Absolute thermometry of human brown adipose tissue by magnetic resonance with laser polarized 129Xe.

BACKGROUND: Absolute temperature measurements of tissues inside the human body are difficult to perform non-invasively. Yet, for brown adipose tissue (BAT), these measurements would enable direct monitoring of its thermogenic activity and its association with metabolic health. METHODS: Here, we report direct measurement of absolute BAT temperature in humans during cold exposure by magnetic resonance (MR) with laser polarized xenon gas. This methodology, which leverages on the sensitivity of the chemical shift of the 129Xe isotope to temperature-induced changes in fat density, is first calibrated in vitro and then tested in vivo in rodents. Finally, it is used in humans along with positron emission tomography (PET) scans with fluorine-18-fluorodeoxyglucose to detect BAT thermogenic activity during cold exposure. RESULTS: Absolute temperature measurements, obtained in rodents with an experimental error of 0.5 °C, show only a median deviation of 0.12 °C against temperature measurements made using a pre-calibrated optical temperature probe. In humans, enhanced uptake of 129Xe in BAT during cold exposure leads to background-free detection of this tissue by MR. Global measurements of supraclavicular BAT temperature, made over the course of four seconds and with an experimental error ranging from a minimum of 0.4 °C to more than 2 °C, in case of poor shimming, reveal an average BAT temperature of 38.8° ± 0.8 °C, significantly higher (p < 0.02 two-sided t test) than 37.7 °C. Hot BAT is also detected in participants with a PET scan negative for BAT. CONCLUSIONS: Non-invasive, radiation-free measurements of BAT temperature by MRI with hyperpolarized 129Xe may enable longitudinal monitoring of human BAT activity under various stimulatory conditions.

Brown adipose tissue (BAT) is a fat tissue specialized in heat production and considered a potential target for the treatment of obesity and diabetes. Detection of this tissue and its metabolic activity in adult humans is challenging as this tissue is often mixed with white fat, which makes up most of the fat in adult humans. Here we demonstrate that magnetic resonance imaging with laser-polarized xenon gas, a medical imaging technique used to assess lung ventilation function, can detect the presence of this tissue in humans and measure its temperature. These temperature measurements, which show that brown fat becomes significantly hotter than 37 °C when humans are exposed to cold, may be useful in future studies to assess the effects of drugs that aim to target BAT's heat-generating activity to regulate blood sugar level.

Background-Free Detection of Spin-Exchange Dynamics at Ultra-Low Magnetic Field.

Ultra-low field nuclear magnetic resonance spectroscopy (NMR) and imaging (MRI) inherently suffer from a low signal-to-noise ratio due to the small thermal polarization of nuclear spins. Transfer of polarization from a pre-polarized spin system to a thermally polarized spin system via the Spin Polarization Induced Nuclear Overhauser Effect (SPINOE) could potentially be used to overcome this limitation. SPINOE is particularly advantageous at ultra-low magnetic field, where the transferred polarization can be several orders of magnitude higher than thermal polarization. Here we demonstrate direct detection of polarization transfer from highly polarized 129 Xe gas spins to 1 H spins in solution via SPINOE. At ultra-low field, where thermal nuclear spin polarization is close to background noise levels and where different nuclei can be simultaneously detected in a single spectrum, the dynamics of the polarization transfer can be observed in real time. We show that by simply bubbling hyperpolarized 129 Xe into solution, we can enhance 1 H polarization levels by a factor of up to 151-fold. While our protocol leads to lower enhancements than those previously reported under extreme Xe gas pressures, the methodology is easily repeatable and allows for on-demand enhanced spectroscopy. SPINOE at ultra-low magnetic field could also be employed to study 129 Xe interactions in solutions.

Enhanced 129 Xe T1 relaxation in whole blood and in the presence of SPIONs at low magnetic field strengths.

