Preserving Hyperpolarization of 129 Xe for Transport Submitted by: Zach Zytner Project Supervisor: Dr. Giles Santyr Medical Biophysics 3970 Date:

Transcription

1 Preserving Hyperpolarization of 129 Xe for Transport Submitted by: Zach Zytner Project Supervisor: Dr. Giles Santyr Medical Biophysics 3970 Date: April 1, 2011

2 Introduction and Theory The effective use of lung imaging techniques is essential to diagnoses of disorders such as chronic obstructive pulmonary disease (COPD). Two prominent methods include x-ray computed tomography (x-ray CT) and magnetic resonance imaging (MRI). 1 Though both techniques have potential to provide adequate information, each has an inherent drawback. X- ray CT exposes patients to radiation; negative connotations associated with radiation may make patients apprehensive of the procedure. Typical MRI involves the magnetic spin of hydrogen nuclei and the atom s interaction with an external magnetic field. 2 Hydrogen nuclei align with the applied magnetic field, and an additional radiofrequency field perpendicular to it causes net magnetization tipping, creating a signal in a receiver coil. The signal is then used to construct an image of the region containing the protons. The disadvantage of lung MRI is that it often does not provide high-quality images. The lung is significantly devoid of water and therefore hydrogen atoms. 1 The lack of protons available to interact with external and radiofrequency fields translates to a decrease in signal. It is therefore beneficial to introduce hyperpolarized noble gases (HNG) as contrast agents when taking MR images of the lungs. Gases typically used include 3 He and 129 Xe, helium-3 and xenon-129. Hyperpolarization describes the high spin polarization attained by the nuclei outside of the MR system. 3 The gases are introduced into the lungs through ventilation, and the high spin nuclei allow for signal acquisition at comparable levels to orthodox proton MRI. Magnetic resonance imaging of the lung with HNG overcomes negative aspects of x-ray CT and proton MRI. However, maximum resolution of images is limited by the longitudinal relaxation time, T 1, of the hyperpolarized gas. 4 Simply put, the gases undergo decay of hyperpolarization over time. A large distance between the site of hyperpolarization and the MRI

3 system poses the problem that the HNG would no longer be effective for imaging once it is delivered. Hence, preserving hyperpolarization is essential and can be accomplished by applying a magnetic field to the HNG. 4 The main focus of this project is to examine the properties, including the T 1 value, of a transportation box for hyperpolarized gas. The outcome of the study will determine the viability of the box to preserve hyperpolarization specifically in 129 Xe, which was used throughout the project. Hyperpolarization of xenon is achieved through spin-exchange optical pumping. 5 This process involves the use of laser light and rubidium (Rb) vapour. The light is circularly polarized by quarter-wave plate, and it then excites the valence electrons of Rb atoms. The polarized rubidium electrons collide with xenon nuclei, and this interaction results in hyperpolarization of xenon. Figure 1 The transfer of energy from circularly polarized light to Rb electrons to Xe nuclei in an optical pumping cell. 5 Extraction of the hyperpolarized 129 Xe typically involves cooling of the gas mixture so that the Rb vapour condenses. 4 The xenon gas can then be collected, though its hyperpolarization will rapidly decay if an external magnetic field is not immediately applied. A transportation box

4 for HNG preserves the hyperpolarization; it is more effective if the gas is placed inside directly following the spin-exchange process. Figure 2 The transportation box for maintenance of hyperpolarization contains a battery supplying current to a solenoid coil. The model of HNG transportation box used in the project includes a 12V nickel metal hydride (NiMH) battery as a power source, found at the bottom of the box. The battery applies a current to a solenoid coil located on the left side of the box, in terms of the orientation shown by Figure 2. The current results in a vertical magnetic field through the middle of the coil, as described by Ampere s Law (Equation 1). 6 [1] Ampere s Law shows that the magnetic field through the coil (B) is directly proportional to the applied current (I enc ). The maximum current that can be applied by the battery is approximately 1650 milliamperes (ma), which corresponds to a maximum magnetic field of

