Measuring 129Xe transfer across the blood‐brain barrier using MR spectroscopy

link to paper

Measuring 129Xe transfer across the blood‐brain barrier using MR spectroscopy

Madhwesha R. Rao, Graham Norquay, Neil J. Stewart, Jim M. Wild

Abstract

Purpose

This study develops a tracer kinetic model of xenon uptake in the human brain to determine the transfer rate of inhaled hyperpolarized 129Xe from cerebral blood to gray matter that accounts for the effects of cerebral physiology, perfusion and magnetization dynamics. The 129Xe transfer rate is expressed using a tracer transfer coefficient, which estimates the quantity of hyperpolarized 129Xe dissolved in cerebral blood under exchange with depolarized 129Xe dissolved in gray matter under equilibrium of concentration.

Theory and Methods

Time‐resolved MR spectra of hyperpolarized 129Xe dissolved in the human brain were acquired from three healthy volunteers. Acquired spectra were numerically fitted with five Lorentzian peaks in accordance with known 129Xe brain spectral peaks. The signal dynamics of spectral peaks for gray matter and red blood cells were quantified, and correction for the 129Xe T 1 dependence upon blood oxygenation was applied. 129Xe transfer dynamics determined from the ratio of the peaks for gray matter and red blood cells was numerically fitted with the developed tracer kinetic model.

Results

For all the acquired NMR spectra, the developed tracer kinetic model fitted the data with tracer transfer coefficients between 0.1 and 0.14.

Conclusion

In this study, a tracer kinetic model was developed and validated that estimates the transfer rate of HP 129Xe from cerebral blood to gray matter in the human brain.

Very interesting work! Nice to see the Xenon MRI field going in this direction. Has there been any work combining this with MR-guided focused ultrasound (FUS) to see the effectiveness of that technique on opening the blood-brain barrier? e.g. see this paper: https://www.nature.com/articles/s41467-019-12426-9

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@mathieu We are not using ultrasound at the moment, however, we are considering other ways to achieve something similar. Thanks for your comment.

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Nice to see 129Xe being used outside the lungs again! You seem to concentrate on gray matter exclusively. However, as far as I understand it, you do consider a white-matter signal in your fit. Is it a sensitivity issue that you don’t include it in your analysis? I suppose that the same model would be applicable?

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Sorry for the delay in reply. Yes, the sensitivity from white matter was poor for a good fit. The same model would work for white matter too.

Thanks

Madhwesha Rao