PURPOSE: To compare the effect of superparamagnetic iron oxide nanoparticles (SPIONs) on the T1 of 129 Xe and 1 H and to measure the relaxation of 129 Xe in blood at low and high magnetic field strengths. METHODS: 129 Xe and 1 H T1 relaxometry was performed at low- and high-field strengths in samples containing different SPION concentrations, while imaging was used to compare the contrast obtainable in these two field regimes. In vivo experiments at variable field strengths were performed to determine the depolarization of 129 Xe in blood and the feasibility of in vivo dissolved-phase spectroscopy and imaging at low field. RESULTS: The SPION relaxivity was substantially greater at low field for 1 H, increasing from 0.92 ± 0.06 mM s-1 at 11.7T to 31.5 ± 1.8 mM s-1 at 0.6 mT, and for 129 Xe, which increased from 0.13 ± 0.03 mM s-1 at 11.7T to 7.32 ± 0.71 mM s-1 at 2.1 mT. The additional MR signal loss increased from 0.7% at 9.4T to 20.6 ± 4.2% at 0.6 mT for 1 H and from -0.7 ± 3.4% at 9.4T to 12.7 ± 3.5% at 2.1 mT for 129 Xe. Blood was found to depolarize 129 Xe below 3T in a manner inversely proportional to the field strength. In vitro studies at 2.1 mT suggest 129 Xe relaxation times below 5 s in blood dilutions as low as 0.4% volume. CONCLUSION: SPIONs longitudinal relaxivity increases at low field both for 1 H and 129 Xe. The depolarization of xenon in blood, which is found to increase below 3T, effectively prevents in vivo dissolved-phase spectroscopy and imaging at low-field strengths.

Low-boiling Point Perfluorocarbon Nanodroplets as Dual-Phase Dual-Modality MR/US Contrast Agent.

Detection of bare gas microbubbles by magnetic resonance (MR) at low concentrations typically used in clinical contrast-ultrasound studies was recently demonstrated using hyperCEST. Despite the enhanced sensitivity achieved with hyperCEST, in vivo translation is challenging as on-resonance saturation of the gas-phase core of microbubbles consequently results in saturation of the gas-phase hyperpolarized 129 Xe within the lungs. Alternatively, microbubbles can be condensed into the liquid phase to form perfluorocarbon nanodroplets, where 129 Xe resonates at a chemical shift that is separated from the gas-phase signal in the lungs. For ultrasound applications, nanodroplets can be acoustically reverted back into their microbubble form to act as a phase-change contrast agent. Here, we show that low-boiling point perfluorocarbons, both in their liquid and gas form, generate phase-dependent hyperCEST contrast. Magnetic resonance detection of ultrasound-mediated phase transition demonstrates that these perfluorocarbons could be used as a dual-phase dual-modality MR/US contrast agent.

Longitudinal nuclear spin relaxation of 129 Xe in solution and in hollow fiber membranes at low and high magnetic field strengths.

PURPOSE: To measure dissolved-phase 129 Xe T1 values at high and low magnetic fields and the field dependence of 129 Xe depolarization by hollow fiber membranes used to infuse hyperpolarized xenon in solution. METHODS: Dissolved-phase T1 measurements were made at 11.7T and 2.1 mT by bubbling xenon in solution and by using a variable delay to allow spins to partially relax back to thermal equilibrium before probing their magnetization. At high field, relaxation values were compared to those obtained by using the small flip angle method. For depolarization studies, we probed the magnetization of the polarized gas diffusing through an exchange membrane module placed at different field strengths. RESULTS: Total loss of polarization was observed for xenon diffusing through hollow fiber membranes at low field, while significant polarization loss (>20%) was observed at magnetic fields up to 2T. Dissolved-phase 129 Xe T1 values were found consistently shorter at 2.1 mT compared to 11.7T. In addition, both O2 and Xe gas concentrations in solution were found to significantly affect dissolved-phase 129 Xe T1 values. CONCLUSION: Dissolved-phase 129 Xe measurements are feasible at low field, but to assess the feasibility of in vivo dissolved-phase imaging and spectroscopy the T1 of xenon in blood will need to be measured. Both O2 and Xe concentrations in solution are found to greatly affect  dissolved-phase 129 Xe T1 values and may explain, along with RF miscalibration, the large discrepancy in previously reported results.

