Skip to main content
Top
Published in: Radiation Oncology 1/2015

Open Access 01-12-2015 | Research

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

Authors: Petr Pospisil, Tomas Kazda, Martin Bulik, Marie Dobiaskova, Petr Burkon, Ludmila Hynkova, Pavel Slampa, Radim Jancalek

Published in: Radiation Oncology | Issue 1/2015

Login to get access

Abstract

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 1H-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 1H-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 1H-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.
Literature
1.
go back to reference Tabouret E, Chinot O, Metellus P, Tallet A, Viens P, Gonçalves A, et al. Recent trends in epidemiology of brain metastases: an overview. Anticancer Res. 2012;32:4655–62. Tabouret E, Chinot O, Metellus P, Tallet A, Viens P, Gonçalves A, et al. Recent trends in epidemiology of brain metastases: an overview. Anticancer Res. 2012;32:4655–62.
2.
go back to reference Laack NN, Brown PD. Cognitive sequelae of brain radiation in adults. Semin Oncol. 2004;31:702–13.CrossRefPubMed Laack NN, Brown PD. Cognitive sequelae of brain radiation in adults. Semin Oncol. 2004;31:702–13.CrossRefPubMed
3.
go back to reference Tallet AV, Azria D, Barlesi F, Spano J-P, Carpentier AF, Gonçalves A, et al. Neurocognitive function impairment after whole brain radiotherapy for brain metastases: actual assessment. Radiat Oncol. 2012;7:77.PubMedCentralCrossRefPubMed Tallet AV, Azria D, Barlesi F, Spano J-P, Carpentier AF, Gonçalves A, et al. Neurocognitive function impairment after whole brain radiotherapy for brain metastases: actual assessment. Radiat Oncol. 2012;7:77.PubMedCentralCrossRefPubMed
4.
go back to reference Gondi V, Pugh SL, Tome WA, Caine C, Corn B, Kanner A, et al. Preservation of Memory With Conformal Avoidance of the Hippocampal Neural Stem-Cell Compartment During Whole-Brain Radiotherapy for Brain Metastases (RTOG 0933): A Phase II Multi-Institutional Trial. J Clin Oncol. 2014;32(34):3810–6.CrossRefPubMed Gondi V, Pugh SL, Tome WA, Caine C, Corn B, Kanner A, et al. Preservation of Memory With Conformal Avoidance of the Hippocampal Neural Stem-Cell Compartment During Whole-Brain Radiotherapy for Brain Metastases (RTOG 0933): A Phase II Multi-Institutional Trial. J Clin Oncol. 2014;32(34):3810–6.CrossRefPubMed
5.
go back to reference Gondi V, Hermann BP, Mehta MP, Tomé WA. Hippocampal dosimetry predicts neurocognitive function impairment after fractionated stereotactic radiotherapy for benign or low-grade adult brain tumors. Int J Radiat Oncol Biol Phys. 2013;85:348–54.CrossRefPubMed Gondi V, Hermann BP, Mehta MP, Tomé WA. Hippocampal dosimetry predicts neurocognitive function impairment after fractionated stereotactic radiotherapy for benign or low-grade adult brain tumors. Int J Radiat Oncol Biol Phys. 2013;85:348–54.CrossRefPubMed
6.
go back to reference Suh JH. Hippocampal-Avoidance Whole-Brain Radiation Therapy: A New Standard for Patients With Brain Metastases? J Clin Oncol. 2014;32(34):3789–91.CrossRefPubMed Suh JH. Hippocampal-Avoidance Whole-Brain Radiation Therapy: A New Standard for Patients With Brain Metastases? J Clin Oncol. 2014;32(34):3789–91.CrossRefPubMed
7.
go back to reference Brown PD, Pugh S, Laack NN, Wefel JS, Khuntia D, Meyers C, et al. Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: a randomized, double-blind, placebo-controlled trial. Neuro Oncol. 2013;15:1429–37.PubMedCentralCrossRefPubMed Brown PD, Pugh S, Laack NN, Wefel JS, Khuntia D, Meyers C, et al. Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: a randomized, double-blind, placebo-controlled trial. Neuro Oncol. 2013;15:1429–37.PubMedCentralCrossRefPubMed
