Functional gas exchange measures on 129Xe MRI and spectroscopy are associated with age, sex, and BMI in healthy subjects

IntroductionHyperpolarized 129Xe MRI and spectroscopy is a rapidly growing technique for assessing lung function, with applications in a wide range of obstructive, restrictive, and pulmonary vascular disease. However, normal variations in 129Xe measures of gas exchange across healthy subjects are not well characterized, presenting an obstacle to differentiating disease processes from the consequences of expected physiological heterogeneity. Here, we use multivariate models to evaluate the role of age, sex, and BMI in a range of commonly used 129Xe measures of gas exchange.Materials and methodsHealthy subjects (N = 40, 16F, age 44.3 ± 17.8 yrs., min-max 22–87 years) with no history of cardiopulmonary disease underwent 129Xe gas exchange MRI and spectroscopy. We used multivariate linear models to assess the associations of age, sex, and body mass index (BMI) with the RBC:Membrane (RBC:M), membrane to gas (Mem:Gas), and red blood cell to gas (RBC:Gas) ratios, as well as measurements of RBC oscillation amplitude and RBC chemical shift.ResultsAge, sex, and BMI were all significant covariates in the RBC:M model. Each additional 10 years of age was associated with a 0.05 decrease in RBC:M (p < 0.001), each additional 10 points of BMI was associated with a decrease of 0.07 (p = 0.02), and males were associated with a 0.17 higher RBC:M than females (p < 0.001). For Mem:Gas, male sex was associated with a decrease and BMI was associated with an increase. For RBC:Gas, age was associated with a decrease and male sex was associated with an increase. RBC oscillation amplitude increased with age and RBC chemical shift was not associated with any of the three covariates.Discussion129Xe MRI and spectroscopy measurements in healthy subjects, particularly the widely used RBC:M measurement, exhibit heterogeneity associated in part with variations in subject age, sex, and BMI. Elucidating the contributions of these and other factors to 129Xe gas exchange measurements is a critical component for differentiating disease processes from expected variation in healthy subjects. Notably, the Mem:Gas and RBC chemical shift appear to be stable with aging, suggesting that unexplained deviations in these metrics may be signs of underlying abnormalities

Surface-sensitive NMR in optically pumped semiconductors

We present a scheme of surface-sensitive nuclear magnetic resonance in optically pumped semiconductors, where an NMR signal from a part of the surface of a bulk compound semiconductor is detected apart from the bulk signal. It utilizes optically oriented nuclei with a long spin-lattice relaxation time as a polarization reservoir for the second (target) nuclei to be detected. It provides a basis for the nuclear spin polarizer [IEEE Trans. Appl. Supercond. 14, 1635 (2004)], which is a polarization reservoir at a surface of the optically pumped semiconductor that polarizes nuclear spins in a target material in contact through the nanostructured interfaces.Comment: 4 pages, 5 figure

New developments in imaging idiopathic pulmonary fibrosis with hyperpolarized xenon magnetic resonance imaging

Idiopathic pulmonary fibrosis (IPF) is a progressive pulmonary disease that is ultimately fatal. Although the diagnosis of IPF has been revolutionized by high-resolution computed tomography, this imaging modality still exhibits significant limitations, particularly in assessing disease progression and therapy response. The need for noninvasive regional assessment has become more acute in light of recently introduced novel therapies and numerous others in the pipeline. Thus, it will likely be valuable to complement 3-dimensional imaging of lung structure with 3-dimensional regional assessment of function. This challenge is well addressed by hyperpolarized (HP) Xe magnetic resonance imaging (MRI), exploiting the unique properties of this inert gas to image its distribution, not only in the airspaces, but also in the interstitial barrier tissues and red blood cells. This single-breath imaging exam could ultimately become the ideal, noninvasive tool to assess pulmonary gas-exchange impairment in IPF. This review article will detail the evolution of HP Xe MRI from its early development to its current state as a clinical research platform. It will detail the key imaging biomarkers that can be generated from the Xe MRI examination, as well as their potential in IPF for diagnosis, prognosis, and assessment of therapeutic response. We conclude by discussing the types of studies that must be performed for HP Xe MRI to be incorporated into the IPF clinical algorithm and begin to positively impact IPF disease diagnosis and management

