J. R. Owers-Bradley

Alveolarization Continues during Childhood and Adolescence: New Evidence from Helium-3 Magnetic Resonance

RATIONALE The current hypothesis that human pulmonary alveolarization is complete by 3 years is contradicted by new evidence of alveolarization throughout adolescence in mammals. OBJECTIVES We reexamined the current hypothesis using helium-3 ((3)He) magnetic resonance (MR) to assess alveolar size noninvasively between 7 and 21 years, during which lung volume nearly quadruples. If new alveolarization does not occur, alveolar size should increase to the same extent. METHODS Lung volumes were measured by spirometry and plethysmography in 109 healthy subjects aged 7-21 years. Using (3)HeMR we determined two independent measures of peripheral airspace dimensions: apparent diffusion coefficient (ADC) of (3)He at FRC (n = 109), and average diffusion distance of helium (X(rms)) by q-space analysis (n = 46). We compared the change in these parameters with lung growth against a model of lung expansion with no new alveolarization. MEASUREMENTS AND MAIN RESULTS ADC increased by 0.19% for every 1% increment in FRC (95% confidence interval [CI], 0.13-0.25), whereas the expected change in the absence of neoalveolarization is 0.41% (95% CI, 0.31-0.52). Similarly, increase of (X(rms)) with FRC was significantly less than the predicted increase in the absence of neoalveolarization. The number of alveoli is estimated to increase 1.94-fold (95% CI, 1.64-2.30) across the age range studied. CONCLUSIONS Our observations are best explained by postulating that the lungs grow partly by neoalveolarization throughout childhood and adolescence. This has important implications: developing lungs have the potential to recover from early life insults and respond to emerging alveolar therapies. Conversely, drugs, diseases, or environmental exposures could adversely affect alveolarization throughout childhood.

Quartz Tuning Fork Viscometers for Helium Liquids

Mechanical resonators, in the form of vibrating wires or torsional oscillators, have long been employed as sensors in liquid 3He and 3He–4He mixtures. The damping of resonators is due to the viscosity of the surrounding liquid which is a strong, well-known function of temperature for bulk Fermi liquids. It is therefore possible to use the viscous damping for thermometry in the millikelvin regime. An alternative sensor is the small quartz tuning fork which is driven by the piezoelectric effect and requires no external magnetic field. In this paper, we present measurements of the viscous damping of such a tuning fork when immersed in a 6.2% 3He–4He mixture, between 3 and 100 mK, and at zero and high (10 T) magnetic field. The measurements indicate that damping of the tuning fork resonance is dominated by the liquid helium properties and is insensitive to the applied magnetic field. The response of the tuning fork to the saturated helium mixture demonstrates that it could potentially be used for thermometry in any magnetic field. There is evidence of slip at the interface between the fork and the helium suggesting specular scattering from the smooth surface of the quartz. The fork is also able to detect the superfluid transition in pure liquid 3He.

MR tagging of human lungs using hyperpolarized 3He gas

To evaluate the use of spin‐tagging in conjunction with hyperpolarized gas imaging for monitoring lung ventilation and gas diffusion.

Multi-scale computational models of the airways to unravel the pathophysiological mechanisms in asthma and chronic obstructive pulmonary disease (AirPROM)

The respiratory system comprises several scales of biological complexity: the genes, cells and tissues that work in concert to generate resultant function. Malfunctions of the structure or function of components at any spatial scale can result in diseases, to the detriment of gas exchange, right heart function and patient quality of life. Vast amounts of data emerge from studies across each of the biological scales; however, the question remains: how can we integrate and interpret these data in a meaningful way? Respiratory disease presents a huge health and economic burden, with the diseases asthma and chronic obstructive pulmonary disease (COPD) affecting over 500 million people worldwide. Current therapies are inadequate owing to our incomplete understanding of the disease pathophysiology and our lack of recognition of the enormous disease heterogeneity: we need to characterize this heterogeneity on a patient-specific basis to advance healthcare. In an effort to achieve this goal, the AirPROM consortium (Airway disease Predicting Outcomes through patient-specific computational Modelling) brings together a multi-disciplinary team and a wealth of clinical data. Together we are developing an integrated multi-scale model of the airways in order to unravel the complex pathophysiological mechanisms occurring in the diseases asthma and COPD.

Nonlinear modal coupling in a high-stress doubly-clamped nanomechanical resonator

We present results from a study of the nonlinear inter-modal coupling between different flexural vibrational modes of a single high-stress, doubly-clamped silicon nitride nanomechanical beam. Using the magnetomotive technique and working at 100 mK we explored the nonlinear behaviour and modal couplings of the first, third and fifth modes of a 25.5 μm long beam. We find very good agreement between our results and a simple analytical model which assumes that the different modes of the resonator are coupled to each other by displacement induced tension in the beam. The small size of our resonator leads to relatively strong nonlinear couplings, for example we find a shift of about 7 Hz in the third mode for a 1 nm displacement in the first mode and frequency shifts ~ 20 times larger than the linewidth (130 Hz) are readily observed.

