Skip to main content

The Physiological Basis of Cerebrovascular Reactivity Measurements

  • Protocol
  • First Online:
Cerebrovascular Reactivity

Part of the book series: Neuromethods ((NM,volume 175))

Abstract

The brain requires a continuous supply of oxygen, which in normal environments is directly related to cerebral blood flow. Accordingly, a number of mechanisms are in place to maintain blood supply in the face of challenges such as variations in arterial blood pressure, hypoxemia, and vascular occlusions. These include the recruitment of collateral flow such as via the circle of Willis, the pial networks, and anastomoses between penetrating arterioles and capillaries. In addition, physiological mechanisms adjust the distribution of flow: (1) autoregulation to maintain flow during supply pressure changes, (2) neurovascular coupling to increase flow in regions of neuronal activity, and (3) hypoxia-induced vasodilatation. The common effector pathway for physiological mechanisms is the adjustment of vascular diameter. In the absence of steno-occlusive vascular disease, the flow response to a vasodilatory challenge, cerebrovascular reactivity (CVR), interrogates the physiological response. In the presence of steno-occlusive disease, CVR reflects both the health of the physiological regulators and the availability of collateral flow. Even in health, CVR varies between anatomical regions. As a result, CVR must be normalized for the region before it can be interpreted.

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

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Helenius J et al (2003) Cerebral hemodynamics in a healthy population measured by dynamic susceptibility contrast MR imaging. Acta Radiol 44(5):538–546

    Article  CAS  PubMed  Google Scholar 

  2. Ito H et al (2004) Database of normal human cerebral blood flow, cerebral blood volume, cerebral oxygen extraction fraction and cerebral metabolic rate of oxygen measured by positron emission tomography with 15O-labelled carbon dioxide or water, carbon monoxide and oxygen: a multicentre study in Japan. Eur J Nucl Med Mol Imaging 31(5):635–643

    Article  PubMed  Google Scholar 

  3. Willie CK et al (2014) Integrative regulation of human brain blood flow. J Physiol 592(5):841–859

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Nishimura N et al (2007) Penetrating arterioles are a bottleneck in the perfusion of neocortex. Proc Natl Acad Sci U S A 104(1):365–370

    Article  CAS  PubMed  Google Scholar 

  5. Hall CN et al (2014) Capillary pericytes regulate cerebral blood flow in health and disease. Nature 508(7494):55–60

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Attwell D et al (2016) What is a pericyte? J Cereb Blood Flow Metab 36(2):451–455

    Article  CAS  PubMed  Google Scholar 

  7. Tan CO, Taylor JA (2014) Integrative physiological and computational approaches to understand autonomic control of cerebral autoregulation. Exp Physiol 99(1):3–15

    Article  PubMed  Google Scholar 

  8. Tzeng Y-C et al (2014) Fundamental relationships between blood pressure and cerebral blood flow in humans. J Appl Physiol (1985) 117(9):1037

    Article  CAS  Google Scholar 

  9. Attwell D et al (2011) Glial and neuronal control of brain blood flow. Nature 468(7321):232–243

    Article  Google Scholar 

  10. Phillips AA et al (2016) Neurovascular coupling in humans: physiology, methodological advances and clinical implications. J Cereb Blood Flow Metab 36(4):647–664

    Article  PubMed  Google Scholar 

  11. Zarrinkoob L et al (2015) Blood flow distribution in cerebral arteries. J Cereb Blood Flow Metab 35(4):648–654

    Article  PubMed  PubMed Central  Google Scholar 

  12. Liebeskind DS (2003) Collateral circulation. Stroke 34(9):2279–2284

    Article  PubMed  Google Scholar 

  13. Moody DM, Bell MA, Challa VR (1990) Features of the cerebral vascular pattern that predict vulnerability to perfusion or oxygenation deficiency: an anatomic study. AJNR Am J Neuroradiol 11(3):431–439

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Willie CK et al (2012) Regional brain blood flow in man during acute changes in arterial blood gases. J Physiol 590(14):3261–3275

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Mardimae A et al (2012) The interaction of carbon dioxide and hypoxia in the control of cerebral blood flow. Pflugers Arch 464(4):345–351

    Article  CAS  PubMed  Google Scholar 

  16. Cohen PJ et al (1967) Effects of hypoxia and normocarbia on cerebral blood flow and metabolism in conscious man. J Appl Physiol 23(2):183–189

    Article  CAS  PubMed  Google Scholar 

  17. Battisti-Charbonney A, Fisher J, Duffin J (2011) The cerebrovascular response to carbon dioxide in humans. J Physiol 589(Pt 12):3039–3048

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Borzage MT et al (2016) Predictors of cerebral blood flow in patients with and without anemia. J Appl Physiol 120(8):976–981

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Duffin J, Hare GMT, Fisher JA (2020) A mathematical model of cerebral blood flow control in anaemia and hypoxia. J Physiol 598(4):717–730

