Skip to main content

Advertisement

SpringerLink
Log in

Quantitative magnetic resonance imaging assessment of brain injury after successful cardiopulmonary resuscitation in a rat model of asphyxia cardiac arrest

  • Original Research
  • Published:
Brain Imaging and Behavior Aims and scope Submit manuscript

Abstract

The aim of this study was to use dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted magnetic resonance imaging (DWI) to measure changes in blood–brain barrier (BBB) permeability and cerebral edema over time in a rat model of asphyxial cardiac arrest (ACA). ACA was established by endotracheal tube clamping. Male rats were randomized into a sham group (n = 5) and three ACA groups (n = 18). After return of spontaneous circulation (ROSC), the rats were randomized to perform DWI and DCE-MRI exam in the 6 h, 24 h and 72 h timepoint (ROSC + 6 h, ROSC + 24 h, and ROSC + 72 h). Results shows that fifteen of 18 animals achieved successful resuscitation in the ACA groups. The average apparent diffusion coefficient(ADC) value of the whole brain in ROSC + 6 h was markedly lower than those of the sham, ROSC + 24 h, and ROSC + 72 h. The aquaporin-4(AQP4) score in ROSC + 6 h was significantly higher than those in the other groups, which were negatively correlated with the ADC values. The ratio of whole brain to masseter muscle of volume transfer constant (rKtrans), tissue interstitium-to-plasma rate constant(rKep), and fractional extra-cellular space volume(rVe) in ROSC + 6 h were all significantly higher than those in the sham, ROSC + 24 h, and ROSC + 72 h. The transforming growth factor β1(TGF-β1) and vascular endothelial growth factor A(VEGF-a) scores in ROSC + 6 h were significantly higher than those in the other groups, which were all positively correlated with rKtrans and rKep. In conclusions, brain injury is a frequent complication after CA and resuscitation. DWI and DCE-MRI can quantitatively evaluate brain injury in term of cerebral edema and BBB permeability after successful CPR.

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
Fig. 4
Fig. 5

Similar content being viewed by others

Data availability

Data available on request from the corresponding author.

Abbreviations

ACA:

Asphyxial cardiac arrest

ROSC:

Return of spontaneous circulation

CPR:

Cardiopulmonary resuscitation

BBB:

Blood–brain barrier

DWI:

Diffusion-weighted magnetic resonance imaging

MRS:

Magnetic resonance spectroscopy

DCE-MRI:

Dynamic contrast-enhanced magnetic resonance imaging6

QMR:

Quantitative MR

NDS:

Neurology deficit score

PC:

Precordial compression.

References

  • Aksoy, D., Bammer, R., Mlynash, M., et al. (2013). Magnetic resonance imaging profile of blood-brain barrier injury in patients with acute intracerebral hemorrhage. J Am Heart Assoc, 2, e000161.

    Article  Google Scholar 

  • Chalkias, A., & Xanthos, T. (2012). Post-cardiac arrest brain injury: Pathophysiology and treatment. Journal of the Neurological Sciences, 315, 1–8.

    Article  Google Scholar 

  • Drabek, T., Foley, L. M., Janata, A., et al. (2014). Global and regional differences in cerebral blood flow after asphyxial versus ventricular fibrillation cardiac arrest in rats using asl-mri. Resuscitation, 85, 964–971.

    Article  Google Scholar 

  • Fink, E. L., Panigrahy, A., Clark, R. S., et al. (2013). Regional brain injury on conventional and diffusion weighted mri is associated with outcome after pediatric cardiac arrest. Neurocritical Care, 19, 31–40.

    Article  Google Scholar 

  • Gong, P., Zhao, S., Wang, J., et al. (2015). Mild hypothermia preserves cerebral cortex microcirculation after resuscitation in a rat model of cardiac arrest. Resuscitation, 97, 109–114.

    Article  Google Scholar 

  • Hendrickx, H. H., Rao, G. R., Safar, P., et al. (1984). Asphyxia, cardiac arrest and resuscitation in rats. I. Short term recovery. Resuscitation, 12, 97–116.

    Article  CAS  Google Scholar 

  • Nagaraja, T. N., Karki, K., Ewing, J. R., et al. (2010). The MRI-measured arterial input function resulting from a bolus injection of Gd-DTPA in a rat model of stroke slightly underestimates that of Gd-[14C]DTPA and marginally overestimates the blood-to-brain influx rate constant determined by Patlak plots. Magnetic Resonance in Medicine, 63, 1502–1509.

