Advertisement

European Radiology

, Volume 29, Issue 3, pp 1308–1317 | Cite as

Quantitative dynamic contrast-enhanced MR imaging shows widespread blood-brain barrier disruption in mild traumatic brain injury patients with post-concussion syndrome

  • Roh-Eul Yoo
  • Seung Hong ChoiEmail author
  • Byung-Mo Oh
  • Sang Do Shin
  • Eun Jung Lee
  • Dong Jae Shin
  • Sang Won Jo
  • Koung Mi Kang
  • Tae Jin Yun
  • Ji-hoon Kim
  • Chul-Ho Sohn
Neuro

Abstract

Objectives

To explore the utility of dynamic contrast-enhanced (DCE) MR imaging for quantitative analysis of blood-brain barrier disruption in mild traumatic brain injury (mTBI) patients with post-concussion syndrome (PCS).

Methods

Forty-four consecutive patients with PCS after mTBI and 32 controls were included in this retrospective study. Ktrans and ve from DCE MR imaging were analyzed at contrast-enhancing lesions, T2 hyperintense white matter (WM) lesions, normal-appearing white matter (NAWM), and predilection sites for diffuse axonal injury (LocationDAI). The Mann-Whitney U-test was performed to compare the parameters between mTBI patients and controls and the parameters were correlated with neuropsychological tests using Mann-Whitney U-test and Spearman rank correlation.

Results

The median ve of the T2 hyperintense WM lesions in mTBI patients (n=21) was higher than that of NAWM in controls (p=.027). Both median Ktrans and ve at NAWM were also significantly higher in mTBI patients than in controls (p=.023 and p=.029, respectively). In addition, mTBI patients had higher Ktrans and ve at LocationDAI than controls (p=.008 and p=.015, respectively). VLT (delayed recall) scores were significantly correlated with ve values at T2 hyperintense WM lesions (p=−0.767, p=.044). The median ve at LocationDAI was significantly higher in patients with atypical performance in the digit span test (forward) than in those with average or good performance (p=.043).

Conclusions

mTBI patients with PCS had higher Ktrans and ve values than controls not only at T2 hyperintense WM lesions but also at NAWM and LocationDAI. BBB disruption may be implicated in development of PCS in mTBI patients.

Key Points

• mTBI patients with PCS had higher permeability than controls at T2 hyperintense WM lesions on DCE MR imaging.

• mTBI patients with PCS had higher permeability than controls also at NAWM and predilection sites for DAI.

• BBB disruption may be implicated in the development of PCS in mTBI patients.

Keywords

Blood-brain barrier Magnetic resonance imaging Perfusion Permeability Post-concussion syndrome (PCS) 

Abbreviations

3D

Three-dimensional

BBB

Blood-brain barrier

CNS

Central nervous system

CNT

Computerized neurocognitive function tests

CPT

Continuous performance test

DAI

Diffuse axonal injury

DCE

Dynamic contrast-enhanced

DTI

Diffusion tensor imaging

DWI

Diffusion-weighted imaging

FLAIR

Fluid-attenuated inversion recovery

FSPGR

Fast spoiled gradient echo

IQR

Interquartile range

mTBI

Mild TBI

NAWM

Normal-appearing white matter

PCS

Post-concussion syndrome

ROC

Receiver operating characteristics

RPQ

Rivermead post-concussion symptoms questionnaire

SWI

Susceptibility-weighted imaging

VLT

Verbal learning test

WM

White matter

Notes

Funding

This study was supported by a grant from Bayer Healthcare, the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare of South Korea (HI16C1111), and by the Ministry of Science, ICT & Future Planning (2016M3C7A1914002), by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2017R1A2B2006526) and by the Ministry of Education (2017R1D1A1B04034838), by Creative-Pioneering Researchers Program through Seoul National University (SNU), and by Project Code (IBS-R006-D1).

Compliance with ethical standards

Guarantor

The scientific guarantor of this publication is Seung Hong Choi.

Conflict of interest

The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article.

Statistics and biometry

No complex statistical methods were necessary for this paper.

Informed consent

Written informed consent was waived by the Institutional Review Board.

Ethical approval

Institutional Review Board approval was obtained.

Methodology

• retrospective

• case-control study / cross sectional study / observational

• performed at one institution

Supplementary material

330_2018_5656_MOESM1_ESM.docx (36 kb)
ESM 1 (DOCX 36 kb)

