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 radical-free 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 T(1) 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.

Fig. 1.

Experimental setup for contrast MRI using continuously flowing hyperpolarized ¹H water. A syringe pump drives the water flow through the polarization cell situated inside the microwave cavity where microwave radiation saturates the ESR transitions of radicals immobilized on a gel matrix. The ¹H signal of water gets instantaneously hyperpolarized upon the transfer of polarization from the radicals and is then introduced into the sample cell contained inside an imaging probe equipped with gradients, where NMR image acquisition takes place. Water flows back out of the imaging area through the microwave cavity into a water reservoir.

Fig. 2.

Recovery of magnetization that has been inverted (dashed blue line) compared with −10-fold enhanced (solid red line) with time constant T₁ = 2.5 s. The two arrows indicate the different time points where magnetization crosses zero at 1.7 and 6 s for the different magnetization recovery curves. In pure water with a T₁ of 2.5 s, a −10-fold hyperpolarization provides an observation time of 6 s, whereas an inverted signal, which is the maximum modulation achievable in conventional MRI methods, only allows for 1.7 s of observation time.

Fig. 3.

Sketch (A), photograph (B), and static MRI (C) of the sample vessel used for contrast flow imaging presented in Fig. 4A. (A) The sketch depicts the PTFE phantom in white and the water in black. (B) The photograph shows the side view with the inlet capillary above the phantom and the exit capillary inside the channel. (C) The image is an xz projection with the long dimension z frequency encoded and the short dimension x phase encoded. [Scale bar: 1 mm (with different scales in the x and z directions).]

Fig. 4.

Contrast flow imaging using ¹H hyperpolarized water. (A) Contrast flow imaging using ¹H hyperpolarized water in the sample vessel depicted in Fig. 3 at varying flow rates between 0.5 and 1.5 ml/min. (Scale bar: 1 mm along both axes.) The first image is without microwave irradiation under a continuous water flow of 1.5 ml/min (MW = off). The next three are contrast images using strong microwave irradiation, where flow rates of 0.5, 1, and 1.5 ml/min were used (MW = on). A phase map (shown in the final image of the series) distinctively shows the flow path of negatively hyperpolarized water. The characteristics and structure of the flow path of water, which enters at the left side of the vessel, then travels across the tube and down into the right channel, and finally exits into the outlet capillary, is visualized. (B) Contrast flow imaging using ¹H hyperpolarized water in a sample vessel without channels connected to the main reservoir, as depicted in the sketch (Left), with the water entering through the longer, center capillary tube. (Right) An image is shown without microwave (MW = off) irradiation under continuous water flow, and a contrast image using strong microwave irradiation (MW = on) with a flow rate of 1.5 ml/min. A phase map distinctively shows the flow path of negatively hyperpolarized water. The creation of vortex structures due to characteristic vessel geometry can be seen. (C) Contrast flow imaging using ¹H hyperpolarized water over a packing of submerged molecular sieve beads (shown in the photograph; Left). (Right) First is an image without microwave irradiation under continuous water flow (MW = off), and next is a contrast image using strong microwave irradiation, where a flow rate of 1.5 ml/min was used (MW = on). A phase map distinctively shows negatively hyperpolarized water. The water can be seen entering at the right side of the vessel, and then it travels below the bead packing, across the tube, and then back up into the outlet capillary.