Theoretical models of spin-exchange optical pumping: Revisited and reconciled

Theoretical models for continuous-flow and stopped-flow spin-exchange optical pumping of 129Xe have long predicted much higher 129Xe polarization values than are measured experimentally, leading to a search for additional depolarization mechanisms. In this work, we show that a misapplication of the general theory of spin-exchange optical pumping along with the incorrect use of previously measured spin-exchange constants has been perpetuated in the past 20 years and is the main cause of the long-held discrepancy between theoretical and experimental 129Xe polarization values. Following the standard theory of spin-exchange optical pumping developed almost 40 years ago by Happer et al., we outline the common mistake made in the application of this theory in modern theoretical models and derive a simplified expression of the spin-exchange cross section that can be used to correctly predict 129Xe polarization values under any set of experimental conditions. We show that the complete expression of the spin-exchange cross section derived using the work of Happer et al. predicts spin-exchange rates tenfold higher than those previously assumed in theoretical models of continuous-flow and stopped-flow spin-exchange optical pumping and can fully rectify the long-standing discrepancy between theoretical and experimental polarization values

Detecting brown adipose tissue activity with BOLD MRI in mice

The recent discovery of active brown adipose tissue (BAT) in adult humans and the correlation found between the activity of this tissue and resting metabolic rate strongly suggest that this tissue may be implicated in the development of obesity in humans, as it is in rodents. Despite the possible physiological role of this tissue in the onset of human obesity, few noninvasive imaging techniques to detect BAT activity in humans exist. The scope of this work is to investigate the possibility of detecting BAT activity using blood-oxygen-level-dependent MRI. Our results show that the strong increase in oxygen consumption and consequent increase in blood deoxyhemoglobin levels following BAT activation lead to a well-localized signal drop in BAT. This strongly suggests the possibility to use blood-oxygen-level-dependent MRI for the noninvasive detection of BAT activity

In vivo NMR detection of diet-induced changes in adipose tissue composition

We introduce an in vivo spectroscopic method to assess the effects of diet on fatty acid composition of the predominant chemical constituent of adipocytes in mice. To do this, we make use of a nonlinear NMR signal that, unlike a standard NMR signal, is intrinsically insensitive to local magnetic field inhomogeneities and which naturally suppresses the large water signal from nonfatty tissues. Our method yields fat composition information from fat depots distributed over large sample volumes in a single experiment, without requiring the use of tedious shimming procedures, voxel selection, or water suppression. Our results suggest that this method can reveal clear differences in adipose tissue composition of mice fed a standard chow diet compared with mice fed a diet rich in polyunsaturated fatty acids. With further developments this method could be used to obtain information on human lipid composition noninvasively and to track changes in lipid composition induced by diet intervention, pharmaceutical drugs, and exercise

In vivo brown adipose tissue detection and characterization using water-lipid intermolecular zero-quantum coherences

Brown adipose tissue and white adipose tissue depots are noninvasively characterized in vitro and in vivo in healthy and obese mice using intermolecular zero-quantum coherence transitions between lipid and water spins. Intermolecular zero-quantum coherences enable selective detection of spatial correlation between water and lipid spins and thereby the hydration of fatty deposits with subvoxel resolution. At about a 100 mm distance scale, the major observed peaks are between water, methylene protons at 1.3 ppm, and olefinic protons at 5.3 ppm. Our in vitro results show that the methylene-olefinic intermolecular zero-quantum coherence signal is strong both in brown and white adipose tissues, but that the water-methylene intermolecular zero-quantum coherence signal is characteristic only of brown adipose tissue. In vivo, the ratio of these peaks is substantially higher in lean or young mice than in old or obese mice

Signal enhancement in CRAZED experiments

Many of the promising applications of the CRAZED (COSY Revamped with Asymmetric Z-gradient Echo Detection) experiments are in biomedical and clinical technologies. In tissue, however, signal from the typical CRAZED experiment is largely limited by transverse relaxation. When relaxation is included, the maximum achievable signal from a prototypical CRAZED sequence, in the linear regime, is proportional to T2/τd. This means that for samples with a short T2, as encountered in vivo, signals from intermolecular multiple-quantum coherences (iMQCs) reach very diminished signal intensities. While relaxation is generally regarded as a fundamental constraint, we show here that when T2 is short but T1 is long, as in tissue, there are simple sequence modifications that can increase signal beyond the T2 limit. To better utilize the available signal intensity from iMQCs we propose a method to substitute part of the transverse magnetization with the longitudinally modulated magnetization. In this paper we show, with both simulations and experimental results, that in the presence of strong transverse relaxation the standard CRAZED scheme is not the optimal method for observing iMQCs, and can be improved upon with simple modifications

