Skip to main content

Advertisement

SpringerLink
Log in

Dose-dependent early white matter alterations in patients with brain metastases after radiotherapy

  • Interventional Neuroradiology
  • Published:
Neuroradiology Aims and scope Submit manuscript

Abstract

Purpose

Previous diffusion tensor imaging (DTI) studies have mainly focused on dose-dependent white matter (WM) alterations 1 month to 1 year after radiation therapy (RT) with a tract-average method. However, WM alterations immediately after RT are subtle, resulting in early WM alterations that cannot be detected by tract-average methods. Therefore, we performed a study with an along-tract method in patients with brain metastases to explore the early dose–response pattern of WM alterations after RT.

Methods

Sixteen patients with brain metastases underwent DTI before and 1–3 days after brain RT. DTI metrics, such as fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD), were calculated. Along-tract statistics were then used to resample WM fibre streamlines and generate a WM skeleton fibre tract. DTI metric alterations (post_RT-pre_RT DTI metrics) and the planned doses (max or mean doses) were mapped to 18 WM tracts. A linear fixed model was performed to analyse the main effect of dose on DTI metric alterations.

Results

AD alterations in the left hemispheric uncinated fasciculus (UNC_L) were associated with max doses, in which decreased AD alterations were associated with higher doses.

Conclusion

Our findings may provide pathological insight into early dose-dependent WM alterations and may contribute to the development of max dose-constrained RT techniques to protect brain microstructure in the UNC_L.

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
Fig. 3

Similar content being viewed by others

Abbreviations

AD:

Axial diffusivity

CG:

Cinguli

CNS:

Central nervous system

CST:

Corticospinal tract

DTI:

Diffusion tensor imaging

FA:

Fractional anisotropy

FACT:

Fibre assignment by continuous

FLAIR:

Fluid-attenuated inversion recovery

IFO:

Inferior fronto-occipital tract

ILF:

Inferior longitudinal fasciculus

MD:

Mean diffusivity

MRI:

Magnetic resonance imaging

RD:

Radial diffusivity

RT:

Radiation therapy

SLF-fp:

Superior longitudinal fasciculus anterior segment

SLF-pt:

Superior longitudinal fasciculus posterior segment

SLF-t:

Superior longitudinal fasciculus long segment

UNC:

Uncinated fasciculus

WM:

White matter

References

  1. Suh JH, Kotecha R, Chao ST, Ahluwalia MS, Sahgal A, Chang EL (2020) Current approaches to the management of brain metastases. Nat Rev Clin Oncol 17:279–299

    Article  Google Scholar 

  2. Olson R, Tyldesley S, Carolan H, Parkinson M, Chhanabhai T, McKenzie M (2011) Prospective comparison of the prognostic utility of the Mini Mental State Examination and the Montreal Cognitive Assessment in patients with brain metastases. Support Care Cancer 19:1849–1855

    Article  Google Scholar 

  3. Li J, Bentzen SM, Li J, Renschler M, Mehta MP (2008) Relationship between neurocognitive function and quality of life after whole-brain radiotherapy in patients with brain metastasis. Int J Radiat Oncol Biol Phys 71:64–70

    Article  Google Scholar 

  4. Mahajan A, Ahmed S, McAleer MF et al (2017) Post-operative stereotactic radiosurgery versus observation for completely resected brain metastases: a single-centre, randomised, controlled, phase 3 trial. Lancet Oncol 18:1040–1048

    Article  Google Scholar 

  5. Brown PD, Jaeckle K, Ballman KV et al (2016) Effect of radiosurgery alone vs radiosurgery with whole brain radiation therapy on cognitive function in patients with 1 to 3 brain metastases: a randomized clinical trial. JAMA 316:401–409

    Article  Google Scholar 

  6. Fan L (2021) Mapping the human brain: what is the next frontier? Innovation (N Y) 2:100073

    Google Scholar 

  7. Brown WR, Thore CR, Moody DM, Robbins ME, Wheeler KT (2005) Vascular damage after fractionated whole-brain irradiation in rats. Radiat Res 164:662–668

    Article  Google Scholar 

  8. Tsuruda JS, Kortman KE, Bradley WG, Wheeler DC, Van Dalsem W, Bradley TP (1987) Radiation effects on cerebral white matter: MR evaluation. AJR Am J Roentgenol 149:165–171

    Article  Google Scholar 

  9. Lee WH, Sonntag WE, Mitschelen M, Yan H, Lee YW (2010) Irradiation induces regionally specific alterations in pro-inflammatory environments in rat brain. Int J Radiat Biol 86:132–144

