@article{6f54b014827642e7ac10e1e8d8a99e4d,
title = "Oxygen-sensitive MRI assessment of tumor response to hypoxic gas breathing challenge",
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.",
keywords = "BOLD, Hypoxia, Intraumoral heterogeneity, TOLD, hypoxic gas, oxygen, rat, tumor",
author = "Yang, {Donghan M.} and Arai, {Tatsuya J.} and Campbell, {James W.} and Gerberich, {Jenifer L.} and Heling Zhou and Mason, {Ralph P.}",
note = "Funding Information: We thank the Histo Pathology Core (John Shelton) for assistance and the Whole Brain Microscopy Facility (supported by the Texas Institute for Brain Injury and Repair) in the Department of Neurology and Neurotherapeutics at UT Southwestern for the access to the Zeiss Axio Scan.Z1. This work was funded in part by CPRIT RP140399 in collaboration with Drs. Kevin G. Pinney and Mary Lynn Trawick at Baylor University and the UT Southwestern Small Animal Imaging Resource, Simmons Comprehensive Cancer Center and AIRC supported by NIH 1P30 CA142543, P41 EB015908 and an ARRA stimulus supplement to 1 U24 CA126608. Funding Information: Cancer Prevention and Research Institute of Texas, Grant/Award Number: RP140399; National Institutes of Health, Grant/Award Numbers: 1P30 CA142543, 1U24 CA126608 and P41 EB015908 Funding Information: *Presented in part at the 26th Annual Meeting of International Society for Magnetic Resonance in Medicine, Paris, France, June 2018 and the recipient of an ISMRM Magna Cum Laude Merit Award. Funding Information: We thank the Histo Pathology Core (John Shelton) for assistance and the Whole Brain Microscopy Facility (supported by the Texas Institute for Brain Injury and Repair) in the Department of Neurology and Neurotherapeutics at UT Southwestern for the access to the Zeiss Axio Scan.Z1. This work was funded in part by CPRIT RP140399 in collaboration with Drs. Kevin G. Pinney and Mary Lynn Trawick at Baylor University and the UT Southwestern Small Animal Imaging Resource, Simmons Comprehensive Cancer Center and AIRC supported by NIH 1P30 CA142543, P41 EB015908 and an ARRA stimulus supplement to 1?U24 CA126608. Publisher Copyright: {\textcopyright} 2019 John Wiley & Sons, Ltd.",
year = "2019",
month = jul,
doi = "10.1002/nbm.4101",
language = "English (US)",
volume = "32",
journal = "NMR in Biomedicine",
issn = "0952-3480",
publisher = "John Wiley and Sons Ltd",
number = "7",
}