3. Methodology

He

He is a

2.3. Hyperpolarized lung imaging

252 Raman Spectroscopy and Applications

fused image (blue arrows) [15].

3

Any noble gas isotope with nonzero spin can theoretically be used as a hyperpolarized contrast agent with a view for clinical lung MRI. Traditionally, helium-3 was most commonly used due to its high gyromagnetic ratio—resulting in stronger MRI signals. However, due to its insolubility in blood and water, perfusion across the alveolar wall cannot occur, primarily limiting the use of

He to gas-phase ventilation and diffusion imaging. The difficulty in wide-spread clinical <sup>3</sup>

nonrenewable by-product of tritium decay in nuclear reactors. As such, most current clinical studies on hyperpolarized noble gases use 129Xe for its solubility in tissue and blood, significant

As discussed previously, higher net spin polarizations directly result in stronger MR signal generation and hence, improved image contrast between areas of interest and background noise. Recent hyperpolarization methods can create near-unity net spin polarizations [13], resulting in spectroscopic signals four to five orders of magnitude greater than nonhyperpolarized samples. Such improvements in image quality facilitate the use of HP noble gas MRI within the lungs as a diagnostic imaging tool for characterizing lung structure and function [14], and consequently may potentially enable earlier and more reliable diagnosis of various respiratory disorders, such as idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) 7]. An

Figure 2. (a) Coronal plane 25 mm slice 129Xe-MR ventilation image of a healthy adult male, with 129Xe appearing bright, upper airways are clearly delineated. (b) Second coronal plane 25 mm slice fused 129Xe-MR ventilation and proton coregistration image, with 129Xe appearing green blue-green. On the fused image, it can be seen that ventilation defects on the ventilation image (yellow arrows) correspond to a diaphragmatic eventration and pulmonary vasculature on the

adoption is further compounded by the difficulty and expense of acquisition, since <sup>3</sup>

chemical shift range, low cost of acquisition, and high natural abundance.

example of a HP 129Xe lung ventilation image can be seen in Figure 2.

Early studies carried out by Happer and coworkers [4] used the N2 rotational temperature to monitor energy transport during optical pumping. These experiments primarily used pump cells loaded with helium and nitrogen gases, and operated under the same experimental conditions as SEOP (without the NMR-active noble gas) using a broadband (2 nm linewidth) 795 nm Rb D1 pump laser. The Raman setup shown in Figure 3(a) consisted of a 514.5 nm probe beam from an argon-ion laser (6 W) that could be focused to a 1 mm waist anywhere within the pump cell; the scattered light was collected using a planoconvex lens and directed into a Spex 1404 double Raman spectrometer (0.85 m focal length) and the photons were counted using a bi-alkali photomultiplier tube (PMT) with computer readout. The results of this work include the observation of convective heat transfer during optical pumping, as the N2 rotational temperature deviated from a linear relationship with absorbed pump laser power, shown in Figure 3(b). This convective heat transfer was further studied by measuring the N2 temperature at differing spatial locations throughout the pump cell as a function of pump laser absorption. For low values of laser absorption (2.9 W), the calculated Rayleigh number (which provides a measure of convective vs. conductive transfer by comparing buoyant and viscous forces) indicates conductive heat transfer to the pump cell walls. As the absorption of the pump laser is increased to 15 W, the Rayleigh number indicates convective heat transfer; this is important in SEOP, as convection can affect the residing time of polarized 129Xe nuclei near the pump cell walls and lead to depolarization. Switching between a cell loading of predominantly helium gas with some nitrogen (1.0 and 0.33 amagat) to a cell with only high density nitrogen (3.2 amagat) increased the Rayleigh number by a factor of 70; simply changing the pump cell volume and geometry further increased the Rayleigh number by an additional factor of 29. This demonstrates how gas composition, density, and pump cell geometry can affect energy transport during SEOP.

Figure 3. (a) Schematic representation of Happer's experimental setup showing SEOP pump cell, 795 nm Rb excitation source, and orthogonal Raman probe/detect configuration. 514.5 nm Raman probe beam furnished by a 15 W water cooled argon-ion laser, with resulting Raman scattering imaged directly into spectrometer. (b) N2 rotational temperature (solid squares) as a function of absorbed laser power for a cell loading of 2 amg He and 0.33 amg N2 in a 40 cm3 OP cell, with an external cell surface temperature of 170°C (open diamonds). Solid line fits to data points up to 4.3 W of absorbed energy, after which the experimental data deviate significantly from a purely conductive energy dissipation model [2].

