Blood Oxygen Level Dependent Magnetization Transfer (BOLDMT) Effect

  • Kejia Cai
  • Mohammad Haris
  • Anup Singh
  • Lin Z. Li
  • Ravinder Reddy
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 765)


A few studies have reported that magnetization transfer (MT) ­preparation interacts with blood oxygen level dependent (BOLD) contrast used for functional magnetic resonance imaging (MRI). However, the mechanism is still not well established. This study shows that blood oxygenation level itself affects MT contrast. MT ratio (MTR) decreases with increased blood oxygenation, which is demonstrated by ex vivo and in vivo experiments. Oxygenated blood shows less MTR contrast compared to deoxygenated blood sample; and higher levels of oxygen inhalation decrease tissue MTR in vivo especially in brain tumor region. The percentage reduction of MTR due to hyperoxia inhalation, referred to as the blood oxygen dependent magnetization transfer (BOLDMT) effect, correlates well with tissue oxygen extraction, which is highest in well-vascularized tumor rim, followed by inner tumor, gray matter (GM), and white matter (WM) normal tissue. Simulations and experiments demonstrate that BOLDMT effect induced with hyperoxia inhalation may be generated by decreased tissue T1 due to increased O2 dissolution and increased tissue T2 due to reduced deoxyhemoglobin (dHb) concentration. Compared to regular T2* weighted BOLD contrast, BOLDMT has higher insensitivity to B0 inhomogeneities. BOLDMT may potentially serve as a reliable and novel biomarker for tumor oxygen extraction.


Blood oxygen level dependent Magnetization transfer Tumor oxygen extraction Hyperoxia inhalation 



The authors thank Drs. Harish Poptani, Ranjit Ittyerah, and Damodar Reddy for their help with the animal model; Matt Fenty, Weixia Liu, Steve Pickup for their technical assistance in using small animal research scanners; Kalli Grasley and Prianka Waghray for literature review. This work was performed at an NIH supported resource with funding from P41RR02305.


  1. 1.
    Grossman RI, Gomori JM, Ramer KN et al (1994) Magnetization transfer: theory and clinical applications in neuroradiology. Radiographics 14:279–290CrossRefGoogle Scholar
  2. 2.
    Henkelman RM, Stanisz GJ, Graham SJ (2001) Magnetization transfer in MRI: a review. NMR Biomed 14:57–64CrossRefGoogle Scholar
  3. 3.
    Ogawa S, Lee TM, Kay AR et al (1990) Brain magnetic resonance imaging with contrast dependent on blood oxygenation. Proc Natl Acad Sci U S A 87:9868–9872CrossRefPubMedGoogle Scholar
  4. 4.
    Prasad PV, Edelman RR, Epstein FH (1996) Noninvasive evaluation of intrarenal oxygenation with BOLD MRI. Circulation 94:3271–3275CrossRefGoogle Scholar
  5. 5.
    Baudelet C, Gallez B (2002) How does blood oxygen level-dependent (BOLD) contrast correlate with oxygen partial pressure (pO2) inside tumors? Magn Reson Med 48:980–986CrossRefGoogle Scholar
  6. 6.
    Jezzard P, Song AW (1996) Technical foundations and pitfalls of clinical fMRI. Neuroimage 4:S63–S75CrossRefGoogle Scholar
  7. 7.
    Port JD, Pomper MG (2000) Quantification and minimization of magnetic susceptibility artifacts on GRE images. J Comput Assist Tomogr 24:958–964CrossRefGoogle Scholar
  8. 8.
    Zhou J, Payen JF, van Zijl PC (2005) The interaction between magnetization transfer and blood-oxygen-level-dependent effects. Magn Reson Med 53:356–366CrossRefGoogle Scholar
  9. 9.
    Kim T, Hendrich K, Kim SG (2008) Functional MRI with magnetization transfer effects: determination of BOLD and arterial blood volume changes. Magn Reson Med 60:1518–1523CrossRefPubMedGoogle Scholar
  10. 10.
    Kim S, Pickup S, Hsu O et al (2008) Diffusion tensor MRI in rat models of invasive and well-demarcated brain tumors. NMR Biomed 21:208–216CrossRefGoogle Scholar
  11. 11.
    Wang S, Kim S, Chawla S et al (2009) Differentiation between glioblastomas and solitary brain metastases using diffusion tensor imaging. Neuroimage 44:653–660CrossRefGoogle Scholar
  12. 12.
    Haris M, Cai K, Singh A et al (2011) In vivo mapping of brain myo-inositol. Neuroimage 54:2079–2085CrossRefGoogle Scholar
  13. 13.
    Woessner DE, Zhang S, Merritt ME et al (2005) Numerical solution of the Bloch equations provides insights into the optimum design of PARACEST agents for MRI. Magn Reson Med 53:790–799CrossRefGoogle Scholar
  14. 14.
    Tadamura E, Hatabu H, Li W et al (1997) Effect of oxygen inhalation on relaxation times in various tissues. J Magn Reson Imaging 7:220–225CrossRefGoogle Scholar
  15. 15.
    Uematsu H, Takahashi M, Hatabu H et al (2007) Changes in T1 and T2 observed in brain magnetic resonance imaging with delivery of high concentrations of oxygen. J Comput Assist Tomogr 31:662–665CrossRefGoogle Scholar
  16. 16.
    Pauling L, Coryell CD (1936) The magnetic properties and structure of hemoglobin, oxyhemoglobin and carbonmonoxyhemoglobin. Proc Natl Acad Sci U S A 22:210–216CrossRefPubMedGoogle Scholar
  17. 17.
    Silvennoinen MJ, Kettunen MI, Kauppinen RA (2003) Effects of hematocrit and oxygen saturation level on blood spin–lattice relaxation. Magn Reson Med 49:568–571CrossRefGoogle Scholar
  18. 18.
    Jezzard P, Clare S (1999) Sources of distortion in functional MRI data. Hum Brain Mapp 8:80–85CrossRefGoogle Scholar
  19. 19.
    Vaupel P, Schlenger K, Knoop C et al (1991) Oxygenation of human tumors: evaluation of tissue oxygen distribution in breast cancers by computerized O2 tension measurements. Cancer Res 51:3316–3322Google Scholar
  20. 20.
    Kavanagh MC, Sun A, Hu Q et al (1996) Comparing techniques of measuring tumor hypoxia in different murine tumors: Eppendorf pO2 Histograph, [3H]misonidazole binding and paired survival assay. Radiat Res 145:491–500CrossRefGoogle Scholar
  21. 21.
    Mason RP, Hunjan S, Constantinescu A et al (2003) Tumor oximetry: comparison of 19F MR EPI and electrodes. Adv Exp Med Biol 530:19–27CrossRefGoogle Scholar
  22. 22.
    Gillies RJ, Raghunand N, Karczmar GS et al (2002) MRI of the tumor microenvironment. J Magn Reson Imaging 16:430–450CrossRefGoogle Scholar
  23. 23.
    Krohn KA, Link JM, Mason RP (2008) Molecular imaging of hypoxia. J Nucl Med 49(Suppl 2):129S–148SCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Kejia Cai
    • 1
  • Mohammad Haris
    • 1
  • Anup Singh
    • 1
  • Lin Z. Li
    • 1
  • Ravinder Reddy
    • 1
  1. 1.Department of Radiology, Center for Magnetic Resonance and Optical ImagingUniversity of PennsylvaniaPhiladelphiaUSA

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