Iga Muradyan

Near-unity nuclear polarization with an open-source 129Xe hyperpolarizer for NMR and MRI

Significance Lung diseases comprise the third leading cause of death in the United States and could benefit from new imaging modalities. “Hyperpolarized” xenon-129 can overcome the ordinarily weak MRI signals from low-density species in lung space or dissolved in tissue; however, clinical progress has been slowed by the difficulty in preparing large amounts of hyperpolarized xenon with high magnetization, as well as the cost and limited availability of xenon hyperpolarization devices. We describe a unique low-cost “open-source” xenon “hyperpolarizer,” characterize its ability to produce xenon-129 with high magnetization, and demonstrate its utility for human lung imaging. The exquisite NMR spectral sensitivity and negligible reactivity of hyperpolarized xenon-129 (HP129Xe) make it attractive for a number of magnetic resonance applications; moreover, HP129Xe embodies an alternative to rare and nonrenewable 3He. However, the ability to reliably and inexpensively produce large quantities of HP129Xe with sufficiently high 129Xe nuclear spin polarization (PXe) remains a significant challenge—particularly at high Xe densities. We present results from our “open-source” large-scale (∼1 L/h) 129Xe polarizer for clinical, preclinical, and materials NMR and MRI research. Automated and composed mostly of off-the-shelf components, this “hyperpolarizer” is designed to be readily implementable in other laboratories. The device runs with high resonant photon flux (up to 200 W at the Rb D1 line) in the xenon-rich regime (up to 1,800 torr Xe in 500 cc) in either single-batch or stopped-flow mode, negating in part the usual requirement of Xe cryocollection. Excellent agreement is observed among four independent methods used to measure spin polarization. In-cell PXe values of ∼90%, ∼57%, ∼50%, and ∼30% have been measured for Xe loadings of ∼300, ∼500, ∼760, and ∼1,570 torr, respectively. PXe values of ∼41% and ∼28% (with ∼760 and ∼1,545 torr Xe loadings) have been measured after transfer to Tedlar bags and transport to a clinical 3 T scanner for MR imaging, including demonstration of lung MRI with a healthy human subject. Long “in-bag” 129Xe polarization decay times have been measured (T1 ∼38 min and ∼5.9 h at ∼1.5 mT and 3 T, respectively)—more than sufficient for a variety of applications.

Diffusion of hyperpolarized 129Xe in the lung: a simplified model of 129Xe septal uptake and experimental results

We used hyperpolarized 129Xe NMR to measure pulmonary alveolar surface area per unit gas volume SA/Vgas, alveolar septal thickness h and capillary transit time ?, three critical determinants of the lungs primary role as a gas exchange organ. An analytical solution for a simplified diffusion model is described, together with a modification of the xenon transfer contrast imaging technique utilizing 90? radio-frequency pulses applied to the dissolved phase, rather than traditional 180? pulses. With this approach, three-dimensional (3D) maps of SA/Vgas were obtained. We measured global SA/Vgas, h and ? in four normal subjects, two subjects with mild interstitial lung disease (ILD) and two subjects with mild chronic obstructive pulmonary disease (COPD). In normals, SA/Vgas decreased with increasing lung volume from ~320 to 80?cm?1; both h~13??m and ?~1.5?s were relatively constant. For the two ILD subjects, h was, respectively, 36 and 97% larger than normal, quantifying an increased gas/blood tissue barrier; SA/Vgas and ? were normal. The two COPD subjects had SA/Vgas values ~25% that of normals, quantifying septal surface loss in emphysema; h and ? were normal. These are the first noninvasive, non-radiation-based, quantitative measurements of h and ? in patients with pulmonary disease.

Single-breath xenon polarization transfer contrast (SB-XTC): implementation and initial results in healthy humans.

To implement and characterize a single‐breath xenon transfer contrast (SB‐XTC) method to assess the fractional diffusive gas transport F in the lung: to study the dependence of F and its uniformity as a function of lung volume; to estimate local alveolar surface area per unit gas volume SA/VGas from multiple diffusion time measurements of F; to evaluate the reproducibility of the measurements and the necessity of B1 correction in cases of centric and sequential encoding.

Novel MR Imaging Applications for Pleural evaluation

Computed tomography is the first-line modality for evaluation of chest diseases primarily because of its spatial resolution. Magnetic resonance (MR) imaging is used as a problem-solving tool to answer key questions that are vital to optimal patient management. MR has the potential to provide qualitative, quantitative, anatomic, and functional information without the use of ionizing radiation or nephrotoxic contrast administration. With new advances in proton MR techniques, MR imaging can overcome some of the inherent problems associated with imaging the lung. This article describes novel MR applications for evaluation of the pleura and pleural diseases.