Happer et al. also noticed that the N2 rotational temperature was elevated compared to the surface temperature of the glass walls of the pump cell (measured via thermocouple). The extent of the temperature elevation changed with absorbed pump laser power and gas loading (density/composition), and often varied from 100 to 200°C above the cell wall temperature. Because of the slower vibrational-to-rotational cross-relaxation, N2 vibrational temperatures were found to be significantly elevated in pump cells containing only nitrogen (Tvib ~ 900°C). Upon the addition of helium gas, N2 vibration temperatures were only elevated ~120°C above the cell surface temperature, due to the significantly faster relaxation time with the helium translational temperature. These studies, which were the first to use Raman spectroscopy to remotely monitor gas temperatures during SEOP, utilized relatively low resonant laser powers and predominantly helium-rich gas loadings—both of which lessen the degree to which energy accumulates in the N2 rotational-vibrational manifold. The authors noted that additional studies would be warranted under conditions of high resonant laser power and the absence of helium buffer gas.

#### 3.1. Orthogonal configuration

Recent advances in laser diode array (LDA) technology have resulted in not only an increase in overall laser power (hundreds of watts), but also a narrowing of the spectral output from several nanometers to a few tenths of a nanometer. This increase in resonant flux leads to more efficient absorption by the relatively narrow alkali metal D1 absorption line (c.a. ~0.1 nm), with the consequence of additional thermal management concerns [6]. Furthermore, recent advances in using high xenon partial pressures (pXe) in SEOP in the absence of helium to attain high xenon nuclear spin polarization values (pXe) [16], and its further application in clinicalscale xenon hyperpolarizers used for pulmonary imaging [6], have furthered the interest in binary Xe/N2 gas mixtures for SEOP. The absence of helium, with its favorable thermal conductivity, is expected to further exacerbate thermal management concerns. Because of these demands of high resonant laser flux and gas density/composition, additional studies of energy transport under these conditions is warranted.

Further work from Whiting et al. [17] conducted remote temperature sensing using Raman scattering to observe energy thermalization during Rb/129Xe SEOP under conditions of high xenon partial pressures and resonant laser powers. These studies used a laser diode array (~70 W) that was frequency-narrowed (~0.25 nm linewidth) using an internal volume holographic grating; this SEOP pump laser was spectrally tunable independent of output power to allow comparative studies at different excitation frequencies. The cylindrical optical pumping cell (2.5 cm inner diameter; 15.5 cm length) was surrounded by an outer glass cylinder that served as a forced-air oven and allowed 360° optical access [18]. Miniature NMR coils were placed directly under the OP cell to allow correlative low-field NMR studies of HP 129Xe gas along with Raman scattering measurements of nitrogen buffer gas. The Raman apparatus shown in Figure 4(a, c) consisted of a Verdi V5 532 nm excitation laser (5 W) that was fibercoupled to a modular lens assembly box to focus the light into the OP cell. Scattered light was collected by a similar lens box (positioned orthogonal to the probe laser) that was fiber-coupled to a Horiba Jobin-Yvon U1000 double 1-m Raman spectrometer with 2400 l/mm grating and CCD receiver. Spatial filtering of the laser and Rayleigh scatter was achieved through adjustment of the internal baffles of the spectrometer; this provided spectra that displayed Stokes and anti-Stokes rotational Raman lines within 6 cm−<sup>1</sup> of the laser line without the use of notch or edge filters—see Figure 4(b). The N2 rotational temperature was calculated using the methods explained in Section 2.2, and calibration studies showed a good correlation with different N2 gas temperatures in the absence of optical pumping as shown in Figure 4(d).

Happer et al. also noticed that the N2 rotational temperature was elevated compared to the surface temperature of the glass walls of the pump cell (measured via thermocouple). The extent of the temperature elevation changed with absorbed pump laser power and gas loading (density/composition), and often varied from 100 to 200°C above the cell wall temperature. Because of the slower vibrational-to-rotational cross-relaxation, N2 vibrational temperatures were found to be significantly elevated in pump cells containing only nitrogen (Tvib ~ 900°C). Upon the addition of helium gas, N2 vibration temperatures were only elevated ~120°C above the cell surface temperature, due to the significantly faster relaxation time with the helium translational temperature. These studies, which were the first to use Raman spectroscopy to remotely monitor gas temperatures during SEOP, utilized relatively low resonant laser powers and predominantly helium-rich gas loadings—both of which lessen the degree to which energy accumulates in the N2 rotational-vibrational manifold. The authors noted that additional studies would be warranted under conditions of high resonant laser power and the

Recent advances in laser diode array (LDA) technology have resulted in not only an increase in overall laser power (hundreds of watts), but also a narrowing of the spectral output from several nanometers to a few tenths of a nanometer. This increase in resonant flux leads to more efficient absorption by the relatively narrow alkali metal D1 absorption line (c.a. ~0.1 nm), with the consequence of additional thermal management concerns [6]. Furthermore, recent advances in using high xenon partial pressures (pXe) in SEOP in the absence of helium to attain high xenon nuclear spin polarization values (pXe) [16], and its further application in clinicalscale xenon hyperpolarizers used for pulmonary imaging [6], have furthered the interest in binary Xe/N2 gas mixtures for SEOP. The absence of helium, with its favorable thermal conductivity, is expected to further exacerbate thermal management concerns. Because of these demands of high resonant laser flux and gas density/composition, additional studies of energy

