Purpose

The sensitivity of the ¹²⁹Xe chemical shift to red blood cell (RBC) oxygenation makes hyperpolarized ¹²⁹Xe MR spectroscopy (MRS) a promising technique for measurement of pulmonary blood oxygenation in vivo. In previous studies of ¹²⁹Xe-RBC chemical shift,¹ the ¹²⁹Xe signal was limited to the pulmonary capillaries (PCs) owing to the TR values (800ms) being of the order of the RBC capillary transit time (~750ms).² In this study, TRs ranging from 100-6000ms were used in order to evaluate the ¹²⁹Xe-RBC signal dynamics as blood travels through the capillaries downstream into the pulmonary veins (PVs) (Fig. 1a).

Methods

Hyperpolarized ¹²⁹Xe pulmonary MRS was performed on three healthy male volunteers (aged 26, 30 and 33) on a clinical 3T (Philips, Achieva) scanner with a quadrature flex T-R coil. All scans were performed at breath-hold apnea after inhalation of 1L gas (500mL Xe, 500mL N2) from functional residual capacity. Two multi-TR sequences were implemented, each preceded by five 90° saturation pulses with TR = 100ms. The first sequence (Fig. 1b) was performed on all volunteers and comprised a single breath-hold with TR values: 100-1500ms with ΔTR = 100ms; and 2000-6000ms with ΔTR = 500ms, giving a total breath-hold time of ~1 min. The second sequence (Fig. 1c) was performed on the 30-year-old volunteer only, and comprised five separate breath-holds, each with a single TR value (100, 750, 1500, 3000 and 6000ms). Parameters for all scans were: hard pulses with FA = 90°, spectral points = 256, BW = 3kHz. The ¹²⁹Xe signal in RBCs, S_RBC, and tissue/plasma (TP), S_TP, was determined by performing zeroth-order phasing on the associated resonances (Fig. 2a,b), followed by numerical integration between the y-axis zero crossings on either side of the resonant peaks. It was not possible to obtain good Lorentzian fits to the individual peaks, as shown in Fig. 2. The ¹²⁹Xe-RBC chemical shift was determined using 0ppm for ¹²⁹Xe-TP as a reference.

Results and Discussion

In all volunteers, the signal ratio, S_RBC/S_TP, was observed to increase with increasing TR (Fig. 3). Since each 90° RF pulse saturates both the RBC and TP signals, longer TR values enable polarized ¹²⁹Xe nuclei to travel further downstream of the capillary bed, essentially sampling a larger effective ¹²⁹Xe-blood volume, increasing S_RBC. The ¹²⁹Xe dissolved in tissue acts a large “DC offset”, as once saturated with Xe from the alveoli (<100ms) its concentration is approximately constant. Therefore, we assume that the additional blood plasma volume that is sampled at longer TRs makes a lesser contribution to S_TP, such that longer TRs result in larger S_RBC/S_TP. In parallel, ¹²⁹Xe-RBC chemical shift, δ_RBC­, was observed to decrease with increasing TR, (~3ppm difference between TR = 100ms and 6000ms) whilst the ¹²⁹Xe-TP chemical shift remained constant for all TRs. Fig. 2c shows a comparison of δ_RBC­ at TR = 100ms and 5000ms. In previous work,^1,3 the ¹²⁹Xe-RBC chemical shift was observed to decrease with decreasing blood oxygenation, suggesting that for longer TRs, the blood oxygenation is apparently lower. During capillary transit, the RBC oxygenation will increase and should remain close to 100% oxygen saturation as the RBCs travel through the veins. The observation that RBC oxygenation apparently decreases as the RBCs travel from the PCs into the PVs is contrary to this. The multi-TR scan with multiple breath-holds (Figure 1) was performed to evaluate whether the decrease in oxygenation for long TR values was a result of decreased alveolar P_AO₂ during breath-hold apnea over the ~1 min single breath-hold scan. As shown in Fig. 3b, the same trend of decreased δ_RBC was observed for the multiple breath-hold scans. However, the measured ¹²⁹Xe-RBC chemical shifts of <20ppm for TR = 6000ms are of the same order as than those measured in vitro for fully deoxygenated blood (20.5ppm),¹ suggesting that the observed decrease in δ_RBC is unlikely to result from RBC oxygen desaturation. Instead, the decrease in δ_RBC may result from a difference in bulk magnetic susceptibility between the PC and PV environments and/or differences in geometry of PC and PV vessels and their orientation with respect to B₀, analogous to a recent report of differences in gas-phase ¹²⁹Xe chemical shift in the conducting airways and alveoli of mice.⁴

Conclusion

In this study, a decrease in the ¹²⁹Xe-RBC chemical shift was observed for increasing TR values probing blood RBCs downstream of the pulmonary capillaries. The observed chemical shift difference is unprecedented, and understanding the nature of the underlying mechanisms causing the shift is crucial for future in vivo experiments using ¹²⁹Xe-RBC chemical shift as a measure of blood oxygenation.

Acknowledgements

No acknowledgement found.