MacKinnon Martin J, Berkowitz Bruce A, Shih Yen-Yu Ian
Center for Animal MRI, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Biomedical Research Imaging Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Magn Reson Med. 2021 Aug;86(2):1058-1066. doi: 10.1002/mrm.28722. Epub 2021 Mar 23.
QuEnch-assiSTed (QUEST) MRI provides a unique biomarker of excessive production of paramagnetic free radicals (oxidative stress) in vivo. The contribution from superoxide, a common upstream species found in oxidative stress-based disease, to the QUEST metric is unclear. Here, we begin to address this question by measuring superoxide spin-lattice relaxivity (r1) in phantoms.
Stable superoxide free radicals were generated in water phantoms of potassium superoxide ( . To measure r1, 1/T of different concentration solutions of KO in the presence and absence of the antioxidant superoxide dismutase were measured. The 1/T confounding factors including acquisition sequence, pH, and water source were also evaluated.
The T -weighted signal intensity increased with KO concentration. No contribution from pH, or reaction products other than superoxide, noted on 1/T . Superoxide r1 was measured to be 0.29 mM s , in agreement with that reported for paramagnetic molecular oxygen and nitroxide free radicals.
Our first-in-kind measurement of superoxide free radical r1 suggests a detection sensitivity of QUEST MRI on the order of tens of μM, within the reported level of free radical production during oxidative stress in vivo. Similar studies for other common free radicals are needed.
淬灭辅助（QUEST）磁共振成像（MRI）可在体内提供一种独特的生物标志物，用于检测顺磁性自由基过度产生（氧化应激）的情况。超氧化物是基于氧化应激的疾病中常见的上游物质，其对QUEST指标的贡献尚不清楚。在此，我们通过测量模型中的超氧化物自旋晶格弛豫率（r1）来开始解决这个问题。
在超氧化钾的水体模中产生稳定的超氧化物自由基。为了测量r1，在存在和不存在抗氧化剂超氧化物歧化酶的情况下，测量不同浓度超氧化钾溶液的1/T。还评估了包括采集序列、pH值和水源等1/T的混杂因素。
T加权信号强度随超氧化钾浓度增加而增加。在1/T方面，未发现pH值或超氧化物以外的反应产物有影响。测得超氧化物的r1为0.29 mM s，与报道的顺磁性分子氧和氮氧化物自由基的r1一致。
我们首次对超氧化物自由基r1进行测量，结果表明QUEST MRI的检测灵敏度约为数十微摩尔，处于体内氧化应激过程中报道的自由基产生水平范围内。还需要对其他常见自由基进行类似研究。
