Sodium Magnetic Resonance Imaging in the Management of Human High-Grade Brain Tumors

  • Keith R. Thulborn
  • Ian C. Atkinson
  • Andrew Shon
  • Neil A. Das Gupta
  • John L. Villano
  • Tamir Y. Hersonskey
  • Aiming Lu


The treatment of high-grade brain tumors involves surgical resection followed by targeted fractionated radiation therapy with concomitant chemotherapy and then follow-up chemotherapy. Conventional proton magnetic resonance (MR) imaging plays a role in the initial detection and anatomical and physiological characterization of the mass, preoperative functional mapping of eloquent cortex for neurosurgical planning, and postoperative imaging for radiation planning usually combined with computed tomography (CT). Subsequent surveillance follow-up MR imaging, usually every 3–4 months beginning after radiation, is used to detect recurrence. These follow-up studies ideally include perfusion and permeability MR imaging techniques to detect increases in tissue vascularity that herald local recurrence of high-grade tumors. Early changes, termed pseudo-progression, induced by the combination of radiation and low-dose chemotherapy with temozolomide (Temodar), occur within weeks to a few months of completing radiation treatment and mimic recurrence, but resolve without further intervention. Later changes of radiation necrosis can also result in a false-positive indication of recurrence, usually beginning many months or even years after completing radiation treatment. Unfortunately, some chemotherapeutic interventions, such as bevacizumab (Avastin), may actually disguise vascular indicators of recurrence (pseudo-response), thereby further delaying the detection of recurrence. Unlike most tumors outside the central nervous system, the failure of treatment for brain tumors results from local recurrence rather than metastatic disease. This behavior of local recurrence along with the poor prognosis suggests that the current standard of medical care for high-grade tumors requires improvement. Despite the multimodality approach to treatment, the assessment of response is currently done retrospectively by the absence of recurrence in follow-up imaging studies rather than prospectively by measuring the response during treatment. Prospective monitoring has been the goal for investigating if tumor response can be measured sensitively in a timely fashion during treatment. Such a detection method would open the possibility for adaptive therapy based on local responses measured in real time or, in the absence of a response, consideration of alternative treatments. Such a detection method should detect cell kill across the tumor volume during treatment. Such a parameter can be measured directly by quantitative sodium MR imaging based on a simple model of sodium ion homeostasis. This chapter describes this investigational methodology in detail and presents preliminary results through individual clinical cases. Other approaches to this measurement such as by water diffusion MR imaging may also indirectly reflect this process, but may be more of a surrogate qualitative marker rather than a direct quantitative parameter.


Magnetic Resonance Signal Sodium Signal Sodium Imaging Proton Imaging Tissue Sodium Concentration 
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.



The authors acknowledge financial support from PHS RO1 CA1295531A1. This work was supported in part by a SPARK award from the Chicago Biomedical Consortium with support from The Searle Funds at The Chicago Community Trust. We thank Dr. Peter Johnstone from the Indiana University Health Proton Therapy Center, Bloomington, Indiana, for the proton beam radiation treatment plan for case #1.


