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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