Revisiting the mean-field picture of dipolar effects in solution NMR

For more than three decades, the classical or mean-field picture describing the distant dipolar field has been almost always simplified to an effective field proportional to the local longitudinal magnetization, differing only by a scale factor of 1.5 for homomolecular (identical resonance frequency) and heteromolecular interactions. We re-examine the underlying assumptions, and show both theoretically and experimentally that the mathematical framework needs to be modified for modern applications such as imaging. We demonstrate new pulse sequences which produce unexpected effects; for example, modulating an arbitrarily small fraction of the magnetization can substantially alter the frequency evolution. Thus, matched gradient pulse pairs (a seemingly innocuous module in thousands of existing pulse sequences) can alter the time evolution in highly unexpected ways, particularly with small flip angle pulses such as those used in hyperpolarized experiments. We also show that specific gradient pulse combinations can retain only dipolar interactions between unlike spins, and the dipolar field can generate a secular Hamiltonian proportional to I x

Resolving the discrepancy between theoretical and experimental polarization of hyperpolarized 129Xe using numerical simulations and in situ optical spectroscopy

For emerging biomedical applications of hyperpolarized xenon, the ability to obtain reliably high nuclear spin polarization levels is paramount. Yet, experimental nuclear spin polarization levels of xenon are highly variable and, more than often than not, well below what theory predicts. Despite rigorous and well-studied theoretical models for hyperpolarization and continuous-flow spin-exchange optical pumping (SEOP), there remains a substantial discrepancy between the theoretical and experimental polarization of 129Xe; inexplicably, seemingly similar experimental parameters can yield very different polarization values. In this paper, the validity of the assumptions typically made about the thermodynamic state of the Rb vapor inside the optical pumping cell and the gas dynamics are investigated through finite element analysis simulations of realistic optical pumping cell models, while in situ optical and nuclear magnetic resonance spectroscopy measurements are used to validate the results of the simulations. Our results show that shorter xenon gas residence times and lower Rb vapor densities than those predicted by empirical saturated vapor pressure curves, along with incorrect SEOP parameters, are the primary cause of the discrepancy between theoretical and experimental polarization values reported in the literature

About the crazed sequence

In this article we report a detailed and understandable analysis of the evolution of various coherence orders in a Correlated 2D spectroscopy Revamped by Asymmetric Z-gradient Echo Detection (CRAZED) like pulse sequence, used to select a signal from intermolecular Multi Quantum Coherences (iMQCs). Because the signal to-noise-ratio of iMQC is much lower than the signal from conventional single quantum coherence (SQC), an optimization of experimental parameters is a necessity when measurements are made with iMQC. For this purpose a phase cycle is shown that not only allows a simpler selection of a particular quantum coherence order, but also removes receiver artifacts

Enhanced nonlinear magnetic resonance signals via square wave dipolar fields

This report introduces a new approach that enhances nonlinear solution magnetic resonance signals from intermolecular dipolar interactions. The resulting signals can theoretically be as large as the full equilibrium magnetization. Simple, readily implemented pulse sequences using square-wave magnetization modulation simultaneously refocus all even order intermolecular multiple quantum coherences, leading to a substantial net signal enhancement, complex nonlinear dynamics, and improved structural sensitivity under realistic conditions

Hyperpolarized carbon-carbon intermolecular multiple quantum coherences

Intermolecular multiple quantum coherences (iMQCs) can provide unique contrast with sub-voxel resolution. However, the characteristic growth rate of iMQCs mostly limits these effects to either hydrogen or hydrogen-coupled systems for thermally polarized samples. Hyperpolarization techniques such as dynamic nuclear polarization (DNP) allow for significant increases in the carbon signal (even more signal than that from hydrogen), making carbon iMQCs achievable. We present the first intermolecular multiple quantum signal between two carbon nuclei