MR of hyperpolarized Xe-129 dissolved in the human brain at 1.5 T and 3.0 T
Madhwesha Rao1, Neil J Stewart1, Graham Norquay1, Paul D Griffiths1, and Jim M Wild1

1Academic unit of Radiology, University of Sheffield, Sheffield, United Kingdom

Synopsis

Xenon is an inert noble gas which can be safely inhaled. In the lungs, it diffuses into the bloodstream and is then transported to distal organs (brain, kidneys and liver). In this study, we have directly imaged the uptake of hyerpolarized 129Xe in the human brain in vivo. Thus demonstrated the feasibility as a safe and non-invasive contrast agent for functional imaging of the brain in diagnosing diseases related to cerebral perfusion such as brain ischemia. In addition, using tracer kinetic analysis we provide quantitative measurement for the intrinsic physiological characteristic of the blood brain barrier.

Purpose

Xenon when inhaled into the lungs, dissolves in the pulmonary bloodstream and is transported to distal organs (heart, brain, kidney and liver). Upon reaching the cerebral vasculature, xenon passively diffuses into the brain tissues. 129Xe exhibits a wide chemical-shift range, providing contrast for different compartments of the brain (grey-matter, white-matter, cerebrospinal fluid and blood)1-3. Exploiting these properties, we demonstrate the feasibility of using hyperpolarized 129Xe for in vivo evaluation of cerebral perfusion and, using tracer kinetic analysis, we enable quantitative measurement of the permeability of the blood-brain barrier.

Method

A bandpass RF birdcage coil (8-leg) tuned to 35.35 MHz (3.0 T 129Xe Larmor frequency) was constructed in-house with capacitors 220 pF on end-rings and 75 pF on legs. The RF coil for 1.5 T was as described previously4. MR of hyperpolarized 129Xe dissolved in the human head was performed at 1.5 T and 3.0 T on GE Signa HDx and Philips Ingenia systems respectively. 129Xe gas was hyperpolarized to ~25% by spin exchange optical pumping5.

High resolution spectroscopy of hyperpolarized 129Xe dissolved in the human head was performed under breath-hold, commencing 4 s after inhalation of a 1 L gas dose. Acquisition parameters for both 1.5 T and 3.0 T were; flip angle = 45°, centre frequency = 198 ppm downfield, receiver bandwidth = 136 ppm, spectral resolution = 0.033 ppm, number of spectra = 10 and TR = 2 s. Spectra were averaged without line broadening filters.

At 1.5 T, 3 sagittal 2D gradient-echo images of the human brain were acquired at 8 s, 16 s and 24 s after inhalation of 1 L xenon gas. Imaging parameters were; flip angle = 12°, centre frequency as above, TE = 1.7 ms, TR = 34 ms, bandwidth = 226 ppm, FOV = 22 cm, slice thickness = 50 mm, matrix = 32 x 32. Acquired images were averaged.

At 1.5 T, a “brain uptake saturation and recovery” (BUSAR) spectroscopy pulse sequence was developed to monitor the movement of hyperpolarized 129Xe between cerebral blood and grey-matter. The sequence, shown in Figure 1(a), was initialized by two 90° RF saturation pulses. Each FID in the time series was acquired after a time-gap of 4 s with a 90° RF pulse (pulse duration = 500 μs) followed by two 90° RF saturation pulses. By de-convolving the time course of signal from grey-matter with the input red blood cell signal, we arrive at the relative quantity of xenon transferred between these two compartments. The de-convolved signal was fitted with a custom-derived two-compartment tracer kinetic model shown in Figure 1(b). FE in the tracer kinetic model is the fraction of xenon atoms transferred from grey-matter to cerebral blood which estimates the permeability and surface area of the blood-brain barrier.