Dissipation due to tunneling two-level systems in gold nanomechanical resonators

We present measurements of the dissipation and frequency shift in gold nanomechanical resonators at temperatures down to 10 mK. The resonators were fabricated as doubly clamped beams above a GaAs substrate and actuated magnetomotively. Measurements on beams with frequencies 7.95 and 3.87 MHz revealed that from 30 to 500 mK the dissipation increases with temperature as T 0.5 , with saturation occurring at higher temperatures. The relative frequency shift of the resonators increases logarithmically with temperature up to at least 400 mK. Similarities with the behavior of bulk amorphous solids suggest that the dissipation in our resonators is dominated by two-level systems.

Airway impedance entropy and exacerbations in severe asthma

Variability of peak flow measurements has been related to clinical outcomes in asthma. We hypothesised that the entropy, or information content, of airway impedance over short time scales may predict asthma exacerbation frequency. 66 patients with severe asthma and 30 healthy control subjects underwent impulse oscillometry at baseline and following bronchodilator administration. On each occasion, airway impedance parameters were measured at 0.2-s intervals for 150 s, yielding a time series that was then subjected to sample entropy (SampEn) analysis. Airway impedance and SampEn of impedance were increased in asthmatic patients compared with healthy controls. In a logistic regression model, SampEn of the resistance at 5 Hz minus the resistance at 20 Hz, a marker of the fluctuation of the heterogeneity of airway constriction over time, was the variable most strongly associated with the frequent exacerbation phenotype (OR 3.23 for every 0.1 increase in SampEn). Increased airway impedance and SampEn of impedance are associated with the frequent exacerbation phenotype. Prospective studies are required to assess their predictive value.

Achievement of high nuclear spin polarization using lanthanides as low-temperature NMR relaxation agents

Many approaches are now available for achieving high levels of nuclear spin polarization. One of these methods is based on the notion that as the temperature is reduced, the equilibrium nuclear polarization will increase, according to the Boltzmann distribution. The main problem with this approach is the length of time it may take to approach thermal equilibrium at low temperatures, since nuclear relaxation times (characterized by the spin-lattice relaxation time T1) can become very long. Here, we show, by means of relaxation time measurements of frozen solutions, that selected lanthanide ions, in the form of their chelates with DTPA, can act as effective relaxation agents at low temperatures. Differential effects are seen with the different lanthanides that were tested, holmium and dysprosium showing highest relaxivity, while gadolinium is ineffective at temperatures of 20 K and below. These observations are consistent with the known electron-spin relaxation time characteristics of these lanthanides. The maximum relaxivity occurs at around 10 K for Ho-DTPA and 20 K for Dy-DTPA. Moreover, these two agents show only modest relaxivity at room temperature, and can thus be regarded as relaxation switches. We conclude that these agents can speed up solid state NMR experiments by reducing the T1 values of the relevant nuclei, and hence increasing the rate at which data can be acquired. They could also be of value in the context of a simple low-cost method of achieving several-hundred-fold improvements in polarization for experiments in which samples are pre-polarized at low temperatures, then rewarmed and dissolved immediately prior to analysis.

Spin-polarized - liquids

Dilute liquid - liquids offer a model system for testing theories of weakly interacting fermions. The ability to spin polarize the nuclei adds an extra dimension to the field. In this review, the extraordinary way in which the polarization of the nuclear spins can modify the macroscopic behaviour of the liquid is explained. Frequent reference to recent experiments and theoretical developments are made and the various techniques for producing high polarizations are described.

Longitudinal and transverse spin diffusion in3He-4He solutions in a strong magnetic field

Using pulsed NMR techniques, we have measured spin diffusion in3He-3He solutions with3He concentrations of 0.05%, 0.1%, 0.46%, 1.0%, 3.8% and 6.4% in a magnetic field of 8.8 Tesla for a temperature range 11 mK⩽ T ⩽ 200 mK. We observe that the temperature dependence of the transverse spin diffusion coefficient D1 deviates from that expected for an unpolarized Fermi liquid in the degenerate region in the 1.0%, 3.8% and 6.4% solutions. Moreover, by measuring both longitudinal and transverse spin diffusion coefficients in the 6.4%-mixture, we have verified experimentally the difference between them, and provided direct evidence for a field-induced anisotropy in spin diffusion. The results from the 0.05% and 0.1% solutions show agreement with the theory of Jeon and Mullin; however, no deviation of D1 from that expected in an unpolarized mixture was observed because the3He is not in the degenerate regime for these very dilute systems for the temperatures we could achieve. The analysis of our measurements in terms of the Leggett-Rice equations also yields values for the spin rotation parameter μM0. Using our results along with previous measurements at various3He concentrations, we deduce a value for the s-wave quasiparticle scattering length of a=−0.88 ± 0.05 Å.