Dynamic oxygen challenge evaluated by NMR T<inf>1</inf> and T<inf>2</inf>* - insights into tumor oxygenation

Dawen Zhao, Jesús Pacheco-Torres, Rami R. Hallac, Derek White, Peter Peschke, Sebastian Cerdán, Ralph P. Mason

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

There is intense interest in developing non-invasive prognostic biomarkers of tumor response to therapy, particularly with regard to hypoxia. It has been suggested that oxygen sensitive MRI, notably blood oxygen level-dependent (BOLD) and tissue oxygen level-dependent (TOLD) contrast, may provide relevant measurements. This study examined the feasibility of interleaved T<inf>2</inf><sup>*-</sup> and T<inf>1</inf>-weighted oxygen sensitive MRI, as well as R<inf>2</inf><sup>*</sup> and R<inf>1</inf> maps, of rat tumors to assess the relative sensitivity to changes in oxygenation. Investigations used cohorts of Dunning prostate R3327-AT1 and R3327-HI tumors, which are reported to exhibit distinct size-dependent levels of hypoxia and response to hyperoxic gas breathing. Proton MRI R<inf>1</inf> and R<inf>2</inf><sup>*</sup> maps were obtained for tumors of anesthetized rats (isoflurane/air) at 4.7 T. Then, interleaved gradient echo T<inf>2</inf><sup>*-</sup> and T<inf>1</inf>-weighted images were acquired during air breathing and a 10 min challenge with carbogen (95% O<inf>2</inf>-5% CO<inf>2</inf>). Signals were stable during air breathing, and each type of tumor showed a distinct signal response to carbogen. T<inf>2</inf><sup>*</sup> (BOLD) response preceded T<inf>1</inf> (TOLD) responses, as expected. Smaller HI tumors (reported to be well oxygenated) showed the largest BOLD and TOLD responses. Larger AT1 tumors (reported to be hypoxic and resist modulation by gas breathing) showed the smallest response. There was a strong correlation between BOLD and TOLD signal responses, but ΔR<inf>2</inf><sup>*</sup> and ΔR<inf>1</inf> were only correlated for the HI tumors. The magnitude of BOLD and TOLD signal responses to carbogen breathing reflected expected hypoxic fractions and oxygen dynamics, suggesting potential value of this test as a prognostic biomarker of tumor hypoxia.

Original languageEnglish (US)
JournalNMR in Biomedicine
DOIs
StateAccepted/In press - 2015

Fingerprint

Oxygenation
Tumors
Nuclear magnetic resonance
Oxygen
Neoplasms
Respiration
Blood
Tissue
Magnetic resonance imaging
Air
Tumor Biomarkers
Rats
Gases
Isoflurane
Feasibility Studies
Protons
Prostate

Keywords

  • BOLD
  • Carbogen
  • Hypoxia
  • MRI
  • Oxygen
  • Prostate
  • TOLD
  • Tumor

ASJC Scopus subject areas

  • Spectroscopy
  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging

Cite this

Dynamic oxygen challenge evaluated by NMR T<inf>1</inf> and T<inf>2</inf>* - insights into tumor oxygenation. / Zhao, Dawen; Pacheco-Torres, Jesús; Hallac, Rami R.; White, Derek; Peschke, Peter; Cerdán, Sebastian; Mason, Ralph P.

In: NMR in Biomedicine, 2015.

Research output: Contribution to journalArticle

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abstract = "There is intense interest in developing non-invasive prognostic biomarkers of tumor response to therapy, particularly with regard to hypoxia. It has been suggested that oxygen sensitive MRI, notably blood oxygen level-dependent (BOLD) and tissue oxygen level-dependent (TOLD) contrast, may provide relevant measurements. This study examined the feasibility of interleaved T2*- and T1-weighted oxygen sensitive MRI, as well as R2* and R1 maps, of rat tumors to assess the relative sensitivity to changes in oxygenation. Investigations used cohorts of Dunning prostate R3327-AT1 and R3327-HI tumors, which are reported to exhibit distinct size-dependent levels of hypoxia and response to hyperoxic gas breathing. Proton MRI R1 and R2* maps were obtained for tumors of anesthetized rats (isoflurane/air) at 4.7 T. Then, interleaved gradient echo T2*- and T1-weighted images were acquired during air breathing and a 10 min challenge with carbogen (95{\%} O2-5{\%} CO2). Signals were stable during air breathing, and each type of tumor showed a distinct signal response to carbogen. T2* (BOLD) response preceded T1 (TOLD) responses, as expected. Smaller HI tumors (reported to be well oxygenated) showed the largest BOLD and TOLD responses. Larger AT1 tumors (reported to be hypoxic and resist modulation by gas breathing) showed the smallest response. There was a strong correlation between BOLD and TOLD signal responses, but ΔR2* and ΔR1 were only correlated for the HI tumors. The magnitude of BOLD and TOLD signal responses to carbogen breathing reflected expected hypoxic fractions and oxygen dynamics, suggesting potential value of this test as a prognostic biomarker of tumor hypoxia.",
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AU - Peschke, Peter

AU - Cerdán, Sebastian

AU - Mason, Ralph P.

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AB - There is intense interest in developing non-invasive prognostic biomarkers of tumor response to therapy, particularly with regard to hypoxia. It has been suggested that oxygen sensitive MRI, notably blood oxygen level-dependent (BOLD) and tissue oxygen level-dependent (TOLD) contrast, may provide relevant measurements. This study examined the feasibility of interleaved T2*- and T1-weighted oxygen sensitive MRI, as well as R2* and R1 maps, of rat tumors to assess the relative sensitivity to changes in oxygenation. Investigations used cohorts of Dunning prostate R3327-AT1 and R3327-HI tumors, which are reported to exhibit distinct size-dependent levels of hypoxia and response to hyperoxic gas breathing. Proton MRI R1 and R2* maps were obtained for tumors of anesthetized rats (isoflurane/air) at 4.7 T. Then, interleaved gradient echo T2*- and T1-weighted images were acquired during air breathing and a 10 min challenge with carbogen (95% O2-5% CO2). Signals were stable during air breathing, and each type of tumor showed a distinct signal response to carbogen. T2* (BOLD) response preceded T1 (TOLD) responses, as expected. Smaller HI tumors (reported to be well oxygenated) showed the largest BOLD and TOLD responses. Larger AT1 tumors (reported to be hypoxic and resist modulation by gas breathing) showed the smallest response. There was a strong correlation between BOLD and TOLD signal responses, but ΔR2* and ΔR1 were only correlated for the HI tumors. The magnitude of BOLD and TOLD signal responses to carbogen breathing reflected expected hypoxic fractions and oxygen dynamics, suggesting potential value of this test as a prognostic biomarker of tumor hypoxia.

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KW - Prostate

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