Radiology Nuclear Medicine and imaging

Cite this

Post-WBRT cognitive impairment and hippocampal neuronal depletion measured by in vivo metabolic MR spectroscopy : Results of prospective investigational study. / Pospisil, Petr; Kazda, Tomas; Hynkova, Ludmila; Bulik, Martin; Dobiaskova, Marie; Burkon, Petr; Laack, Nadia N; Slampa, Pavel; Jancalek, Radim.

In: Radiotherapy and Oncology, 14.02.2016.

Research output: Contribution to journalArticle

Pospisil, Petr ; Kazda, Tomas ; Hynkova, Ludmila ; Bulik, Martin ; Dobiaskova, Marie ; Burkon, Petr ; Laack, Nadia N ; Slampa, Pavel ; Jancalek, Radim. / Post-WBRT cognitive impairment and hippocampal neuronal depletion measured by in vivo metabolic MR spectroscopy : Results of prospective investigational study. In: Radiotherapy and Oncology. 2016.
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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. ×. 3.0. Gy, 6. MV 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 (8.52-7.42. mM; -12.9{\%}, 95{\%}CI: -7.6 to -16.4{\%}) as well as in the left hippocampus (8.64-7.60. mM; -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.",
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T2 - Results of prospective investigational study

AU - Pospisil, Petr

AU - Kazda, Tomas

AU - Hynkova, Ludmila

AU - Bulik, Martin

AU - Dobiaskova, Marie

AU - Burkon, Petr

AU - Laack, Nadia N

AU - Slampa, Pavel

AU - Jancalek, Radim

PY - 2016/2/14

Y1 - 2016/2/14

N2 - 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. ×. 3.0. Gy, 6. MV 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 (8.52-7.42. mM; -12.9%, 95%CI: -7.6 to -16.4%) as well as in the left hippocampus (8.64-7.60. mM; -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.

AB - 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. ×. 3.0. Gy, 6. MV 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 (8.52-7.42. mM; -12.9%, 95%CI: -7.6 to -16.4%) as well as in the left hippocampus (8.64-7.60. mM; -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.

KW - Hippocampus

KW - Magnetic resonance spectroscopy

KW - Neurocognitive function

KW - Radiation injury

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