Skip to main content
SpringerLink
Log in

Early volume reduction of the hippocampus after whole-brain radiation therapy: an automated brain structure segmentation study

  • Original Article
  • Published:
Japanese Journal of Radiology Aims and scope Submit manuscript

Abstract

Purpose

To assess atrophy differences among brain regions and time-dependent changes after whole-brain radiation therapy (WBRT).

Materials and methods

Twenty patients with lung cancer who underwent both WBRT and chemotherapy (WBRT group) and 18 patients with lung cancer who underwent only chemotherapy (control group) were recruited. Three-dimensional T1WI were analyzed to calculate volume reduction ratio after WBRT in various brain structures. The volume reduction ratio of the hippocampus was compared among following 3 periods: 0–3, 4–7, and 8–11 months after WBRT.

Results

The volume reduction ratio of the hippocampus was significantly higher in the WBRT group than in the control group (p < 0.05). In WBRT group, the volume reduction ratio of the hippocampus was significantly higher than that of the cortex and white matter (p < 0.05). There were significant differences in the volume reduction ratio between of 0–3 months and that of 4–7 months (p = 0.02) and between 4–7 months and that of 8–11 months (p = 0.01).

Conclusion

The hippocampus is more vulnerable to the radiation compared with other brain regions and may become atrophic even in the early stage after WBRT.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Roman DD, Sperduto PW. Neuropsychological effects of cranial radiation: current knowledge and future directions. Int J Radiat Oncol Biol Phys. 1995;31:983–98.

    Article  CAS  Google Scholar 

  2. Shaw MG, Ball DL. Treatment of brain metastases in lung cancer: strategies to avoid/reduce late complications of whole brain radiation therapy. Curr Treat Options Oncol. 2013;14:553–67.

    Article  Google Scholar 

  3. Raber J, Rola R, LeFevour A, Morhardt D, Curley J, Mizumatsu S, et al. Radiation-induced cognitive impairments are associated with changes in indicators of hippocampal neurogenesis. Radiat Res. 2004;162:39–47.

    Article  CAS  Google Scholar 

  4. Rola R, Raber J, Rizk A, Otsuka S, VandenBerg SR, Morhardt DR, et al. Radiation-induced impairment of hippocampal neurogenesis is associated with cognitive deficits in young mice. Exp Neurol. 2004;188:316–30.

    Article  CAS  Google Scholar 

  5. Gondi V, Hermann BP, Mehta MP, Tome 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.

    Article  Google Scholar 

  6. Redmond KJ, Mahone EM, Horska A. Association between radiation dose to neuronal progenitor cell niches and temporal lobes and performance on neuropsychological testing in children: a prospective study. Neuro Oncol. 2013;15(3):360–9.

    Article  CAS  Google Scholar 

  7. Gondi V, Tome WA, Mehta MP. Why avoid the hippocampus? A comprehensive review. Radiother Oncol. 2010;97:370–6.

    Article  Google Scholar 

  8. Oskan F, Ganswindt U, Schwarz SB, Manapov F, Belka C, et al. Hippocampus sparing in whole-brain radiotherapy. A review. Strahlenther Onkol. 2014;190(4):337–41.

    Article  CAS  Google Scholar 

  9. Zhao R, Kong W, Shang J, Zhe H, Wang YY. Hippocampal-sparing whole-brain radiotherapy for lung cancer. Clin Lung Cancer. 2017;18(2):127–31.

    Article  Google Scholar 

  10. Seibert TM, Karunamuni R, Bartsch H, Kaifi S, Krishnan AP, Dalia Y, et al. Radiation dose-dependent hippocampal atrophy detected with longitudinal volumetric magnetic resonance imaging. Int J Radiat Oncol Biol Phys. 2017;97:263–9.

    Article  Google Scholar 

  11. Hong A, Hallock H, Valenzuela M, Lo S, Steel V, Paton E, et al. Change in the hippocampal volume after whole-brain radiation therapy with or without hippocampal avoidance technique. Int J Radiat Oncol Biol Phys. 2015;93:E82.