Further work from Whiting et al. [17] conducted remote temperature sensing using Raman scattering to observe energy thermalization during Rb/129Xe SEOP under conditions of high xenon partial pressures and resonant laser powers. These studies used a laser diode array (~70 W) that was frequency-narrowed (~0.25 nm linewidth) using an internal volume holographic grating; this SEOP pump laser was spectrally tunable independent of output power to allow comparative studies at different excitation frequencies. The cylindrical optical pumping cell (2.5 cm inner diameter; 15.5 cm length) was surrounded by an outer glass cylinder that served as a forced-air oven and allowed 360° optical access [18]. Miniature NMR coils were placed directly under the OP cell to allow correlative low-field NMR studies of HP 129Xe gas along with Raman scattering measurements of nitrogen buffer gas. The Raman apparatus shown in Figure 4(a, c) consisted of a Verdi V5 532 nm excitation laser (5 W) that was fibercoupled to a modular lens assembly box to focus the light into the OP cell. Scattered light was collected by a similar lens box (positioned orthogonal to the probe laser) that was fiber-coupled to a Horiba Jobin-Yvon U1000 double 1-m Raman spectrometer with 2400 l/mm grating and CCD receiver. Spatial filtering of the laser and Rayleigh scatter was achieved through

absence of helium buffer gas.

254 Raman Spectroscopy and Applications

3.1. Orthogonal configuration

transport under these conditions is warranted.

Figure 4. (a) Schematic representation of orthogonal Raman apparatus. (b) Example N2 rotational Raman spectrum (baseline-corrected) at room temperature, without SEOP (3 atm N2). (c) Photograph of orthogonal Raman apparatus. (d) Plot of oven temperature (Tcell) measured via thermocouple (located in the oven inlet airstream) versus TN2 measured via Raman spectroscopy without SEOP; experimental data (squares) are shown in comparison with simulation assuming 1:1 correlation (dotted line); error bars are least-squares fit errors of Bhc/kT plots [19].

In this work, different xenon partial pressures were studied to determine the effects from increasing incident laser power on both 129Xe hyperpolarization level and N2 rotational temperature—see Figure 5(a, b). Both HP 129Xe signal and N2 rotational temperatures increased with laser power for the different gas loadings (100/1900, 500/1500, and 1500/500 Torr Xe/N2), with the highest 129Xe signal and N2 temperature observed at the highest xenon partial pressure. This increased temperature at high xenon partial pressure was not primarily attributed to increased laser absorption, but rather to the combination of the lower concentration of nitrogen (increasing the energy absorption per N2) and low thermal conductivity of xenon (which was the significant fraction of total gas volume). Gas loadings with the lowest xenon partial pressure exhibited a relatively weak dependence of N2 rotational temperature on incident laser light. Despite the high nitrogen temperatures, the high xenon density loading provided the highest overall 129Xe NMR signal—typically the overall figure of merit for applications of hyperpolarized contrast agents.

Additional studies examined the effects of heating as a function of longitudinal position within the cylindrical pump cell. Because the external heat source was provided in the rear of the cell, and the forced air oven was poorly insulated, there was a significant temperature gradient (~30–40°C surface temperature) along the length of the cell. Both the 129Xe NMR signal and the N2 rotational temperature reflected the presence of this gradient and showed the maximal values were at the rear of the cell (close to the heating source). This type of back-to-front temperature gradient has both benefits and detriments. One benefit is that the total cell illumination may improve, as the optical density of absorbers gradually increases with penetration depth (unlike other OP systems, which may have conditions where all the laser light is absorbed in the front portion of the cell—leaving the rear of the cell optically opaque); this improved illumination should increase global HP 129Xe signal. On the other hand, an unfavorable result of temperature gradients is longitudinal convective heat transport, which potentially brings the polarized gas in close contact with paramagnetic relaxation centers in the cell wall surface for longer periods of time. These studies were carried out at different illumination wavelengths to examine how changes to the Rb D1 lineshape [6] (through altering the gas density and composition) affect the N2 rotational temperature. The highest HP 129Xe NMR signals and N2 rotational temperatures were found nearest to the Rb D1 line, and elevated values were observed at red-shifted excitation wavelengths (as expected, given the effects of different gas loadings on the Rb absorption lineshape [6]).

