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Assessment of repeatability of imaging inhaled hyperpolarized xenon-129 in the human brain
Madhwesha Rao1, Graham Norquay1, and Jim Wild1

1University Of Sheffield, Sheffield, United Kingdom

Synopsis

This study assesses the repeatability of image quality of inhaled hyperpolarized 129Xe brain MRI by assessing the signal-to-noise ratio of 129Xe brain images for five healthy subjects. A maximum signal-to-noise ratio of 18.8 ±6.1 and mean signal-to-noise ratio of 12.1 ±3.8 was observed over the five volunteers. An intra-subject variability between ±6 % and ±30 %, and inter-subject variability of ±30 % was observed. By using an optimized polarizer, RF coil and pulse sequence as in this study, we believe the signal-to-noise ratio is sufficiently reproducible for further clinical evaluation.

Introduction

Recent studies have shown the feasibility of MR imaging of inhaled hyperpolarized (HP) 129Xe in the human brain in vivo1,2. Demonstrations of dynamic uptake and image contrast of HP 129Xe brain MRI in pilot studies in Alzheimer’s diseases3 and stroke4 encourage the clinical evaluation of the method. However, a major challenge in HP 129Xe brain MRI is the achievable signal-to-noise ratio (SNR)2. Unlike the imaging protocols followed for pre-clinical studies5-8, where the animals underwent continuous breathing of HP 129Xe using respiratory apparatus, imaging HP 129Xe in the human brain is typically restricted to a 1 L gas dose followed by breath-hold of 24 s2 or less due the anesthetic properties of xenon9,10. In order to establish protocols for clinical evaluation of HP 129Xe brain MRI, it is necessary to assess the repeatability of the method and the consistency of the achievable SNR. This study assesses the intra-subject and inter-subject repeatability of HP 129Xe brain MRI for 5 healthy volunteers.

Methods

Five healthy male volunteers (age 26, 28, 32, 35 and 36 years) were imaged on a 1.5 T GE HDx scanner. Informed written consent was obtained from all the volunteers. Imaging for each of the volunteers was repeated three times on different days, over the span of four weeks. The xenon gas dose for each of the imaging session was 1 L (± 5%). The xenon gas dose was polarized to approximately 30% polarization using a high-yield spin exchange optical pumping polarizer11.

MR imaging was performed with a 4 channel receiver RF coil2. Imaging parameters were: 2D spoiled gradient echo pulse sequence; center frequency = 17660720 Hz (196 ppm, centered on gray matter1); TE 1.7 ms; TR 34 ms; flip angle 12.5°; bandwidth 4 kHz; field of view 24 cm; slice thickness 50 mm and the acquisition matrix size of 32 x 32 was reconstructed to 64 x 64. Three images were acquired at 8, 16 and 24 s during the breath hold after the inhalation of the xenon gas dose and three additional images were acquired at 32, 40 and 48 s. The first four images were averaged. The average SNR was calculated as a ratio of average of the whole brain to $$$\sqrt{2}$$$ times the standard deviation of the background noise. Similarly, the maximum SNR was calculated considering the pixel with maximum intensity.

Results

The averaged images from three MR imaging sessions from all the five subjects are shown in Figure 1, and the achievable SNR and variability is provided in Table 1. Over the 5 volunteers, the maximum SNR of 18.8 ± 6.1 and mean SNR of 12.1 ± 3.8 was achievable. The average intra-subject variability of mean SNR was ± 20.4 %.

Discussion

The SNR achieved is a function of several factors; (a) polarization of the 129Xe gas, which is at the optimal performance for this application11, (b) sensitivity of the receiver RF coil array, which is optimized in terms of quality factor12 and filling factor2,13, (c) the pulse sequence design and (d) concentration of HP 129Xe in the brain tissue, which is limited here by the 1 L inhaled gas dose. Whilst small gains could be made with further optimization in (a-c) we believe the SNR achieved here at 1.5 T is near optimal level for the 129Xe inhaled dose used (d). Some additional opportunities to improve the SNR would be to investigate ultralow noise amplifiers or imaging at 3.0 T (or higher field) with high density RF coils.

Intra-subject variability (Table 1, ± 6 to 30 %) can be attributed to the environmental variables such as polarization on a particular day, quantity of xenon dose dispensed, T1 relaxation of HP 129Xe gas during the storage after being dispensed and before being administered, concentration of xenon in the lung due to lung inflation state and subject’s physiology (for example, reduced cerebral blood flow due to consumption of caffeine14). Inter-subject variability (Table 1, ± 28 %) can be attributed to variation in resting-state physiology such as lung volume, pulmonary blood volume, pulmonary mean transit time, arterial transit time, cerebral blood volume, cerebral mean transit time and permeability-surface area product of the blood-brain barrier.

Conclusion

This work establishes that the typical mean signal to noise ratio for imaging hyperpolarized 129Xe in the human brain is 12 and typical maximum value is 18 respectively, for a voxel size of 2.8 cm3. The repeatability of the method of ± 20.4 % warrants further investigation as a non-ionizing and injection free means to clinically assess brain tissue perfusion and gas exchange.

Acknowledgements

This work was funded by the Engineering and Physical Sciences Research Council (EPSRC - EP/D070252/1), National Institute for Health Research (NIHR - RP-R3-12-027) and Medical Research Council (MRC - MR/M008894/1).

References

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  11. Norquay G, Collier GJ, Rao M, Stewart NJ, Wild JM. 129Xe-Rb Spin-Exchange Optical Pumping with High Photon Efficiency. Physical Review Letters 2018;121(15):153201.
  12. Hayes CE, Edelstein WA, Schenck JF, Mueller OM, Eash M. An efficient, highly homogeneous radiofrequency coil for whole-body NMR imaging at 1.5 T. Journal of Magnetic Resonance (1969) 1985;63(3):622-628.
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Figures

Figure 1: Hyperpolarized 129Xe brain images from 5 healthy normal male volunteers. Number inset is the average SNR for the respective image.

Table 1: The achievable SNR (maximum and average) and variability for 5 healthy normal volunteers

Proc. Intl. Soc. Mag. Reson. Med. 27 (2019)
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