8.
go back to reference Kazda T, Jancalek R, Pospisil P, Sevela O, Prochazka T, Vrzal M, et al. Why and how to spare the hippocampus during brain radiotherapy: the developing role of hippocampal avoidance in cranial radiotherapy. Radiat Oncol. 2014;9:139.PubMedCentralCrossRefPubMed Kazda T, Jancalek R, Pospisil P, Sevela O, Prochazka T, Vrzal M, et al. Why and how to spare the hippocampus during brain radiotherapy: the developing role of hippocampal avoidance in cranial radiotherapy. Radiat Oncol. 2014;9:139.PubMedCentralCrossRefPubMed
9.
go back to reference Moffett JR, Ross B, Arun P, Madhavarao CN, Namboodiri AMA. N-Acetylaspartate in the CNS: from neurodiagnostics to neurobiology. Prog Neurobiol. 2007;81:89–131.PubMedCentralCrossRefPubMed Moffett JR, Ross B, Arun P, Madhavarao CN, Namboodiri AMA. N-Acetylaspartate in the CNS: from neurodiagnostics to neurobiology. Prog Neurobiol. 2007;81:89–131.PubMedCentralCrossRefPubMed
10.
go back to reference Greene-Schloesser D, Robbins ME, Peiffer AM, Shaw EG, Wheeler KT, Chan MD, et al. Radiation-induced brain injury: A review. Front Oncol. 2012;2:73. Greene-Schloesser D, Robbins ME, Peiffer AM, Shaw EG, Wheeler KT, Chan MD, et al. Radiation-induced brain injury: A review. Front Oncol. 2012;2:73.
11.
go back to reference Monje ML, Mizumatsu S, Fike JR, Palmer TD. Irradiation induces neural precursor-cell dysfunction. Nat Med. 2002;8:955–62.CrossRefPubMed Monje ML, Mizumatsu S, Fike JR, Palmer TD. Irradiation induces neural precursor-cell dysfunction. Nat Med. 2002;8:955–62.CrossRefPubMed
12.
13.
go back to reference Sperduto PW, Berkey B, Gaspar LE, Mehta M, Curran W. A new prognostic index and comparison to three other indices for patients with brain metastases: an analysis of 1,960 patients in the RTOG database. Int J Radiat Oncol Biol Phys. 2008;70(2):510–4.CrossRefPubMed Sperduto PW, Berkey B, Gaspar LE, Mehta M, Curran W. A new prognostic index and comparison to three other indices for patients with brain metastases: an analysis of 1,960 patients in the RTOG database. Int J Radiat Oncol Biol Phys. 2008;70(2):510–4.CrossRefPubMed
14.
go back to reference Mrzílkova J, Koutela A, Kutova M, Patzelt M, Ibrahim I, Al-Kayssi D, et al. Hippocampal spatial position evaluation on MRI for research and clinical practice. PLoS One. 2014;9(12):e115174.PubMedCentralCrossRefPubMed Mrzílkova J, Koutela A, Kutova M, Patzelt M, Ibrahim I, Al-Kayssi D, et al. Hippocampal spatial position evaluation on MRI for research and clinical practice. PLoS One. 2014;9(12):e115174.PubMedCentralCrossRefPubMed
15.
go back to reference Provencher SW. Automatic quantitation of localized in vivo 1H spectra with LCModel. NMR Biomed. 2001;14(4):260–4.CrossRefPubMed Provencher SW. Automatic quantitation of localized in vivo 1H spectra with LCModel. NMR Biomed. 2001;14(4):260–4.CrossRefPubMed
16.
go back to reference Jiru F, Skoch A, Wagnerova D, Dezortova M, Hajek M. jSIPRO - analysis tool for magnetic resonance spectroscopic imaging. Comput Methods Programs Biomed. 2013;112(1):173–88.CrossRefPubMed Jiru F, Skoch A, Wagnerova D, Dezortova M, Hajek M. jSIPRO - analysis tool for magnetic resonance spectroscopic imaging. Comput Methods Programs Biomed. 2013;112(1):173–88.CrossRefPubMed
17.
go back to reference Jiru F, Skoch A, Klose U, Grodd W, Hajek M. Error images for spectroscopic imaging by LCModel using Cramer-Rao bounds. MAGMA. 2006;19(1):1–14.CrossRefPubMed Jiru F, Skoch A, Klose U, Grodd W, Hajek M. Error images for spectroscopic imaging by LCModel using Cramer-Rao bounds. MAGMA. 2006;19(1):1–14.CrossRefPubMed
