Radio frequency continuous‐wave and time‐domain EPR imaging and Overhauser‐enhanced magnetic resonance imaging of small animals: instrumental developments and comparison of relative merits for functional imaging

Abstract

Electron paramagnetic resonance (EPR) imaging in the continuous wave (CW) and time-domain modes, as well as Overhauser-enhanced magnetic resonance imaging in vivo is described. The review is based mainly on the CW and time-domain EPR instrumentation at 300 MHz developed in our laboratory, and the relative merits of these methods for functional in vivo imaging of small animals to assess hypoxia and tissue redox status are described. Overhauser imaging of small animals at magnetic fields in the range 10-15 mT that is being carried out in our laboratory for tumor imaging and the evaluation of tumor hypoxia based on quantitative evaluation of Overhauser enhancement is also described. Alternate approaches to spectral-spatial imaging using the transverse decay constants to infer in situ line widths and hence in vivo pO 2 using CW and time-domain EPR imaging are also discussed. The nature of the spin probes used, the quality of the images obtained in all the three methods, the achievable resolution, limitations and possible future directions in small animal functional imaging with these modalities are summarized.

Intracellular and Extracellular Redox Environments Surrounding Redox-Sensitive Contrast Agents under Oxidative Atmosphere

“…Such highly oxidative atmospheres can modify the pharmacokinetics and/or pharmacodynamics of nitroxyl contrast agents. Therefore a method for monitoring tissue redox status [7][8][9][10][11] might help plan cancer chemotherapy and/or radiotherapy strategy.…”

“…When the decay rate of EPR image intensities was calculated using pixels and re-plotted as decay rate mapping, the different redox states among different tissues, such as a tumor and normal tissues, can be clearly seen. 7,8) In addition, paramagnetic nitroxyl radicals can be utilized as redox-sensitive contrast agents combined with a T 1 -weighted magnetic resonance imaging (MRI) technique, so-called magnetic resonance (MR) redox imaging. [9][10][11] Such a redox imaging technique is a possible candidate to probe tumor pathophysiology.…”

“…12) Another EPR imaging experiment also showed that the nitroxyl contrast agent decays faster in squamous cell carcinoma (SCC) tumor than in normal tissue. 7) Using high-resolution MR redox imaging, the different decay rate of the nitroxyl contrast agent between SCC tumor tissues and normal tissues around tumor tissues can also be observed 9) ; however, only membrane-permeable nitroxyl contrast agents show a faster reduction in tumor compared with in normal tissue. 10) Loss in contrast of those nitroxyl contrast agents is due to intracellular reduction of the nitroxyl radical to the corresponding hydroxylamine.…”

Single loop multi-gap resonator for whole body EPR imaging of mice at 1.2GHz

“…For these applications, it is essential to maximize both system sensitivity and stability. For small animal EPR imaging, typically low frequencies have been used such as 300 MHz (3)(4)(5)(6). However, the selection of low microwave frequency limits the obtainable sensitivity (7)(8)(9)(10)(11).…”

Simultaneous molecular imaging of redox reactions monitored by Overhauser-enhanced MRI with 14 N- and 15 N-labeled nitroxyl radicals

“…The spatial resolution of an ESRI image is poorer than that of MRI because of the large ESR line-width. It is usually at the mm level unless high field gradients are used.Overhauser-enhanced MRI (OMRI) is a double resonance technique that uses the presence of paramagnetic agents to enhance the signal intensity from nuclear spins by means of a process known as dynamic nuclear polarization (DNP) or Overhauser effect (23)(24)(25)(26)(27)(28). In this phenomenon, the relatively stronger magnetic moment of the electron is used to enhance the polarization of the nuclear spins, thereby enhancing their signal.…”