Assessment of cerebral hemodynamic parameters using pulsatile versus non-pulsatile cerebral blood outflow models

  • Agnieszka Uryga
  • Magdalena Kasprowicz
  • Leanne Calviello
  • Rolf R. Diehl
  • Katarzyna Kaczmarska
  • Marek Czosnyka
Original Research



Prior methods evaluating the changes in cerebral arterial blood volume (∆CaBV) assumed that brain blood transport distal to big cerebral arteries can be approximated with a non-pulsatile flow (CFF) model. In this study, a modified ∆CaBV calculation that accounts for pulsatile blood flow forward (PFF) from large cerebral arteries to resistive arterioles was investigated. The aim was to assess cerebral hemodynamic indices estimated by both CFF and PFF models while changing arterial blood carbon dioxide concentration (EtCO2) in healthy volunteers.

Materials and methods

Continuous recordings of non-invasive arterial blood pressure (ABP), transcranial Doppler blood flow velocity (CBFVa), and EtCO2 were performed in 53 young volunteers at baseline and during both hypo- and hypercapnia. The time constant of the cerebral arterial bed (τ) and critical closing pressure (CrCP) were estimated using mathematical transformations of the pulse waveforms of ABP and CBFVa, and with both pulsatile and non-pulsatile models of ∆CaBV estimation. Results are presented as median values ± interquartile range.


Both CrCP and τ gave significantly lower values with the PFF model when compared with the CFF model (p ≪ 0.001 for both). In comparison to normocapnia, both CrCP and τ determined with the PFF model increased during hypocapnia [CrCPPFF (mm Hg): 5.52 ± 8.78 vs. 14.36 ± 14.47, p = 0.00006; τPFF (ms): 47.4 ± 53.9 vs. 72.8 ± 45.7, p = 0.002] and decreased during hypercapnia [CrCPPFF (mm Hg): 5.52 ± 8.78 vs. 2.36 ± 7.05, p = 0.0001; τPFF (ms): 47.4 ± 53.9 vs. 29.0 ± 31.3, p = 0.0003]. When the CFF model was applied, no changes were found for CrCP during hypercapnia or in τ during hypocapnia.


Our results suggest that the pulsatile flow forward model better reflects changes in CrCP and in τ induced by controlled alterations in EtCO2.


Transcranial Doppler ultrasound Cerebral arterial blood volume Cerebral arterial compliance Time constant of cerebral arterial bed Critical closing pressure Hypercapnia Hypocapnia 



We thank Krystian Gruszczyński, Msc. Eng. for assistance with data collection and Tomasz Szczepański, PhD for reviewing medical history and physical examination.


This research was supported by the National Science Center (Poland) under Grant No. UMO-2013/10/E/ST7/00117.

Compliance with ethical standards

Conflict of interest

ICM + Software is licensed by Cambridge Enterprise, Cambridge, UK, Prof. Czosnyka has a financial interest in a fraction of the licensing fee for ICM + software. The other authors declare that they have no conflicts of interest.

Informed consent

The protocol complied with the Declaration of Helsinki of the World Medical Association, and all participants gave written informed consent before participating in the study.

Research involving human and animal rights

The study was approved by the bioethical committee of the Wroclaw Medical University (Permission No. KB-170/2014).


