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Quantitative Estimation of Tissue Blood Flow Rate

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Angiogenesis Protocols

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1430))

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Abstract

The rate of blood flow through a tissue (F) is a critical parameter for assessing the functional efficiency of a blood vessel network following angiogenesis. This chapter aims to provide the principles behind the estimation of F, how F relates to other commonly used measures of tissue perfusion, and a practical approach for estimating F in laboratory animals, using small readily diffusible and metabolically inert radio-tracers. The methods described require relatively nonspecialized equipment. However, the analytical descriptions apply equally to complementary techniques involving more sophisticated noninvasive imaging.

Two techniques are described for the quantitative estimation of F based on measuring the rate of tissue uptake following intravenous administration of radioactive iodo-antipyrine (or other suitable tracer). The Tissue Equilibration Technique is the classical approach and the Indicator Fractionation Technique, which is simpler to perform, is a practical alternative in many cases. The experimental procedures and analytical methods for both techniques are given, as well as guidelines for choosing the most appropriate method.

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References

  1. Stewart GN (1894) Researches on the circulation time in organs and on the influences which affect it: parts I-III. J Physiol (Lond) 15:1–89

    Article  Google Scholar 

  2. Reyes-Aldasoro CC, Akerman S, Tozer GM (2008) Measuring the velocity of fluorescently labelled red blood cells with a keyhole tracking algorithm. J Microsc 229:162–173

    Article  CAS  PubMed  Google Scholar 

  3. Intaglietta M, Tompkins WR (1973) Microvascular measurements by video image shearing and splitting. Microvasc Res 5:309–312

    Article  CAS  PubMed  Google Scholar 

  4. Fontanella AN, Schroeder T, Hochman DW, Chen RE, Hanna G, Haglund MM, Secomb TW, Palmer GM, Dewhirst MW (2013) Quantitative mapping of hemodynamics in the lung, brain, and dorsal window chamber-grown tumors using a novel, automated algorithm. Microcirculation 20:724–735

    PubMed  PubMed Central  Google Scholar 

  5. Brizel DM, Klitzman B, Cook JM, Edwards J, Rosner G, Dewhirst MW (1993) A comparison of tumor and normal tissue microvascular hematocrits and red cell fluxes in a rat window chamber model. Int J Radiat Oncol Biol Phys 25:269–276

    Article  CAS  PubMed  Google Scholar 

  6. Tozer GM, Prise VE, Wilson J, Cemazar M, Shan S, Dewhirst MW, Barber PR, Vojnovic B, Chaplin DJ (2001) Mechanisms associated with tumor vascular shut-down induced by combretastatin A-4 phosphate: intravital microscopy and measurement of vascular permeability. Cancer Res 61:6413–6422

    Google Scholar 

  7. Oye KS, Gulati G, Graff BA, Gaustad JV, Brurberg KG, Rofstad EK (2008) A novel method for mapping the heterogeneity in blood supply to normal and malignant tissues in the mouse dorsal window chamber. Microvasc Res 75:179–187

    Article  CAS  PubMed  Google Scholar 

  8. Stern MD (1975) In vivo evaluation of microcirculation by coherent light scattering. Nature 254:56–58

    Article  CAS  PubMed  Google Scholar 

  9. Smith KA, Hill SA, Begg AC, Denekamp J (1988) Validation of the fluorescent dye hoechst 33342 as a vascular space marker in tumours. Br J Cancer 57:247–253

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Hill SA, Tozer GM, Chaplin DJ (2002) Preclinical evaluation of the antitumour activity of the novel vascular targeting agent Oxi 4503. Anticancer Res 22:1453–1458

    CAS  PubMed  Google Scholar 

  11. Lunt SJ, Akerman S, Hill SA, Fisher M, Wright VJ, Reyes-Aldasoro CC, Tozer GM, Kanthou C (2011) Vascular effects dominate solid tumor response to treatment with combretastatin A-4-phosphate. Int J Cancer 129:1979–1989

    Article  CAS  PubMed  Google Scholar 

  12. Chalkley HW (1943) Method for quantitative morphologic analysis of tissues. J Natl Cancer Inst 4:47–53

    Google Scholar 

  13. Vermeulen PB, Gasparini G, Fox SB, Colpaert C, Marson LP, Gion M, Belien JA, de Waal RM, Van Marck E, Magnani E, Weidner N, Harris AL, Dirix LY (2002) Second international consensus on the methodology and criteria of evaluation of angiogenesis quantification in solid human tumours. Eur J Cancer 38:1564–1579

    Article  CAS  PubMed  Google Scholar 

  14. Weiskoff RM (1993) Pitfalls in MR measurement of tissue blood flow with intravascular tracers: which mean transit time? Magn Reson Med 29:553–559

    Article  Google Scholar 

  15. Messmer K (1979) Radioactive microspheres for regional blood flow measurements. Actual state and perspectives. Bibl Anat 18:194–197

    PubMed  Google Scholar 

  16. Jirtle RL (1980) Blood flow to lymphatic metastases in conscious rats. Eur J Cancer 17:53–60

    Article  Google Scholar 

  17. Jirtle RL, Hinshaw WM (1981) Estimation of malignant tissue blood flow with radioactively labelled microspheres. Eur J Cancer Clin Oncol 17:1353–1355

    Article  CAS  PubMed  Google Scholar 

  18. Sapirstein LA (1958) Regional blood flow by fractional distribution of indicators. Am J Physiol 193:161–168

    CAS  PubMed  Google Scholar 

  19. Obrist WD, Thompson HK, King CH, Wang HS (1967) Determination of regional cerebral blood flow by inhalation of 133-xenon. Circ Res 20:124–135