The effects of slight changes in temperature of the forced air oven on both HP 129Xe NMR signal and N2 rotational temperature over the course of an SEOP experiment were also monitored—see Figure 5(c, d). Increasing the external cell temperature from ~110°C to ~140°C resulted in significant changes to these parameters. At the lower cell temperature, the N2 rotational temperature reached steady state (~190°C) quickly and held the value throughout the course of the experiment (40 min); correspondingly, other conditions within the OP cell remained stable (e.g., laser absorption, Rb density, PXe value, etc.). By raising the external cell temperature a mere ~30°C, the N2 rotational temperature climbed to ~730°C in less than 15 minutes of OP; a steep rise in HP 129Xe signal was also observed in the initial portion of the SEOP experiment. However, once the N2 rotational temperature peaks, both it and the PXe values begin to drop significantly. The N2 rotational temperature remains quite high (~530°C), but fluctuates greatly over the remainder of the experiment; the amount of absorbed laser light continues to increase for the remainder of the experiment. These occurrences likely indicate both Rb runaway as well as increased turbulence inside the OP cell. These results, showing the effects of slight external cell surface temperature changes on the SEOP efficiency, indicate that (under some experimental regimes) overall cell illumination can be more critical than the Rb/129Xe spin-exchange rate (which is often viewed as the most important parameter of SEOP).

In summary, this work expanded on the previous studies of Happer et al. [4] by examining a regime of high resonant laser power and xenon-dominant binary gas mixtures in the absence of helium. It also used in situ low-field 129Xe NMR in addition to the N2 rotational temperatures observed using Raman spectroscopy. These relatively extreme conditions showed that elevated N2 rotational temperatures correlated with 129Xe hyperpolarization across a range of experimental conditions and that internal gas temperatures of ~730°C could be observed within 15 minutes of SEOP. While the results of these experiments effectively displayed the interdependence of laser power, cell temperature, gas density/composition, and laser centroid offset during SEOP, the experimental Raman setup could be significantly improved. Although the internal baffles of the Raman spectrometer were used for spectral/spatial filtering (in the absence of notch or edge filters), detection sensitivity was an issue, as were significant problems with the baseline. Furthermore, the orthogonal excitation/detection setup was difficult to precisely focus (with an associated hysteresis). Both the probe beam and Raman scattering collection optics needed to be focused to the same point within ~1 mm spatial resolution in three dimensions using only manual translational stages. An improved design, in which the excitation and collection optics were colinear, would simplify the setup and overcome many of these shortfalls.

(which was the significant fraction of total gas volume). Gas loadings with the lowest xenon partial pressure exhibited a relatively weak dependence of N2 rotational temperature on incident laser light. Despite the high nitrogen temperatures, the high xenon density loading provided the highest overall 129Xe NMR signal—typically the overall figure of merit for

Additional studies examined the effects of heating as a function of longitudinal position within the cylindrical pump cell. Because the external heat source was provided in the rear of the cell, and the forced air oven was poorly insulated, there was a significant temperature gradient (~30–40°C surface temperature) along the length of the cell. Both the 129Xe NMR signal and the N2 rotational temperature reflected the presence of this gradient and showed the maximal values were at the rear of the cell (close to the heating source). This type of back-to-front temperature gradient has both benefits and detriments. One benefit is that the total cell illumination may improve, as the optical density of absorbers gradually increases with penetration depth (unlike other OP systems, which may have conditions where all the laser light is absorbed in the front portion of the cell—leaving the rear of the cell optically opaque); this improved illumination should increase global HP 129Xe signal. On the other hand, an unfavorable result of temperature gradients is longitudinal convective heat transport, which potentially brings the polarized gas in close contact with paramagnetic relaxation centers in the cell wall surface for longer periods of time. These studies were carried out at different illumination wavelengths to examine how changes to the Rb D1 lineshape [6] (through altering the gas density and composition) affect the N2 rotational temperature. The highest HP 129Xe NMR signals and N2 rotational temperatures were found nearest to the Rb D1 line, and elevated values were observed at red-shifted excitation wavelengths (as expected, given the effects of

The effects of slight changes in temperature of the forced air oven on both HP 129Xe NMR signal and N2 rotational temperature over the course of an SEOP experiment were also monitored—see Figure 5(c, d). Increasing the external cell temperature from ~110°C to ~140°C resulted in significant changes to these parameters. At the lower cell temperature, the N2 rotational temperature reached steady state (~190°C) quickly and held the value throughout the course of the experiment (40 min); correspondingly, other conditions within the OP cell remained stable (e.g., laser absorption, Rb density, PXe value, etc.). By raising the external cell temperature a mere ~30°C, the N2 rotational temperature climbed to ~730°C in less than 15 minutes of OP; a steep rise in HP 129Xe signal was also observed in the initial portion of the SEOP experiment. However, once the N2 rotational temperature peaks, both it and the PXe values begin to drop significantly. The N2 rotational temperature remains quite high (~530°C), but fluctuates greatly over the remainder of the experiment; the amount of absorbed laser light continues to increase for the remainder of the experiment. These occurrences likely indicate both Rb runaway as well as increased turbulence inside the OP cell. These results, showing the effects of slight external cell surface temperature changes on the SEOP efficiency, indicate that (under some experimental regimes) overall cell illumination can be more critical than the Rb/129Xe spin-exchange rate (which is often viewed as the most important parameter of SEOP).

In summary, this work expanded on the previous studies of Happer et al. [4] by examining a regime of high resonant laser power and xenon-dominant binary gas mixtures in the absence of

applications of hyperpolarized contrast agents.