References

  1. 1.
    Cassidy JD, Carroll LJ, Peloso PM et al (2004) Incidence, risk factors and prevention of mild traumatic brain injury: results of the WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury. J Rehabil Med:28–60Google Scholar
  2. 2.
    Daneshvar DH, Riley DO, Nowinski CJ, McKee AC, Stern RA, Cantu RC (2011) Long-term consequences: effects on normal development profile after concussion. Phys Med Rehabil Clin N Am 22:683–700 ixCrossRefGoogle Scholar
  3. 3.
    Evans RW (1992) The postconcussion syndrome and the sequelae of mild head injury. Neurol Clin 10:815–847CrossRefGoogle Scholar
  4. 4.
    Riedy G, Senseney JS, Liu W et al (2015) Findings from Structural MR Imaging in Military Traumatic Brain Injury. Radiology.  https://doi.org/10.1148/radiol.2015150438:150438
  5. 5.
    Rosenfeld JV, Maas AI, Bragge P, Morganti-Kossmann MC, Manley GT, Gruen RL (2012) Early management of severe traumatic brain injury. Lancet 380:1088–1098CrossRefGoogle Scholar
  6. 6.
    Bouix S, Pasternak O, Rathi Y, Pelavin PE, Zafonte R, Shenton ME (2013) Increased gray matter diffusion anisotropy in patients with persistent post-concussive symptoms following mild traumatic brain injury. PLoS One 8:e66205CrossRefGoogle Scholar
  7. 7.
    Yuh EL, Cooper SR, Mukherjee P et al (2014) Diffusion tensor imaging for outcome prediction in mild traumatic brain injury: a TRACK-TBI study. J Neurotrauma 31:1457–1477CrossRefGoogle Scholar
  8. 8.
    Ge Y, Patel MB, Chen Q et al (2009) Assessment of thalamic perfusion in patients with mild traumatic brain injury by true FISP arterial spin labelling MR imaging at 3T. Brain Inj 23:666–674CrossRefGoogle Scholar
  9. 9.
    Grossman EJ, Jensen JH, Babb JS et al (2013) Cognitive impairment in mild traumatic brain injury: a longitudinal diffusional kurtosis and perfusion imaging study. AJNR Am J Neuroradiol 34:951–957 S951-953CrossRefGoogle Scholar
  10. 10.
    Liu W, Wang B, Wolfowitz R et al (2013) Perfusion deficits in patients with mild traumatic brain injury characterized by dynamic susceptibility contrast MRI. NMR Biomed 26:651–663Google Scholar
  11. 11.
    Nag S, Kapadia A, Stewart DJ (2011) Review: molecular pathogenesis of blood-brain barrier breakdown in acute brain injury. Neuropathol Appl Neurobiol 37:3–23CrossRefGoogle Scholar
  12. 12.
    Haroon HA, Buckley DL, Patankar TA et al (2004) A comparison of Ktrans measurements obtained with conventional and first pass pharmacokinetic models in human gliomas. J Magn Reson Imaging 19:527–536CrossRefGoogle Scholar
  13. 13.
    Harrer JU, Parker GJ, Haroon HA et al (2004) Comparative study of methods for determining vascular permeability and blood volume in human gliomas. J Magn Reson Imaging 20:748–757CrossRefGoogle Scholar
  14. 14.
    Tofts PS, Brix G, Buckley DL et al (1999) Estimating kinetic parameters from dynamic contrast-enhanced T(1)-weighted MRI of a diffusable tracer: standardized quantities and symbols. J Magn Reson Imaging 10:223–232CrossRefGoogle Scholar
  15. 15.
    Wei XE, Wang D, Li MH, Zhang YZ, Li YH, Li WB (2011) A useful tool for the initial assessment of blood-brain barrier permeability after traumatic brain injury in rabbits: dynamic contrast-enhanced magnetic resonance imaging. J Trauma 71:1645–1650 discussion 1650-1641Google Scholar
  16. 16.
    Weissberg I, Veksler R, Kamintsky L et al (2014) Imaging blood-brain barrier dysfunction in football players. JAMA Neurol 71:1453–1455CrossRefGoogle Scholar
  17. 17.
    Winter C, Bell C, Whyte T, Cardinal J, Macfarlane D, Rose S (2015) Blood-brain barrier dysfunction following traumatic brain injury: correlation of K(trans) (DCE-MRI) and SUVR (99mTc-DTPA SPECT) but not serum S100B. Neurol Res 37:599–606CrossRefGoogle Scholar
  18. 18.
    King NS, Crawford S, Wenden FJ, Moss NE, Wade DT (1995) The Rivermead Post Concussion Symptoms Questionnaire: a measure of symptoms commonly experienced after head injury and its reliability. J Neurol 242:587–592CrossRefGoogle Scholar
  19. 19.
    Ryan LM, Warden DL (2003) Post concussion syndrome. Int Rev Psychiatry 15:310–316CrossRefGoogle Scholar
  20. 20.
    Abbott NJ, Rönnbäck L, Hansson E (2006) Astrocyte-endothelial interactions at the blood-brain barrier. Nat Rev Neurosci 7:41–53CrossRefGoogle Scholar
  21. 21.
    Adelson PD, Whalen MJ, Kochanek PM, Robichaud P, Carlos TM (1998) Blood brain barrier permeability and acute inflammation in two models of traumatic brain injury in the immature rat: a preliminary report. Acta Neurochir Suppl 71:104–106Google Scholar
  22. 22.
    Hawkins BT, Davis TP (2005) The blood-brain barrier/neurovascular unit in health and disease. Pharmacol Rev 57:173–185CrossRefGoogle Scholar
  23. 23.
    Sharma HS, Patnaik R, Patnaik S, Mohanty S, Sharma A, Vannemreddy P (2007) Antibodies to serotonin attenuate closed head injury induced blood brain barrier disruption and brain pathology. Ann N Y Acad Sci 1122:295–312CrossRefGoogle Scholar
  24. 24.
    Tomkins O, Shelef I, Kaizerman I et al (2008) Blood-brain barrier disruption in post-traumatic epilepsy. J Neurol Neurosurg Psychiatry 79:774–777CrossRefGoogle Scholar
  25. 25.
    Unterberg AW, Stover J, Kress B, Kiening KL (2004) Edema and brain trauma. Neuroscience 129:1021–1029CrossRefGoogle Scholar
  26. 26.
    van Vliet EA, da Costa Araújo S, Redeker S, van Schaik R, Aronica E, Gorter JA (2007) Blood-brain barrier leakage may lead to progression of temporal lobe epilepsy. Brain 130:521–534CrossRefGoogle Scholar
  27. 27.
    Zlokovic BV (2008) The blood-brain barrier in health and chronic neurodegenerative disorders. Neuron 57:178–201CrossRefGoogle Scholar
  28. 28.
    Csuka E, Morganti-Kossmann MC, Lenzlinger PM, Joller H, Trentz O, Kossmann T (1999) IL-10 levels in cerebrospinal fluid and serum of patients with severe traumatic brain injury: relationship to IL-6, TNF-alpha, TGF-beta1 and blood-brain barrier function. J Neuroimmunol 101:211–221CrossRefGoogle Scholar
  29. 29.
    Kapural M, Krizanac-Bengez Lj, Barnett G et al (2002) Serum S-100beta as a possible marker of blood-brain barrier disruption. Brain Res 940:102–104CrossRefGoogle Scholar
  30. 30.
    Kassner A, Roberts TP, Moran B, Silver FL, Mikulis DJ (2009) Recombinant tissue plasminogen activator increases blood-brain barrier disruption in acute ischemic stroke: an MR imaging permeability study. AJNR Am J Neuroradiol 30:1864–1869CrossRefGoogle Scholar
  31. 31.
    van Vliet EA, Otte WM, Gorter JA, Dijkhuizen RM, Wadman WJ (2014) Longitudinal assessment of blood-brain barrier leakage during epileptogenesis in rats. A quantitative MRI study. Neurobiol Dis 63:74–84CrossRefGoogle Scholar
  32. 32.
    Yun TJ, Park CK, Kim TM et al (2015) Glioblastoma treated with concurrent radiation therapy and temozolomide chemotherapy: differentiation of true progression from pseudoprogression with quantitative dynamic contrast-enhanced MR imaging. Radiology 274:830–840CrossRefGoogle Scholar
  33. 33.
    Zhang CE, Wong SM, van de Haar HJ et al (2017) Blood-brain barrier leakage is more widespread in patients with cerebral small vessel disease. Neurology 88:426–432CrossRefGoogle Scholar
  34. 34.
    Korn A, Golan H, Melamed I, Pascual-Marqui R, Friedman A (2005) Focal cortical dysfunction and blood-brain barrier disruption in patients with Postconcussion syndrome. J Clin Neurophysiol 22:1–9CrossRefGoogle Scholar
  35. 35.
    Parizel PM, Ozsarlak, Van Goethem JW et al (1998) Imaging findings in diffuse axonal injury after closed head trauma. Eur Radiol 8:960–965Google Scholar
  36. 36.
    Shlosberg D, Benifla M, Kaufer D, Friedman A (2010) Blood-brain barrier breakdown as a therapeutic target in traumatic brain injury. Nat Rev Neurol 6:393–403CrossRefGoogle Scholar

