Hyperpolarized water as an authentic magnetic resonance imaging contrast agent

Abstract

Pure water in a highly 1 H spin-polarized state is proposed as a contrast-agent-free contrast agent to visualize its macroscopic evolution in aqueous media by MRI. Remotely enhanced liquids for image contrast (RELIC) utilizes a 1 H signal of water that is enhanced outside the sample in continuous-flow mode and immediately delivered to the sample to obtain maximum contrast between entering and bulk fluids. Hyperpolarization suggests an ideal contrast mechanism to highlight the ubiquitous and specific function of water in physiology, biology, and materials because the physiological, chemical, and macroscopic function of water is not altered by the degree of magnetization. We present an approach that is capable of instantaneously enhancing the 1 H MRI signal by up to 2 orders of magnitude through the Overhauser effect under ambient conditions at 0.35 tesla by using highly spin-polarized unpaired electrons that are covalently immobilized onto a porous, water-saturated gel matrix. The continuous polarization of radicalfree flowing water allowed us to distinctively visualize vortices in model reactors and dispersion patterns through porous media. A 1 H signal enhancement of water by a factor of ؊10 and ؊100 provides for an observation time of >4 and 7 s, respectively, upon its injection into fluids with a T1 relaxation time of >1.5 s. The implications for chemical engineering or biomedical applications of using hyperpolarized solvents or physiological fluids to visualize mass transport and perfusion with high and authentic MRI contrast originating from water itself, and not from foreign contrast agents, are immediate.Water is the driver of nature.Leonardo da Vinci I n a world where water is so ubiquitous and vital, the exchange and transport characteristics of water are fundamental for the function of an endless range of biological and industrial processes: blood physiology, protein folding, plant metabolism, biomaterial function, and oil recovery from reservoir rocks are only drops in the bucket. However, there exists a paucity of analytical tools capable of directly tracing and quantifying the transport and function of water through these already-watersaturated materials in a chemically selective and noninvasive manner. Although NMR and MRI are the best tools for this purpose, they face two main challenges. One is the lack of sensitivity inherent to all NMR experiments, especially for in vivo NMR studies of transport in biological and biomedical samples. A general approach to this sensitivity issue is the employment of high magnetic fields and cryoprobes, which is not only expensive technology but also is limited to Ͻ1 order of magnitude improvement in sensitivity. The other challenge is the lack of contrast, e.g., between the flowing water molecules being traced and the bulk water or water contained in the specimen. Current perfusion MRI techniques that address this contrast issue are dynamic susceptibility contrast-enhanced imaging (1, 2) and proton electron double-resonance imaging (PEDRI), also known as Overhaus...

A Mobile DNP Polarizer for Clinical Applications

“…Despite the fact that our measured maximum enhancements of #50, #36 and #12 are slightly lower than those reported for similar systems and hardware setups [14,17], it is noteworthy that the ENDOR probehead employed in this study is used at EPR resonance conditions (8.41 GHz/0.30 T) for which this commercial probehead is not optimized. The microwave absorption characteristics are rather poor: it is highly overcoupled and microwave reflections already significantly diminish the performance.…”

“…Furthermore, one can devise schemes to extract spin-labeled polyelectrolytes from the solutions before injection by using them as a fixed polyelectrolyte gel matrix (similar to the system in ref. 17) or by extracting them through electrostatic interactions (e.g., by adding oppositely charged polyelectrolytes or surfaces).…”

“…Reasons for that are low natural abundance of 13 C, low concentration of 13 C-compounds, and physiological temperature, etc. However, this obstacle could be overcome by in vitro hyperpolarization of a 13 Ccontaining molecule with long spinlattice relaxation time via dynamic nuclear polarization (DNP) or parahydrogen-induced polarization and subsequent injection into the animal or patient under study as has been demonstrated recently [17]. MR angiography and perfusion measurements can benefit significantly from using hyperpolarized 13 C-containing molecules since there is no background signal from the thermally polarized 13 C nuclei in the tissue, and therefore the contrastto-noise ratio (CNR) approaches the signal-to-noise ratio (SNR) [24].…”

Renal MR angiography and perfusion in the pig using hyperpolarized water

“…Utilizing hyperpolarized water for angiographic and perfusion imaging overcomes several of these limitations. Water protons for imaging have previously been hyperpolarized by use of the Overhauser effect (23). However, the maximum achievable magnetization is limited.…”

MRI contrast agents for functional molecular imaging of brain activity

“…Principal difficulties involve the relatively rapid decay of MRI signal from the tracer (time constant 15−20 s in vivo), the fact that other metabolites (e.g. glucose) have much shorter decay times, and the need in fMRI applications for periodic or continuous supply [38] of polarized agents to the brain.…”