Under ordinary circumstances it would be impossible to make a high-resolution magnetic resonance image of inert gases like 3He and 129Xe. That is because the density of these gases is nearly 4 orders of magnitude lower than the density of tissues that are normally visualized on MRI. This problem is overcome by hyperpolarization, which enhances the MRI signal strength of these gases by 5 orders of magnitude. This is more than sufficient to overcome the low density of gases relative to the tissues that are normally imaged on MRI. Hyperpolarization makes 3D imaging of inhaled inert gases possible in a single breath-hold.
Hyperpolarization simply means aligning (polarizing) the nuclei of gases to a much greater extent than what is achieved by being in the MRI scanner. Even the largest magnets only align a tiny fraction of the nuclei (0.001%). But hyperpolarization can align them to nearly 100%. To do so we exploit the simple idea that the only difference between an aligned vs unaligned nucleus is the addition of one quantum unit of angular momentum. It turns out that light (photons) carry one quantum of angular momentum each, so these provide a means to solve our problem. Since it’s not possible for nuclei to directly absorb light (and thus angular momentum quanta), we use an intermediary – namely alkali metal vapors. Specifically we use the alkali metal rubidium, which is a heavier cousin of the better known sodium in table salt. The rubidium vapor has one outer electron, which when it absorbs resonant, circularly polarized laser light, becomes polarized. This step is called optical pumping. Nature takes care of the rest. When polarized rubidium atoms collide with inert 3He or 129Xe atoms, they can transfer that polarization to the 3He or 129Xe nuclei through a process called optical pumping and spin exchange. The physics of these processes has been studied for several decades, but the advent of high-power lasers now make it possible to produce liter quantities of hyperpolarized gases. The basic process is illustrated in the figure below
Hyperpolarized gases, 3He and 129Xe, can be be safely inhaled by a human subject lying down inside an MRI scanner (for investigational use only, pending FDA approval for clinical use). Images of HP gas atoms in the airways can then be rapidly acquired by an MRI scan through the direct visualization of respiratory gas distribution in pulmonary airways. The acquirable imaging signal-to-noise ratio (SNR) from HP gases is proportional to their polarization level and their concentration in the airways. Below are two representative cases showing MRI chest scans of a healthy subject (top row) and a COPD patient (bottom row) with a major ventilation defect in right upper lobe. It is clearly evident that the conventional 1H image does not show any evidence of the ventilation defect in the COPD subject, whereas the overlaid ventilation image of HP 129Xe on top of the standard scan clearly manifests the boundary of the defect region.
When inhaled hyperpolarized 129Xe travels through the pulmonary airway tree and eventually diffuses from alveolar air spaces into alveolar septa (5–8 µm thickness, consisting of blood and tissue). HP 129Xe atoms dissolved in lung tissue exhibit a large chemical shift of about 200 ppm relative to their gas-phase resonance frequency, which enables image acquisition methods to distinguish gas from dissolved-phase xenon. This characteristic permits imaging of regional pulmonary gas exchange and alveolar-capillary gas uptake.