Dismantling Inequities in Adolescent and Young Adult Health through a Sexual and Reproductive Health Justice Approach.

This article provides an overview of the social determinants of adolescents and young adults' (AYAs') sexual and reproductive health (SRH), from a global health perspective. The status of AYAs' SRH constitutes leading health indicators across nations and globally, and reveals the well-being of this population. Throughout the article, AYAs' SRH is approached from a health equity perspective, which includes SRH health rights and reproductive justice. Using this health equity lens, salient topics are presented: sexual abuse/assault among AYAs; immigrant and refugee populations; child, early, and forced marriage; human trafficking; and female genital mutilation. The article also discusses access to SRH services and comprehensive education. Practical implications and resources are offered for healthcare providers for their daily encounters with AYAs, as well as for community, institutional level, and advocacy action. Healthcare providers are well positioned to advance AYAs SRH through mitigating inequities and in so doing, they are assuring the health of the population and future generations.

In vivo hyperCEST imaging: Experimental considerations for a reliable contrast.

PURPOSE: HyperCEST contrast relies on the reduction of the solvent signal after selective saturation of the solute magnetization. The scope of this work is to outline the experimental conditions needed to obtain a reliable hyperCEST contrast in vivo, where the "solvent" signal (ie, the dissolved-phase signal) may change over time due to the increase in xenon (Xe) accumulation into tissue. METHODS: Hyperpolarized 129 Xe was delivered to mice at a constant volume and rate using a mechanical ventilator, which triggered the saturation, excitation, and acquisition of the MR signal during the exhale phase of the breath cycle-either every breath or every 2, 3, or 4 breaths. Serial Z-spectra and hyperCEST images were acquired before and after a bolus injection of cucurbit[6]uril to assess possible signal fluctuations and instabilities. RESULTS: The intensity of the dissolved-phase Xe signal was observed to first increase immediately after the beginning of the hyperpolarized gas inhalation and NMR acquisition, and then decrease before reaching a steady-state condition. Once a steady-state dissolved-phase magnetization was established, a reliable hyperCEST contrast, exceeding 40% signal reduction, was observed. CONCLUSION: A reliable hyperCEST contrast can only be obtained after establishing a steady-state dissolved phase 129 Xe magnetization. Under stable physiological conditions, a steady-state dissolved-phase Xe magnetization is only achieved after a series of Xe inhalations and RF excitations, and it requires synchronization of the breathing rate with the MR acquisition.

Measurement of Charge and Refractive Indices in Optically Trapped and Ionized Living Cells.

The post-ionization dynamics of chemo-treated and untreated 4T1 breast cancer cells ionized by laser trapping techniques are studied. We have determined each cell's charge and refractive index by developing a theoretical model for the forces determining the post-ionization dynamics. The shift in a cell's refractive index due to an intense oscillating electric field was studied, and the results are reported here. We observed that a trapped cell, as it becomes charged, will eventually exit the trap perpendicular to the beam's direction; this means that the electric force of the cell overcomes the trapping force. As a result, the cell's conductivity changes due to the oscillating field, causing a decrease in the cell's refractive index.

An open-source, low-cost NMR spectrometer operating in the mT field regime.