256 Raman Spectroscopy and Applications

different gas loadings on the Rb absorption lineshape [6]).

Figure 5. (a) Plot of 129Xe NMR signal versus incident laser power for three Xe/N2 gas mixtures (values in Torr): 100/1900 (solid); 500/1500 (dotted); and 1500/500 (dashed). (b) Concurrent N2 rotational temperatures for the experiment in (a) (y-axis baseline set to Tcell). (c) Time course of 129Xe NMR signal recorded during SEOP performed at two different oven surface temperatures: 383 K (squares) and 413 K (circles) for a cell loading of 1500/500 Torr Xe/N2. (d) Concurrent N2 rotational temperatures for the experiment in (c). Upper limits of Tcell are shown as dotted (383 K) and dashed (413 K) lines [17].

#### 3.2. In-line superhead

In an attempt to overcome the limitations of the orthogonal Raman probe arrangement, a confocal approach was taken whereby scattered photons were detected in the same plane as probe laser photon emission. To realize this, the same 532 nm probe laser and Horiba Jobin-Yvon U1000 double 1-m Raman spectrometer (from Section 3.1) were fiber-coupled instead to an on-axis optical module. This design greatly improved the sensitivity and reliability of the measurements due to the significantly reduced chance of misalignment relative to the orthogonal arrangement. Two ultra-narrowband VHG notch filters were used to discard the vast majority of dominant Rayleigh scattered light, allowing resolution of both Stokes and anti-Stokes ultra-low frequency Raman lines as close as 10 cm−<sup>1</sup> to the probe laser wavelength. Rayleigh scattered light was further reduced by an order of magnitude through the inclusion of an ultra-narrow-band beamsplitter filter, which also facilitated the minimization of spontaneous laser diode emissions and fluorescence, thus greatly improving the spectra of the incoming probe photons [19]. Additionally, the entire configuration is mounted on a translational x-axis stage, allowing different positions within the optical cell to be probed independently. Schematics of the inline configuration are shown in Figure 6, along with a typical Raman spectrum and temperature calibration plot to illustrate the improvements in sensitivity.

Figure 6. (a) Schematic representation of in-line Raman module. (b) Example N2 rotational Raman spectrum (baselinecorrected) at room temperature, without SEOP (3 atm N2). The inset shows a close-up of the ultra-low frequency region that is spectrally resolvable using the in-line apparatus. (c) Photograph of in-line Raman module. The inline module is mounted onto a translational stage to allow three-dimensional mapping of TN2 within the cell. (d) Plot of oven temperature (Tcell) measured via thermocouple (located in the oven inlet airstream) versus TN2 measured via Raman spectroscopy; experimental data (triangles) are shown in comparison with simulation assuming 1:1 correlation (line); error bars are least-squares fit errors of Bhc/kT plots [19].

A comparison of Raman spectra acquired using the orthogonal and in-line methods was made under identical conditions at room temperature, with no pump laser illumination and over a 15 s integration time in an optical cell containing 100/1900 Torr Xe/N2. The results of this experiment are shown in Figure 7, indicating a ~23-fold improvement in SNR [19], facilitating much more accurate determination of temperature. It can be seen from the spectra that additional Raman signals arise from atmospheric N2 and O2 along the optical path of the probe laser external to the optical cell. In later studies, these contributions to the Raman spectrum were mitigated by collection of spectra from an evacuated optical cell, which were subsequently subtracted from the data to remove "background" signals. Care must be taken during this correction process, however, as spectral drift can result in unrealistic difference spectra and less precise temperature measurements.

3.2. In-line superhead

258 Raman Spectroscopy and Applications

least-squares fit errors of Bhc/kT plots [19].

In an attempt to overcome the limitations of the orthogonal Raman probe arrangement, a confocal approach was taken whereby scattered photons were detected in the same plane as probe laser photon emission. To realize this, the same 532 nm probe laser and Horiba Jobin-Yvon U1000 double 1-m Raman spectrometer (from Section 3.1) were fiber-coupled instead to an on-axis optical module. This design greatly improved the sensitivity and reliability of the measurements due to the significantly reduced chance of misalignment relative to the orthogonal arrangement. Two ultra-narrowband VHG notch filters were used to discard the vast majority of dominant Rayleigh scattered light, allowing resolution of both Stokes and anti-Stokes ultra-low frequency Raman lines as close as 10 cm−<sup>1</sup> to the probe laser wavelength. Rayleigh scattered light was further reduced by an order of magnitude through the inclusion of an ultra-narrow-band beamsplitter filter, which also facilitated the minimization of spontaneous laser diode emissions and fluorescence, thus greatly improving the spectra of the incoming probe photons [19]. Additionally, the entire configuration is mounted on a translational x-axis stage, allowing different positions within the optical cell to be probed independently. Schematics of the inline configuration are shown in Figure 6, along with a typical Raman

spectrum and temperature calibration plot to illustrate the improvements in sensitivity.

