Superoxide free radical spin‐lattice relaxivity: A quench‐assisted MR study

Abstract

Purpose: 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. Methods: Stable superoxide free radicals were generated in water phantoms of potassium superoxide (KO 2 ). To measure r1, 1/T 1 of different concentration solutions of KO 2 in the presence and absence of the antioxidant superoxide dismutase were measured. The 1/T 1 confounding factors including acquisition sequence, pH, and water source were also evaluated. Results:The T 1 -weighted signal intensity increased with KO 2 concentration. No contribution from pH, or reaction products other than superoxide, noted on 1/T 1 . Superoxide r1 was measured to be 0.29 mM −1 s −1 , in agreement with that reported for paramagnetic molecular oxygen and nitroxide free radicals. Conclusion: 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.

MRI of radiation chemistry: First images and investigation of potential mechanisms

“…this relaxivity value is approximately 20%. The relaxivity of the superoxide radical, O •− 2 , has been reported to be similar to that of O 2 , with a value of 0.29 s −1 mM −1 in water at 9 T and 20 • C. 32 In stark contrast, the relaxivity of hydroxyl radical, • OH, has a reported value of 3.4 × 107 s −1 mM −1 in egg white at 9.4 T and 21 • C, which is eight orders of magnitude higher than the reported relaxivity of O 2 , O •− 2 , and typical gadoliniumbased contrast agents. 33 Other radicals produced by water radiolysis, including hydrogen radical, H • , and hydroperoxyl radical, HO • 2 , do not currently have published relaxivity values.…”

“…The reported uncertainty for this relaxivity value is approximately 20%. The relaxivity of the superoxide radical, $${\rm{O}}_2^{{\bullet}-}$$, has been reported to be similar to that of O 2 , with a value of 0.29 s −1 mM −1 in water at 9 T and 20°C 32 . In stark contrast, the relaxivity of hydroxyl radical, • OH, has a reported value of 3.4 × 107 s −1 mM −1 in egg white at 9.4 T and 21°C, which is eight orders of magnitude higher than the reported relaxivity of O 2 , $${\rm{O}}_2^{{\bullet}-}$$, and typical gadolinium‐based contrast agents 33 .…”

Correcting QUEST Magnetic Resonance Imaging–Sensitive Free Radical Production in the Outer Retina In Vivo Does Not Correct Reduced Visual Performance in 24-Month-Old C57BL/6J Mice

“…Importantly, the biophysical sensitivity of QUEST MRI to sustained superoxide production has been demonstrated in phantoms of the xanthine/xanthine oxidase reaction or in solutions of KO 2 . 58 , 90 In mice, the noninvasive free radical readout of QUEST MRI under physiologic conditions has also been validated against gold-standard ex vivo assays during dark and light adaptation of (i) rods and (ii) cones, and (iii) in postnatal day seven mice that have anatomical but not yet functioning rods. 40 , 56 Finally, the accuracy of QUEST MRI as a type zero biomarker of oxidative stress has been confirmed to be a reliable measure of ongoing production of free radicals in excess of antioxidant defenses in the retina in several mouse models including (i) after the RPE-toxin sodium iodate, (ii) in RPE-specific MnSOD knockout mice, (iii) in diabetes, (iv) in phosphodiesterase 6b knockout mice, and (v) after pharmaceutical inhibition of phosphodiesterase 6.…”