Hyperpolarization (physics)

Hyperpolarization is the spin polarization of the atomic nuclei of a material in a magnetic field far beyond thermal equilibrium conditions determined by the Boltzmann distribution. It can be applied to gases such as and , and small molecules where the polarization levels can be enhanced by a factor of 10⁴–10⁵ above thermal equilibrium levels. Hyperpolarized noble gases are typically used in magnetic resonance imaging (MRI) of the lungs.

Hyperpolarized small molecules are typically used for in vivo metabolic imaging. For example, a hyperpolarized metabolite can be injected into animals or patients and the metabolic conversion can be tracked in real-time. Other applications include determining the function of the neutron spin-structures by scattering polarized electrons from a very polarized target (³He), surface interaction studies, and neutron polarizing experiments.

Spin-exchange optical pumping

Introduction

Spin exchange optical pumping (SEOP) Noble gases are required because SEOP is performed in the gas phase, they are chemically inert, non-reactive, chemically stable with respect to alkali metals, and their T₁ is long enough to build up polarization. Spin 1/2 noble gases meet all these requirements, and spin 3/2 noble gases do to an extent, although some spin 3/2 do not have a sufficient T₁. Each of these noble gases has their own specific application, such as characterizing lung space and tissue via in vivo molecular imaging and functional imaging of lungs, to study changes in metabolism of healthy versus cancer cells, During this process, circularly polarized infrared laser light, tuned to the appropriate wavelength, is used to excite electrons in an alkali metal, such as caesium or rubidium inside a sealed glass vessel. Infrared light is necessary because it contains the wavelengths necessary to excite the alkali metal electrons, although the wavelength necessary to excite sodium electrons is below this region (Table 1).

{| class="wikitable"

|+Table 1. Wavelengths required to excite alkali metal electrons.

!Alkali Metal

!Wavelength (nm)

|-

|Sodium

|590.0

|-

|Rubidium

|794.7

|-

|Cesium

|894.0

|}

The angular momentum is transferred from the alkali metal electrons to the noble gas nuclei through collisions. Nitrogen is used as a quenching gas, which prevents the fluorescence of the polarized alkali metal, which would lead to de-polarization of the noble gas. If fluorescence was not quenched, the light emitted during relaxation would be randomly polarized, working against the circularly polarized laser light. While different sizes of glass vessels (also called cells), and therefore different pressures, are used depending on the application, one amagat of total pressure of noble gas and nitrogen is sufficient for SEOP and 0.1 amagat of nitrogen density is needed to quench fluorescence.

History

The discovery of SEOP took decades for all the pieces to fall into place to create a complete technique. First, in 1897, Zeeman's studies of sodium vapor led to the first result of optical pumping. The next piece was found in 1950 when Kastler determined a method to electronically spin-polarize rubidium alkali metal vapor using an applied magnetic field and illuminating the vapor with resonant circularly polarized light. The D₁ and D₂ transitions can occur if the rubidium atoms are illuminated with light at a wavelength of 794.7 nm and 780 nm, respectively (Figure 1). Here, m_s is the spin angular momentum with possible values of + (spin up) or − (spin down), often drawn as vectors pointing up or down, respectively. The difference in population between these two energy levels is what produces an NMR signal. For example, the two electrons in the spin down state cancel two of the electrons in the spin up state, leaving only one spin up nucleus to be detected with NMR. However, the populations of these states can be altered via hyperpolarization, allowing the spin up energy level to be more populated and therefore increase the NMR signal. This is done by first optically pumping alkali metal, then transferring the polarization to a noble gas nucleus to increase the population of the spin up state.

alt=|left|thumb|Figure 3. Transitions that occur when circularly polarized light interacts with the alkali metal atoms.

The absorption of laser light by the alkali metal is the first process in SEOP.

thumb|Figure 4. Transfer of polarization via A) binary collisions and B) van der Waals forces.

Next, the optically pumped alkali metal collides with the noble gas, allowing for spin exchange to occur where the alkali metal electron polarization is transferred to the noble gas nuclei (Figure 4). There are two mechanisms in which this can occur. The angular momentum can be transferred via binary collisions (Figure 4A, also called two-body collisions) or while the noble gas, N₂ buffer gas, and vapor phase alkali metal are held in close proximity via van der Waals forces (Figure 4B, also called three body collisions). Relaxation of the nuclear polarization can occur via several mechanisms and is written as a sum of these contributions:

:<math>\Gamma=\Gamma_t+\Gamma_p+\Gamma_g+\Gamma_w</math>

Where Γ_t, Γ_p, Γ_g, and Γ_w represent the relaxation from the transient Xe₂ dimer, the persistent Xe₂ dimer, diffusion through gradients in the applied magnetic field, and wall relaxation, respectively. It is similar to Xe-Rb during spin exchange (spin transfer) where they are held in close proximity to each other via van der Waals forces. This plot should be linear, where γ' is the slope and Γ_SD is the y-intercept.