Figure 6. (a) Schematic representation of in-line Raman module. (b) Example N2 rotational Raman spectrum (baselinecorrected) at room temperature, without SEOP (3 atm N2). The inset shows a close-up of the ultra-low frequency region that is spectrally resolvable using the in-line apparatus. (c) Photograph of in-line Raman module. The inline module is mounted onto a translational stage to allow three-dimensional mapping of TN2 within the cell. (d) Plot of oven temperature (Tcell) measured via thermocouple (located in the oven inlet airstream) versus TN2 measured via Raman spectroscopy; experimental data (triangles) are shown in comparison with simulation assuming 1:1 correlation (line); error bars are

Figure 7. Comparison of typical rotational Raman spectra from N2 gas at 24°C using the 'orthogonal' detection system (a) or the 'inline' module (b). Spectra were obtained under identical conditions (OP cell containing 100/1900 Torr Xe/N2, 15 s acquisition time, no pump laser illumination), and indicate a SNR improvement of ~23-fold when using the in-line apparatus [19].

As an initial demonstration of temperature determination in situ during SEOP, the effects of cell heating due to the pump laser were investigated by comparing the TN2 spatial profile along the z-axis after 5 min of pump laser illumination at 60 W, for both a frequencynarrowed and broadband laser diode array. The gas mixture was an identical 100/1900 Torr Xe/N2 mixture, while the temperature at the inlet to the external forced air oven was 150°C. Measurements were taken across the optical cell at intervals of 1 mm transverse to the pump laser beam, at an x-position 21 mm behind the front window. The resulting Raman spectra were analyzed to calculate TN2 across the width of the cell. It was observed that for both pump laser sources, temperatures were elevated relative to thermocouple readings in the external forced air oven; by roughly 40°C in the case of broadband pump laser illumination, but by as much as 200°C when using the frequency-narrowed pump laser. This can be explained by a greater proportion of photons from the frequency-narrowed pump laser possessing the energy required to induce an energy level transition within the alkali metal electrons. The higher number of polarized electrons directly leads to an increase in the amount of energy imparted to the rovibrational states of N2 as a result of quenching collisions. The results of this experiment are shown in Figure 8 along with spectral profiles of the two different lasers used.

Figure 8. (a) Plots showing the spatial variation of the steady-state values of TN2 during SEOP, as induced by the 'pump' LDAs [acquired after 5 min of illumination by either a 60 W broadband (red squares) or 60 W VHG-narrowed LDA (black circles)]. Plots are compared to the temperature of the external glass wall near the front of the cell, as measured with a thermocouple (dotted line). (b) Schematic representation detailing the collection of TN2 data; values for TN2 were measured in 1-mm increments by translating the focused spot horizontally across the cross-section of the cell, transverse to the pump beam. (c, d) Spectral profiles of the VHG-narrowed and broadband LDAs, respectively; FWHM = 0.26 and 2.13 nm [19].

## 4. Current work and future directions

Since demonstrating its utility and improved performance, the in-line Raman module has become central to our current work: a series of experiments that provide greater insight into xenon-rich stopped-flow SEOP. So far, these experiments have examined SEOP as a function of (1) buffer gas, in which the ratio of N2 to He was varied; (2) position within the optical cell, in which the portable nature of the in-line Raman module was harnessed to probe in-cell temperatures at multiple points along the length of the optical cell; and (3) alkali metal ratio (the socalled hybrid SEOP), in which pure Rb SEOP was compared to SEOP with Cs also present in the optical cell in varying amounts. The rationale, results, and implications of these experiments are described in the following sections.

#### 4.1. Function of buffer gas/mixture composition

4. Current work and future directions

2.13 nm [19].

260 Raman Spectroscopy and Applications

ments are described in the following sections.

Since demonstrating its utility and improved performance, the in-line Raman module has become central to our current work: a series of experiments that provide greater insight into xenon-rich stopped-flow SEOP. So far, these experiments have examined SEOP as a function of (1) buffer gas, in which the ratio of N2 to He was varied; (2) position within the optical cell, in which the portable nature of the in-line Raman module was harnessed to probe in-cell temperatures at multiple points along the length of the optical cell; and (3) alkali metal ratio (the socalled hybrid SEOP), in which pure Rb SEOP was compared to SEOP with Cs also present in the optical cell in varying amounts. The rationale, results, and implications of these experi-

