Pathway to cryogen free production of hyperpolarized krypton-83 and xenon-129

yperpolarized (hp) 129Xe and hp 83Kr for magnetic resonance imaging (MRI) are typically obtained through spin-exchange optical pumping (SEOP) in gas mixtures with dilute concentrations of the respective noble gas. The usage of dilute noble gases mixtures requires cryogenic gas separation after SEOP, a step that makes clinical and preclinical applications of hp 129Xe MRI cumbersome. For hp 83Kr MRI, cryogenic concentration is not practical due to depolarization that is caused by quadrupolar relaxation in the condensed phase. In this work, the concept of stopped flow SEOP with concentrated noble gas mixtures at low pressures was explored using a laser with 23.3 W of output power and 0.25 nm linewidth. For 129Xe SEOP without cryogenic separation, the highest obtained MR signal intensity from the hp xenon-nitrogen gas mixture was equivalent to that arising from 15.561.9% spin polarized 129Xe in pure xenon gas. The production rate of the hp gas mixture, measured at 298 K, was 1.8 cm3/min. For hp 83Kr, the equivalent of 4.460.5% spin polarization in pure krypton at a production rate of 2 cm3/min was produced. The general dependency of spin polarization upon gas pressure obtained in stopped flow SEOP is reported for various noble gas concentrations. Aspects of SEOP specific to the two noble gas isotopes are discussed and compared with current theoretical opinions. A non-linear pressure broadening of the Rb D1 transition was observed and taken into account for the qualitative description of the SEOP process

Molecular hydrogen and catalytic combustion in the production of hyperpolarized 83Kr and 129Xe MRI contrast agents

Hyperpolarized (hp) 83Kr is a promising MRI contrast agent for the diagnosis of pulmonary diseases affecting the surface of the respiratory zone. However, the distinct physical properties of 83Kr that enable unique MRI contrast also complicate the production of hp 83Kr. This work presents a radically new approach in the generation of hp 83Kr that can likewise be utilized for the production of hp 129Xe. Molecular nitrogen, typically used as buffer gas in spin exchange optical pumping (SEOP), was replaced by molecular hydrogen without penalty for the achievable hyperpolarization. In this particular study, the highest obtained nuclear spin polarizations were P = 29 % for 83Kr and P = 63 % for 129Xe. The results were reproduced over many SEOP cycles despite the laser induced on-resonance formation of rubidium hydride (RbH). Following SEOP, the H2 was reactively removed via catalytic combustion without measurable losses in hyperpolarized spin state of either 83Kr or 129Xe. Highly spin polarized 83Kr can now be purified for the first time to provide high signal intensity for the advancement of in vivo hp 83Kr MRI. More generally, a chemical reaction appears as a viable alternative to the cryogenic separation process, the primary purification method of hp 129Xe for the past 2 . decades. The inherent simplicity of the combustion process will facilitate hp 129Xe production and should allow for on-demand continuous flow of purified and highly spin polarized 129Xe

Pulmonary MRI contrast using Surface Quadrupolar Relaxation (SQUARE) of hyperpolarized 83Kr

Hyperpolarized 83Kr has previously been demonstrated to enable MRI contrast that is sensitive to the chemical composition of the surface in a porous model system. Methodological advances have lead to a substantial increase in the 83Kr hyperpolarization and the resulting signal intensity. Using the improved methodology for spin exchange optical pumping of isotopically enriched 83Kr, internal anatomical details of ex vivo rodent lung were resolved with hyperpolarized 83Kr MRI after krypton inhalation. Different 83Kr relaxation times were found between the main bronchi and the parenchymal regions in ex vivo rat lungs. The T1 weighted hyperpolarized 83Kr MRI provided a first demonstration of surface quadrupolar relaxation (SQUARE) pulmonary MRI contrast

Cryogenics free production of hyperpolarized 129Xe and 83Kr for biomedical MRI applications

As an alternative to cryogenic gas handling, hyperpolarized (hp) gas mixtures were extracted directly from the spin exchange optical pumping (SEOP) process through expansion followed by compression to ambient pressure for biomedical MRI applications. The omission of cryogenic gas separation generally requires the usage of high xenon or krypton concentrations at low SEOP gas pressures to generate hp 129Xe or hp 83Kr with sufficient MR signal intensity for imaging applications. Two different extraction schemes for the hp gasses were explored with focus on the preservation of the nuclear spin polarization. It was found that an extraction scheme based on an inflatable, pressure controlled balloon is sufficient for hp 129Xe handling, while 83Kr can efficiently be extracted through a single cycle piston pump. The extraction methods were tested for ex vivo MRI applications with excised rat lungs. Precise mixing of the hp gases with oxygen, which may be of interest for potential in vivo applications, was accomplished during the extraction process using a piston pump. The 83Kr bulk gas phase T1 relaxation in the mixtures containing more than approximately 1% O2 was found to be slower than that of 129Xe in corresponding mixtures. The experimental setup also facilitated 129Xe T1 relaxation measurements as a function of O2 concentration within excised lungs