Copyright information

© European Society of Radiology 2018

Authors and Affiliations

  • Roh-Eul Yoo
    • 1
  • Seung Hong Choi
    • 1
    • 2
    • 3
    Email author
  • Byung-Mo Oh
    • 4
  • Sang Do Shin
    • 5
  • Eun Jung Lee
    • 6
  • Dong Jae Shin
    • 7
  • Sang Won Jo
    • 8
  • Koung Mi Kang
    • 1
  • Tae Jin Yun
    • 1
  • Ji-hoon Kim
    • 1
  • Chul-Ho Sohn
    • 1
  1. 1.Department of Radiology, Seoul National University HospitalSeoul National University College of MedicineSeoulKorea
  2. 2.Center for Nanoparticle Research, Institute for Basic Science (IBS)Seoul National UniversitySeoulKorea
  3. 3.School of Chemical and Biological EngineeringSeoul National UniversitySeoulKorea
  4. 4.Department of Rehabilitation Medicine, Seoul National University HospitalSeoul National University College of MedicineSeoulKorea
  5. 5.Department of Emergency MedicineSeoul National University College of MedicineSeoulKorea
  6. 6.Department of RadiologyChung-Ang University HospitalSeoulKorea
  7. 7.Department of RadiologySeran General HospitalSeoulKorea
  8. 8.Department of RadiologyKangbuk Samsung HospitalSeoulKorea

Personalised recommendations