In recent years, low field and ultra-low field NMR spectrometers have gained interest due to their portability, lower cost, and reduced subject-induced magnetic field inhomogeneities. Here, we describe the design of a low-cost multinuclear NMR spectrometer operating in the ultra-low field regime (ULF), which possesses high spectral resolution and enables arbitrary pulse programming. An inexpensive multifunction input/output (I/O) device is used to handle waveform generation and digitization in the kHz operating range. A home-built radio frequency (RF) mixing circuit is used to down-mix the NMR signals, allowing for the slower sampling rates and lower memory requirements needed to enable minute-long acquisitions using a standard Windows PC. The LabVIEW code, along with a bill of materials for all components used in the spectrometer, is included. As proof of concept, 1H relaxation measurements and the simultaneous detection of 1H with gas phase and dissolved 129Xe frequencies using the described low field NMR spectrometer are demonstrated.

Magnetic Resonance Detection of Gas Microbubbles via HyperCEST: A Path Toward Dual Modality Contrast Agent.

Gas microbubbles are an established clinical ultrasound contrast agent. They could also become a powerful magnetic resonance (MR) intravascular contrast agent, but their low susceptibility-induced contrast requires high circulating concentrations or the addition of exogenous paramagnetic nanoparticles for MR detection. In order to detect clinical in vivo concentrations of raw microbubbles via MR, an alternative detection scheme must be used. HyperCEST is an NMR technique capable of indirectly detecting signals from very dilute molecules (concentrations well below the NMR detection threshold) that exchange hyperpolarized 129 Xe. Here, we use quantitative hyperCEST to show that microbubbles are very efficient hyperCEST agents. They can accommodate and saturate millions of 129 Xe atoms at a time, allowing for their indirect detection at concentrations as low as 10 femtomolar. The increased MR sensitivity to microbubbles achieved via hyperCEST can bridge the gap for microbubbles to become a dual modality contrast agent.

Volunteerism and Cardiovascular Health: The HCHS/SOL Sociocultural Ancillary Study.

OBJECTIVES: The objective of this study was to examine the association between volunteerism and favorable cardiovascular health (CVH) among Hispanics/Latinos living in the US. METHODS: Data from the Hispanic Community Health Study/Study of Latinos (2008-2011) Sociocultural Ancillary Study were used (N = 4,926; ages 18-74 years). Favorable CVH was defined as positive profiles of all major CVD risk factors: low total serum cholesterol, blood pressure, and body mass index; not having diabetes; and not smoking. Survey-weighted logistic regression models were adjusted for sociodemographic, lifestyle, and psychological factors. In secondary analyses, we tested whether the volunteerism-CVH association was modified by sex, age, or years lived in the US (<10 vs. ≥10 years; a proxy acculturation measure). RESULTS: Prevalence of volunteerism was 14.5%. Compared to non-volunteers, volunteers had 1.67 higher odds of favorable CVH in the fully-adjusted model (Odds Ratio [OR] = 1.67, 95% Confidence Interval [CI] = 1.11, 2.52). There was evidence of effect modification by acculturation; only volunteers who had lived in the US ≥10 years had 2.41 higher odds of favorable CVH (OR = 2.41, 95% CI=1.53, 3.80). There was no evidence of effect modification by sex or age. CONCLUSIONS: Volunteerism was associated with favorable CVH among US Hispanics/Latinos.

Corner Store Owners as Health Promotion Agents in Low-Income Communities.

Reports of small business owner motivations for participation in health promotion interventions are rarely reported in the literature, particularly in relation to healthy eating interventions. This study explicates and defines the development of healthy corner stores as community-based enterprises (CBEs) within eight low-income, suburban communities. CBEs are defined as community-oriented small businesses with a common goal to improve population health. The corner stores assessed in this study were participants in Healthy HotSpot (HH), a corner store initiative of the Cook County Department of Public Health. To determine store alignment with the CBE construct, a case study design was used for qualitative inquiry. Participant narratives from store owners (n = 21), community-based organizations (CBOs; n = 8) and consumer focus groups (n = 51) were analyzed using an iterative process to determine how store owners aligned with the CBE construct, and how this influenced continuation of health promotion activities. Several key factors influenced the strength of store owners' alignment with the CBE construct. They included the following: (a) shared ethno-cultural identities and residential area as consumers; (b) positive, trustworthy relationships with consumers; (c) store owners valuing and prioritizing community health, often over profits; and (d) collaboration with a highly engaged CBO in the HH project. Results can assist in theory development and intervention design in working with corner store owners, and other small business owners, as health promotion agents to improve and sustain health outcomes and help ensure the economic vitality of low-income communities.