    Article  CAS  Google Scholar 

  • Heye, A. K., Thrippleton, M. J., Armitage, P. A., et al. (2016). Tracer kinetic modelling for dce-mri quantification of subtle blood-brain barrier permeability. NeuroImage, 125, 446–455.

    Article  Google Scholar 

  • Hirsch, K. G., Mlynash, M., Jansen, S., et al. (2015). Prognostic value of a qualitative brain mri scoring system after cardiac arrest. Journal of Neuroimaging, 25, 430–437.

    Article  Google Scholar 

  • Iwai, M., Cao, G., Chen, J., et al. (2007). Erythropoietin promotes neuronal replacement through revascularization and neurogenesis after neonatal hypoxia/ischemia in rats. Stroke, 38, 2795–2803.

    Article  CAS  Google Scholar 

  • Jarnum, H., Knutsson, L., Rundgren, M., et al. (2009). Diffusion and perfusion mri of the brain in comatose patients treated with mild hypothermia after cardiac arrest: A prospective observational study. Resuscitation, 80, 425–430.

    Article  Google Scholar 

  • Laver, S., Farrow, C., Turner, D., et al. (2004). Mode of death after admission to an intensive care unit following cardiac arrest. Intensive Care Medicine, 30, 2126–2128.

    Article  Google Scholar 

  • Luyt, C. E., Galanaud, D., Perlbarg, V., et al. (2012). Diffusion tensor imaging to predict long-term outcome after cardiac arrest: A bicentric pilot study. Anesthesiology, 117, 1311–1321.

    Article  Google Scholar 

  • McMillin, M. A., Frampton, G. A., Seiwell, A. P., et al. (2015). Tgfbeta1 exacerbates blood-brain barrier permeability in a mouse model of hepatic encephalopathy via upregulation of mmp9 and downregulation of claudin-5. Laboratory Investigation, 95, 903–913.

    Article  CAS  Google Scholar 

  • Memar, M., Geara, S. J., Hjalmarsson, P., et al. (2018). Long-term mortality and morbidity among 30-day survivors after in-hospital cardiac arrests - a swedish cohort study. Resuscitation, 124, 76–79.

    Article  Google Scholar 

  • Moler, F. W., Silverstein, F. S., Holubkov, R., et al. (2017). Therapeutic hypothermia after in-hospital cardiac arrest in children. New England Journal of Medicine, 376, 318–329.

    Article  Google Scholar 

  • Moon, H. K., Jang, J., Park, K. N., et al. (2018). Quantitative analysis of relative volume of low apparent diffusion coefficient value can predict neurologic outcome after cardiac arrest. Resuscitation, 126, 36–42.

    Article  Google Scholar 

  • Nolan, J. P., Neumar, R. W., Adrie, C., et al. (2008). Post-cardiac arrest syndrome: Epidemiology, pathophysiology, treatment, and prognostication. A scientific statement from the international liaison committee on resuscitation; the american heart association emergency cardiovascular care committee; the council on cardiovascular surgery and anesthesia; the council on cardiopulmonary, perioperative, and critical care; the council on clinical cardiology; the council on stroke. Resuscitation, 79, 350–379.

    Article  Google Scholar 

  • Pan, A., Kumar, R., Macey, P. M., et al. (2013). Visual assessment of brain magnetic resonance imaging detects injury to cognitive regulatory sites in patients with heart failure. Journal of Cardiac Failure, 19, 94–100.

    Article  Google Scholar 

  • Pillai, D. R., Dittmar, M. S., Baldaranov, D., et al. (2009). Cerebral ischemia-reperfusion injury in rats–a 3 t mri study on biphasic blood-brain barrier opening and the dynamics of edema formation. Journal of Cerebral Blood Flow and Metabolism, 29, 1846–1855.

    Article  Google Scholar 

  • Pluta, R., Lossinsky, A. S., Wisniewski, H. M., et al. (1994). Early blood-brain barrier changes in the rat following transient complete cerebral ischemia induced by cardiac arrest. Brain Research, 633, 41–52.