    Article  Google Scholar 

  12. Lee YY, Nauert C, Glass JP. Treatment-related white matter changes in cancer patients. Cancer. 1986;57:1473–82.

    Article  CAS  Google Scholar 

  13. Karunamuni R, Bartsch H, White NS, Moiseenko V, Carmona R, Marshall DC, et al. Dose-dependent cortical thinning after partial brain irradiation in high-grade glioma. Int J Radiat Oncol Biol Phys. 2016;94:297–304.

    Article  Google Scholar 

  14. Reuter M, Fischl B. Avoiding asymmetry-induced bias in longitudinal image processing. Neuroimage. 2011;57:19–211.

    Article  Google Scholar 

  15. Reuter M, Schmansky NJ, Rosas HD, Fischl B. Within-subject template estimation for unbiased longitudinal image analysis. Neuroimage. 2012;61:1402–18.

    Article  Google Scholar 

  16. Schuff N, Woerner N, Boreta L, Kornfield T, Shaw LM, Trojanowski JQ, et al. Alzheimer's disease neuroimaging initiative. MRI of hippocampal volume loss in early Alzheimer’s disease in relation to ApoE genotype and biomarkers. Brain. 2009;132:1067–77.

    Article  CAS  Google Scholar 

  17. Martin P, Bender B, Focke NK. Post-processing of structural MRI for individualized diagnostics. Quant Imaging Med Surg. 2015;5:188–203.

    PubMed  PubMed Central  Google Scholar 

  18. Yazlovitskaya EM, Edwards E, Thotala D, Fu A, Osusky KL, Whetsell WO Jr, et al. Lithium treatment prevents neurocognitive deficit resulting from cranial irradiation. Cancer Res. 2006;66:11179–86.

    Article  CAS  Google Scholar 

  19. Bellinzona M, Gobbel GT, Shinohara C, Fike JR. Apoptosis is induced in the subependyma of young adult rats by ionizing irradiation. Neurosci Lett. 1996;208:163–6.

    Article  CAS  Google Scholar 

  20. Snyder JS, Kee N, Wojtowicz JM. Effects of adult neurogenesis on synaptic plasticity in the rat dentate gyrus. J Neurophysiol. 2001;85:2423–31.

    Article  CAS  Google Scholar 

  21. Monje ML, Mizumatsu S, Fike JR, Palmer TD. Irradiation induces neural precursor cell dysfunction. Nat Med. 2002;8:955–62.

    Article  CAS  Google Scholar 

  22. Mizumatsu S, Monje ML, Morhardt DR, Rola R, Palmer TD, Fike JR. Extreme sensitivity of adult neurogenesis to low doses of X-irradiation. Cancer Res. 2003;63:4021–7.

    CAS  PubMed  Google Scholar 

  23. Farjam R, Pramanik P, Aryal MP, Srinivasan A, Chapman CH, Tsien CI, et al. A radiation-induced hippocampal vascular injury surrogate marker predicts late neurocognitive dysfunction. Int J Radiat Oncol Biol Phys. 2015;93:908–15.

    Article  Google Scholar 

  24. Ferrer I, Serrano T, Alcantara S, Tortosa A, Graus F. X-ray-induced cell death in the developing hippocampal complex involves neurons and requires protein synthesis. J Neuropathol Exp Neurol. 1993;52:370–8.

    Article  CAS  Google Scholar 

  25. Nagai R, Tsunoda S, Hori Y, Asada H. Selective vulnerability to radiation in the hippocampal dentate granule cells. Surg Neurol. 2000;53:503–6.

    Article  CAS  Google Scholar 

  26. Ramanan S, Kooshki M, Zhao W, Hsu FC, Robbins ME. PPARalpha ligands inhibit radiation-induced microglial inflammatory responses by negatively regulating NF-kappaB and AP-1 pathways. FreeRadic Biol Med. 2008;45:1695–704.

    Article  CAS  Google Scholar 

  27. Lee WH, Sonntag WE, Mitschelen M, Yan H, Lee YW. Irradiation induces regionally specific alterations in proinflammatory environments in rat brain. Int J Radiat Biol. 2010;86:132–44.