Developing a medical device-grade T2 phantom optimized for myocardial T2 mapping by cardiovascular magnetic resonance

INTRODUCTION: A long T2 relaxation time can reflect oedema, and myocardial inflammation when combined with increased plasma troponin levels. Cardiovascular magnetic resonance (CMR) T2 mapping therefore has potential to provide a key diagnostic and prognostic biomarkers. However, T2 varies by scanner, software, and sequence, highlighting the need for standardization and for a quality assurance system for T2 mapping in CMR. AIM: To fabricate and assess a phantom dedicated to the quality assurance of T2 mapping in CMR. METHOD: A T2 mapping phantom was manufactured to contain 9 T1 and T2 (T1|T2) tubes to mimic clinically relevant native and post-contrast T2 in myocardium across the health to inflammation spectrum (i.e., 43-74 ms) and across both field strengths (1.5 and 3 T). We evaluated the phantom's structural integrity, B0 and B1 uniformity using field maps, and temperature dependence. Baseline reference T1|T2 were measured using inversion recovery gradient echo and single-echo spin echo (SE) sequences respectively, both with long repetition times (10 s). Long-term reproducibility of T1|T2 was determined by repeated T1|T2 mapping of the phantom at baseline and at 12 months. RESULTS: The phantom embodies 9 internal agarose-containing T1|T2 tubes doped with nickel di-chloride (NiCl2) as the paramagnetic relaxation modifier to cover the clinically relevant spectrum of myocardial T2. The tubes are surrounded by an agarose-gel matrix which is doped with NiCl2 and packed with high-density polyethylene (HDPE) beads. All tubes at both field strengths, showed measurement errors up to ≤ 7.2 ms [< 14.7%] for estimated T2 by balanced steady-state free precession T2 mapping compared to reference SE T2 with the exception of the post-contrast tube of ultra-low T1 where the deviance was up to 16 ms [40.0%]. At 12 months, the phantom remained free of air bubbles, susceptibility, and off-resonance artifacts. The inclusion of HDPE beads effectively flattened the B0 and B1 magnetic fields in the imaged slice. Independent temperature dependency experiments over the 13-38 °C range confirmed the greater stability of shorter vs longer T1|T2 tubes. Excellent long-term (12-month) reproducibility of measured T1|T2 was demonstrated across both field strengths (all coefficients of variation < 1.38%). CONCLUSION: The T2 mapping phantom demonstrates excellent structural integrity, B0 and B1 uniformity, and reproducibility of its internal tube T1|T2 out to 1 year. This device may now be mass-produced to support the quality assurance of T2 mapping in CMR

Accuracy, repeatability, and interplatform reproducibility of T1 quantification methods used for DCEâ MRI: Results from a multicenter phantom study

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142505/1/mrm26903_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142505/2/mrm26903.pd

Rubidium IR absorption linewidth as a function of gas pressure.

<p><b>A</b>. IR absorption spectrum of Rb in the SEOP cell containing pure krypton gas at 433 K at three different pressures as detailed in the figure legend. The absorption lines experience a pressure broadening and, to a lesser extent, a shift to higher wavelengths with increasing pressure. <b>B</b>. Rb D₁ absorption linewidth as a function of SEOP cell pressure at 433 K for pure krypton (solid red triangles), for pure N₂ at 433 K (solid green squares), for pure xenon at 373 K (solid black circles), and for a mixture of 50% xenon with 50% N₂ (open black circles). The pressure dependence of the absorption linewidth can be approximately described by (dashed lines). Eq. 9 was concluded from the observed linewidth dependence. The linewidth of the narrowed laser and the broadband laser are 0.25 nm and 2.0 nm respectively, and are indicated in the figure by horizontal dotted lines.</p

Values for and from fitting experimental data of ⁸³Kr spin polarization as a function of SEOP cell pressure in Fig. 2 using Eq. 8.^A.

A<p>A rubidium correction factor of was used for the fittings of data in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0049927#pone-0049927-g002" target="_blank">Fig. 2</a> with Eq. 8. The rate constant typically resulted to values close to zero but with large error values. Within its error margins had little influence on the other fitting parameters and was set to for the fittings reported in this table.</p