    Article  CAS  Google Scholar 

  • Ramont, L., Thoannes, H., Volondat, A., et al. (2005). Effects of hemolysis and storage condition on neuron-specific enolase (nse) in cerebrospinal fluid and serum: Implications in clinical practice. Clinical Chemistry and Laboratory Medicine, 43, 1215–1217.

    Article  CAS  Google Scholar 

  • Rossetti, A. O., Rabinstein, A. A., & Oddo, M. (2016). Neurological prognostication of outcome in patients in coma after cardiac arrest. Lancet Neurology, 15, 597–609.

    Article  Google Scholar 

  • Ryoo, S. M., Jeon, S. B., Sohn, C. H., et al. (2015). Predicting outcome with diffusion-weighted imaging in cardiac arrest patients receiving hypothermia therapy: Multicenter retrospective cohort study. Critical Care Medicine, 43, 2370–2377.

    Article  CAS  Google Scholar 

  • Samaniego, E. A., Mlynash, M., Caulfield, A. F., et al. (2011). Sedation confounds outcome prediction in cardiac arrest survivors treated with hypothermia. Neurocritical Care, 15, 113–119.

    Article  Google Scholar 

  • Sharma, H. S., Miclescu, A., & Wiklund, L. (2011). Cardiac arrest-induced regional blood-brain barrier breakdown, edema formation and brain pathology: A light and electron microscopic study on a new model for neurodegeneration and neuroprotection in porcine brain. Journal of Neural Transmission (Vienna), 118, 87–114.

    Article  Google Scholar 

  • Shim, J. W., & Madsen, J. R. (2018). Vegf signaling in neurological disorders. International Journalof Molecular Sciences, 19, 275.

    Article  Google Scholar 

  • Soslow, R. A., Dannenberg, A. J., Rush, D., et al. (2000). Cox-2 is expressed in human pulmonary, colonic, and mammary tumors. Cancer, 89, 2637–2645.

    Article  CAS  Google Scholar 

  • Stammet, P., Collignon, O., Hassager, C., et al. (2015). Neuron-specific enolase as a predictor of death or poor neurological outcome after out-of-hospital cardiac arrest and targeted temperature management at 33 degrees c and 36 degrees c. Journal of the American College of Cardiology, 65, 2104–2114.

    Article  CAS  Google Scholar 

  • Tang, Z. R., Li, C. S., Zhao, H., et al. (2013). Effects of hypothermia on brain injury assessed by magnetic resonance imaging after cardiopulmonary resuscitation in a porcine model of cardiac arrest. American Journal of Emergency Medicine, 31, 86–93.

    Article  Google Scholar 

  • Tjepkema-Cloostermans, M. C., Hofmeijer, J., Beishuizen, A., et al. (2017). Cerebral recovery index: Reliable help for prediction of neurologic outcome after cardiac arrest. Critical Care Medicine, 45, e789–e797.

    Article  Google Scholar 

  • Tress, E. E., Clark, R. S., Foley, L. M., et al. (2014). Blood brain barrier is impermeable to solutes and permeable to water after experimental pediatric cardiac arrest. Neuroscience Letters, 578, 17–21.

    Article  CAS  Google Scholar 

  • Vlachos, F., Tung, Y. S., & Konofagou, E. (2011). Permeability dependence study of the focused ultrasound-induced blood-brain barrier opening at distinct pressures and microbubble diameters using dce-mri. Magnetic Resonance in Medicine, 66, 821–830.

    Article  Google Scholar 

  • Wallin, E., Larsson, I. M., Kristofferzon, M. L., et al. (2018). Acute brain lesions on magnetic resonance imaging in relation to neurological outcome after cardiac arrest. Acta Anaesthesiologica Scandinavica, 62, 635–647.

    Article  CAS  Google Scholar 

  • Wang, P., Li, Y., Yang, Z., et al. (2018). Inhibition of dynamin-related protein 1 has neuroprotective effect comparable with therapeutic hypothermia in a rat model of cardiac arrest. Translational Research, 194, 68–78.

    Article  CAS  Google Scholar 

  • Wijman, C. A., Mlynash, M., Caulfield, A. F., et al. (2009). Prognostic value of brain diffusion-weighted imaging after cardiac arrest. Annals of Neurology, 65, 394–402.

