Imaging Of Redox Status Research Articles

Dynamic-Reversible Photoacoustic Probe for Continuous Ratiometric Sensing and Imaging of Redox Status in Vivo.

Here, we report a reversible photoacoustic (PA) probe, BDP-DOH, to image the localized redox state in vivo via monitoring the dynamic changes of the redox couple, superoxide anion (O2•-) and glutathione (GSH). The probe features a significant shift in absorption between 680 and 750 nm during selective oxidation with O2•- and the reductive recovery of GSH, thus showing a reversible responsiveness in the photoacoustic intensity ratio (PA750/PA680) to successfully visualize the redox status of the tissue in situ. This redox probe with specific and sensitive photoacoustic response provides a potential technical tool toward understanding pathological formation processes.

Label-free imaging of redox status and collagen deposition showing metabolic differences in the heart.

The heart has high metabolic demand to maintain function. The primary source of energy supply to support correct contractile muscle function differs between a fetus and an adult. In fetal life, ATP is primarily generated by glycolysis and lactate oxidation, whereas following birth, there is a shift towards a reliance on mitochondrial metabolism and fatty acid oxidation. This change in metabolic status is an adaptation to different fuel availability, oxygenation and growth patterns. In this study, we have employed 2-photon excitation fluorescence microscopy to define the relationship between two critical metabolic cofactors nicotinamide adenine dinucleotide(P)H and flavin adenine dinucleotide, effectively utilizing a redox ratio to differentiate between the metabolic status in fetal (proliferative) and adult (quiescent/hypertrophic) hearts. Two-photon imaging was also used to visually confirm the known increase in collagen deposition in the adult heart. The changes observed were consistent with a hypertrophic growth profile and greater availability of fatty acids in the adult heart, compared to the proliferative fetal heart. Two-photon excitation fluorescence microscopy is therefore a convenient imaging technology that enables the monitoring of striated muscle architecture and the metabolic status of heart tissue. This imaging technology can potentially be employed to visualize cardiac and other muscle pathologies.

81 - Development and Clinical Trial of Novel Field-cycling DNP-MRI for Free Radical Imaging

Probe-free imaging of redox intermediate radicals must become a crucial method and diagnosis. DNP (dynamic nuclear polarization)-MRI, a new imaging method for free radical (Lurie, et al. 1988), utilizes Overhauser effect that nuclear spin close to free radical is 300 times higher polarized than that of natural state by inducing the electron spin resonance of free radical. The advantage of DNP-MRI is the high sensitivity and resolution, theoretically similar to that in MRI. We installed the custom-made DNP-MRI from Philips and succeeded in the imaging of redox status in disease models and the spectroscopic imaging of redox intermediate radicals from FMN, FAD, CoQ10, and vitamin E. It has, however, the large disadvantage of poor sensitivity and heating by ESR irradiation, because of its low magnetic field (15mT MRI). Here, we developed the novel field-cycling DNP-MRI system for clinical trial, in which free radicals are visualized with 0.3T MRI as the polarized proton by irradiating the free radicals at 5mT, and demonstrated the clear images of the phantoms containing FAD radical with less than 0.5 mm of the spatial resolution. The image of FAD radical placed under healthy volunteer hand was superimposed on the anatomical MRI image. The intrinsic radical, melanin, could be also visualized. Overhauser effect is known to be occurred in the various kind of free radicals, metal-complex, etc., and also in lipid membranes. The newly developed DNP-MRI could demonstrate the functional/metabolic imaging by visualizing intrinsic radials, redox intermediates and/or metal enzymes in disease models and also in patients.

In vivo measurement of regional oxygenation and imaging of redox status in RIF-1 murine tumor: effect of carbogen-breathing.

The purpose of this study was to noninvasively monitor tumor oxygenation and redox status during hyperoxygenation treatment, such as carbogen-breathing, in a murine tumor model using in vivo electron paramagnetic resonance (EPR) spectroscopy and imaging techniques. The study was performed using implanted lithium phthalocyanine (LiPc) microcrystals as the oximetry probe and 3-carbamoylproxyl (3-CP) as the redox probe in RIF-1 tumors implanted in the upper hind leg of C3H mice. Repetitive measurements of pO(2) from the same tumors as a function of tumor growth (8-24 mm in size) showed that the tumors were hypoxic and that the tumor pO(2) values were decreasing with tumor growth. Carbogen-breathing mostly showed an increase in the tumor oxygenation, although there were considerable variations in the magnitude of change among the tumors. The pharmacokinetic studies with 3-CP showed a significant decrease in the overall tumor reduction status in the carbogen-breathing mice. Spatially resolved (imaging) pharmacokinetic data over the tumor volume were obtained to visualize the distribution of the redox status within the tumor. The redox images of the tumor in the air-breathing mice showed significant heterogeneity in the magnitude and spatial distribution of reducing equivalents. On carbogen-breathing the tissue reduction status decreased considerably, with a concomitant decrease in the heterogeneity of distribution of the redox status. The results suggest that 1) carbogen-breathing considerably enhances tissue oxygenation and significantly decreases the redox status in RIF-1 tumor, and 2) changes in the magnitude and distribution of the redox status within the tumor volume during carbogen-breathing are correlated with the increased tissue oxygenation.