  1. 1.
    Avezaat CJJ, van Eijndhoven JHM. The role of the pulsatile pressure variations in intracranial pressure monitoring. Neurosurg Rev. 1986;9:113–20.CrossRefPubMedGoogle Scholar
  2. 2.
    Alperin N, Sivaramakrishnan A, Lichtor T. Magnetic resonance imaging-based measurements of cerebrospinal fluid and blood flow as indicators of intracranial compliance in patients with Chiari malformation. J Neurosurg. 2005;103:46–52.CrossRefPubMedGoogle Scholar
  3. 3.
    Stoquart-Elsankari S, Lehmann P, Villette A, Czosnyka M, Meyer M-E, Deramond H, et al. A phase-contrast MRI study of physiologic cerebral venous flow. J Cereb Blood Flow Metab. 2009;29:1208–15.CrossRefPubMedGoogle Scholar
  4. 4.
    Kim DJ, Kasprowicz M, Carrera E, Castellani G, Zweifel C, Lavinio A, et al. The monitoring of relative changes in compartmental compliances of brain. Physiol Meas. 2009;30:647–59.CrossRefPubMedGoogle Scholar
  5. 5.
    Carrera E, Kim DJ, Castellani G, Zweifel C, Smielewski P, Pickard JD, et al. Effect of hyper- and hypocapnia on cerebral arterial compliance in normal subjects. J Neuroimaging. 2011;21:121–5.CrossRefPubMedGoogle Scholar
  6. 6.
    Nasr N, Czosnyka M, Pavy-Le Traon A, Custaud M-A, Liu X, Varsos GV, et al. Baroreflex and cerebral autoregulation are inversely correlated. Circ J. 2014;78:2460–7.CrossRefPubMedGoogle Scholar
  7. 7.
    Czosnyka M, Richards HK, Reinhard M, Steiner L, Budohoski K, Smielewski P, et al. Cerebrovascular time constant: dependence on cerebral perfusion pressure and end-tidal carbon dioxide concentration. Neurol Res. 2012;34:17–24.CrossRefPubMedGoogle Scholar
  8. 8.
    Kasprowicz M, Diedler J, Reinhard M, Carrera E, Steiner LA, Smielewski P, et al. Time constant of the cerebral arterial bed in normal subjects. Ultrasound Med Biol. 2012;38:1129–37.CrossRefPubMedGoogle Scholar
  9. 9.
    Kasprowicz M, Diedler J, Reinhard M, Carrera E, Smielewski P, Budohoski KP, et al. Time constant of the cerebral arterial bed. Acta Neurochir Suppl. 2012;114:17–21.CrossRefPubMedGoogle Scholar
  10. 10.
    Varsos GV, Richards H, Kasprowicz M, Budohoski KP, Brady KM, Reinhard M, et al. Critical closing pressure determined with a model of cerebrovascular impedance. J Cereb Blood Flow Metab. 2013;33:235–43.CrossRefPubMedGoogle Scholar
  11. 11.
    Kasprowicz M, Czosnyka M, Soehle M, Smielewski P, Kirkpatrick PJ, Pickard JD, et al. Vasospasm shortens cerebral arterial time constant. Neurocrit Care. 2012;16:213–8.CrossRefPubMedGoogle Scholar
  12. 12.
    Carrera E, Kim D-J, Castellani G, Zweifel C, Smielewski P, Pickard JD, et al. Cerebral arterial compliance in patients with internal carotid artery disease. Eur J Neurol. 2011;18:711–8.CrossRefPubMedGoogle Scholar
  13. 13.
    Varsos GV, Budohoski KP, Czosnyka M, Kolias AG, Nasr N, Donnelly J, et al. Cerebral vasospasm affects arterial critical closing pressure. J Cereb Blood Flow Metab. 2015;35:285–91.CrossRefPubMedGoogle Scholar
  14. 14.
    Varsos GV, Kolias AG, Smielewski P, Brady KM, Varsos VG, Hutchinson PJ, et al. A noninvasive estimation of cerebral perfusion pressure using critical closing pressure. J Neurosurg. 2015;123:638–48.CrossRefPubMedGoogle Scholar
  15. 15.
    Carrera E, Kim D-J, Castellani G, Zweifel C, Czosnyka Z, Kasprowicz M, et al. What shapes pulse amplitude of intracranial pressure? J Neurotrauma. 2010;27:317–24.CrossRefPubMedGoogle Scholar
  16. 16.
    Ambarki K, Baledent O, Kongolo G, Bouzerar R, Fall S, Meyer ME. A new lumped-parameter model of cerebrospinal hydrodynamics during the cardiac cycle in healthy volunteers. IEEE Trans Biomed Eng. 2007;54:483–91.CrossRefPubMedGoogle Scholar
  17. 17.
    Czosnyka M, Smielewski P, Kirkpatrick P, Piechnik S, Laing R, Pickard JD. Continuous monitoring of cerebrovascular pressure-reactivity in head injury. Acta Neurochir Suppl. 1998;71:74–7.PubMedGoogle Scholar
  18. 18.
    Czosnyka M, Guazzo E, Whitehouse M, Smielewski P, Czosnyka Z, Kirkpatrick P, et al. Significance of intracranial pressure waveform analysis after head injury. Acta Neurochir. 1996;138:531–42.CrossRefPubMedGoogle Scholar
  19. 19.