Figure 8. (a) Plots showing the spatial variation of the steady-state values of TN2 during SEOP, as induced by the 'pump' LDAs [acquired after 5 min of illumination by either a 60 W broadband (red squares) or 60 W VHG-narrowed LDA (black circles)]. Plots are compared to the temperature of the external glass wall near the front of the cell, as measured with a thermocouple (dotted line). (b) Schematic representation detailing the collection of TN2 data; values for TN2 were measured in 1-mm increments by translating the focused spot horizontally across the cross-section of the cell, transverse to the pump beam. (c, d) Spectral profiles of the VHG-narrowed and broadband LDAs, respectively; FWHM = 0.26 and There are two primary buffer gases that are typically utilized in SEOP experiments—N2 and He. N2 is used to perform radiation trapping, quenching the emission of resonant unpolarized photons by excited alkali metal atoms that would otherwise depolarize other Rb atoms. He meanwhile was originally added in high fractions to collisionally broaden the absorption line of the alkali metal to more optimally couple the incident laser line [20], a job to which it was well suited due to its low Rb spin-destruction rate—see Table 1. N2 also provides pressure-broadening effects, albeit at the cost of increased spin-destruction. This practice was necessary because the pump laser linewidths were initially at least an order of magnitude wider than the Rb D1 transition line, resulting in inefficient optical pumping. Although the role of He for pressure-broadening has become increasingly redundant as pump laser linewidths narrow to approach the Rb linewidth, its high thermal conductivity relative to N2 and Xe is important to note. In the emerging regime of 129Xe-rich stoppedflow SEOP, where both the poor thermal conductivity of the Xe and longer gas residence time in the cell compound thermal runaway issues, He may be uniquely situated to facilitate the dissipation of thermal energy from the optical cell, ultimately improving yields of polarized 129Xe.


Table 1. Thermal conductivities and spin destruction rates for Xe and N2/He buffer gases used in the SEOP hyperpolarization process [21].

The impact of He on the thermal behavior within the optical cell can be seen in Figure 9. Here, three SEOP experiments are compared in which the partial pressure of Xe and the total cell pressure were held constant at 100 Torr and 2000 Torr, respectively, but increasing amounts of He gas were substituted in place of N2. As the fraction of He within the cell was increased it can be seen that TN2 is reduced from roughly 200°C with no He present, to 100°C with 1400 Torr He included in the mixture. The onset of Rb runaway is evident from the sharp spike in 129Xe polarization in the first mix, where the polarization initially climbs sharply, peaking abruptly at ~6 min before dropping. At this point the high Rb vapor density creates optical opacity that limits the polarization process. It can be seen that this effect is suppressed as more He is added to the mixture at little cost to the ultimate 129Xe polarization. Given that existing 129Xe-rich stoppedflow polarizers operate with substantially higher powered lasers, which only further exacerbate these thermal management issues, it may be that He becomes a valuable tool for optimization.

Figure 9. Comparison of SEOP as a function of buffer gas composition—(a), (c), and (e) show Xe polarization (red) and power absorbed (blue). (b), (d), and (f) show N2 Raman temperature (orange) and oven thermocouple temperature (green). Gas compositions were 100/1900 Torr Xe/N2 with no He (a, b), 100/1700 Torr Xe/N2 and 200 Torr He (c, d), and 100/500 Torr Xe/N2 and 1400 Torr He (e, f) [22].

#### 4.2. Position-dependent temperature mapping

The experiments that vary buffer gas density/composition indicate that polarization and temperature are likely to vary along the length of the cell, particularly under conditions of Rb runaway. Figure 10 illustrates how Raman measurements were taken at coincident locations to NMR measurements at the front, middle, and back of the optical cell (a) using the translational stage (b). Figure 11 shows the results of two experiments where this configuration was used. Both experiments were conducted on a gas mix of 1000/1000 Torr Xe/N2 but at oven temperatures of 120 and 130°C, respectively. At 120°C, the temperature at the front, middle, and back correspond well to the xenon polarizations, which are both highest at the back for the cell. However, it can be seen that a mere 10°C increase in oven temperature is enough to induce significant variation in TN2 along the length of the cell. Closer examination shows that after 4 min of pump laser illumination during SEOP, when the 129Xe polarization prematurely spikes, a switch in the Raman temperatures occurs–indicative of a change in the thermal flow patterns within the cell. This effect is likely caused by Rb runaway, a conclusion corroborated by the elevated pump laser light absorption, which indicates a spike in absorbers.

Figure 10. (a) Schematic representation showing in-line Raman module probe and NMR surface coil alignment at three positions within the optical pumping cell. (b) Photograph of in-line Raman module and NMR surface coils placed within the oven [23].

4.2. Position-dependent temperature mapping

100/500 Torr Xe/N2 and 1400 Torr He (e, f) [22].

262 Raman Spectroscopy and Applications

The experiments that vary buffer gas density/composition indicate that polarization and temperature are likely to vary along the length of the cell, particularly under conditions of Rb runaway. Figure 10 illustrates how Raman measurements were taken at coincident locations to NMR measurements at the front, middle, and back of the optical cell (a) using the translational stage (b). Figure 11 shows the results of two experiments where this configuration was used. Both experiments were conducted on a gas mix of 1000/1000 Torr Xe/N2 but at oven temperatures of 120 and 130°C, respectively. At 120°C, the temperature at the front, middle, and back correspond well to the xenon polarizations, which are both highest at the back for the cell.