Relaxation: T₁

Spin exchange optical pumping can continue indefinitely with continuous illumination, but there are several factors that cause relaxation of polarization and thus a return to the thermal equilibrium populations when illumination is stopped. In order to use hyperpolarized noble gases in applications such as lung imaging, the gas must be transferred from the experimental setup to a patient. As soon as the gas is no longer actively being optically pumped, the degree of hyperpolarization begins to decrease until thermal equilibrium is reached. However, the hyperpolarization must last long enough to transfer the gas to the patient and obtain an image. The longitudinal spin relaxation time, denoted as T₁, can be measured easily by collecting NMR spectra as the polarization decreases over time once illumination is stopped. This relaxation rate is governed by several depolarization mechanisms and is written as:

:<math>\frac{1}{\mathrm{T}_1}=\left ( \frac{1}{T_1} \right )_{CR}+\left ( \frac{1}{T_1} \right )_{MFI}+\left ( \frac{1}{T_1} \right )_{O2}</math>

Where the three contributing terms are for collisional relaxation (CR), magnetic field inhomogeneity (MFI) relaxation, and relaxation caused by the presence of paramagnetic oxygen (O2). The T₁ duration could be anywhere from minutes to several hours, depending on how much care is put into lessening the effects of CR, MFI, and O₂. The last term has been quantified to be 0.360 s⁻¹ amagat⁻¹, but the first and second terms are hard to quantify since the degree of their contribution to the overall T₁ is dependent on how well the experimental setup and cell are optimized and prepared. Decreasing wall relaxation leads to longer and higher polarization of the noble gas. In the distillation method, the cell is connected to a glass manifold equipped to hold both pressurized gas and vacuum, where an ampoule of alkali metal is connected. The manifold and cell are vacuumed, then the ampoule seal is broken and the alkali metal is moved into the cell using the flame of a gas torch. or by 3D printing the coil. Commonly, the oven is a forced-air oven, with two faces made of glass for the laser light to pass through the cell, a removable lid, and a hole through which a hot air line is connected, which allows the cell to be heated via conduction. The magnetic field generating coils can be a pair of Helmholtz coils, used to generate the desired magnetic field strength, A set of four electromagnetic coils can also be used (i.e. from Acutran) Studies involving hyperpolarization of ¹³¹Xe are underway, piquing the interest of physicists. There are also improvements being made to allow not only rubidium to be utilized in the spin transfer, but also cesium. In principle, any alkali metal can be used for SEOP, but rubidium is usually preferred due to its high vapor pressure, allowing experiments to be carried out at relatively low temperatures (80&nbsp;°C-130&nbsp;°C), decreasing the chance of damaging the glass cell.

Rationale

Our target is to identify the infection or disease (cancer, for example) anywhere in our body like cerebral, brain, blood, and fluid, and tissues. This infectious cell is called collectively biomarker. According to the World Health Organization (WHO) and collaborating with United Nations and International Labor organization have convincingly defined the Biomarker as "any substance, structure, or process that can be measured in the body or its products and influence or predict the incidence of outcome or disease". Biomarker has to be quantifiable up-to certain level in biological process in well-being.

Other common biomarkers are breast cancer, Ovarian cancer, Colorectal cancer, Lung cancer and brain tumor.

This disease-causing verdict agent is the biomarker is existing extremely trace amount especially initial state of the disease. Therefore, identifying or getting images of biomarker is tricky and, in few circumstances, uncertain by NMR tech. Hence, we must use the contrasting agent to enhance the images at least to visualize level to Physicians. As molecules of biomarker is less abundant in vivo system. The NMR or MRI experiment provides a very small signal even in some cases, the analyzer can miss the signal peak in data due to the lack in abundance of biomarkers. Therefore, to make sure, to reach the true conclusion about the existence of trouble-causing biomarkers, we need to enhance the probe (contrasting mechanisms) to get the clear peak at the most visible level of peak height as well as the position of the peak in data. If it is possible to gather the acceptable and clearly interpretable data from NMR or MRI experiment by using the contrasting agent, then experts can take a right initial step to recover the patients who already have been suffering from cancer.

• Among them top sharp peak at 194.7ppm. In addition, at 189 ppm peak come out from the non-brain tissues.
• Another two peaks are still unknown at 191.6 ppm and 197.8 ppm. At 209.5 ppm smaller but broad peak has been found in NMR data when ¹²⁹Xe was dissolved in the blood stream.
• Hyperpolarized ¹²⁹Xe is very sensitive detector of biomarker (form of cancer in living system).
• The nuclear spin polarization of ¹²⁹Xe or in generally for noble gases we can increase up to fivefold via SEOP technique.