    Poulin MJ, Robbins PA. Indexes of flow and cross-sectional area of the middle cerebral artery using doppler ultrasound during hypoxia and hypercapnia in humans. Stroke. 1996;27:2244–50.CrossRefPubMedGoogle Scholar
  20. 20.
    Valdueza JM, Balzer JO, Villringer A, Vogl TJ, Kutter R, Einhäupl KM. Changes in blood flow velocity and diameter of the middle cerebral artery during hyperventilation: assessment with MR and transcranial Doppler sonography. Am J Neuroradiol. 1997;18:1929–34.PubMedGoogle Scholar
  21. 21.
    Henriksen JH, Fuglsang S, Bendtsen F, Christensen E, Møller S. Arterial compliance in patients with cirrhosis: stroke volume-pulse pressure ratio as simplified index. Am J Physiol Gastrointest Liver Physiol. 2001;280:G584–94.CrossRefPubMedGoogle Scholar
  22. 22.
    Panerai RB, Salinet ASM, Brodie FG, Robinson TG. The influence of calculation method on estimates of cerebral critical closing pressure. Physiol Meas. 2011;32:467–82.CrossRefPubMedGoogle Scholar
  23. 23.
    Altman BjM. DG. Statistics notes: calculating correlation coefficients with repeated observations: part 1-correlation within subjects. BMJ. 1995;310:446.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Bland JM, Altman DG. Calculating correlation coefficients with repeated observations: Part 2-correlation between subjects. BMJ. 1995;310:633.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Varsos GV, Kasprowicz M, Smielewski P, Czosnyka M. Model-based indices describing cerebrovascular dynamics. Neurocrit Care. 2014;20:142–57.CrossRefPubMedGoogle Scholar
  26. 26.
    Brothers RM, Zhang R. CrossTalk opposing view: the middle cerebral artery diameter does not change during alterations in arterial blood gases and blood pressure. J Physiol. 2016;594:4077–9.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Hoiland RL, Ainslie PN. CrossTalk proposal: The middle cerebral artery diameter does change during alterations in arterial blood gases and blood pressure. J Physiol. 2016;594:4073–5.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Djurberg HG, Seed RF, Price Evans DA, Brohi FA, Pyper DL, Tjan GT, et al. Lack of effect of CO2 on cerebral arterial diameter in man. J Clin Anesth. 1998;10:646–51.CrossRefPubMedGoogle Scholar
  29. 29.
    Serrador JM, Picot P, Rutt BK, Shoemaker JK, Bondar RL. MRI measures of middle cerebral artery diameter in conscious humans during simulated orthostasis. Stroke. 2000;31:1672–8.CrossRefPubMedGoogle Scholar
  30. 30.
    Schreiber SJ, Gottschalk S, Weih M, Villringer A, Valdueza JM. Assessment of blood flow velocity and diameter of the middle cerebral artery during the acetazolamide provocation test by use of transcranial Doppler sonography and MR imaging. AJNR Am J Neuroradiol. 2000;21:1207–11.PubMedGoogle Scholar
  31. 31.
    Verbree J, Bronzwaer A-SGT, Ghariq E, Versluis MJ, Daemen MJAP., van Buchem MA, et al. Assessment of middle cerebral artery diameter during hypocapnia and hypercapnia in humans using ultra-high-field MRI. J Appl Physiol. 2014;117:1084–9.CrossRefPubMedGoogle Scholar
  32. 32.
    Coverdale NS, Lalande S, Perrotta A, Shoemaker JK. Heterogeneous patterns of vasoreactivity in the middle cerebral and internal carotid arteries. Am J Physiol- Hear Circ Physiol. 2015;308:H1030–8.CrossRefGoogle Scholar
  33. 33.
    Kim S-G, Harel N, Jin T, Kim T, Lee P, Zhao F. Cerebral blood volume MRI with intravascular superparamagnetic iron oxide nanoparticles. NMR Biomed. 2013;26:949–62.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Biomedical Engineering, Faculty of Fundamental Problems of TechnologyWroclaw University of Science and TechnologyWroclawPoland
  2. 2.Brain Physics Laboratory, Department of Clinical Neurosciences, Division of NeurosurgeryUniversity of CambridgeCambridgeUK
  3. 3.Department of NeurologyAlfried-Krupp-KrankenhausEssenGermany
  4. 4.Department of NeurosurgeryMossakowski Medical Research Centre Polish Academy of SciencesWarsawPoland
  5. 5.Institute of Electronic SystemsWarsaw University of TechnologyWarsawPoland

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