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Investigating gas-exchange and tissue perfusion in the human brain using a combination of proton and hyperpolarized xenon-129 MRI
Madhwesha Rao1, Graham Norquay1, and Jim Wild1

1University Of Sheffield, Sheffield, United Kingdom

Synopsis

This study establishes a correlation between cerebral perfusion and gas uptake using 1H arterial spin labeling and T2 weighted imaging for cerebral blood perfusion, and inhaled hyperpolarized 129Xe brain MR imaging for cerebral uptake of a free-diffusible noble gas. Using arterial transit time and cerebral blood volume maps, along with xenon images, correlation coefficients between 0.34 and 0.63 was observed for healthy subjects between the ages 26 and 36 years. The distinct properties of water and noble gas opens up the opportunity to use them in conjunction to understand aspects of brain physiology.

Introduction

Human brain perfusion can be quantified in terms of arterial transit time (ATT), cerebral blood flow (CBF) and arterial cerebral blood volume (CBV) using a set of 1H arterial spin labelling (ASL) difference images acquired at various post labelling delay (PLD) times, representing the underlying dynamics of water molecules within the blood vessels1-6. Recent studies have demonstrated hyperpolarized (HP) 129Xe MRI in the human brain using inhaled gas7,8. Due to its passive nature8, xenon gas uptake in cerebral tissue is by diffusive gas-exchange from the capillaries to brain tissue; in addition, the MR signal is sensitive to residency time and oxygenation of arterial blood9-11. Using images obtained with 1H ASL and T2 weighted (T2W) MRI, this work establishes correlations between cerebral perfusion and gas-exchange/uptake observed with hyperpolarized 129Xe brain MRI in the human brain.

Methods

Five healthy male volunteers (age 26, 28, 32, 35 and 36 years) were imaged on a 3.0 T Philips Ingenia scanner for 1H ASL and T2W MRI and then on a 1.5 T GE HDx scanner for HP 129Xe brain MRI, after obtaining informed written consent. 1 L of xenon gas dose was polarized to 30% polarization using a high-yield spin exchange optical pumping polarizer12.

HP 129Xe brain images were acquired with the imaging parameters as described in8, with field of view 24 cm and slice thickness 50 mm. Three sets of pulsed continuous ASL difference images were acquired with PLD times of 1225, 1525 and 1825 ms. Other imaging parameters were identical; Gradient echo EPI, field of view 24 cm, slice thickness 7 mm, flip angle 40°, TE=14 ms, TR=4.25 s and labeling duration 1650 ms. ATT (ms), CBF (mL per minute per 100 g of tissue) and CBV (mL per 100 g of tissue) maps were generated as descried in literature1-6. T2W images were acquired with spin echo, TE=80 ms, TR=3 s, flip angle 90° and with same voxel grid as the ASL. Partial volume of gray matter (PGM) was estimated using T2W images13,14. Arterial cerebral blood volume for gray matter (CBVGM, mL per 100 g of gray matter) was estimated using CBV and PGM. In order to spatially correlate 1H MRI based model of cerebral xenon perfusion (xenon perfusion model) with the acquired HP 129Xe brain MRI, CBVGM map was weighted for regional depolarization that HP 129Xe would experience during its transit in the blood using ATT map and T1 relaxation of HP 129Xe in arterial blood (7 s9,11) and gray matter (GM) (16 s15). 7 continuous slices of the same anatomical location as 129Xe MRI were summed for effective thickness of 49 mm. The intensity of pixels in the xenon perfusion model was spatially correlated with that of 129Xe MRI.

Results

Images obtained from 1H ASL and T2W MRI, and the derived maps of ATT, CBF, CBV, PGM and CBVGM for 26 year old volunteer for a representative slice is shown in Figure 1. A schematic of the steps involved in deriving a xenon perfusion model is shown in Figure 2. The 129Xe brain MRI from all volunteers are shown in Figure 3 and 4. Correlation between 129Xe MRI and the xenon perfusion model for the 26 year old volunteer is shown in Figure 4, and indicates a voxel-wise correlation coefficient of 0.53. The correlation coefficients for volunteers 36, 35, 32 and 28 years old were 0.44, 0.63, 0.43 and 0.34 respectively.

Discussion

The correlation obtained is moderate with the correlation coefficient between 0.34 and 0.63, and can be attributed to:

  1. Xenon perfusion model based on 1H images is a manifestation of blood perfusion and uptake of water in the GM, whereas a 129Xe brain MR image is a manifestation of delivery and uptake of a free-diffusible noble gas which passively crosses the blood-brain barrier.
  2. Xenon perfusion model inherits uncertainty from ASL1-6, image segmentation13,14, image registration, signal-to-noise ratio and assumptions such as blood-brain water partition coefficient (0.9)16, T1 relaxation of 1H in blood at 3.0 T (1650 ms)17, T1 relaxation of 1H in GM at 3.0 T (1550 ms)18, T1 relaxation of 129Xe in arterial blood9,11, T1 relaxation of 129Xe in GM15, labelling efficiency (0.85)19 and weighted delay4.
  3. Although 129Xe image is heavily weighted towards well-perfused GM8, there is appreciable uptake in the white matter as well7, which is neglected in the xenon perfusion model.

Conclusion

This work establishes spatial correlations between ASL maps of water-uptake and maps of 129Xe gas-uptake in the human brain, and opens up the opportunity to use them together to understand aspects of brain physiology such as blood-brain barrier 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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  2. Buxton RB, Frank LR, Wong EC, Siewert B, Warach S, Edelman RR. A general kinetic model for quantitative perfusion imaging with arterial spin labeling. Magn Reson Med 1998;40(3):383-396.
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  15. 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.
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Figures

Figure 1: Images obtained from 1H ASL and T2 weighted MRI, and derivation of arterial transit time, cerebral blood flow, arterial cerebral blood volume, partial volume for gray matter and arterial cerebral blood volume for gray matter maps for 26 year old volunteer for a particular slice, imaged at 3.0 T.

Figure 2: Derivation of 1H MRI based model of cerebral xenon perfusion (xenon perfusion model) from arterial cerebral blood volume for gray matter to correlate with hyperpolarized 129Xe brain image, considering the depolarization that hyperpolarized 129Xe would experience during its transit in the blood by using arterial transit time map, T1 decay of hyperpolarized 129Xe in arterial blood of 7 s9,11 and T1 decay of hyperpolarized 129Xe in gray matter of 16 s15.

Figure 3: HP 129Xe brain images obtained with healthy male volunteers aged 36, 35, 32 and 28 years, imaged at 1.5 T. Inserts are the respective xenon perfusion model maps.

Figure 4: (a) Image of summation of 7 continuous slices of xenon perfusion model at the same anatomical location as HP 129Xe brain image to obtain an effective slice thickness of 49 mm and (b) image of HP 129Xe brain image with the slice thickness of 50 mm. (c) Voxel-wise correlation between the xenon perfusion model and HP 129Xe brain image. Volunteer: 26 year old.

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