18.
go back to reference Koay E, Sulman EP. Management of brain metastasis: past lessons, modern management, and future considerations. Curr Oncol Rep. 2012;14(1):70–8.CrossRefPubMed Koay E, Sulman EP. Management of brain metastasis: past lessons, modern management, and future considerations. Curr Oncol Rep. 2012;14(1):70–8.CrossRefPubMed
19.
go back to reference Kazda T, Pospíšil P, Doleželová H, Jančálek R, Slampa P. Whole brain radiotherapy: Consequences for personalized medicine. Rep Pract Oncol Radiother. 2013;18(3):133–8.PubMedCentralCrossRefPubMed Kazda T, Pospíšil P, Doleželová H, Jančálek R, Slampa P. Whole brain radiotherapy: Consequences for personalized medicine. Rep Pract Oncol Radiother. 2013;18(3):133–8.PubMedCentralCrossRefPubMed
20.
go back to reference Rock EP, Fine HA, Meyers CA. Refining endpoints in brain tumor clinical trials. J Neurooncol. 2012;108(2):227–30.CrossRefPubMed Rock EP, Fine HA, Meyers CA. Refining endpoints in brain tumor clinical trials. J Neurooncol. 2012;108(2):227–30.CrossRefPubMed
21.
go back to reference Taphoorn MJB, Klein M. Cognitive deficits in adult patients with brain tumours. Lancet Neurol. 2004;3(3):159–68.CrossRefPubMed Taphoorn MJB, Klein M. Cognitive deficits in adult patients with brain tumours. Lancet Neurol. 2004;3(3):159–68.CrossRefPubMed
22.
go back to reference Wong CS, Van der Kogel AJ. Mechanisms of radiation injury to the central nervous system: implications for neuroprotection. Mol Interv. 2004;4(5):273–84.CrossRefPubMed Wong CS, Van der Kogel AJ. Mechanisms of radiation injury to the central nervous system: implications for neuroprotection. Mol Interv. 2004;4(5):273–84.CrossRefPubMed
24.
go back to reference Awad R, Fogarty G, Hong A, Kelly P, Ng D, Santos D, et al. Hippocampal avoidance with volumetric modulated arc therapy in melanoma brain metastases - the first Australian experience. Radiat Oncol. 2013;8:62.PubMedCentralCrossRefPubMed Awad R, Fogarty G, Hong A, Kelly P, Ng D, Santos D, et al. Hippocampal avoidance with volumetric modulated arc therapy in melanoma brain metastases - the first Australian experience. Radiat Oncol. 2013;8:62.PubMedCentralCrossRefPubMed
25.
go back to reference Mehta MP, Shapiro WR, Phan SC, Gervais R, Carrie C, Chabot P, et al. Motexafin gadolinium combined with prompt whole brain radiotherapy prolongs time to neurologic progression in non-small-cell lung cancer patients with brain metastases: results of a phase III trial. Int J Radiat Oncol Biol Phys. 2009;73(4):1069–76.CrossRefPubMed Mehta MP, Shapiro WR, Phan SC, Gervais R, Carrie C, Chabot P, et al. Motexafin gadolinium combined with prompt whole brain radiotherapy prolongs time to neurologic progression in non-small-cell lung cancer patients with brain metastases: results of a phase III trial. Int J Radiat Oncol Biol Phys. 2009;73(4):1069–76.CrossRefPubMed
26.
go back to reference Rooney JW, Laack NN. Pharmacological interventions to treat or prevent neurocognitive decline after brain radiation. CNS Oncol. 2013;2(6):531–41.CrossRefPubMed Rooney JW, Laack NN. Pharmacological interventions to treat or prevent neurocognitive decline after brain radiation. CNS Oncol. 2013;2(6):531–41.CrossRefPubMed
28.
go back to reference Tumati S, Martens S, Aleman A. Magnetic resonance spectroscopy in mild cognitive impairment: systematic review and meta-analysis. Neurosci Biobehav Rev. 2013;37(10 Pt 2):2571–86.CrossRefPubMed Tumati S, Martens S, Aleman A. Magnetic resonance spectroscopy in mild cognitive impairment: systematic review and meta-analysis. Neurosci Biobehav Rev. 2013;37(10 Pt 2):2571–86.CrossRefPubMed
29.