Inhalation heterogeneity from subresidual volumes in elite divers

Punctate reopening of the lung from subresidual volumes (sub-RV) is commonly observed in excised lung preparations, either degassed or collapsed to zero transpulmonary pressure, and in the course of reinflation of human lungs when the chest is open, secondary to traumatic or surgical pneumothoraxes. In the course of physiological studies on two elite breath-hold divers, who are able to achieve lung volumes well below traditional RV with glossopharyngeal exsufflation, we used MRI lung imaging with inhaled hyperpolarized (129)Xe to visualize ventilatory patterns. We observed strikingly inhomogeneous inhalation patterns with small inhalation volumes from sub-RV, consistent with reopening of frankly closed airways. On the other hand, two age-matched and two older controls, inhaling from just above RV, showed a much more homogeneous pattern. Our results demonstrate the concept of frank airway closure below RV in young healthy adults with an intact chest wall.

A portable single‐sided magnet system for remote NMR measurements of pulmonary function

In this work, we report initial results from a light‐weight, low field magnetic resonance device designed to make relative pulmonary density measurements at the bedside. The development of this device necessarily involves special considerations for the magnet, RF and data acquisition schemes as well as a careful analysis of what is needed to provide useful information in the ICU. A homogeneous field region is created remotely from the surface of the magnet such that when the magnet is placed against the chest, an NMR signal is measured from a small volume in the lung. In order to achieve portability, one must trade off field strength and therefore spatial resolution. We report initial measurements from a ping‐pong ball size region in the lung as a function of lung volume. As expected, we measured decreased signal at larger lung volumes since lung density decreases with increasing lung volume. Using a CPMG sequence with ΔTE=3.5 ms and a 20 echo train, a signal to noise ratio ~1100 was obtained from an 8.8mT planar magnet after signal averaging for 43 s. This is the first demonstration of NMR measurements made on a human lung with a light‐weight planar NMR device. We argue that very low spatial resolution measurements of different lobar lung regions will provide useful diagnostic information for clinicians treating Acute Respiratory Distress Syndrome as clinicians want to avoid ventilator pressures that cause either lung over distension (too much pressure) or lung collapse (too little pressure). Copyright

Hyperpolarized 129 Xenon MRI of the Lung

Pulmonary imaging is the least evolved branch of proton MRI, primarily due to the low volume fraction of tissue in the lung; only ~20% of the volume contains tissue or blood while the remainder is filled with air. By comparison, most of the volume in other organs is hydrogen. Another source of the inherently weak MR signal in the lungs is the extremely large area of the tissue-gas interface. The 3 ppm difference in magnetic susceptibility between tissue and air causes an alteration of the local magnetic field resulting in very short signal coherence times. Despite having limited SNR, several promising techniques have been developed (Edelman et al. 1996; Mai et al. 2001; Hatabu et al. 2001; Jakob et al. 2004; Detre et al. 1994; Hopkins and Prisk 2010; Deimling et al. 2008; Bauman et al. 2009). These techniques work better at low magnetic fields (such as 1.5 T) because of the air/tissue susceptibility issue. This may be problematic for the future as the overall drive for clinical imaging is in the direction of higher field strengths. In preclinical small animal imaging, Kuethe et al. (2007) used 1.89 T field strength system to produce lung images approaching the quality of CT.

Chapter 19:Xenon Septal Uptake

The main function of the lungs, gas exchange, is accomplished through diffusion processes driven by concentration gradients: after filling the lungs with air, oxygen diffuses into the lung parenchyma and blood, while carbon dioxide is driven from the blood out into the gas state, and exhaled. The efficiency of this process is high due to the large surface area available for gas exchange and the extreme thinness of the gas–blood barrier. However, lung diseases can affect both, the surface area and the thickness of the barrier, thus decreasing the efficiency. Therefore, any method capable of evaluating the different sub-components of gas exchange will be valuable both in assessing the specific cause of any lung dysfunction and in evaluating efficacy of therapeutic intervention. Measurement of pulmonary septal uptake of hyperpolarized xenon offers the opportunity to obtain such information. Over the last two decades a significant body of research has been done in this direction, developing several models of the uptake of hyperpolarized xenon by the pulmonary tissue and blood. In this chapter we introduce these theoretical treatments of the xenon uptake in the lung and review the up to date research in the area.