Chemical shift of ¹²⁹Xe dissolved in red blood cells: Application to a rat model of bronchopulmonary dysplasia

Abstract

Purpose To measure the chemical shift of hyperpolarized 129Xe dissolved in the red blood cells(δRBC) of a cohort of rats exposed to hyperoxia and intermittent hypoxia (IH) to mimic human bronchopulmonary dysplasia, and to investigate the effect of xenon‐blood distribution time on δRBC. Methods δRBC was measured from spectra acquired using a chemical shift saturation recovery sequence from 15 Sprague‐Dawley rats exposed to hyperoxia‐IH and 10 age‐matched control rats. Sensitization to the xenon‐blood distribution time was achieved by varying the time between saturation pulses, τ. δRBC was compared with blood fraction measured by histology of the cohort and blood oxygenation measured directly using pulse oximetry following a hypoxic challenge in an identically exposed cohort. Results The mean δRBC in the hyperoxia‐IH exposed rats was 0.55 ± 0.04 ppm lower than that of the healthy cohort (P = .0038), and this difference did not depend on τ (P = .996). The blood fraction of the exposed cohort was lower than that of the healthy cohort (P = .0397). Oximetry measurements showed that the baseline arterial oxygen saturation (SaO2) of each cohort was not different (P = .72), but after a hypoxic challenge, the SaO2 of the exposed cohort was lower than that of the healthy cohort (P = .003). Conclusion δRBC is reduced in rats exposed to hyperoxia‐IH compared with control rats. The change in δRBC is consistent with enhanced blood oxygen desaturation of the exposed cohort measured by pulse oximetry during a hypoxic challenge. This suggests that the observed change in δRBC reflects enhanced desaturation in the hyperoxia‐IH exposed cohort compared with the healthy cohort.

Investigating biases in the measurement of apparent alveolar septal wall thickness with hyperpolarized 129Xe MRI

“…3,9,[23][24][25][26][27][28][29][30] Both approaches have already been shown to be sensitive to various forms of lung disease. [31][32][33][34][35][36][37][38][39][40][41][42] More recently, efforts have been made to combine these methods by adding 2D or 3D spatial information to dynamic gas uptake measurements at the expense of lengthened scan times. 43,44 Nevertheless, although xenon uptake MR techniques for quantifying lung function have been in use for over 20 years, little attention has been paid to the impact of the acquisition parameters on the metrics extracted.…”

“…The DP imaging techniques currently in use can be divided into two general types: (1) static measurements of the regional xenon distribution within the lung parenchyma as dictated by the structure and physiology of the lung, 9‐19 and the MR acquisition parameters, in particular the flip angle and the TR 20‐22 ; and (2) dynamic measurements that capture the xenon gas uptake by the lung tissue and transport by the pulmonary circulation as a function of time 3,9,23‐30 . Both approaches have already been shown to be sensitive to various forms of lung disease 31‐42 . More recently, efforts have been made to combine these methods by adding 2D or 3D spatial information to dynamic gas uptake measurements at the expense of lengthened scan times 43,44 .…”

Effect of inhaled oxygen concentration on 129Xe chemical shift of red blood cells in rat lungs

“…In a previous study, our group reported lower δ RBC in rats exposed to hyperoxia/intermittent-hypoxia to model BPD in comparison to untreated control rats. 26 In that study, the exposed rats exhibited elevated oxygen desaturation following a hypoxic challenge as measured by pulse oximetry. Therefore, we surmised that the lower δ RBC observed in that study may be reflective of lower blood oxygenation during the anoxic breath holds used to administer 129 Xe.…”

“…Following previously described methods, 26 the RF pulses used for excitation and saturation were 90‐degree hard pulses (290 μs) calibrated using a series of constant flip angle excitation pulses applied to the in vivo gas signal. The center frequency of the RF pulses was then set to 197 ppm from the gas‐phase resonance (approximately at δ Plasma ).…”

“…23,24 Conversely, 129 Xe spectroscopy of rat blood in vitro suggests that an opposite relationship between oxygenation and δ RBC may exist pointing toward a possible species-specific dependence, 25 but this has not yet been corroborated in vivo. δ RBC has also been studied in disease models, where it was shown to be higher in control rats than rats exposed to a model of bronchopulmonary dysplasia (BPD), 26 and the pulsatility of δ RBC has been shown to differentiate between healthy human subjects and subjects with idiopathic pulmonary fibrosis. 27 However, in vivo corroboration of the relationship between δ RBC and oxygenation has yet to be presented.…”