Oxygen‐sensitive MRI assessment of tumor response to hypoxic gas breathing challenge*. (7th May 2019)

• Record Type: Journal Article
• Authors: Yang, Donghan M.; Arai, Tatsuya J.; Campbell, James W.; Gerberich, Jenifer L.; Zhou, Heling; Mason, Ralph P.
• Is Part Of: NMR in biomedicine. Volume 32:Number 7(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-05-07
• Subjects: BOLD -- Hypoxia -- hypoxic gas -- Intraumoral heterogeneity -- oxygen -- rat -- TOLD -- tumor; Nuclear magnetic resonance -- Periodicals; Magnetic Resonance Spectroscopy -- Periodicals; 574
• DOI: 10.1002/nbm.4101
• Languages: English
• ISSNs: 0952-3480

Abstract

Abstract : Oxygen‐sensitive MRI has been extensively used to investigate tumor oxygenation based on the response (R2 * and/or R1 ) to a gas breathing challenge. Most studies have reported response to hyperoxic gas indicating potential biomarkers of hypoxia. Few studies have examined hypoxic gas breathing and we have now evaluated acute dynamic changes in rat breast tumors. Rats bearing syngeneic subcutaneous ( n = 15) or orthotopic ( n = 7) 13762NF breast tumors were exposed to a 16% O2 gas breathing challenge and monitored using blood oxygen level dependent (BOLD) R2 * and tissue oxygen level dependent (TOLD) T1 ‐weighted measurements at 4.7 T. As a control, we used a traditional hyperoxic gas breathing challenge with 100% O2 on a subset of the subcutaneous tumor bearing rats ( n = 6). Tumor subregions identified as responsive on the basis of R2 * dynamics coincided with the viable tumor area as judged by subsequent H&E staining. As expected, R2 * decreased and T1 ‐weighted signal increased in response to 100% O2 breathing challenge. Meanwhile, 16% O2 breathing elicited an increase in R2 *, but divergent response (increase or decrease) in T1 ‐weighted signal. The T1 ‐weighted signal increase may signify a dominating BOLD effect triggered by 16% O2 in the relatively more hypoxic tumors, whereby the influence of increased paramagnetic deoxyhemoglobin outweighs decreased pO2 . The results emphasize the importance of combined BOLD and TOLD measurements for the correct interpretation of tumor oxygenation properties. Abstract : Oxygen‐sensitive MRI was performed on 13762NF breast tumors growing subcutaneously and orthotopically in syngeneic rats. As expected opposite R2 * (BOLD) responses were observed with 16% O2 and 100% O2 gas breathing challenges, but T1 ‐weighted signal (TOLD) showed divergent response (increase or decrease) to 16% O2 . In light of R2 * responses as well as pimonidazole staining, we attribute the apparent anomaly to the influence of deoxyhemoglobin on R1 under hypoxia conditions generating a caveat for interpretation of oxygen‐sensitive data.