Spin-Exchange Optical Pumping and Nuclear Magnetic Resonance of 129Xe

The nuclear spin polarisation of 129Xe can be increased by four to five orders of magnitude using the technique spin-exchange optical pumping. The resulting enhancement in polarisation can be utilised to dramatically enhance the sensitivity of 129Xe in nuclear magnetic resonance (NMR) applications. This thesis is concerned with the physics of spin-exchange optical pumping and NMR spectroscopy of hyperpolarised 129Xe. Its general aims are to optimise the production of hyperpolarised 129Xe and to evaluate the underlying NMR mechanisms of 129Xe in blood (in vitro and in vivo). Chapters 3 and 4 detail experiments and modelling on a spin-exchange optical pumping polariser with the aim to optimise the production of hyperpolarised 129Xe for nuclear magnetic resonance NMR spectroscopy. This optimisation has enabled high-quality imaging of the airspaces of the human lungs as well as spectroscopy of 129Xe dissolved in blood and lung tissue. In addition to 129Xe polarisation optimisation, in Chapter 5, NMR experiments on 129Xe in human blood were performed to determine constants underpinning 129Xe NMR relaxation and exchange dynamics in whole blood samples. These constants should enable accurate modelling of 129Xe signal dynamics during in vivo experiments involving xenon transport from the lungs to distal tissues. Lastly, in Chapter 6, hyperpolarised 129Xe NMR was used to probe pulmonary blood oxygenation in vivo. A non-linear relationship between the 129Xe chemical shift in red blood cells was determined in vitro on human blood samples at 1.5 T and 3 T. This relationship was used for dynamic measurements of pulmonary blood oxygenation in a healthy volunteer during breath-hold apnoea on a 3 T scanner

Assessment of the influence of lung inflation state on the quantitative parameters derived from hyperpolarized gas lung ventilation MRI in healthy volunteers.

In this study, the effect of lung volume on quantitative measures of lung ventilation was investigated using MRI with hyperpolarized 3He and 129Xe. Six volunteers were imaged with hyperpolarized 3He at five different lung volumes (residual volume (RV), RV+1L, functional residual capacity (FRC), FRC+1L and total lung capacity (TLC)), and three were also imaged with hyperpolarized 129Xe. Imaging at each of the lung volumes was repeated twice on the same day with corresponding 1H lung anatomical images. Percentage lung ventilated volume (%VV) and variation of signal intensity (heterogeneity score, Hscore) were evaluated. Increased ventilation heterogeneity, quantified by reduced %VV and increased Hscore, was observed at lower lung volumes with the least ventilation heterogeneity observed at TLC. For 3He MRI data, the coefficient of variation of %VV was less than 1.5% and less than 5.5% for Hscore at all lung volumes, whilst for 129Xe data the values were 4% and 10% respectively. Generally, %VV generated from 129Xe images was lower than that seen from 3He images. The good repeatability of 3He %VV found here supports prior publications showing that percentage lung ventilated volume is a robust method for assessing global lung ventilation. The greater ventilation heterogeneity observed at lower lung volumes indicates that there may be partial airway closure in healthy lungs and that lung volume should be carefully considered for reliable longitudinal measurements of %VV and Hscore. The results suggest that imaging patients at different lung volumes may help to elucidate obstructive disease pathophysiology and progression

Detection of early sub-clinical lung disease in children with cystic fibrosis by lung ventilation imaging with hyperpolarized gas MRI

Hyperpolarised 3He ventilation-MRI, anatomical lung MRI, lung clearance index (LCI), low-dose CT and spirometry were performed on 19 children (6–16 years) with clinically stable mild cystic fibrosis (CF) (FEV1>−1.96), and 10 controls. All controls had normal spirometry, MRI and LCI. Ventilation-MRI was the most sensitive method of detecting abnormalities, present in 89% of patients with CF, compared with CT abnormalities in 68%, LCI 47% and conventional MRI 22%. Ventilation defects were present in the absence of CT abnormalities and in patients with normal physiology, including LCI. Ventilation-MRI is thus feasible in young children, highly sensitive and provides additional information about lung structure–function relationships

Reproducibility of Quantitative Indices of Lung Function and Microstructure from 129Xe Chemical Shift Saturation Recovery (CSSR) MR Spectroscopy

Purpose: To evaluate the reproducibility of indices of lung microstructure and function derived from 129Xe chemical shift saturation recovery (CSSR) spectroscopy in healthy volunteers and patients with chronic obstructive pulmonary disease (COPD). To study the sensitivity of CSSR-derived parameters to pulse sequence design and lung inflation level. Methods: Preliminary data was collected from five volunteers on three occasions, using two implementations of the CSSR sequence. Separately, three volunteers each underwent CSSR at three different lung inflation levels. After analysis of these preliminary data, nine age-matched volunteers were scanned three times on one day, and five COPD patients were scanned on three separate days to assess short and long-term reproducibility. Results: CSSR-derived alveolar septal thickness (ST) and surface-area-to-volume (S/V) ratio values decreased with lung inflation level (P<0.001; P=0.057, respectively). Intra-subject standard deviations of ST were lower than previously-measured differences between volunteers and subjects with interstitial lung disease. Coefficient of variation (CV) values of ST were 4.3±1.9% and 6.0±4.3% in volunteers and COPD patients, respectively, which are comparable to CV values for whole-lung diffusing capacity. The mean CV of S/V in volunteers and patients was 14.1±8.1% and 17.8±19.5%, respectively. Conclusion: 129Xe CSSR presents a reproducible method for estimation of alveolar septal thickness

Image phenotyping of preterm-born children using hyperpolarised 129Xe lung MRI and multiple-breath washout

Rationale: Preterm birth is associated with low lung function in childhood, but little is known about the lung microstructure in childhood. Objectives: We assessed the differential associations between the historical diagnosis of bronchopulmonary dysplasia (BPD) and current lung function phenotypes on lung ventilation and microstructure in preterm-born children using hyperpolarised 129Xe ventilation and diffusion-weighted MRI, and multiple breath washout (MBW). Methods: Data were available from 63 children (aged 9-13 years) including 44 born preterm (≤34 weeks’ gestation) and 19 term-born controls (≥37 weeks’ gestation). Preterm-born children were classified, using spirometry, into prematurity-associated obstructive lung disease (POLD, FEV