go back to reference Targosz-Gajniak MG, Siuda JS, Wicher MM, Banasik TJ, Bujak MA, Augusciak-Duma AM, et al. Magnetic resonance spectroscopy as a predictor of conversion of mild cognitive impairment to dementia. J Neurol Sci. 2013;335(1–2):58–63.CrossRefPubMed Targosz-Gajniak MG, Siuda JS, Wicher MM, Banasik TJ, Bujak MA, Augusciak-Duma AM, et al. Magnetic resonance spectroscopy as a predictor of conversion of mild cognitive impairment to dementia. J Neurol Sci. 2013;335(1–2):58–63.CrossRefPubMed
30.
go back to reference Kantarci K, Weigand SD, Przybelski SA, Preboske GM, Pankratz VS, Vemuri P, et al. MRI and MRS predictors of mild cognitive impairment in a population-based sample. Neurology. 2013;81(2):126–33.PubMedCentralCrossRefPubMed Kantarci K, Weigand SD, Przybelski SA, Preboske GM, Pankratz VS, Vemuri P, et al. MRI and MRS predictors of mild cognitive impairment in a population-based sample. Neurology. 2013;81(2):126–33.PubMedCentralCrossRefPubMed
31.
go back to reference Usenius T, Usenius JP, Tenhunen M, Vainio P, Johansson R, Soimakallio S, et al. Radiation-induced changes in human brain metabolites as studied by 1H nuclear magnetic resonance spectroscopy in vivo. Int J Radiat Oncol Biol Phys. 1995;33(3):719–24.CrossRefPubMed Usenius T, Usenius JP, Tenhunen M, Vainio P, Johansson R, Soimakallio S, et al. Radiation-induced changes in human brain metabolites as studied by 1H nuclear magnetic resonance spectroscopy in vivo. Int J Radiat Oncol Biol Phys. 1995;33(3):719–24.CrossRefPubMed
32.
go back to reference Estève F, Rubin C, Grand S, Kolodié H, Le Bas JF. Transient metabolic changes observed with proton MR spectroscopy in normal human brain after radiation therapy. Int J Radiat Oncol Biol Phys. 1998;40(2):279–86.CrossRefPubMed Estève F, Rubin C, Grand S, Kolodié H, Le Bas JF. Transient metabolic changes observed with proton MR spectroscopy in normal human brain after radiation therapy. Int J Radiat Oncol Biol Phys. 1998;40(2):279–86.CrossRefPubMed
33.
go back to reference Movsas B, Li BS, Babb JS, Fowble BL, Nicolaou N, Gonen O, et al. Quantifying radiation therapy-induced brain injury with whole-brain proton MR spectroscopy: initial observations. Radiology. 2001;221(2):327–31. Movsas B, Li BS, Babb JS, Fowble BL, Nicolaou N, Gonen O, et al. Quantifying radiation therapy-induced brain injury with whole-brain proton MR spectroscopy: initial observations. Radiology. 2001;221(2):327–31.
34.
go back to reference Lee MC, Pirzkall A, McKnight TR, Nelson SJ. 1H-MRSI of radiation effects in normal-appearing white matter: dose-dependence and impact on automated spectral classification. J Magn Reson Imaging. 2004;19(4):379–88.CrossRefPubMed Lee MC, Pirzkall A, McKnight TR, Nelson SJ. 1H-MRSI of radiation effects in normal-appearing white matter: dose-dependence and impact on automated spectral classification. J Magn Reson Imaging. 2004;19(4):379–88.CrossRefPubMed
35.
go back to reference Kaminaga T, Shirai K. Radiation-induced brain metabolic changes in the acute and early delayed phase detected with quantitative proton magnetic resonance spectroscopy. J Comput Assist Tomogr. 2005;29(3):293–7.CrossRefPubMed Kaminaga T, Shirai K. Radiation-induced brain metabolic changes in the acute and early delayed phase detected with quantitative proton magnetic resonance spectroscopy. J Comput Assist Tomogr. 2005;29(3):293–7.CrossRefPubMed
36.
go back to reference Sundgren PC, Nagesh V, Elias A, Tsien C, Junck L, Gomez Hassan DM, et al. Metabolic alterations: a biomarker for radiation-induced normal brain injury-an MR spectroscopy study. J Magn Reson Imaging. 2009;29(2):291–7.PubMedCentralCrossRefPubMed Sundgren PC, Nagesh V, Elias A, Tsien C, Junck L, Gomez Hassan DM, et al. Metabolic alterations: a biomarker for radiation-induced normal brain injury-an MR spectroscopy study. J Magn Reson Imaging. 2009;29(2):291–7.PubMedCentralCrossRefPubMed