5 36.5 Gauss (G) or 3.65 millitesla (mt). The magnitude of the current applied by the battery to the coil can be controlled by an adjustment knob located on the right side of the box s face. The current display is directly above the knob. The purpose of this project was to examine the transportation box s absolute potential for maintaining hyperpolarization of xenon. Therefore, the maximum current possible was always applied to the coil. However, the current of the box decreases as it loses its charge, so the maxima of 1650 ma and 36.5 G decrease as the power supply is constantly maintained. The longitudinal relaxation time of the box (T 1 ) describes its ultimate utility in transporting hyperpolarized 129 Xe. Signal data from the HNG can be used to calculate T 1 by Equation 2. [2] The variable S 0 describes the signal acquired from the hyperpolarized 129 Xe gas immediately after it was extracted from the spin-exchange system. The variable S is the signal acquired from the xenon after a time interval t that the gas has been mounted within the magnetic field of the box s solenoid coil. Equation 2 shows that large T 1 values are the result of a high degree of hyperpolarization maintenance. Additionally, Equation 2 shows that the attainment of signal data is essential to the calculation of T 1. A polarimetry station can be used to obtain that data from a sample of hyperpolarized xenon. The station includes a large Helmholtz coil, which applies a magnetic field of G to a xenon sample placed inside. 7 The sample is placed on a radiofrequency coil on the station s surface, and it is through this coil that signal data is acquired. Signal magnitude describes the amount of hyperpolarization present in a sample at an instant.

6 Figure 3 The polarimetry station includes arching Helmholtz coils providing a magnetic field and a radiofrequency coil located underneath the sample stage on its bottom surface. A pulse frequency is sent from the radiofrequency coil to the nuclei of the hyperpolarized xenon gas sample, and a response frequency is sent back. In order for the polarimetry software to display accurate signal data, these frequencies must be within proper resonance. A difference in the frequencies greater than 50 Hz results in erroneous signals yielded by the software, skewing T 1 values. 7 Figure 4 A screenshot of the Polarimetry v.4.1 software shows a frequency difference of 40 Hz, resulting in accurate output signal data. In all, the processes of spin-exchange optical pumping, polarimetry and the

7 understanding of longitudinal relaxation time provide knowledge to determine the viability of the transportation box for hyperpolarized noble gases. Methods Before working with any 129 Xe gas, the properties of the transportation box were explored. The relationship between the box s magnetic field, current and time provided necessary information such as the battery s required charging time to apply maximum current. A Gaussmeter was used to measure the magnetic field through the solenoid coil. Figure 5 The box s magnetic field in G versus its current in ma. The linear relationship shown is predicted by Ampere s Law. Figure 5 shows that the maximum current of 1650mA approximately corresponds to the maximum magnetic field in the box s coil of 36.5G by a trend line. The magnetic field through the coil over time was also observed for different charging periods. Figure 6 shows those observations, which were necessary to ensure the box could maintain a strong enough field to

8 maintain 129 Xe hyperpolarization. Figure 6 The box s magnetic field versus time after two different charging periods. A charge of 120 hours was adequate to maintain proper magnetic field, but an 18-hour charge was not. Figure 6 shows that the NiMH battery required significant amount of charging time in order for the box to operate at its maximum utility. Once the box s properties were determined, hyperpolarized 129 Xe was obtained in a 90mL bag via spin-exchange optical pumping, as described earlier. Initial signal data for the 90mL sample was acquired at the polarimetry station, and the bag was placed into the magnetic field of the transportation box for two hours. The sample was removed every 30 minutes to obtain further signal data at the polarimetry station as hyperpolarization decayed. Polarimetry v.4.1 software was used to obtain signal data. Approximately 8000 signal data points over duration of 20 milliseconds were acquired at each time interval. Three methods of determining the signal value at each time interval were then used. Firstly, the software provided a trend line on the graph of signal data acquired over each 20ms time frame. Signal

9 values at the beginning of each time frame (0ms) as per the software trend lines were used to calculate T 1 values. Another method included applying a trend line against each set of signal data in Excel. Those trend lines yielded slightly different signal values from the polarimetry software at the beginning of each time frame. The final method involved simply using the maximum signal value over the entire 20ms time frame as the data point for that 30-minute interval. The three methods yielded three different T 1 values for the transportation box. Results Figure 7 shows the signal of the 129 Xe sample at 2 minutes after the gas was collected (2 minutes were needed to take the sample from the 129 Xe polarizer to the polarimetry station). The trend line applied by the software is shown in yellow; it corresponds to a signal value of 42mV. Figure 7 Response signal in millivolts vs. time at the 2 minute interval from polarimetry software

10 Figure 8 shows the same signal data as Figure 7, except that the negative signal values have been filtered out to apply a trend line. The Excel trend line corresponds to a signal value of mV (the line s intercept) at the 2 minute interval. Figure 8 Excel graph of response signal vs. time at the 2 minute interval Figure 9 shows the signal of the hyperpolarized xenon sample at the 122-minute interval. The yellow trend line shows a signal value of 2mV at the beginning of the 20ms time frame. 122 mins Figure 9 Signal vs. time at the 122 minute interval from polarimetry software

11 Figure 10 shows the same signal data as Figure 9, but the negative signal data has once again been filtered out in order to apply a trend line. The trend line corresponds to a signal of mV at the beginning of the signal acquisition time frame. Figure 10 Excel graph of signal versus time at the 122 minute interval Table 1 shows a complete summary of the signal data acquired at each time interval for the three different methods. The data was also extrapolated back to time at 0 minutes in order to account for initial slight decay, and to receive the most accurate S 0 values. The signal data at the time interval t of 122 minutes were used as the S values for all methods. All T 1 values were then calculated using Equation 2.

