The Effects of Tumour Blood Flow and Oxygenation Modifiers on Subcutaneous Tumours as Determined by NIRS

  • Franklyn A. Howe
  • James P. Connelly
  • Simon P. Robinson
  • Roger Springett
  • John R. Griffiths
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 566)


Modulation of tumour oxygenation may be used to increase or decrease tumour hypoxia in order to improve the effect of radiotherapy or bioreductive drugs, respectively. Magnetic resonance imaging (MRI) and near infrared spectroscopy (NIRS) are techniques sensitive to blood deoxyhemoglobin concentration (Hb) that can be used to investigate tumour hypoxia indirectly via blood oxygenation levels. In this study we have used NIRS to determine absolute Hb and changes in deoxyhemoglobin and oxyhemoglobin (HbO) in subcutaneous rodent tumours for challenges that alter blood flow and oxygenation, with the aim to better interpret our MRI data. Both carbogen [95% O2 + 5% CO2] and 100% O2 breathing produced a similar and significant reduction in Hb and increase in HbO, but a negligible change in HbT (= Hb + HbO). In contrast, N2 breathing to terminal anoxia and intravenous hydralazine produced a negligible increase in Hb, but large reductions in HbO and HbT. HbT is proportional to blood volume, so our data suggests large blood volume decreases occur with challenges likely to cause reduced arterial blood pressure. Hence MRI techniques that measure the R2* relaxation rate, which varies linearly with total Hb, will underestimate the effects of hypotensive agents at increasing tumour hypoxia.


Tumour Hypoxia Magnetic Resonance Imaging Data Near Infrared Spectroscopy Tumour Blood Flow Tumour Oxygenation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    M. R. Horsman, Measurement of tumor oxygenation, Int. J. Radiat. Oncol. Biol. Phys. 42, 701–704 (1998).PubMedCrossRefGoogle Scholar
  2. 2.
    D. J. Chaplin, M. R. Horsman, and D. S. Aoki, Nicotinamide, Fluosol DA, and carbogen: A strategy to reoxygenate acutely and chronically hypoxic cells in vivo, Br. J. Cancer 63, 109–112 (1991).PubMedGoogle Scholar
  3. 3.
    I. J. Stratford, G. E. Adams, J. C. Bremner, S. Cole, H. S. Edwards, N. Robertson, and P. J. Wood, Manipulation and exploitation of the tumor microenvironment for therapeutic benefit, Int. J. Radiat. Biol. 65, 85–94 (1994).PubMedGoogle Scholar
  4. 4.
    F. A. Howe, S. P. Robinson, D. J. O. McIntyre, M. Stubbs, and J. R. Griffiths, Issues in flow and oxygenation dependent contrast (FLOOD) imaging of tumours, NMR Biomed. 14, 497–506 (2001).PubMedCrossRefGoogle Scholar
  5. 5.
    S. P. Robinson, D. R. Collingridge, F. A. Howe, L. M. Rodrigues, D. J. Chaplin, and J. R. Griffiths, Tumor response to hypercapnia and hyperoxia monitored by FLOOD magnetic resonance imaging, NMR Biomed. 12, 98–106 (1999).PubMedCrossRefGoogle Scholar
  6. 6.
    C. E. Cooper, C. E. Elwell, J. H. Meek, S. J. Matcher, J. S. Wyatt, M. Cope, and D. T. Delpy, The non-invasive measurement of absolute cerebral deoxyhemoglobin concentration and mean optical pathlength in the neonatal brain by second derivative near infrared spectroscopy, Pediatr. Res. 39, 32–38 (1996).PubMedGoogle Scholar
  7. 7.
    R. Springett, J. Newman, M. Cope, and D. T. Delpy, Oxygen dependency and precision of cytochrome oxidase signal from full spectral NIRS of the piglet brain, Am. J. Physiol. Heart. Circ. Physiol. 279, H2202–H2209 (2000).PubMedGoogle Scholar
  8. 8.
    E. L. Hull, D. L. Conover, and T. H. Foster, Carbogen-induced changes in rat mammary tumour oxygenation reported by near infrared spectroscopy, Br. J. Cancer 79, 1709–1716 (1999).PubMedCrossRefGoogle Scholar
  9. 9.
    Y. Gu, V. A. Bourke, J. G. Kim, A. Constantinescu, R. P. Mason, and H. Liu, Dynamic response of breast tumor oxygenation to hyperoxic respiratory challenge monitored with three oxygen-sensitive parameters, App. Optics 16, 2960–2966 (2003).Google Scholar
  10. 10.
    J. F. Dunn, Y. Zaim-Wadghiri, B. W. Pogue, and I. Kida, BOLD MRI vs. NIR spectrophotometry: will the best technique come forward, Adv. Exp. Med. Biol. 44, 103–113 (1998).Google Scholar
  11. 11.
    S. Punwani, R. J. Ordidge, C. E. Cooper, P. Amess, and M. Clemence, MRI measurements of cerebral deoxyhemoglobin concentration [dHb] — correlation with near infrared spectroscopy, NMR Biomed. 11, 281–289 (1998).PubMedCrossRefGoogle Scholar
  12. 12.
    C. Aalkjjær, and L. Poston, Effects of pH on vascular tension: which are the important mechanisms? J. Vase. Res. 33, 347–359 (1996).Google Scholar
  13. 13.
    I. T. Demchenko, T. D. Oury, J. D. Crapo, and C. A. Piantidosi, Regulation of the brain’s vascular response to oxygen, Circ. Res. 91, 1031–1037 (2002).PubMedCrossRefGoogle Scholar
  14. 14.
    J. A. Kruuv, W. R. Inch, and J. A. McCredie, Blood flow and oxygenation of tumors in mice, Cancer 20, 51–59 (1967).PubMedGoogle Scholar
  15. 15.
    D. M. Brizel, S. Lin, J. L. Johnson, J. Brooks, M. W. Dewhirst, and C. A. Piantadosi, The mechanisms by which hyperbaric oxygen and carbogen improve tumour oxygenation, Br. J. Cancer 72, 1120–1124 (1995).PubMedGoogle Scholar
  16. 16.
    G. M. Tozer, R. J. Maxwell, J. R. Griffiths, and P. Pham, Modification of the 31P magnetic resonance spectra of a rat tumour using vasodilators and its relationship to hypotension, Br. J. Cancer 62, 553–560 (1990).PubMedGoogle Scholar
  17. 17.
    R. G. Steen, D. A. Wilson, C. Bowser, J. P. Wehrle, S. S. Rajan, and J. D. Glickson, 31P NMR spectroscopic and near infrared spectrophotometric studies of effects of anesthetics on in vivo RIF-1 tumors: relationship to tumor radiosensitivity, NMR Biomed. 2, 87–92 (1989).PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2005

Authors and Affiliations

  • Franklyn A. Howe
  • James P. Connelly
  • Simon P. Robinson
  • Roger Springett
  • John R. Griffiths

There are no affiliations available

Personalised recommendations