The SLAC high‐density 3He target polarized by spin‐exchange optical plumbing

A new high‐density 3He target polarized by spin exchange with optically pumped rubidium vapor has recently been used at the Stanford Linear Accelerator in an experiment to measure the longitudinal spin‐dependent structure function of the neutron. The 3He target operated at a density of 2.3×1020 atoms/cm3 in a 30 cm long scattering region with polarizations between 30% and 40% measured with NMR techniques. Target cells with several day spin‐relaxation times were developed in order to achieve these polarizations.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87509/2/244_1.pd

SABRE hyperpolarisation of vitamin B3 as a function of pH

In this work we describe how the signal enhancements obtained through the SABRE process in methanol-d4 solution are significantly affected by pH. Nicotinic acid (vitamin B3, NA) is used as the agent, and changing pH is shown to modify the level of polarisation transfer by over an order of magnitude, with significant improvements being seen in terms of the signal amplitude and relaxation rate at high pH values. These observations reveal that manipulating pH to improve SABRE enhancements levels may improve the potential of this method to quantify low concentrations of analytes in mixtures.1H NMR spectroscopy results link this change to the form of the SABRE catalyst, which changes with pH, resulting in dramatic changes in the magnitude of the ligand exchange rates. The presented data also uses the fact that the chemical shifts of the nicotinic acids NMR resonances are affected by pH to establish that hyperpolarised 1H-based pH mapping with SABRE is possible. Moreover, the strong polarisation transfer field dependence shown in the amplitudes of the associated higher order longitudinal terms offers significant opportunities for the rapid detection of hyperpolarised NA in H2O itself without solvent suppression. 1H and 13C MRI images of hyperpolarised vitamin B3 in a series of test phantoms are presented that show pH dependent intensity and contrast. This study therefore establishes that when the pH sensitivity of NA is combined with the increase in signal gain provided for by SABRE hyperpolarisation, a versatile pH probe results

Temperature-ramped 129Xe spin-exchange optical pumping

We describe temperature-ramped spin-exchange optical pumping (TR-SEOP) in an automated high-throughput batch-mode 129Xe hyperpolarizer utilizing three key temperature regimes: (i) “hot”where the 129Xe hyperpolarization rate is maximal, (ii) “warm”-where the 129Xe hyperpolarization approaches unity, and (iii) “cool” where hyperpolarized 129Xe gas is transferred into a Tedlar bag with low Rb content (<5 ng per ∼1 L dose) suitable for human imaging applications. Unlike with the conventional approach of batch-mode SEOP, here all three temperature regimes may be operated under continuous high-power (170 W) laser irradiation, and hyperpolarized 129Xe gas is delivered without the need for a cryocollection step. The variable-temperature approach increased the SEOP rate by more than 2-fold compared to the constant-temperature polarization rate (e.g., giving effective values for the exponential buildup constant γSEOP of 62.5 ± 3.7 × 10−3 min−1 vs 29.9 ± 1.2 × 10−3 min−1) while achieving nearly the same maximum %PXe value (88.0 ± 0.8% vs 90.1% ± 0.8%, for a 500 Torr (67 kPa) Xe cell loadingcorresponding to nuclear magnetic resonance/magnetic resonance imaging (NMR/MRI) enhancements of ∼3.1 × 105 and ∼2.32 × 108 at the relevant fields for clinical imaging and HP 129Xe production of 3 T and 4 mT, respectively); moreover, the intercycle “dead” time was also significantly decreased. The higher-throughput TR-SEOP approach can be implemented without sacrificing the level of 129Xe hyperpolarization or the experimental stability for automation-making this approach beneficial for improving the overall 129Xe production rate in clinical settings

Cryogenics free production of hyperpolarized 129Xe and 83Kr for biomedical MRI applications