[[File:Figure-10.png|thumb|Figure 10. Measurements of the Polarization of ¹²⁹Xe(g) in presence of low and intermediate magnetic fields. All (A-D) figures are NMR signal amplitude in μV/KHz vs Larmor Frequency in KHz. (A) Enhanced ¹²⁹Xe(g) NMR signal at 62&nbsp;kHz Larmor Frequency from the SEOP cell;

Xenon(g) has 1545 torr and Nitrogen(g) has 455 torr pressure and NMR data was collected in presence of 5.26mT magnetic field. (B) Reference NMR signal for water Proton Spin (111M), doping with CuSO_4. 5H₂O(s), 5.0mM and polarization has been created thermally in presence of 1.46 mT magnetic fields (number of scans was 170,000 times). (C) NMR data for Hyperpolarized ¹²⁹Xe was collected in presence of 47.5mT magnetic fields.(¹²⁹Xe was 300 torr and N₂ was 1700 torr).(D) Reference NMR signal for ¹³C was collected from 170.0mM CH₃COONa(l) in presence of 47.5mT magnetic field.³²]]

(Figure-10)

¹²⁹Xe_(g) shows satisfactory enhancement in polarization during SEOP compared to the thermal enhancement in polarization. This is demonstrated by the experimental data values when NMR spectra are acquired at different magnetic field strengths.

• Chemical composition of materials can influence the longitudinal relaxation of hyperpolarized ⁸³Kr. This results in an image of the spaces in the lungs filled with the gas. While the process to get to the point of imaging the patient may require knowledge from scientists very familiar with this technique and the equipment, steps are being taken to eliminate the need for this knowledge so that a hospital technician would be able to produce the hyperpolarized gas using a polarizer. Xenon MRI is being used to monitor patients with pulmonary-vascular, obstructive, or fibrotic lung disease.

Temperature-ramped ¹²⁹Xe SEOP in an automated high-output batch model hyperpolarized ¹²⁹Xe can utilize three prime temperature range to put certain conditions: First, ¹²⁹Xe hyperpolarization rate is superlative high at hot condition. Second, in warm condition the hyperpolarization of ¹²⁹Xe is unity. Third, at cold condition, the level of hyperpolarization of ¹²⁹Xe gas at least can get the (at human body's temperature) imaging although during the transferring into the Tedlar bag having poor percentage of ⁸⁷Rb (less than 5&nbsp;ng/L dose).

Multiparameter analysis of ⁸⁷Rb/¹²⁹Xe SEOP at high xenon pressure and photon flux could be used as 3D-printing and stopped flow contrasting agent in clinical scale. In situ technique, the NMR machine was run for tracking the dynamics of ¹²⁹Xe polarization as a function of SEOP-cell conditioning with different operating parameters such as data collecting temperature, photon flux, and ¹²⁹Xe partial pressure to enhance the ¹²⁹Xe polarization (P_Xe). In this method, glass wool is coated with CsH salt, increasing the surface area of the CsH and therefore increasing the chances of spin transfer, yielding 80-fold enhancements at low field (0.56 T). This liquid can be used in in vivo metabolic imaging for oncology and other applications. The ¹³C polarization levels in solid compounds can reach up to ≈64% and the losses during dissolution and transfer of the sample for NMR measurements can be minimized to a few percent. Compounds containing NMR-active nuclei can also be hyperpolarized using chemical reactions with para-hydrogen, see Para-Hydrogen Induced Polarization (PHIP).

Parahydrogen induced polarization

Molecular hydrogen, H₂, contains two different spin isomers, para-hydrogen and ortho-hydrogen, with a ratio of 25:75 at room temperature. Creating para-hydrogen induced polarization (PHIP) means that this ratio is increased, in other words that para-hydrogen is enriched. This can be accomplished by cooling hydrogen gas and then inducing ortho-to-para conversion via an iron-oxide or charcoal catalyst. When performing this procedure at ≈70 K (i.e. with liquid nitrogen), para-hydrogen is enriched from 25% to ca. 50%. When cooling to below 20 K and then inducing the ortho-to-para conversion, close to 100% parahydrogen can be obtained.

For practical applications, the PHIP is most commonly transferred to organic molecules by reacting the hyperpolarized hydrogen with precursor molecules in the presence of a transition metal catalyst. Proton NMR signals with ca. 10,000-fold increased intensity can be obtained compared to NMR signals of the same organic molecule without PHIP and thus only "thermal" polarization at room temperature.

Signal amplification by reversible exchange (SABRE)

Signal amplification by reversible exchange (SABRE) is a technique to hyperpolarize samples without chemically modifying them. Compared to orthohydrogen or organic molecules, a much greater fraction of the hydrogen nuclei in parahydrogen align with an applied magnetic field. In SABRE, a metal center reversibly binds to both the test molecule and a parahydrogen molecule facilitating the target molecule to pick up the polarization of the parahydrogen. This technique can be improved and utilized for a wide range of organic molecules by using an intermediate "relay" molecule like ammonia. The ammonia efficiently binds to the metal center and picks up the polarization from the parahydrogen. The ammonia then transfers it other molecules that don't bind as well to the metal catalyst. This enhanced NMR signal allows the rapid analysis of very small amounts of material.

See also

• Dynamic nuclear polarization
• Electron paramagnetic resonance
• Hyperpolarized carbon-13 MRI

References

External links

• Europhysics - "Take a breath of polarized noble gas"
• University of Virginia - "Hyperpolarized Gas MR Imaging"
• Swiss DNP Initiative - "DNP-NMR ¹³C Hyperpolarization"