37.
go back to reference Chawla S, Wang S, Kim S, Sheriff S, Lee P, Rengan R, et al. Radiation Injury to the Normal Brain Measured by 3D-Echo-Planar Spectroscopic Imaging and Diffusion Tensor Imaging: Initial Experience. J Neuroimaging. 2015;25(1):97–104.CrossRefPubMed Chawla S, Wang S, Kim S, Sheriff S, Lee P, Rengan R, et al. Radiation Injury to the Normal Brain Measured by 3D-Echo-Planar Spectroscopic Imaging and Diffusion Tensor Imaging: Initial Experience. J Neuroimaging. 2015;25(1):97–104.CrossRefPubMed
38.
go back to reference Lee TM, Yip JT, Jones-Gotman M. Memory deficits after resection from left or right anterior temporal lobe in humans: a meta-analytic review. Epilepsia. 2002;43(3):283–91.CrossRefPubMed Lee TM, Yip JT, Jones-Gotman M. Memory deficits after resection from left or right anterior temporal lobe in humans: a meta-analytic review. Epilepsia. 2002;43(3):283–91.CrossRefPubMed
39.
go back to reference Patel SK, Wong AL, Wong FL, Breen EC, Hurria A, Smith M, et al. Inflammatory Biomarkers, Comorbidity, and Neurocognition in Women With Newly Diagnosed Breast Cancer. J Natl Cancer Inst. 2015;107(8):djv 131.CrossRef Patel SK, Wong AL, Wong FL, Breen EC, Hurria A, Smith M, et al. Inflammatory Biomarkers, Comorbidity, and Neurocognition in Women With Newly Diagnosed Breast Cancer. J Natl Cancer Inst. 2015;107(8):djv 131.CrossRef
40.
go back to reference Perssons J, Herlitz A, Engman J, Morell A, Sjölie D, Wikström J, et al. Remembering our origin: Gender differences in spatial memory are reflected in gender differences in hippocampal lateralization. Behav Brain Res. 2013;256(8):219–28.CrossRef Perssons J, Herlitz A, Engman J, Morell A, Sjölie D, Wikström J, et al. Remembering our origin: Gender differences in spatial memory are reflected in gender differences in hippocampal lateralization. Behav Brain Res. 2013;256(8):219–28.CrossRef
41.
go back to reference Sidhu MK, Stretton J, Winston GP, Symms M, Thompson PJ, Koepp MJ, et al. Memory fMRI predicts verbal memory decline after anterior temporal lobe resection: Gender differences in spatial memory are reflected in gender differences in hippocampal lateralization. Neurology. 2015;84(15):1512–9.PubMedCentralCrossRefPubMed Sidhu MK, Stretton J, Winston GP, Symms M, Thompson PJ, Koepp MJ, et al. Memory fMRI predicts verbal memory decline after anterior temporal lobe resection: Gender differences in spatial memory are reflected in gender differences in hippocampal lateralization. Neurology. 2015;84(15):1512–9.PubMedCentralCrossRefPubMed
42.
go back to reference Chang EL, Wefel JS, Hess KR, Allen PK, Lang FF, Kornguth DG, et al. Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol. 2009;10(11):1037–44.CrossRefPubMed Chang EL, Wefel JS, Hess KR, Allen PK, Lang FF, Kornguth DG, et al. Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol. 2009;10(11):1037–44.CrossRefPubMed
Metadata
Title
Hippocampal proton MR spectroscopy as a novel approach in the assessment of radiation injury and the correlation to neurocognitive function impairment: initial experiences
Authors
Petr Pospisil
Tomas Kazda
Martin Bulik
Marie Dobiaskova
Petr Burkon
Ludmila Hynkova
Pavel Slampa
Radim Jancalek
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Radiation Oncology / Issue 1/2015
Electronic ISSN: 1748-717X
DOI
https://doi.org/10.1186/s13014-015-0518-1

Other articles of this Issue 1/2015

Radiation Oncology 1/2015 Go to the issue