Results

A comparison of high resolution spectroscopy of hyperpolarized 129Xe dissolved in the human head at 1.5 T and 3.0 T is shown in Figure 2. Both the spectra exhibited similar features with 5 distinct peaks at 187 ppm, 192 ppm, 195 ppm, 199 ppm and 217 ppm associated with 129Xe dissolved in soft muscular tissue, white-matter, grey-matter, cerebrospinal/interstitial fluid and red blood cells1-4. The sagittal image of hyperpolarized 129Xe dissolved in the human brain is shown in Figure 3. A typical spectroscopic time series acquisition from the BUSAR sequence is shown in Figure 4(a). The time course of signal from grey-matter in Figure 4(c) was de-convolved with signal from red blood cells in Figure 4(d). The de-convolved signal was fitted with the tracer kinetic model as shown in Figure 4(b) using FE = 0.388. Which implies, 38.8% of xenon atoms dissolved in grey-matter is transferred to cerebral blood within time-interval TR = 4 s.

Discussion

Chemical shifts of the resonances observed in the high resolution spectra of 129Xe dissolved in the human head at both 1.5 T and 3.0 T are consistent with previous studies1-3, however this is the first time side-by-side comparison have been made in the same subject. The image of hyperpolarized 129Xe dissolved in the human brain indicates cerebral perfusion. The SNR of the image is limited by the quantity of 129Xe that is transported and diffused into the brain tissue before the polarization decays, but demonstrates the feasibility of direct brain imaging with inhaled xenon.

Conclusion

This is the first time the feasibility of using hyperpolarized 129Xe to estimate the intrinsic physiological characteristics of the blood-brain barrier such as permeability and surface area has been investigated. We have demonstrated the feasibility of imaging the human brain at both clinical field strengths with inhaled hyperpolarized 129Xe.

Acknowledgements

This work was funded by the Engineering and Physical Sciences Research Council (EPSRC), National Institute for health research (NIHR), Medical Research Council (MRC) and University of Sheffield Hyperpolarised Imaging Group - POLARIS. The views expressed in this abstract are those of the author and not necessarily those of EPSRC, NHS, NIHR, MRC or the Department of Health.

References

1. Kershaw J, Nakamura K, Kondoh Y, Wakai A, Suzuki N, Kanno I. Confirming the existence of five peaks in 129Xe rat head spectra. Magnetic Resonance in Medicine 2007;57(4):791-797.

2. Kilian W, Seifert F, Rinneberg H. Dynamic NMR Spectroscopy of Hyperpolarized 129Xe in Human Brain Analyzed by an Uptake Model. Magnetic Resonance in Medicine 2004;51(4):843-847

3. Nakamura K, Kondoh Y, Wakai A, Kershaw J, Wright D, Kanno I. 129Xe spectra from the heads of rats with and without ligation of the external carotid and pterygopalatine arteries. Magnetic Resonance in Medicine 2005;53(3):528-534.

4. Rao M, Stewart N, Norquay G, Griffiths P, Wild J. Imaging the human brain with dissolved xenon MRI at 1.5 T. Proc. Intl. Soc. Mag. Reson. Med. 23 (2015). P 1254.

5. Norquay, G. Parnell, S. R. Xu, X. Parra-Robles, J. Wild, J. M. Optimized production of hyperpolarized 129Xe at 2 bars for in vivo lung magnetic resonance imaging. JAP (113) 2013.

Figures

Figure 1: (a) Illustration of "brain uptake saturation and recovery" (BUSAR) pulse sequence and (b) Tracer kinetic model for infusion of 129Xe from cerebral blood to grey-matter.

Figure 2: Comparison of spectroscopy of hyperpolarized 129Xe dissolved in the human head at 1.5 T and 3.0 T.

Figure 3: A 2D sagittal image of hyperpolarized 129Xe dissolved in the human brain at 1.5 T.

Figure 4: Illustration of BUSAR sequence at 1.5 T. (a) A typical BUSAR acquisition, (b) De-convolved grey-matter time course signal fit with the derived tracer kinetic model, (c) Time course of signal from grey-matter and (d) Time course of signal from blood.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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