As an alternative to cryogenic gas handling, hyperpolarized (hp) gas mixtures were extracted directly from the spin exchange optical pumping (SEOP) process through expansion followed by compression to ambient pressure for biomedical MRI applications. The omission of cryogenic gas separation generally requires the usage of high xenon or krypton concentrations at low SEOP gas pressures to generate hp 129Xe or hp 83Kr with sufficient MR signal intensity for imaging applications. Two different extraction schemes for the hp gasses were explored with focus on the preservation of the nuclear spin polarization. It was found that an extraction scheme based on an inflatable, pressure controlled balloon is sufficient for hp 129Xe handling, while 83Kr can efficiently be extracted through a single cycle piston pump. The extraction methods were tested for ex vivo MRI applications with excised rat lungs. Precise mixing of the hp gases with oxygen, which may be of interest for potential in vivo applications, was accomplished during the extraction process using a piston pump. The 83Kr bulk gas phase T1 relaxation in the mixtures containing more than approximately 1% O2 was found to be slower than that of 129Xe in corresponding mixtures. The experimental setup also facilitated 129Xe T1 relaxation measurements as a function of O2 concentration within excised lungs

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Direcció: Leo Driehuys ; Direcció d'escena: Frans BoerlageEmpresa: Juan A. PamiasDe cada obra s'ha digitalitzat un programa sencer. De la resta s'han digitalitzat les parts que són diferents

129 Xe chemical shift in human blood and pulmonary blood oxygenation measurement in humans using hyperpolarized 129 Xe NMR

Purpose: To evaluate the dependency of the 129 Xe-red blood cell (RBC) chemical shift on blood oxygenation, and to use this relation for noninvasive measurement of pulmonary blood oxygenation in vivo with hyperpolarized 129 Xe NMR. Methods: Hyperpolarized 129 Xe was equilibrated with blood samples of varying oxygenation in vitro, and NMR was performed at 1.5 T and 3 T. Dynamic in vivo NMR during breath hold apnea was performed at 3 T on two healthy volunteers following inhala- tion of hyperpolarized 129 Xe. Results: The 129 Xe chemical shift in RBCs was found to increase nonlinearly with blood oxygenation at 1.5 T and 3 T. During breath hold apnea, the 129 Xe chemical shift in RBCs exhibited a periodic time modulation and showed a net decrease in chemical shift of ~ 1 ppm over a 35 s breath hold, corresponding to a decrease of 7–10 % in RBC oxygenation. The 129 Xe-RBC signal amplitude showed a modulation with the same frequency as the 129 Xe-RBC chemical shift. Conclusion: The feasibility of using the 129 Xe-RBC chemical shift to measure pulmonary blood oxygenation in vivo has been dem- onstrated. Correlation between 129 Xe-RBC signal and 129 Xe-RBC chemical shift modulations in the lung warrants further investiga- tion, with the aim to better quantify temporal blood oxygenation changes in the cardiopulmonary vascular circuit

Investigating lung responses with functional hyperpolarized xenon-129 MRI in an ex vivo rat model of asthma

Purpose: Asthma is a disease of increasing worldwide importance that calls for new investigative methods. Ex vivo lung tissue is being increasingly used to study functional respiratory parameters independent of confounding systemic considerations but also to reduce animal numbers and associated research costs. In this work, a straightforward laboratory method is advanced to probe dynamic changes in gas inhalation patterns by using an ex vivo small animal ovalbumin (OVA) model of human asthma. Methods: Hyperpolarized (hp)129Xe was actively inhaled by the excised lungs exposed to a constant pressure differential that mimicked negative pleural cavity pressure. The method enabled hp129Xe MRI of airway responsiveness to intravenous methacholine (MCh) and airway challenge reversal through salbutamol. Results: Significant differences were demonstrated between control and OVA challenged animals on global lung hp129Xegas inhalation with P < 0.05 at MCh dosages above 460 µg. Spatial mapping of the regional hp gas distribution revealed an approximately three-fold increase in heterogeneity for the asthma model organs. Conclusion: The experimental results from this proof of concept work suggest that the ex vivo hp noble gas imaging arrangement and the applied image analysis methodology may be useful as an adjunct to current diagnostic techniques