Krypton-83 as a Contrast Agent for MRI

In an effort to develop new tools for magnetic resonance imagining, our group has recently applied the use of hyperpolarized krypton-83 to MRI. The relaxation of the nuclear spin of 83Kr atoms (I = 9/2) is driven by quadrupolar interactions during brief adsorption periods on surrounding material interfaces. Experiments in model systems reveal that the longitudinal relaxation of hp 83Kr gas strongly depends on the chemical composition of the materials. The relaxation weighted contrast in hp 83Kr MRI allows for the distinction between hydrophobic and hydrophilic surfaces. The feasibility of hp 83Kr MRI of airways is tested in canine lung tissue using krypton gas with natural abundance isotopic distribution. Additionally, the influence of magnetic field strength and the presence of a breathable concentration of molecular oxygen on longitudinal relaxation are investigated.

Hyperpolarized 83Kr MRI of gas flowing around glass structures. The inset figure (lower right hand corner of Fig. 1A) is a photograph of the phantom used to produce the MRI. Gas flow was held constant at 125 cm3/min. All figures are displayed after zero filling.

Hyperpolarized 83Kr MRI of a porous polyethylene sample with 70 m average pore size obtained under continuous flow (100 cm3/min) conditions. The inset sketch (lower right hand portion of Fig. 1B) is of the phantom used for the MRI. The center of the sample (i) is a 1.65 mm void space surrounded by a 0.76 mm PFA wall and an 11 mm wide area of a porous polymer (ii). The measurement at 9.4 T took about 2.1 h and led to a resolution of 650 x 650 m (raw data).

83Kr MRI of canine lung tissue obtained using krypton stopped flow optical pumping. The time needed for each of the 16 individual measurements is 10 minutes for the optical pumping process, approximately 3 seconds for the krypton transfer and 103 ms for radio frequency (r.f.) pulse, gradient pulse and acquisition at 9.4 T field strength. The resolution is 480 x 655 m (raw data) with no slice selection applied.
83Kr MRI of a lung sample using only one krypton stopped flow optical pumping cycle. The measurement takes 15 minutes for the pumping process, 3 seconds for the gas transfer and 0.46 s for the r.f. pulses, gradient pulses, and signal acquisition. The FLASH image was produced using sixteen 12 degreeflip angle pulses. The resolution is 1080 x 655 m (raw data) with no slice selection.
Micrograph of lung tissue demonstrating that the drying process preserves the alveolar structure. That microscopic anatomic structure is maintained as evidenced by the intact alveolar septum walls (long arrows) and alveolar epithelium (short arrows).

Fig. 3A. Photograph of the phantom used to obtain surface dependent contrast. Surface siliconized 1.0 mm closest packed glass beads (hydrophobic) are located in the center ring (i). Separated by an untreated glass tube (seen as a white ring in the photograph because of illumination from below) is the outer region (ii) that contains untreated 1.0 mm glass beads (hydrophilic). Fig. 3B. 83Kr MRI of the glass bead sample (Fig. 3A) reconstructed from 16 individual krypton stopped flow optical pumping cycles. The MRI sequence is applied approximately 3 s after filling the sample with hyperpolarized krypton leading to no appreciable MRI contrast between the two regions (note, the glass wall is not resolved since the resolution is 424 x 864 m). Fig. 3C. Same as Fig. 3B except a 9 s waiting period has been added. A clear contrast between the hydrophobic inner sample region (T1 = 9 s) and the hydrophilic outer region (T1 = 35 s) appears. Increasing the waiting time will lead to increased contrast but an overall reduced signal intensity.

In conclusion, we have demonstrated for the first time the use of a hyperpolarized noble gas with spin I > 1/2 separated from the rubidium vapor of the optical pumping process for MRI in a variety of media. Hp 83Kr MR images have been obtained at sub-millimeter resolution at 9.4 T in porous media with pore sizes similar to alveolar dimensions and in desiccated canine lung tissue at ambient pressure. The 83Kr spin-lattice relaxation times in the lung tissue remain reasonably long and should allow for in vivo MRI even in the presence of 20 % oxygen. It is shown that hp 83Kr provides a source of contrast that can distinguish between different chemical compositions of surfaces in a simple test system. These results are of potential value for the development of novel in vivo MRI techniques that can be used for the diagnosis of lung diseases where the surfactant concentration on the parenchyma surface is affected. Beyond in vivo applications, hp 83Kr NMR and MRI will be of importance in materials science for the study of porous media and surfaces. A potential application is the investigation of the homogeneity of surface grafting, coating and the spatial fluctuations of surface to volume ratios in porous media.