    Article  Google Scholar 

  10. Warrington JP, Ashpole N, Csiszar A, Lee YW, Ungvari Z, Sonntag WE (2013) Whole brain radiation-induced vascular cognitive impairment: mechanisms and implications. J Vasc Res 50:445–457

    Article  Google Scholar 

  11. Ljubimova NV, Levitman MK, Plotnikova ED, Eidus L (1991) Endothelial cell population dynamics in rat brain after local irradiation. Br J Radiol 64:934–940

    Article  Google Scholar 

  12. Wu PH, Coultrap S, Pinnix C et al (2012) Radiation induces acute alterations in neuronal function. PLoS ONE 7:e37677

    Article  Google Scholar 

  13. Greene-Schloesser D, Robbins ME, Peiffer AM, Shaw EG, Wheeler KT, Chan MD (2012) Radiation-induced brain injury: a review. Front Oncol 2:73

    Article  Google Scholar 

  14. Makale MT, McDonald CR, Hattangadi-Gluth JA, Kesari S (2017) Mechanisms of radiotherapy-associated cognitive disability in patients with brain tumours. Nat Rev Neurol 13:52–64

    Article  Google Scholar 

  15. Cramer CK, Cummings TL, Andrews RN et al (2019) Treatment of radiation-induced cognitive decline in adult brain tumor patients. Curr Treat Options Oncol 20:42

    Article  Google Scholar 

  16. Tournier JD (2019) Diffusion MRI in the brain - theory and concepts. Prog Nucl Magn Reson Spectrosc 112–113:1–16

    Article  Google Scholar 

  17. Zhu T, Chapman CH, Tsien C et al (2016) Effect of the maximum dose on white matter fiber bundles using longitudinal diffusion tensor imaging. Int J Radiat Oncol Biol Phys 96:696–705

    Article  Google Scholar 

  18. Connor M, Karunamuni R, McDonald C et al (2017) Regional susceptibility to dose-dependent white matter damage after brain radiotherapy. Radiother Oncol 123:209–217

    Article  Google Scholar 

  19. Raschke F, Wesemann T, Wahl H et al (2019) Reduced diffusion in normal appearing white matter of glioma patients following radio (chemo)therapy. Radiother Oncol 140:110–115

    Article  Google Scholar 

  20. Hope TR, Vardal J, Bjornerud A et al (2015) Serial diffusion tensor imaging for early detection of radiation-induced injuries to normal-appearing white matter in high-grade glioma patients. J Magn Reson Imaging 41:414–423

    Article  Google Scholar 

  21. Chapman CH, Nagesh V, Sundgren PC et al (2012) Diffusion tensor imaging of normal-appearing white matter as biomarker for radiation-induced late delayed cognitive decline. Int J Radiat Oncol Biol Phys 82:2033–2040

    Article  Google Scholar 

  22. Connor M, Karunamuni R, McDonald C et al (2016) Dose-dependent white matter damage after brain radiotherapy. Radiother Oncol 121:209–216

    Article  Google Scholar 

  23. Colby JB, Soderberg L, Lebel C, Dinov ID, Thompson PM, Sowell ER (2012) Along-tract statistics allow for enhanced tractography analysis. Neuroimage 59:3227–3242

    Article  Google Scholar 

  24. Oldfield RC (1971) The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia 9:97–113

    Article  Google Scholar 

  25. Cox RW (2012) AFNI: what a long strange trip it’s been. Neuroimage 62:743–747

    Article  Google Scholar 

  26. Zhang Y, Zhang J, Oishi K et al (2010) Atlas-guided tract reconstruction for automated and comprehensive examination of the white matter anatomy. Neuroimage 52:1289–1301

    Article  Google Scholar 

  27. Oishi K, Faria A, Jiang H et al (2009) Atlas-based whole brain white matter analysis using large deformation diffeomorphic metric mapping: application to normal elderly and Alzheimer’s disease participants. Neuroimage 46:486–499

    Article  Google Scholar 

  28. Mori S, Crain BJ, Chacko VP, van Zijl PC (1999) Three-dimensional tracking of axonal projections in the brain by magnetic resonance imaging. Ann Neurol 45:265–269

    Article  Google Scholar 

  29. Corouge I, Gouttard S, Gerig G (2004) Towards a shape model of white matter fiber bundles using diffusion tensor MRI2004 2nd IEEE International Symposium on Biomedical Imaging: Nano to Macro (IEEE Cat No 04EX821), pp 344–347 Vol. 341

  30. Pinheiro JC, Bates DM (1996) Unconstrained parametrizations for variance-covariance matrices. Stat Comput 6:289–296

    Article  Google Scholar 

  31. Parihar VK, Pasha J, Tran KK, Craver BM, Acharya MM, Limoli CL (2015) Persistent changes in neuronal structure and synaptic plasticity caused by proton irradiation. Brain Struct Funct 220:1161–1171