12 Table 1 The complete summary of signal values for each method of T 1 measurement at each time interval. The maximum signals of 57.9mV at t = 2 and 22.4mV at t = 122 can also be seen in Figures 7-10 as the uppermost points on each graph. Discussion Before commenting on the transportation box s absolute capability to preserve hyperpolarization in 129 Xe, the accuracy of the T 1 values must be considered. There is a 218% increase in T 1 from the lowest result to the highest, indicating that one of the methods is not entirely reliable. The purpose of applying and using trend lines to obtain data is to observe the overall trend of signal acquisition over 20ms. The ideal signal used to calculate T 1 from Equation 2 is at the start of that short time frame; Figure 9 in particular shows variation in the signal data over 20ms due to the polarimetry station s inherent frequency. The use of absolute signal maxima to calculate T 1 is not an accurate practice because this method includes noise in signal data. Subtracting the noise from the signal is not a simple exercise and requires complicated processing. Using trend lines to estimate the signal is a much easier way to obtain approximate

13 T 1 values. It is clear that the T 1 value of 127 minutes is a large overestimate because it does not consider the noise included in the signal data at all. Therefore, the T 1 value for the transportation box is between 40 and 75 minutes. The box could likely maintain hyperpolarization of 129 Xe if it is used to transport the gas for less than an hour. Longitudinal relaxation times increase when a magnetic field of greater magnitude is applied to the HNG. For example, a T 1 of up to 3 hours is exhibited when a 1.5 T magnetic field is applied to hyperpolarized 129 Xe. 4 The maximum magnetic field of 3.65 mt through the box s solenoid coil is considerably less than that value. Therefore, a T 1 value for the box of less than an hour is intuitive. The power source of the transportation box is questionable. The battery needed a charge of more than a day to exhibit a useful magnetic field for a long period of time. In a situation where a portable power source is available, the battery s charging time is irrelevant to the box s ability to preserve hyperpolarization. However, when considering the box as stand-alone technology, a proper battery with decreased charging time would increase its effectiveness. Conclusions and Future Work The transportation box for HNG is capable of maintaining hyperpolarization of 129 Xe for travel times less than an hour. Signal noise at the polarimetry station must be considered when calculating the longitudinal relaxation time T 1. Relevant future work includes the exploration of alternate power sources for the box. A battery with shorter charging time is recommended. Additionally, the exploration of power sources that supply stronger current to the solenoid coil is a relevant area of study. An increase

14 in current results in increased magnetic field; the effect on the box s T 1 could be explored. The effects of alternate solenoid coil size on T 1 could also be examined. Acknowledgements Thanks go to Dr. Giles Santyr, Adam Farag and the rest of the Santyr research group for their support and feedback throughout my project.

15 References 1. Hoffman EA, Clough AV, Christensen GE, Lin C. The Comprehensive Imaging-Based Analysis of the Lung. Acad Radiol. 2004; 11: Faulkner, Wm. Basic Principles of MRI. Outsource Inc Kraayvanger, R. Measurements of Alveolar Oxygen Partial Pressure and Apparent Diffusion Coefficient of Hyperpolarized Gas in Rat Lung at 74 mt. The University of Western Ontario Zhao L, Mulkern R, Tseng CH, Williamson D, Patz S. Gradient-Echo Imaging Considerations for Hyperpolarized 129 Xe MR. J Magn Reson B. 1996; 113: Whiting N, Nikolaou P, Eschmann NA, Goodson BM, Barlow MJ. Interdependence of in-cell xenon density and temperature during Rb/ 129 Xe spin-exchange optical pumping using VHG-narrowed laser diode arrays. J Magn Reson. 2011; 208: Lowther DA, Freeman EM. The application of the research work of James Clerk Maxwell in electromagnetics to industrial frequency problems. Philos Transact A Math Phys Eng Sci. 2008; 366(1871): Farag A. Preliminary tests and results for basement polarimetry station. Robarts Research Institute