Figure 9. Comparison of SEOP as a function of buffer gas composition—(a), (c), and (e) show Xe polarization (red) and power absorbed (blue). (b), (d), and (f) show N2 Raman temperature (orange) and oven thermocouple temperature (green). Gas compositions were 100/1900 Torr Xe/N2 with no He (a, b), 100/1700 Torr Xe/N2 and 200 Torr He (c, d), and

Figure 11. Comparison of Xe polarization build-up and TN2 Raman measurements during a 30-min SEOP experiment in an optical pumping cell containing 1000/1000 Torr Xe/N2 at 120°C (a, b) and 130°C (c, d). Line color is indicative of cell position as outlined in Figure 10(a). The shaded area in figures (a) and (c) represents the percentage of pump laser light absorbed [23].

These measurements as a function of position will be improved by introducing an automated translational stage that will permit more reliable positioning of the Raman probe relative to the cell with increased speed and precision. This will facilitate N2 temperature maps in two dimensions—both along the width and the length of the optical cell.

Figure 12. Rb-Cs hybrid SEOP. (a) 129Xe polarization build-up curves using pure Rb, 20Rb:1Cs, 10Rb:1Cs, 2Rb:1Cs. Solid colored symbols denote a premixing of the AMs before loading; empty symbols denote separate loading. (b), (d), and (f) show xenon polarizations for the front middle and back positions within the cell for pure Rb, 20Rb:1Cs, 10Rb:1Cs and (c), (e), and (g) show the corresponding Raman temperatures. Cell oven temperature was set to 140°C and the gas mixture was 100/1900 Torr Xe/N2 [24].

#### 4.3. Function of alkali metal ratio (Rb-Cs hybrid SEOP)

These measurements as a function of position will be improved by introducing an automated translational stage that will permit more reliable positioning of the Raman probe relative to the cell with increased speed and precision. This will facilitate N2 temperature

Figure 12. Rb-Cs hybrid SEOP. (a) 129Xe polarization build-up curves using pure Rb, 20Rb:1Cs, 10Rb:1Cs, 2Rb:1Cs. Solid colored symbols denote a premixing of the AMs before loading; empty symbols denote separate loading. (b), (d), and (f) show xenon polarizations for the front middle and back positions within the cell for pure Rb, 20Rb:1Cs, 10Rb:1Cs and (c), (e), and (g) show the corresponding Raman temperatures. Cell oven temperature was set to 140°C and the gas mixture

was 100/1900 Torr Xe/N2 [24].

264 Raman Spectroscopy and Applications

maps in two dimensions—both along the width and the length of the optical cell.

Rubidium has long been the alkali metal of choice for SEOP, owing to its large absorption cross-section and the availability of affordable, high-powered lasers that are well matched to its D1 transition line. Additionally, Rb is solid at room temperature, with a low melting point that facilitates easy storage and transfer into optical cells. However, it has been shown that cesium can produce greater polarization under similar experimental conditions [25], but comparably high-powered lasers at the Cs D1 transition wavelength are not commonplace. Alternatively, for <sup>3</sup> He hyperpolarization by SEOP, it was shown that using two alkali metals simultaneously—rubidium and potassium—resulted in four times faster build-up of net spin polarization once the optimal ratio of the alkali metals had been achieved [26]. In this example it was Rb that underwent optical pumping, with angular momentum transferred to He by two distinct spin-exchange routes; one directly from Rb to He, and from Rb to He via K. The reason for the increase in speed is that the exchange cross sections for Rb-K and K-He are both larger than those for Rb-He alone. Inspired by these findings, we conducted analogous experiments in an Rb-Cs SEOP system to hyperpolarize 129Xe. The SE cross-sections for Rb-Cs and Cs-Xe have been shown to be greater than for Rb-Xe in separate experiments [27, 28]. If successful, the performance of existing polarizers could be improved with the simple addition of Cs to the existing Rb within the optical cell. As with previous studies, a 60 W pump laser tuned to the Rb D1 transition wavelength was used for polarization.

Figure 12(a) shows a summary of major hybrid results to date. From this figure it can be seen that, contrary to that suggested by the SE cross-sections, the resulting 129Xe polarization in our initial efforts decreases as more Cs is added to the alkali metal hybrid mixture. The data in Figure 12(b–g) can be used to explain this observation, indicating that 129Xe polarization and TN2 actually decrease with increasing Cs fraction. The latter is indicative of decreasing rates of optical pumping, likely caused by a suppression of the Rb vapor by a dominant Cs vapor. Indeed, the intrinsic vapor pressure of Cs is higher than that of rubidium due to its lower boiling point, a relation that is reversed in the analogous K-Rb system for <sup>3</sup> He hyperpolarization. Thus, our Rb-Cs hybrid experiments to date indicate that the addition of Cs to the standard Rb-129Xe SEOP method serves only to suppress the 129Xe polarization. However, considering only a small number of different Rb-Cs ratios and conditions have been investigated, future studies on leaner Cs mixtures, where the Rb vapor density is not suppressed to such an extent, may yet yield a more favorable outcome.