Direct detection of brown adipose tissue thermogenesis in UCP1-/- mice by hyperpolarized 129Xe MR thermometry.

Brown adipose tissue (BAT) is a type of fat specialized in non-shivering thermogenesis. While non-shivering thermogenesis is mediated primarily by uncoupling protein 1 (UCP1), the development of the UCP1 knockout mouse has enabled the study of possible UCP1-independent non-shivering thermogenic mechanisms, whose existence has been shown so far only indirectly in white adipose tissue and still continues to be a matter of debate in BAT. In this study, by using magnetic resonance thermometry with hyperpolarized xenon, we produce the first direct evidence of UCP1-independent BAT thermogenesis in knockout mice. We found that, following adrenergic stimulation, the BAT temperature of knockout mice increases more and faster than rectal temperature. While with this study we cannot exclude or separate the physiological effect of norepinephrine on core body temperature, the fast increase of iBAT temperature seems to suggest the existence of a possible UCP1-independent thermogenic mechanism responsible for this temperature increase.

Mexican American Adolescent Mothers' Lived Experience: Grounded Ethnicity and Authentic Mothering.

We conducted this qualitative, phenomenological study to further understanding of how second-generation Mexican American adolescent mothers perceive their young motherhood experience, drawing on the context of their Mexican heritage background. Through in-person interviews with 18 young mothers, we discerned shared essential meanings reconstructed around two major domains: (a) grounded ethnicity, a firm desire to remain true to and share their heritage culture, and (b) authentic mothering, strong relationality to their infants. We found that young mothers embraced their Mexican heritage mothering approaches, such as fostering familismo, valuing family above other obligations. The adolescents in this study sensed their young motherhood as an opportunity to protect and improve qualities of traditional familial cultural heritage, while absorbing elements of American culture to enhance the future for themselves and their infants. We discuss how providers can help reduce stigmatization and promote self-efficacy by respecting and partnering with young mothers to provide culturally congruent services.

Laser trap ionization for identification of human erythrocytes with variable hemoglobin quantitation.

An approach to an established technique that is potentially applicable for a more comprehensive understanding of the electrical properties of red blood cells (RBCs) is presented. Using a high-intensity gradient laser trap, RBCs can be singly trapped and consequentially ionized. The subsequent dynamics of the ionized cell allows one to calculate the charge developed and the ionization energy (IE) through a Newtonian-based analysis. RBCs with two different hemoglobin (Hb) types were ionized. The first sample was identified as carrying Hb HbAA (normal Hb) and the second one was identified as carrying HbAC (HbC trait). By analyzing the charge developed on each cell and several other related factors, we were able to discern a difference between the main Hb types contained within the individual RBC, independent of cell size. A relationship between the charge developed and the IE of the cell was also established based on the electrical properties of RBCs. Thus, we present this laser trapping technique as a study of the electrical properties of RBCs and as possible biomedical tool to be used for the differentiation of Hb types.

Exploring the Meanings of Place Attachment Among Civically Engaged Puerto Rican Youth.

Although research has shown that place attachment may promote socially responsible behaviors, it has not been studied from the perspective of youth civic engagement. This study explored the meanings of community-based place attachment among civically-engaged Puerto Rican youth within an ethnic enclave. Photovoice methods were employed using a phenomenological design to enhance our understanding of the participants' lived experiences. Findings suggest that community-based place attachment was characterized as multidimensional, identity-affirming, and embedded in participants' narratives about personal involvement in local engagement. Implications for initiatives that actively engage youth in community change efforts and future research are presented.