    Article  Google Scholar 

  28. Tofilon PJ, Fike JR. The radioresponse of the central nervous system: a dynamic process. Radiat Res. 2000;153:357–70.

    Article  CAS  Google Scholar 

  29. Sasaki R, Matsumoto A, Itoh K, Kawabe T, Ota Y, Yamada K, et al. Target cells of apoptosis in the adult murine dentate gyrus and O4 immunoreactivity after ionizing radiation. Neurosci Lett. 2000;279:57–60.

    Article  CAS  Google Scholar 

  30. Schultheiss TE, Stephens LC. Permanent radiation myelopathy. Br J Radiol. 1992;65:737–53.

    Article  CAS  Google Scholar 

  31. Monje ML, Vogel H, Masek M, Ligon KL, Fisher PG, Palmer TD. Impaired human hippocampal neurogenesis after treatment for central nervous system malignancies. Ann Neurol. 2007;62:515–20.

    Article  Google Scholar 

  32. Gebicke-Haerter PJ. Microglia in neurodegeneration: molecular aspects. Microsc Res Tech. 2001;54:47–58.

    Article  CAS  Google Scholar 

  33. Joo KM, Jin J, Kang BG, Lee SJ, Kim KH, Yang H, et al. Trans-differentiation of neural stem cells: a therapeutic mechanism against the radiation induced brain damage. PLoS ONE. 2012;7:e25936.

    Article  CAS  Google Scholar 

  34. Nagel BJ, Palmer SL, Reddick WE, Glass JO, Helton KJ, et al. Abnormal hippocampal development in children with medulloblastoma treated with risk-adapted irradiation. AJNR Am J Neuroradiol. 2004;25:1575–82.

    PubMed  Google Scholar 

  35. Olsson E, Eckerström C, Berg G, Borga M, Ekholm S, et al. Hippocampal volumes in patients exposed to low-dose radiation to the basal brain. A case-control study in long-term survivors from cancer in the head and neck region. Radiat Oncol. 2012;7:202.

    Article  Google Scholar 

  36. Oehlke O, Wucherphennig D, Fels F, Frings L, Egger K, et al. Whole brain irradiation with hippocampal sparing and dose escalation on multiple brain metastases. Strablenther Onkol. 2015;38:439–49.

    Google Scholar 

  37. Lin SY, Yang CC, Wu YM, Tseng CK, Wei KC, et al. Evaluating the impact of hippocampal sparing during whole brain radiotherapy on neurocognitive functions: a preliminary report of a prospective phase II study. Biomed J. 2015;38(5):439–49.

    Article  Google Scholar 

  38. Gondi V, Pugh SL, Tome WA, Caine C, Corn B, 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.

    Article  Google Scholar 

  39. Molly S, Soh C, Williams TL. Reversible delayed posthypoxic leukoencephalopathy. AJNR Am J Neuroradiol. 2006;27:1763–5.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Radiology, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan

    Yohei Takeshita, Keita Watanabe, Shingo Kakeda, Toshihiko Hamamura, Koichiro Sugimoto, Hiromi Masaki, Issei Ueda, Natsuki Igata, Takayuki Ohguri & Yukunori Korogi

Authors
  1. Yohei Takeshita
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Keita Watanabe
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shingo Kakeda
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Toshihiko Hamamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Koichiro Sugimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hiromi Masaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Issei Ueda
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Natsuki Igata
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Takayuki Ohguri
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Yukunori Korogi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Keita Watanabe.

Ethics declarations

Ethical statement

All applicable institutional and national guidelines for the care and use of animals were followed.

Conflict of interest

The authors declare that they have no conflict of interest.

Informed consent

This study was approved by our institutional review board. Informed consent was obtained in the form of opt-out on the website.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Takeshita, Y., Watanabe, K., Kakeda, S. et al. Early volume reduction of the hippocampus after whole-brain radiation therapy: an automated brain structure segmentation study. Jpn J Radiol 38, 118–125 (2020). https://doi.org/10.1007/s11604-019-00895-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11604-019-00895-3

Keywords

Search

Navigation