Category Archives: in-vivo DNP

Free Radical Imaging Using In Vivo Dynamic Nuclear Polarization-MRI #DNPNMR #ODNP

Utsumi, H. and F. Hyodo, Free Radical Imaging Using In Vivo Dynamic Nuclear Polarization-MRI. Methods Enzymol, 2015. 564: p. 553-71.

Redox reactions that generate free radical intermediates are essential to metabolic processes, and their intermediates can produce reactive oxygen species, which may promote diseases related to oxidative stress. The development of an in vivo electron spin resonance (ESR) spectrometer and its imaging enables us noninvasive and direct measurement of in vivo free radical reactions in living organisms. The dynamic nuclear polarization magnetic resonance imaging (DNP-MRI), also called PEDRI or OMRI, is also a new imaging method for observing free radical species in vivo. The spatiotemporal resolution of free radical imaging with DNP-MRI is comparable with that in MRI, and each of the radical species can be distinguished in the spectroscopic images by changing the frequency or magnetic field of ESR irradiation. Several kinds of stable nitroxyl radicals were used as spin probes to detect in vivo redox reactions. The signal decay of nitroxyl probes, which is determined with in vivo DNP-MRI, reflects the redox status under oxidative stress, and the signal decay is suppressed by prior administration of antioxidants. In addition, DNP-MRI can also visualize various intermediate free radicals from the intrinsic redox molecules. This noninvasive method, in vivo DNP-MRI, could become a useful tool for investigating the mechanism of oxidative injuries in animal disease models and the in vivo effects of antioxidant drugs.

Hyperpolarized choline as an MR imaging molecular probe: feasibility of in vivo imaging in a rat model

Friesen-Waldner, L.J., et al., Hyperpolarized choline as an MR imaging molecular probe: feasibility of in vivo imaging in a rat model. J Magn Reson Imaging, 2015. 41(4): p. 917-23.

PURPOSE: To assess the feasibility of choline MRI using a new choline molecular probe for dynamic nuclear polarization (DNP) hyperpolarized MRI. MATERIALS AND METHODS: Male Sprague-Dawley rats with an average weight of 400 +/- 20 g (n = 5), were anesthetized and injection tubing was placed in the tail vein. [1,1,2,2-D4 , 1-(13) C]choline chloride (CMP1) was hyperpolarized by DNP and injected into rats at doses ranging from 12.6 to 50.0 mg/kg. Coronal projection (13) C imaging was performed on a 3 Tesla clinical MRI scanner (bore size 60 cm) using a variable flip angle gradient echo sequence. Images were acquired 15 to 45 s after the start of bolus injection. Signal intensities in regions of interest were determined at each time point and compared. RESULTS: (13) C MRI images of hyperpolarized CMP1 at a 50 mg/kg dose showed time-dependent organ distribution patterns. At 15 s, high intensities were observed in the inferior vena cava, heart, aorta, and kidneys. At 30 s, most of the signal intensity was localized to the kidneys. These distribution patterns were reproduced using 12.6 and 25 mg/kg doses. At 45 s, only signal in the kidneys was detected. CONCLUSION: Hyperpolarized choline imaging with MRI is feasible using a stable-isotope labeled choline analog (CMP1). Nonradioactive imaging of choline accumulation may provide a new investigatory dimension for kidney physiology. J. Magn. Reson. Imaging 2015;41:917-923. (c) 2014 Wiley Periodicals, Inc.

In vivo Overhauser-enhanced MRI of proteolytic activity

Koonjoo, N., et al., In vivo Overhauser-enhanced MRI of proteolytic activity. Contrast Media Mol Imaging, 2014. 9(5): p. 363-71.

There is an increasing interest in developing novel imaging strategies for sensing proteolytic activities in intact organisms in vivo. Overhauser-enhanced MRI (OMRI) offers the possibility to reveal the proteolysis of nitroxide-labeled macromolecules thanks to a sharp decrease of the rotational correlation time of the nitroxide moiety upon cleavage. In this paper, this concept is illustrated in vivo at 0.2 T using nitroxide-labeled elastin orally administered in mice. In vitro, this elastin derivative was OMRI-visible and gave rise to high Overhauser enhancements (19-fold at 18 mm nitroxide) upon proteolysis by pancreatic porcine elastase. In vivo three-dimensional OMRI detection of proteolysis was carried out. A keyhole fully balanced steady-state free precession sequence was used, which allowed 3D OMRI acquisition within 20 s at 0.125 mm(3) resolution. About 30 min after mouse gavage, proteolysis was detected in the duodenum, where Overhauser enhancements were 7.2 +/- 2.4 (n = 7) and was not observed in the stomach. Conversely, orally administered free nitroxides or pre-digested nitroxide-labeled elastin were detected in the mouse’s stomach by OMRI. Combined with specific molecular probes, this Overhauser-enhanced MRI technique can be used to evaluate unregulated proteolytic activities in various models of experimental diseases and for drug testing.

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