    Article  Google Scholar 

  32. Gondi V, Pugh SL, Tome WA et al (2014) 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 32:3810–3816

    Article  Google Scholar 

  33. Gondi V, Pugh S, Brown PD et al (2018) NCOG-01. Preservation of neurocognitive function (NCF) with hippocampal avoidance during whole-brain radiotherapy (WBRT) For brain metastases: preliminary results of phase iii trial nrg oncology CC001. Neuro-Oncology 20:vi172

    Article  Google Scholar 

  34. Follin C, Svärd D, van Westen D et al (2019) Microstructural white matter alterations associated to neurocognitive deficits in childhood leukemia survivors treated with cranial radiotherapy - a diffusional kurtosis study. Acta Oncol 58:1021–1028

    Article  Google Scholar 

  35. Von Der Heide RJ, Skipper LM, Klobusicky E, Olson IR (2013) Dissecting the uncinate fasciculus: disorders, controversies and a hypothesis. Brain 136:1692–1707

    Article  Google Scholar 

  36. Hein TC, Mattson WI, Dotterer HL et al (2018) Amygdala habituation and uncinate fasciculus connectivity in adolescence: a multi-modal approach. Neuroimage 183:617–626

    Article  Google Scholar 

  37. Wang HZ, Qiu SJ, Lv XF et al (2012) Diffusion tensor imaging and 1H-MRS study on radiation-induced brain injury after nasopharyngeal carcinoma radiotherapy. Clin Radiol 67:340–345

    Article  Google Scholar 

  38. Hwang SY, Jung JS, Kim TH et al (2006) Ionizing radiation induces astrocyte gliosis through microglia activation. Neurobiol Dis 21:457–467

    Article  Google Scholar 

  39. Kurita H, Kawahara N, Asai A, Ueki K, Shin M, Kirino T (2001) Radiation-induced apoptosis of oligodendrocytes in the adult rat brain. Neurol Res 23:869–874

    Article  Google Scholar 

  40. Witzmann K, Raschke F, Troost EGC (2021) MR image changes of normal-appearing brain tissue after radiotherapy. Cancers (Basel) 13:1573

    Article  Google Scholar 

Download references

Acknowledgements

We thank the Hefei Cancer hospital, Chinese Academy of Science, for their help and support in this project.

Funding

This work was supported by the Key R&D Program of Anhui Province (grant numbers:201904a07020104), the Natural Science Fund of Anhui Province (grant numbers:2008085MC69), Collaborative Innovation Program of Hefei Science Center (grant numbers:2020HSC-CIP001, 2021HSC-CIP013), the General scientific research project of Anhui Provincial Health Commission (grant numbers: AHWJ2021b150), the Natural Science Fund of Hefei City (grant numbers:2021033), CAS Anhui Province Key Laboratory of Medical Physics and Technology (grant numbers: LMPT201904) and Director’s Fund of Hefei Cancer Hospital of CAS (grant numbers: YZJJ2019C14, YZJJ2019A04).

Author information

Authors and Affiliations

  1. Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, People’s Republic of China

    Yixin Wang, Jin Liu, Jinwei Lang, Zongtao Hu, Lizhuang Yang, Hongzhi Wang & Hai Li

  2. University of Science and Technology of China, Hefei, 230026, People’s Republic of China

    Yixin Wang, Jin Liu, Jinwei Lang, Zongtao Hu, Lizhuang Yang, Hongzhi Wang & Hai Li

  3. Department of Oncology, Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei, 230031, People’s Republic of China

    Xiuli Xu, Yongkang Zhang & Qi Chen

Authors
  1. Yixin Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jin Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jinwei Lang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zongtao Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xiuli Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yongkang Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Qi Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Lizhuang Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Hongzhi Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Hai Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Hongzhi Wang or Hai Li.

Ethics declarations

Ethics approval

All study participants provided written informed consent. The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Institutional Review Board (or Ethics Committee) of Hefei Cancer hospital, Chinese academy of science (protocol code SL-KY2020-001 and date of approval,20 January 2020).

Informed consent

Informed consent was obtained from all individual participants included in the study.

Competing interests

The authors declare no competing interests or personal relationships that could have appeared to influence the work reported in this paper.

Additional information

Publisher’s note

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

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 372 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, Y., Liu, J., Lang, J. et al. Dose-dependent early white matter alterations in patients with brain metastases after radiotherapy. Neuroradiology 65, 167–176 (2023). https://doi.org/10.1007/s00234-022-03020-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00234-022-03020-w

Keywords

Search

Navigation