    Article  CAS  PubMed  Google Scholar 

  20. Brown MM, Wade JP, Marshall J (1985) Fundamental importance of arterial oxygen content in the regulation of cerebral blood flow in man. Brain 108(Pt 1):81–93

    Article  PubMed  Google Scholar 

  21. Bush AM et al (2016) Determinants of resting cerebral blood flow in sickle cell disease. Am J Hematol 91(9):912–917

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Wolff CB (2000) Cerebral blood flow and oxygen delivery at high altitude. High Alt Med Biol 1(1):33–38

    Article  CAS  PubMed  Google Scholar 

  23. Powell FL, Fu Z (2008) HIF-1 and ventilatory acclimatization to chronic hypoxia. Respir Physiol Neurobiol 164(1–2):282–287

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Poellinger L, Johnson RS (2004) HIF-1 and hypoxic response: the plot thickens. Curr Opin Genet Dev 14(1):81–85

    Article  CAS  PubMed  Google Scholar 

  25. Hulbert ML et al (2017) Normalization of cerebral hemodynamics after hematopoietic stem cell transplant in children with sickle cell anemia. Blood 130(Suppl 1):2245–2245

    Google Scholar 

  26. Victor M, Ropper AH, Adams R (2000) Adams and Victor’s principles of neurology, 7th edn. McGraw-Hill Professional, New York, NY

    Google Scholar 

  27. Fierstra J et al (2010) Steal physiology is spatially associated with cortical thinning. J Neurol Neurosurg Psychiatry 81(3):290–293

    Article  PubMed  Google Scholar 

  28. Sam K et al (2016) Impaired dynamic cerebrovascular response to hypercapnia predicts development of white matter hyperintensities. NeuroImage: Clin 11:796–801

    Article  Google Scholar 

  29. Sam K et al (2016) Development of white matter hyperintensity is preceded by reduced cerebrovascular reactivity. Ann Neurol 80:277

    Article  CAS  PubMed  Google Scholar 

  30. Balucani C et al (2012) Cerebral hemodynamics and cognitive performance in bilateral asymptomatic carotid stenosis. Neurology 79(17):1788–1795

    Article  PubMed  Google Scholar 

  31. Ben Hassen W et al (2019) Inter- and intraobserver reliability for angiographic leptomeningeal collateral flow assessment by the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) scale. J Neurointerv Surg 11(4):338–341

    Article  PubMed  Google Scholar 

  32. Lima FO et al (2010) The pattern of leptomeningeal collaterals on CT angiography is a strong predictor of long-term functional outcome in stroke patients with large vessel intracranial occlusion. Stroke 41(10):2316–2322

    Article  PubMed  PubMed Central  Google Scholar 

  33. Cipolla MJ (2010) The cerebral circulation. Morgan & Claypool, San Rafael, CA

    Google Scholar 

  34. Powers WJ (1991) Cerebral hemodynamics in ischemic cerebrovascular disease. Ann Neurol 29(3):231–240

    Article  CAS  PubMed  Google Scholar 

  35. Reinhard M et al (2014) Cerebrovascular reactivity predicts stroke in high-grade carotid artery disease. Neurology 83(16):1424–1431

    Article  PubMed  PubMed Central  Google Scholar 

  36. Fierstra J et al (2013) Measuring cerebrovascular reactivity: what stimulus to use? J Physiol 591(Pt 23):5809–5821

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Reivich M (1964) Arterial Pco2 and cerebral hemodynamics. Am J Phys 206:25–35

    Article  CAS  Google Scholar 

  38. Lassen NA (1968) Brain extracellular pH: the main factor controlling cerebral blood flow. Scand J Clin Lab Invest 22(4):247–251

    Article  CAS  PubMed  Google Scholar 

  39. Murkin JM (2007) Cerebral autoregulation: the role of CO2 in metabolic homeostasis. Semin Cardiothorac Vasc Anesth 11(4):269–273

    Article  PubMed  Google Scholar 

  40. Kontos HA et al (1977) Local mechanism of CO2 action of cat pial arterioles. Stroke 8(2):226–229

    Article  CAS  PubMed  Google Scholar 

  41. Wei EP, Kontos HA (1999) Blockade of ATP-sensitive potassium channels in cerebral arterioles inhibits vasoconstriction from hypocapnic alkalosis in cats. Stroke 30(4):851–853. discussion 854

    Article  CAS  PubMed  Google Scholar 

  42. Longden TA, Nelson MT (2015) Vascular inward rectifier K+ channels as external K+ sensors in the control of cerebral blood flow. Microcirculation 22(3):183–196

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Rasmussen JK, Boedtkjer E (2018) Carbonic anhydrase inhibitors modify intracellular pH transients and contractions of rat middle cerebral arteries during CO2/HCO3(-) fluctuations. J Cereb Blood Flow Metab 38(3):492–505

    Article  CAS  PubMed  Google Scholar 

  44. Chesler M (2003) Regulation and modulation of pH in the brain. Physiol Rev 83(4):1183–1221

    Article  CAS  PubMed  Google Scholar 

  45. Hughes R, Brain MJ (2013) A simplified bedside approach to acid–base: fluid physiology utilizing classical and physicochemical approaches. Anaesth Inten Care Med 14(10):445–452

