Tumor physiological changes during hypofractionated stereotactic body radiation therapy assessed using multi-parametric magnetic resonance imaging

Heling Zhou, Zhang Zhang, Rebecca Denney, Jessica S. Williams, Jeni Gerberich, Strahinja Stojadinovic, Debabrata Saha, John M. Shelton, Ralph P. Mason

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Radiation therapy is a primary treatment for non-resectable lung cancer and hypoxia is thought to influence tumor response. Hypoxia is expected to be particularly relevant to the evolving new radiation treatment scheme of hypofractionated stereotactic body radiation therapy (SBRT). As such, we sought to develop noninvasive tools to assess tumor pathophysiology and response to irradiation. We applied blood oxygen level dependent (BOLD) and tissue oxygen level dependent (TOLD) MRI, together with dynamic contrast enhanced (DCE) MRI to explore the longitudinal effects of SBRT on tumor oxygenation and vascular perfusion using A549 human lung cancer xenografts in a subcutaneous rat model. Intra-tumor heterogeneity was seen on multi-parametric maps, especially in BOLD, T2* and DCE. At baseline, most tumors showed a positive BOLD signal response (%ΔSI) and increased T2* in response to oxygen breathing challenge, indicating increased vascular oxygenation. Control tumors showed similar response 24 hours and 1 week later. Twenty-four hours after a single dose of 12 Gy, the irradiated tumors showed a significantly decreased T2* (-2.9±4.2 ms) and further decrease was observed (-4.0±6.0 ms) after 1 week, suggesting impaired vascular oxygenation. DCE revealed tumor heterogeneity, but showed minimal changes following irradiation. Rats were cured of the primary tumors by 3x12 Gy, providing long term survival, though with ultimate metastatic recurrence.

Original languageEnglish (US)
Pages (from-to)37464-37477
Number of pages14
JournalOncotarget
Volume8
Issue number23
DOIs
Publication statusPublished - 2017

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Keywords

  • Blood oxygen level dependent (BOLD)
  • Dynamic contrast enhanced (DCE)
  • Hypofractionated stereotactic body radiation therapy (SBRT)
  • Oxygen-sensitive MRI
  • Treatment response

ASJC Scopus subject areas

  • Oncology

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