    Article  Google Scholar 

  • Wissenberg, M., Lippert, F. K., Folke, F., et al. (2013). Association of national initiatives to improve cardiac arrest management with rates of bystander intervention and patient survival after out-of-hospital cardiac arrest. JAMA, 310, 1377–1384.

    Article  CAS  Google Scholar 

  • Wormsbecker, A., Sekhon, M. S., Griesdale, D. E., et al. (2017). The association between anemia and neurological outcome in hypoxic ischemic brain injury after cardiac arrest. Resuscitation, 112, 11–16.

    Article  Google Scholar 

  • Wu, O., Sorensen, A. G., Benner, T., et al. (2009). Comatose patients with cardiac arrest: Predicting clinical outcome with diffusion-weighted mr imaging. Radiology, 252, 173–181.

    Article  Google Scholar 

  • Zhu, J., Li, X., Yin, J., et al. (2018). Glycocalyx degradation leads to blood-brain barrier dysfunction and brain edema after asphyxia cardiac arrest in rats. Journal of Cerebral Blood Flow and Metabolism, 38, 1979–1992.

    Article  CAS  Google Scholar 

Download references

Funding

This study was supported by the research grants from projects of Leading Talents in Pearl River Talent Plan of Guangdong Province (No. 81000-42020004), Guangzhou Science, Technology and Innovation Commission (CN) (No. 202102080580) and Natural Science Foundation of Guangdong Province (No. 2021A1515011433).

Author information

Author notes

    Authors and Affiliations

    1. The Fourth Affiliated Hospital of Guanzhou Medical University, Guangzhou, 511300, China

      Zhifeng Liu, Jinhui Cai & Gongfa Wu

    2. Zengcheng District People’s Hospital of Guangzhou, Guangzhou, 511300, China

      Zhifeng Liu, Jinhui Cai & Gongfa Wu

    3. Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yan Jiang Xi Road, Guangzhou, 510120, China

      Tangchun Liu, Yue Wang, Wanchun Tang & Zhengfei Yang

    4. Guangdong Provincial People’s Hospital, Guangzhou, 510080, China

      Guangyi Wang

    5. Weil Institute of Emergency and Critical Care Research, School of Medicine, Virginia Commonwealth University, Richmond, VA, USA

      Wanchun Tang & Zhengfei Yang

    6. The Seventh Affiliated Hospital, Sun Yat-Sen University, 628 Zhenyuan Road, Xinhu Street, Guangming New District, Shenzhen, 518107, Guangdong, China

      Jinhui Cai & Qingyu Liu

    Authors
    1. Zhifeng Liu
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Tangchun Liu
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Jinhui Cai
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Gongfa Wu
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Guangyi Wang
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Yue Wang
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Wanchun Tang
      View author publications

      You can also search for this author in PubMed Google Scholar

    8. Zhengfei Yang
      View author publications

      You can also search for this author in PubMed Google Scholar

    9. Qingyu Liu
      View author publications

      You can also search for this author in PubMed Google Scholar

    Contributions

    Zhifeng Liu, Tangchun Liu and Jinhui Cai: Performed the experiments, data interpretation, wrote the manuscript.

    Gongfa Wu, Gaungyi Wang, Yue Wang and Wanchun Tang: Performed the experiments, data interpretation.

    Zhengfei Yang and Qingyu Liu: Study design, data interpretation, edited the manuscript.

    All authors read and approved the final manuscript.

    Corresponding authors

    Correspondence to Zhengfei Yang or Qingyu Liu.

    Ethics declarations

    Ethical approval

    The animal experiments were approved by the Institutional Animal Care and Use Committee of the Tang Wanchun Laboratories of Emergency & Critical Care Medicine at Sun Yat-sen Memorial Hospital, Sun Yat-sen University (IACUC-SYSU -R17010).

    Consent to participate

    Not applicable.

    Consent to publish

    Not applicable.

    Competing interests

    The authors declare that they have no conflict of interest.

    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 39 KB)

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Liu, Z., Liu, T., Cai, J. et al. Quantitative magnetic resonance imaging assessment of brain injury after successful cardiopulmonary resuscitation in a rat model of asphyxia cardiac arrest. Brain Imaging and Behavior 16, 270–280 (2022). https://doi.org/10.1007/s11682-021-00500-0

    Download citation

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s11682-021-00500-0

    Keywords

    Search

    Navigation