  1. 1.
    Gilbert MR, Armstrong TS. Management of patients with newly diagnosed malignant primary brain tumors with a focus on the evolving role of temozolomide. Ther Clin Risk Manag. 2007;3(6):1027–33.PubMedGoogle Scholar
  2. 2.
    Lacroix M, Abi-Said D, Fourney DR, et al. A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. J Neurosurg. 2001;95(2):190–8.PubMedCrossRefGoogle Scholar
  3. 3.
    Hall WA, Kowalik K, Liu H, Truwit CL, Kucharezyk J. Costs and benefits of intraoperative MR-guided brain tumor resection. Acta Neurochir Suppl. 2003;85:137–42.PubMedCrossRefGoogle Scholar
  4. 4.
    Dolecek TA, Propp JM, Stroup NE, Kruchko C. CBTRUS Statistical Report: Primary brain and central nervous system tumors diagnosed in the United States in 2005–2009. Neuro-oncology 2012;14(suppl 5):v1–v49.Google Scholar
  5. 5.
    Tofts PS, Kermode AG. Measurement of the blood-brain barrier permeability and leakage space using dynamic MR imaging. 1. Fundamental concepts. Magn Reson Med. 1991;17(2):357–67.PubMedCrossRefGoogle Scholar
  6. 6.
    Roberts HC, Roberts TPL, Brasch RC, Dillon WP. Quantitative measurement of microvascular permeability in human brain tumors achieved using dynamic contrast-enhanced MR imaging: correlation with histologic grade. Am J Neuroradiol. 2000;21(5):891–9.PubMedGoogle Scholar
  7. 7.
    Thulborn KR, Lu A, Atkinson IC, Damen F, Villano JL. Quantitative sodium MR imaging and sodium bioscales for the management of brain tumors. Neuroimaging Clin N Am. 2009;19(4):615–24.PubMedCrossRefGoogle Scholar
  8. 8.
    Lu A, Atkinson IC, Claiborne T, Damen F, Thulborn KR. Quantitative sodium imaging with a flexible twisted projection pulse sequence. Magn Reson Med. 2010;63(6):1583–93.PubMedCrossRefGoogle Scholar
  9. 9.
    Hamstra DA, Galban CJ, Meyer CR, Johnson TD, Sundgren PC, Tsien C, Lawrence TS, Junck L, Ross DJ, Rehemtulla A, Ross BD, Chenevert TL. Functional diffusion map as an early imaging biomarker for high-grade glioma: correlation with conventional radiologic response and overall survival. J Clin Oncol. 2008;26:3387–94.PubMedCrossRefGoogle Scholar
  10. 10.
    Somjen GG. Ions of the brain, normal function, seizures and stroke. New York, NY: Oxford University Press; 2004.Google Scholar
  11. 11.
    Nicholson C, Sykova E. Extracellular space structure revealed by diffusion analysis. Trends Neurosci. 1998;21(5):207–15.PubMedCrossRefGoogle Scholar
  12. 12.
    Neeb H, Ermer V, Stocker T, Shah NJ. Fast quantitative mapping of absolute water content with full brain coverage. Neuroimage. 2008;42:1094–109.PubMedCrossRefGoogle Scholar
  13. 13.
    Atkinson IC, Lu A, Thulborn KR. Clinically constrained optimization of flexTPI acquisition parameters for the tissue sodium concentration bioscale. Magn Reson Med. 2011;66(4):1089–99.PubMedCrossRefGoogle Scholar
  14. 14.
    Johnson LA, Pearlman JD, Miller CA, Young TI, Thulborn KR. MR quantification of cerebral ventricular volume using a semi-automated algorithm. Am J Neuroradiol. 1993;14:1373–8.PubMedGoogle Scholar
  15. 15.
    Hilal SK, Maudsley AA, Ra JB, Simon HE, Roschmann P, Wittekoek S, Cho ZH, Mun SK. In vivo NMR imaging of sodium-23 in the human head. J Comput Assist Tomogr. 1985;9(1):1–7.PubMedCrossRefGoogle Scholar
  16. 16.
    Ouwerkerk R, Bleich KB, Gillen JS, Pomper MG, Bottomley PA. Tissue sodium concentration in human brain tumors as measured with 23Na MR imaging. Radiology. 2003;227:529–37.PubMedCrossRefGoogle Scholar
  17. 17.
    Thulborn KR, Davis D, Adams H, Gindin T, Zhou J. Quantitative tissue sodium concentration mapping of the growth of focal cerebral tumors with sodium magnetic resonance imaging. Magn Reson Med. 1999;41:351–9.PubMedCrossRefGoogle Scholar
  18. 18.
    Thulborn KR. Chapter 5. The challenges of integrating a 9.4T MR scanner for human brain imaging. In: Ultra high field magnetic resonance imaging. Volume 26, Robitaille P-M, Berliner LJ, editors. New York, Springer; 2006. pp105–126.Google Scholar
  19. 19.
    Robitaille PM, Warner R, Jagadeesh J, Abduljalil AM, Kangarlu A, Burgess RE, Yu Y, Yang L, Zhu H, Jiang Z, Bailey RE, Chung W, Somawiharja Y, Feynan P, Rayner DL. Design and assembly of an 8 tesla whole-body MR scanner. J Comput Assist Tomogr. 1999;23(6):808.PubMedCrossRefGoogle Scholar
  20. 20.
    Atkinson IC, Sonstegaard R, Pliskin NH, Thulborn KR. Vital signs and cognitive function are not affected by 23-sodium and 17-oxygen MR imaging of the human brain at 9.4 tesla. J Magn Reson Imaging. 2010;32:82–7.PubMedCrossRefGoogle Scholar
  21. 21.
    Atkinson IC, Renteria L, Burd H, Pliskin NH, Thulborn KR. Safety of human MRI at static fields above the FDA 8T guideline: sodium imaging at 9.4T does not affect vital signs or cognitive ability. J Magn Reson Imaging. 2007;26:1227–52.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Keith R. Thulborn
    • 1
  • Ian C. Atkinson
    • 1
  • Andrew Shon
    • 2
  • Neil A. Das Gupta
    • 3
  • John L. Villano
    • 4
  • Tamir Y. Hersonskey
    • 5
  • Aiming Lu
    • 1
  1. 1.Center for Magnetic Resonance ResearchUniversity of Illinois Medical CenterChicagoUSA
  2. 2.Department of Radiology, Physiology and Biophysics, Center for Magnetic Resonance ResearchUniversity of Illinois Medical CenterChicagoUSA
  3. 3.Department of Radiation OncologyFox Valley Radiation OncologyNapervilleUSA
  4. 4.Neuro-Oncology ProgramUniversity of IllinoisChicagoUSA
  5. 5.Provena St. Joseph Medical CenterJolietUSA

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