A new way to look into the lungs

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Imaging lungs with use of hyperpolarized (HP) noble gases (helium 3He, xenon 129Xe) is a novel technique allowing us to obtain images of ventilation with polarized gas, which can be a tool for evaluating lung disease phenotypes and showing responses to medical therapy.

Standard magnetic resonance imaging (MRI) is based on measuring the nuclear magnetic resonance signal (NMR) from protons present in a human body. For protons, the thermal equilibrium polarization of protons is low, although the density of protons is high in tissues and the signal is measurable, allowing for high-resolution images of the human body's interior. Unfortunately, from the viewpoint of nuclear magnetic resonance, the lungs seem empty since water vapor is not abundant. Nonetheless, a simple way to overcome this obstacle has been discovered. A gas that is both inert and sensitive to the MRI technique was proposed. Only one change must be made – the gas must be polarized with optical techniques, since thermal polarization of helium or xenon is of too low density to provide a strong NMR signal.

Lung images are obtained in a medical scanner after inhaling a portion of hyperpolarized gas. The scanner first needs to be tuned to the resonance frequency of 3He or 129Xe, and a modified MR sequence must be used.

Polarizing methods

Work on developing methods for obtaining high nuclear polarization is the task that Noble Gas Optical Polarization Group has at hand. There are two methods of polarizing gas: the metastability exchange optical pumping (MEOP) and the spin exchange optical pumping (SEOP), dedicated to 3He and 3He or 129Xe, respectively. MEOP is performed only in 3He under low gas pressure and a low magnetic field (standard method), and high gas pressure and high magnetic field (non-standard method). The Group has built two 3He MEOP polarizers working in those two regimes. The MEOP in the non-standard method was the Group's great achievement, which led to the construction of a unique polarizer operating inside a medical scanner in the scanner's magnetic field and achievement of creating the first human lung image filled with hyperpolarized 3He. The Group is currently working on optimizing gas distribution protocol and making the polarizer more user-friendly.


The second method – SEOP – is quite a bit more demanding, as it is performed in a gas mixture (129Xe and buffer gases N2 and 4He) in the presence of rubidium vapors and at different pressure, temperature, laser powers, and flow-rated regimes, which have to be optimized for a given polarizer. The problem of balancing the tradeoffs of 129Xe SEOP polarization, production rates, and volumes involves the ability to explore a space with large number of parameters.

The SEOP process has two stages. The first one consists of the optical pumping of valence electrons of rubidium vapor with a high power laser light tuned to a wavelength of 795 nm, while the second is an electron polarization transfer to 129Xe nuclei via collisions. Polarizing 129Xe requires high laser power; here 60 Watts and thick rubidium vapor are used for the optical pumping, which is obtained by elevating the temperature to 160ºC. The polarizer consists of the SEOP glass cell, a high-powered laser with optics, a set of magnetic coils, a gas distribution system, a cryogenic system, and two turbomolecular pumps for cleaning purposes. The SEOP polarizer was constructed at the beginning of 2014 and the first initial tests are raising optimism. At the present time, several units are under construction such as the HP 129Xe gas unit for accumulation for further medical tests. Experiments show that freezing HP 129Xe at the temperature of liquid nitrogen in the presence of a homogenous magnetic field enables scientists to maintain polarization for long hours. Thus, developing such a system is crucial to providing a stable source of polarized gas. The polarizer is a unique design developed by Anna Wojna- Pelczar and Tadeusz Pałasz, PhD, as a result of two years of experimental work combined with mathematical modeling and project design.

Due to their large electron cloud, 129Xe atoms generate a large chemical shift in the presence of neighboring atoms of molecules, which makes 129Xe a promising candidate for other spectroscopic applications. 129Xe dissolves in blood, organic lipophilic solvents, and biological tissue. This enables 129Xe to become a biosensor for magnetic resonance imaging with the evidence that this hyperpolarized gas is bound to produce measurable changes in the 129Xe chemical shift in different chemical environments. This can be a great tool for protein, enzyme, and cell studies. As far as lung imaging is concerned, it brings about a new way to characterize parameters such as an alveolar surface area, septal thickness, interphase diffusion kinetics, and blood kinetic exchange rates, as well as a new way to notice changes in those parameters due to spreading pulmonary disease.

The Future

Pulmonary diseases can be nonspecific, a fact that causes a need for direct imaging, leading to the use of multidetected computed tomography (MDCT), positron emission transition tomography (PET) and single photon emission computed tomography (SPECT). Although the techniques listed above brought exploitable parameters, they are still unable to create an image of regional ventilation and perfusion. Moreover, their resolutions are limited and the subjects are exposed to ionizing radiation. The MRI provides three-dimensional images without exposure to ionizing radiation, high resolution, and several mapping techniques, combined with polarized 129Xe as a unique contrast, which finally gives us an opportunity to diagnose regional heterogeneity, evaluate ventilation and perfusion, and allows us to provide animated frames, showing the propagation of gas in airways over time.

Research team: Anna Wojna-Pelczar, MSc; Tadeusz Pałasz, PhD; Bartosz Głowacz, PhD; Zbigniew Olejniczak, PhD; Professor Tomasz Dohnalik; Mateusz Suchanek, PhD -The University of Agriculture in Kraków