    Article  Google Scholar 

  46. Duffin J (2005) Role of acid-base balance in the chemoreflex control of breathing. J Appl Physiol 99(6):2255–2265

    Article  CAS  PubMed  Google Scholar 

  47. Sobczyk O et al (2014) A conceptual model for CO2-induced redistribution of cerebral blood flow with experimental confirmation using BOLD MRI. NeuroImage 92:56–68

    Article  CAS  PubMed  Google Scholar 

  48. Bhogal A et al (2014) Investigating the non-linearity of the BOLD cerebrovascular reactivity response to targeted hypo/hypercapnia at 7T. NeuroImage 98:296

    Article  PubMed  Google Scholar 

  49. Bhogal AA et al (2016) The BOLD cerebrovascular reactivity response to progressive hypercapnia in young and elderly. NeuroImage 139:94–102

    Article  PubMed  Google Scholar 

  50. Regan RE, Fisher JA, Duffin J (2014) Factors affecting the determination of cerebrovascular reactivity. Brain Behav 4(5):775–788

    Article  PubMed  PubMed Central  Google Scholar 

  51. Fan J-L et al (2015) AltitudeOmics: resetting of cerebrovascular CO2 reactivity following acclimatization to high altitude. Front Physiol 6:394

    PubMed  Google Scholar 

  52. Faraci F, Heistad D (1990) Regulation of large cerebral arteries and cerebral microvascular pressure. Circ Res 66(1):8–17

    Article  CAS  PubMed  Google Scholar 

  53. Brawley BW (1968) The pathophysiology of intracerebral steal following carbon dioxide inhalation, an experimental study. Scand J Clin Lab Investig Suppl XIII:B:102

    Google Scholar 

  54. Symon L (1968) Experimental evidence for “intracerebral steal” following CO2 inhalation. Scand J Clin Lab Investig Suppl XIII:A:102

    Google Scholar 

  55. Conklin J et al (2010) Impaired cerebrovascular reactivity with steal phenomenon is associated with increased diffusion in white matter of patients with Moyamoya disease. Stroke 41(8):1610–1616

    Article  PubMed  Google Scholar 

  56. Bhogal AA et al (2015) Examining the regional and cerebral depth-dependent BOLD cerebrovascular reactivity response at 7T. NeuroImage 114:239–248

    Article  PubMed  Google Scholar 

  57. Duffin J et al (2018) Cerebrovascular resistance: the basis of cerebrovascular reactivity. Front Neurosci 12:409

    Article  PubMed  PubMed Central  Google Scholar 

  58. Fisher JA et al (2017) Assessing cerebrovascular reactivity by the pattern of response to progressive hypercapnia. Hum Brain Mapp 38:3415

    PubMed  PubMed Central  Google Scholar 

  59. Poublanc J et al (2015) Measuring cerebrovascular reactivity: the dynamic response to a step hypercapnic stimulus. J Cereb Blood Flow Metab 35:1–11

    Article  Google Scholar 

  60. Duffin J et al (2015) The dynamics of cerebrovascular reactivity shown with transfer function analysis. NeuroImage 114:207–216

    Article  CAS  PubMed  Google Scholar 

  61. Blockley NP et al (2011) An improved method for acquiring cerebrovascular reactivity maps. Magn Reson Med 65(5):1278–1286

    Article  PubMed  Google Scholar 

  62. Mandell DM et al (2008) Mapping cerebrovascular reactivity using blood oxygen level-dependent MRI in patients with arterial steno-occlusive disease: comparison with arterial spin labeling MRI. Stroke 39(7):2021–2028

    Article  PubMed  Google Scholar 

  63. Spano VR et al (2013) CO2 blood oxygen level-dependent MR mapping of cerebrovascular reserve in a clinical population: safety, tolerability, and technical feasibility. Radiology 266(2):592–598

    Article  PubMed  Google Scholar 

  64. Sobczyk O et al (2015) Assessing cerebrovascular reactivity abnormality by comparison to a reference atlas. J Cereb Blood Flow Metab 35(2):213–220

    Article  PubMed  Google Scholar 

  65. Sobczyk O et al (2016) Identifying significant changes in cerebrovascular reactivity to carbon dioxide. AJNR Am J Neuroradiol 37(5):818–824

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Joseph A. Fisher .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2022 Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Sobczyk, O., Duffin, J., Fisher, J.A., Mikulis, D.J. (2022). The Physiological Basis of Cerebrovascular Reactivity Measurements. In: Chen, J., Fierstra, J. (eds) Cerebrovascular Reactivity. Neuromethods, vol 175. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1763-2_1

Download citation

  • DOI: https://doi.org/10.1007/978-1-0716-1763-2_1

  • Published:

  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-1762-5

  • Online ISBN: 978-1-0716-1763-2

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics