Skip to main content
PMC home page
Neurotherapeutics logoLink to Neurotherapeutics
. 2007 Jul;4(3):511–522. doi: 10.1016/j.nurt.2007.04.007

Changing concepts of cerebrospinal fluid hydrodynamics: Role of phase-contrast magnetic resonance imaging and implications for cerebral microvascular disease

Stavros Michael Stivaros 1, Alan Jackson 1,✉
PMCID: PMC7479718  PMID: 17599715

Summary

Phase-contrast magnetic resonance imaging (PC-MRI) or flow-sensitive MRI can be used to noninvasively measure intracranial vascular and CSF flow. Monro-Kellie homeostasis is the complex compensatory mechanism for the increase in intracranial blood volume during systole. Through PC-MRI techniques, our understanding of Monro-Kellie homeostasis and the associated intracranial hydrodynamics has greatly improved. Failure of this homeostatic mechanism has been implicated in a wide range of cerebral disorders, including vascular and Alzheimer’s dementia, late-onset depression, benign and secondary intracranial hypertension, communicating and normal pressure hydrocephalus, and age-related white matter changes. The most common mode of homeostatic failure is due to vascular disease with decreased cerebral arterial compliance. This has wide-reaching implications in the investigation of patients with cerebral vascular disease. Here we discuss the role of PC-MRI in the study of cerebral hydrodynamics and the our understanding of Monro-Kellie homeostasis in both healthy and disease states. Quantitative assessment of the changes in this homeostatic mechanism using PC-MRI has important implications in the development of biomarkers of vascular involvement in disease with application in diagnosis, treatment planning, phenotype identification, and outcome assessment in clinical trials.

Key Words: Phase-contrast MRI, cerebrospinal fluid, hydrodynamics, homeostasis, hydrocephalus

References

  • 1.Bateman GA. Pulse-wave encephalopathy: a comparative study of the hydrodynamics of leukoaraiosis and normal-pressure hydrocephalus. Neuroradiology. 2002;44:740–748. doi: 10.1007/s00234-002-0812-0. [DOI] [PubMed] [Google Scholar]
  • 2.Baledent O, Gondry-Jouet C, Stoquart-Elsankari S, et al. Value of phase contrast magnetic resonance imaging for investigation of cerebral hydrodynamics. J Neuroradiol. 2006;33:292–303. doi: 10.1016/S0150-9861(06)77287-X. [DOI] [PubMed] [Google Scholar]
  • 3.Baledent O, Gondry-Jouet C, Meyer ME, et al. Relationship between cerebrospinal fluid and blood dynamics in healthy volunteers and patients with communicating hydrocephalus. Invest Radiol. 2004;39:45–55. doi: 10.1097/01.rli.0000100892.87214.49. [DOI] [PubMed] [Google Scholar]
  • 4.Greitz D, Wirestam R, Franck A, et al. Pulsatile brain movement and associated hydrodynamics studied by magnetic resonance phase imaging: the Monro-Kellie doctrine revisited. Neuroradiology. 1992;34:370–380. doi: 10.1007/BF00596493. [DOI] [PubMed] [Google Scholar]
  • 5.Levy LM, Di Chiro G. MR phase imaging and cerebrospinal fluid flow in the head and spine. Neuroradiology. 1990;32:399–406. doi: 10.1007/BF00588473. [DOI] [PubMed] [Google Scholar]
  • 6.Hashemi RH, Bradley WG. MR Angiography. In: Mitchell CW, editor. MRI: the basics. Baltimore: Williams & Wilkins; 1997. pp. 280–283. [Google Scholar]
  • 7.Spilt A, Box FM, Van der Geest RJ, et al. Reproducibility of total cerebral blood flow measurements using phase contrast magnetic resonance imaging. J Magn Reson Imaging. 2002;16:1–5. doi: 10.1002/jmri.10133. [DOI] [PubMed] [Google Scholar]
  • 8.Ho SS, Chan YL, Yeung DK, et al. Blood flow volume quantification of cerebral ischemia: comparison of three noninvasive imaging techniques of carotid and vertebral arteries. AJR Am J Roentgenol. 2002;178:551–556. doi: 10.2214/ajr.178.3.1780551. [DOI] [PubMed] [Google Scholar]
  • 9.Gill RW. Measurement of blood flow by ultrasound: accuracy and sources of error. Ultrasound Med Biol. 1985;11:625–641. doi: 10.1016/0301-5629(85)90035-3. [DOI] [PubMed] [Google Scholar]
  • 10.Bakker CJ, Kouwenhoven M, Hartkamp MJ, et al. Accuracy and precision of time-averaged flow as measured by nontriggered 2D phase-contrast MR angiography, a phantom evaluation. Magn Reson Imaging. 1995;13:959–965. doi: 10.1016/0730-725X(95)02005-E. [DOI] [PubMed] [Google Scholar]
  • 11.Bakker CJ, Hartkamp MJ, Mali WP. Measuring blood flow by nontriggered 2D phase-contrast MR angiography. Magn Reson Imaging. 1996;14:609–614. doi: 10.1016/0730-725X(96)00092-6. [DOI] [PubMed] [Google Scholar]
  • 12.Tarnawski M, Padayachee S, West DJ, et al. The measurement of time-averaged flow by magnetic resonance imaging using continuous acquisition in the carotid arteries and its comparison with Doppler ultrasound. Clin Phys Physiol Meas. 1990;11:27–36. doi: 10.1088/0143-0815/11/1/002. [DOI] [PubMed] [Google Scholar]
  • 13.Bateman GA. Vascular compliance in normal pressure hydrocephalus. Am J Neuroradiol. 2000;21:1574–1585. [PMC free article] [PubMed] [Google Scholar]
  • 14.Bateman GA. Association between arterial inflow and venous outflow in idiopathic and secondary intracranial hypertension. J Clin Neurosci. 2006;13:550–556. doi: 10.1016/j.jocn.2005.06.005. [DOI] [PubMed] [Google Scholar]
  • 15.Bateman GA. Vascular hydraulics associated with idiopathic and secondary intracranial hypertension. AJNR Am J Neuroradiol. 2002;23:1180–1186. [PMC free article] [PubMed] [Google Scholar]
  • 16.Evans AJ, Iwai F, Grist TA, et al. Magnetic resonance imaging of blood flow with a phase subtraction technique: in vitro and in vivo validation. Invest Radiol. 1993;28:109–115. doi: 10.1097/00004424-199302000-00004. [DOI] [PubMed] [Google Scholar]
  • 17.Laffon E, Valli N, Latrabe V, et al. A validation of a flow quantification by MR phase mapping software. Eur J Radiol. 1998;27:166–172. doi: 10.1016/S0720-048X(97)00105-8. [DOI] [PubMed] [Google Scholar]
  • 18.Powell AJ, Maier SE, Chung T, et al. Phase-velocity cine magnetic resonance imaging measurement of pulsatile blood flow in children and young adults: in vitro and in vivo validation. Pediatr Cardiol. 2000;21:104–110. doi: 10.1007/s002469910014. [DOI] [PubMed] [Google Scholar]
  • 19.Kim J, Thacker NA, Bromiley NA, et al. Prediction of the Jugular Waveform using a model of CSF dynamics. Am J Neuroradiol. 2007;28:983–989. [PMC free article] [PubMed] [Google Scholar]
  • 20.Felgenhauer K. Protein size and cerebrospinal fluid composition. Klin Wochenschr. 1974;52:1158–1164. doi: 10.1007/BF01466734. [DOI] [PubMed] [Google Scholar]
  • 21.Greitz D. Radiological assessment of hydrocephalus: new theories and implications for therapy. Neurosurg Rev. 2004;27:145–165. doi: 10.1007/s10143-004-0326-9. [DOI] [PubMed] [Google Scholar]
  • 22.Dandy WE, Blackfan WD. Internal hydrocephalus: an experimental, clinical and pathological study. Am J Dis Child. 1914;8:406–481. [Google Scholar]
  • 23.Greitz D. On the active vascular absorption of plasma proteins from tissue: rethinking the role of the lymphatic system. Med Hypotheses. 2002;59:696–702. doi: 10.1016/S0306-9877(02)00297-9. [DOI] [PubMed] [Google Scholar]
  • 24.Vanneste JA. Diagnosis and management of normal-pressure hydrocephalus. J Neurol. 2000;247:5–14. doi: 10.1007/s004150050003. [DOI] [PubMed] [Google Scholar]
  • 25.Vanneste JA. Three decades of normal pressure hydrocephalus: are we wiser now? J Neurol Neurosurg Psychiatry. 1994;57:1021–1025. doi: 10.1136/jnnp.57.9.1021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Vanneste J, Van Acker R. Normal pressure hydrocephalus: did publications alter management? J Neurol Neurosurg Psychiatry. 1990;53:564–568. doi: 10.1136/jnnp.53.7.564. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Kellie G. An account of the appearances observed in the dissection of two of the three individuals presumed to have perished in the storm of the 3rd, and whose bodies were discovered in the vicinity of Leith on the morning of the 4th November 1821, with some reflections on the pathology of the brain. Trans Medico-Chirurg Soc Edinb. 1824;1:84–169. [PMC free article] [PubMed] [Google Scholar]
  • 28.Monro A. Observations on the structure and function of the nervous system. Edinburgh: Creech and Johnson; 1823. [Google Scholar]
  • 29.Cushing H. Studies in intracranial physiology and surgery. London: Oxford University Press, London; 1926. The third circulation; pp. 1–51. [Google Scholar]
  • 30.Greitz D, Greitz T, Hindmarsh T. A new view on the CSF-circulation with the potential for pharmacological treatment of childhood hydrocephalus. Acta Paediatr. 1997;86:125–132. doi: 10.1111/j.1651-2227.1997.tb08850.x. [DOI] [PubMed] [Google Scholar]
  • 31.Stolz E, Kaps M, Kern A, et al. Transcranial color-coded duplex sonography of intracranial veins and sinuses in adults: reference data from 130 volunteers. Stroke. 1999;30:1070–1075. doi: 10.1161/01.str.30.5.1070. [DOI] [PubMed] [Google Scholar]
  • 32.Greitz D, Hannerz J, Rahn T, et al. MR imaging of cerebrospinal fluid dynamics in health and disease: on the vascular pathogenesis of communicating hydrocephalus and benign intracranial hypertension. Acta Radiol. 1994;35:204–211. [PubMed] [Google Scholar]
  • 33.Greitz D, Hannerz J, Bellander J, et al. In: Takahashi M, Korogi Y, Moseley I, et al., editors. Restricted arterial expansion as a universal causative factor in communicating hydrocephalus; Heidelberg: Springer Verlag Berlin; 1995. pp. 14–18. [Google Scholar]
  • 34.Greitz D, Greitz T. The pathogenesis and hemodynamics of hydrocephalus: a proposal for a new understanding. Int J Neuroradiol. 1997;3:367–375. [Google Scholar]
  • 35.Greitz D. The hydrodynamic hypothesis versus the bulk flow hypothesis. Neurosurg Rev. 2004;27:299–300. doi: 10.1007/s10143-004-0349-2. [DOI] [PubMed] [Google Scholar]
  • 36.Greitz D. Cerebrospinal fluid circulation and associated intracranial dynamics: a radiologic investigation using MR imaging and radionuclide cistemography. Acta Radiol Suppl. 1993;386:1–23. [PubMed] [Google Scholar]
  • 37.Hakim S. Biomechanics of hydrocephalus. Acta Neurol Latinoam. 1971;1(Suppl 1):169–194. [PubMed] [Google Scholar]
  • 38.Hakim S. Considerations on the physics of hydrocephalus and its treatment. Exp Eye Res. 1977;25:391–399. doi: 10.1016/0014-4835(77)90106-3. [DOI] [PubMed] [Google Scholar]
  • 39.Hakim S, Venegas JG, Burton JD. The physics of the cranial cavity, hydrocephalus and normal pressure hydrocephalus: mechanical interpretation and mathematical model. Surg Neurol. 1976;5:187–210. [PubMed] [Google Scholar]
  • 40.Johnston I, Paterson A. Benign intracranial hypertension. I. Diagnosis and prognosis. Brain. 1974;97:289–300. doi: 10.1093/brain/97.1.289. [DOI] [PubMed] [Google Scholar]
  • 41.Johnston I, Paterson A. Benign intracranial hypertension. II. CSF pressure and circulation. Brain. 1974;97:301–312. doi: 10.1093/brain/97.1.301. [DOI] [PubMed] [Google Scholar]
  • 42.Biousse V, Ameri A, Bousser MG. Isolated intracranial hypertension as the only sign of cerebral venous thrombosis. Neurology. 1999;53:1537–1542. doi: 10.1212/wnl.53.7.1537. [DOI] [PubMed] [Google Scholar]
  • 43.Gross CE, Tranmer BI, Adey G, et al. Increased cerebral blood flow in idiopathic pseudotumour cerebri. Neurol Res. 1990;12:226–230. doi: 10.1080/01616412.1990.11739948. [DOI] [PubMed] [Google Scholar]
  • 44.Foley J. Benign forms of intracranial hypertension; toxic and otitic hydrocephalus. Brain. 1955;78:1–41. doi: 10.1093/brain/78.1.1. [DOI] [PubMed] [Google Scholar]
  • 45.Breteler MM, Van Swieten JC, Bots ML, et al. Cerebral white matter lesions, vascular risk factors, and cognitive function in a population-based study: the Rotterdam Study. Neurology. 1994;44:1246–1252. doi: 10.1212/wnl.44.7.1246. [DOI] [PubMed] [Google Scholar]
  • 46.Lindgren A, Roijer A, Rudling O, et al. Cerebral lesions on magnetic resonance imaging, heart disease, and vascular risk factors in subjects without stroke: a population-based study. Stroke. 1994;25:929–934. doi: 10.1161/01.str.25.5.929. [DOI] [PubMed] [Google Scholar]
  • 47.Klassen AC, Sung JH, Stadlan EM. Histological changes in cerebral arteries with increasing age. J Neuropathol Exp Neurol. 1968;27:607–623. doi: 10.1097/00005072-196810000-00006. [DOI] [PubMed] [Google Scholar]
  • 48.Furuta A, Ishii N, Nishihara Y, et al. Medullary arteries in aging and dementia. Stroke. 1991;22:442–446. doi: 10.1161/01.str.22.4.442. [DOI] [PubMed] [Google Scholar]
  • 49.Ravens JR. Vascular changes in the human senile brain. Adv Neurol. 1978;20:487–501. [PubMed] [Google Scholar]
  • 50.Hommel M, Gray F. Microvascular pathology. In: Caplan LR, editor. Brain ischaemia: basic concepts and clinical relevance. New York: Springer-Verlag; 1995. pp. 215–223. [Google Scholar]
  • 51.Poirier J, Derouesne C. Cerebral lacunae: a proposed new classification. Clin Neuropathol. 1984;3:266–266. [PubMed] [Google Scholar]
  • 52.Kapeller P, Barber R, Vermeulen RJ, et al. Visual rating of age-related white matter changes on magnetic resonance imaging: scale comparison, interrater agreement, and correlations with quantitative measurements. Stroke. 2003;34:441–445. doi: 10.1161/01.STR.0000049766.26453.E9. [DOI] [PubMed] [Google Scholar]
  • 53.Fazekas F, Barkhof F, Wahlund LO, et al. CT and MRI rating of white matter lesions. Cerebrovasc Dis. 2002;13(Suppl 2):31–36. doi: 10.1159/000049147. [DOI] [PubMed] [Google Scholar]
  • 54.Patankar TF, Mitra D, Varma A, et al. Dilatation of the Virchow-Robin space is a sensitive indicator of cerebral microvascular disease: study in elderly patients with dementia. Am J Neuroradiol. 2005;26:1512–1520. [PMC free article] [PubMed] [Google Scholar]
  • 55.Naish JH, Baldwin RC, Patankar T, et al. Abnormalities of CSF flow patterns in the cerebral aqueduct in treatment-resistant late-life depression: a potential biomarker of microvascular angiopathy. Magn Reson Med. 2006;56:509–516. doi: 10.1002/mrm.20999. [DOI] [PubMed] [Google Scholar]
  • 56.Kalaria RN. The role of cerebral ischemia in Alzheimer’s disease. Neurobiol Aging. 2000;21:321–330. doi: 10.1016/S0197-4580(00)00125-1. [DOI] [PubMed] [Google Scholar]
  • 57.Kivipelto M, Helkala EL, Laakso MP, et al. Midlife vascular risk factors and Alzheimer’s disease in later life: longitudinal, population based study. BMJ. 2001;322:1447–1451. doi: 10.1136/bmj.322.7300.1447. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 58.Skoog I, Lernfelt B, Landahl S, et al. 15-year longitudinal study of blood pressure and dementia. Lancet. 1996;347:1141–1145. doi: 10.1016/S0140-6736(96)90608-X. [DOI] [PubMed] [Google Scholar]
  • 59.Hofman A, Ott A, Breteler M, et al. Atherosclerosis, apolipoprotein E, and prevalence of dementia and Alzheimer’s disease in the Rotterdam Study. Lancet. 1997;349:151–154. doi: 10.1016/S0140-6736(96)09328-2. [DOI] [PubMed] [Google Scholar]
  • 60.Snowdon DA. Aging and Alzheimer’s disease: lessons from the Nun Study. Gerontologist. 1997;37:150–6. doi: 10.1093/geront/37.2.150. [DOI] [PubMed] [Google Scholar]
  • 61.Frolich L, Klinger T, Berger FM. Treatment with donepezil in Alzheimer patients with and without cerebrovascular disease. J Neurol Sci. 2002;203-204:137–139. doi: 10.1016/S0022-510X(02)00275-7. [DOI] [PubMed] [Google Scholar]
  • 62.De Leeuw FE, Barkhof F, Scheltens P. Alzheimer’s disease-one clinical syndrome, two radiological expressions: a study on blood pressure. J Neurol Neurosurg Psychiatry. 2004;75:1270–1274. doi: 10.1136/jnnp.2003.030189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 63.Simons M, Schwarzler F, Lutjohann D, et al. Treatment with simvastatin in normocholesterolemic patients with Alzheimer’s disease: a 26-week randomized, placebo-controlled, double-blind trial. Ann Neurol. 2002;52:346–350. doi: 10.1002/ana.10292. [DOI] [PubMed] [Google Scholar]
  • 64.Grobe-Einsler R, Traber J. Clinical results with nimodipine in Alzheimer disease. Clin Neuropharmacol. 1992;15(Suppl 1):416A–417A. doi: 10.1097/00002826-199201001-00217. [DOI] [PubMed] [Google Scholar]
  • 65.Lopez-Arrieta JM, Birks J. Nimodipine for primary degenerative, mixed and vascular dementia. Cochrane Database Syst Rev. 2002;3:CD000147–CD000147. doi: 10.1002/14651858.CD000147. [DOI] [PubMed] [Google Scholar]
  • 66.Silverberg GD, Levinthal E, Sullivan EV, et al. Assessment of low-flow CSF drainage as a treatment for AD: results of a randomized pilot study. Neurology. 2002;59:1139–1145. doi: 10.1212/01.wnl.0000031794.42077.a1. [DOI] [PubMed] [Google Scholar]
  • 67.Bateman GA, Levi CR, Schofield P, et al. Quantitative measurement of cerebral haemodynamics in early vascular dementia and Alzheimer’s disease. J Clin Neurosci. 2006;13:563–568. doi: 10.1016/j.jocn.2005.04.017. [DOI] [PubMed] [Google Scholar]
  • 68.Bateman GA. The role of altered impedance in the pathophysiology of normal pressure hydrocephalus, Alzheimer’s disease and syringomyelia. Med Hypotheses. 2004;63:980–985. doi: 10.1016/j.mehy.2004.04.019. [DOI] [PubMed] [Google Scholar]

Articles from Neurotherapeutics are provided here courtesy of Elsevier

RESOURCES