    Article  CAS  PubMed  Google Scholar 

  20. Young W (1980) H2 clearance measurement of blood flow: a review of technique and polarographic principles. Stroke 11:552–564

    Article  CAS  PubMed  Google Scholar 

  21. Sakurada O, Kennedy C, Lehle J, Brown JD, Carbin JL, Sokoloff L (1978) Measurement of local cerebral blood flow with iodo [14C] antipyrine. Am J Physiol 234:H59–H66

    CAS  PubMed  Google Scholar 

  22. Tozer GM, Shaffi KM (1993) Modification of tumour blood flow using the hypertensive agent, angiotensin II. Br J Cancer 67:981–988

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Trivedi MA (1996) A rapid method for the synthesis of 4-iodoantipyrine. J Labelled Compd Radiopharm 38:489–496

    Article  CAS  Google Scholar 

  24. Graham MM, Spence AM, Abbott GL, O’Gorman L, Muzi M (1987) Blood flow in an experimental rat brain tumor by tissue equilibration and indicator fractionation. J Neuro-Oncol 5:37–46

    Article  CAS  Google Scholar 

  25. Kety SS (1960) Theory of blood tissue exchange and its application to measurements of blood flow. Methods Med Res 8:223–227

    Google Scholar 

  26. Tozer GM, Shaffi KM, Prise VE, Cunningham VJ (1994) Characterisation of tumour blood flow using a “tissue-isolated” preparation. Br J Cancer 70:1040–1046

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Tozer GM, Morris C (1990) Blood flow and blood volume in a transplanted rat fibrosarcoma: comparison with various normal tissues. Radiother Oncol 17:153–166

    Article  CAS  PubMed  Google Scholar 

  28. Patlak CS, Blasberg RG, Fenstermacher JD (1984) An evaluation of errors in the determination of blood flow by the indicator fractionation and tissue equilibration (Kety) methods. J Cerebr Blood Flow Metab 4:47–60

    Article  CAS  Google Scholar 

  29. Goldman H, Sapirstein LA (1973) Brain blood flow in the conscious and anaesthetized rat. Am J Physiol 224:122–126

    CAS  PubMed  Google Scholar 

  30. Gjedde SB, Gjedde A (1980) Organ blood flow rates and cardiac output of the Balb/c mouse. Comp Biochem Physiol 67A:671–674

    Article  Google Scholar 

  31. Renkin EM (1959) Transport of potassium-42 from blood to tissue in isolated mammalian skeletal muscles. Am J Physiol 197:1205–1210

    CAS  PubMed  Google Scholar 

  32. Crone C (1963) The permeability of capillaries in various organs as determined by use of “indicator diffusion” method. Acta Physiol Scand 58:292–305

    Article  CAS  PubMed  Google Scholar 

  33. Jespersen SN, Ostergaard L (2012) The roles of cerebral blood flow, capillary transit time heterogeneity, and oxygen tension in brain oxygenation and metabolism. J Cerebr Blood flow Metab 32:264–277

    Article  CAS  Google Scholar 

  34. Ostergaard L, Tietze A, Nielsen T, Drasbek KR, Mouridsen K, Jespersen SN, Horsman MR (2013) The relationship between tumor blood flow, angiogenesis, tumor hypoxia, and aerobic glycolysis. Cancer Res 73:5618–5624

    Article  CAS  PubMed  Google Scholar 

  35. Herrero P, Kim J, Sharp TL, Engelbach JA, Lewis JS, Gropler RJ, Welch MJ (2006) Assessment of myocardial blood flow using 15O-water and 1-11C-acetate in rats with small-animal pet. J Nucl Med 47:477–485

    Google Scholar 

  36. Tozer GM, Prise VE, Wilson J, Locke RJ, Vojnovic B, Stratford MRL, Dennis MF, Chaplin DJ (1999) Combretastatin A-4 phosphate as a tumor vascular-targeting agent: early effects in tumors and normal tissues. Cancer Res 59:1626–1634

    Google Scholar 

  37. Richardson CA, Flecknell PA (2005) Anaesthesia and post-operative analgesia following experimental surgery in laboratory rodents: are we making progress? Altern Lab Anim 33:119–127

    CAS  PubMed  Google Scholar 

  38. Meyer E (1989) Simultaneous correction for tracer arrival delay and dispersion in CBF measurements by the H215O autoradiographic method and dynamic PET. J Nucl Med 30:1069–1078

    CAS  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Oncology and Metabolism, University of Sheffield Medical School, Beech Hill Road, Sheffield, S10 2RX, UK

    Gillian M. Tozer

  2. Centre for Cancer Research and Cell Biology, Queen’s University Belfast, 97 Lisburn Road, Belfast, BT9 7AE, UK

    Vivien E. Prise

  3. Aberdeen Biomedical Imaging Centre, School of Medical Sciences, University of Aberdeen, Aberdeen, AB252ZD, UK

    Vincent J. Cunningham

Authors
  1. Gillian M. Tozer
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  2. Vivien E. Prise
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  3. Vincent J. Cunningham
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Corresponding author

Correspondence to Gillian M. Tozer .

Editor information

Editors and Affiliations

  1. Nottingham, United Kingdom

    Stewart G. Martin

  2. UNIV BIRMINGHAM/MEDICAL SCHOOL, BIRMINGHAM B15 2TT, United Kingdom

    Peter W. Hewett

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Tozer, G.M., Prise, V.E., Cunningham, V.J. (2016). Quantitative Estimation of Tissue Blood Flow Rate. In: Martin, S., Hewett, P. (eds) Angiogenesis Protocols. Methods in Molecular Biology, vol 1430. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3628-1_18

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  • DOI: https://doi.org/10.1007/978-1-4939-3628-1_18

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-3626-7

  • Online ISBN: 978-1-4939-3628-1

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