Synopsis

The change in T₂ due to the oxygen saturation sO₂ in blood has been well characterised at high fields, and has been successfully applied for in-vivo oximetry measurements. The effect is known to increase with B₀ field strength, but there are few studies at low field. In this work, the relationship between the T₂ relaxation rate and blood oxygenation sO₂ has been characterised at a range of magnetic fields below 1 Tesla to determine whether changes in oxygenation can be practically observed and accurately quantified at lower fields.

Introduction

The T₂ of blood is linked to its oxygen saturation, creating a very useful intrinsic contrast mechanism. This relaxation effect is caused by the conversion of oxy- to deoxy-haemoglobin inside red blood cells, which produces stronger magnetic field inhomogeneities and thus higher rates of dephasing. As they are generated by variations in susceptibility, the strength of the inhomogeneities is also dependent on B₀. In the literature, this effect has been described using a variant of the Luz-Meiboom equation^1–3.

$$\frac{1}{T_2} = \frac{1}{T_{2_0}} + \gamma^2 K_0 \tau_{ex} (1-\frac{2\tau_{ex}}{\tau_{180}} \tanh(\frac{\tau_{180}}{2\tau_{ex}})){\quad\quad}(1)$$

where T_2o is the intrinsic blood T₂, $$$\tau_{ex}$$$ is the average exchange time, $$$\tau_{180}$$$ is the refocusing interval and K₀ is the variance of the magnetic field inhomogeneity due to changes in sO₂ (see equation 2). This relaxation effect has been well characterised at field strengths used for clinical imaging^3–6, and T₂ measurements have been used to quantify changes in oxygen saturation in-vivo^7,8. The development of low field portable magnetic resonance systems presents new opportunities for leveraging this MRI contrast. However, previous studies of this contrast at lower fields have been limited to extreme levels of oxygenation/ deoxygenation^2,9,10.

Method

In this study, the T₂ of blood is measured as it circulates around a benchtop setup of a cardiopulmonary bypass circuit, shown in Figure 1. An oxygenation membrane provides dynamic control of the oxygen saturation and other physiological parameters of the blood. By altering the gas mix fed into the membrane, the circuit can produce a slow ramp of increasing or decreasing oxygen saturation. This is continuously tracked by an optical sensor (MAX30102), so that the sensitivity of the relaxation effect to small changes in oxygen saturation can be tested.

A cryogen-free superconducting variable field magnet (Cryogenic Ltd, London UK ) with custom built RF coils was used to perform measurements at 5 fields strengths between 0.12-1 T, with T₂ tracked using the CPMG experiment. Additionally, the effect of 5 different refocusing intervals (time between refocusing pulses, $$$\tau_{180}$$$) on the observed relaxation rate was tested, and compared to current literature.

Whole human blood was collected from healthy volunteers by venipuncture of the ante-cubital vein (approved by ethics committee). These were collected into standard 475ml CPD (Haemonetics, Braintree, MA) anticoagulant bags and stored at 4^oC for no more than 10 days before experiments. This meant the haematocrit was around 0.34 which is slightly lower than average in-vivo.

Results

The experiments at each field strength produced a series of correlated T₂/sO₂ data points, with T₂ values for each of the 5 refocusing intervals. Figure 2 shows the results from the 0.3 T experiment, which clearly shows the blood’s T₂ decreases as it is deoxygenated, with the change increasing as $$$\tau_{180}$$$ increases. We observed similar trends at all field strengths, with the size of the T₂ decrease becoming larger as B₀ increased, as suggested in the literature.^1,2,9 A downward trend in T₂ is also visible across the experiment, which we attribute to the breakdown of blood cells as they circulate through the cardiopulmonary bypass circuit, this was later verified by UV-VIS spectroscopy of plasma samples.

For a more quantitative analysis, data points from the deoxygenation periods in the experiment were extracted and to produce curves of T₂ as a function of sO₂. These T₂ values were fit to Equation 1 to obtain values for the intrinsic T_2o and K₀. $$$\tau_{ex}$$$ was assumed to be 3.0 ms, following Stefanovic and Pike’s result at 1.5 T³. Plotting this value against (1-sO₂)² shows a linear relationship (Figure 3), which has been shown in the literature at higher fields^3,5. We found the slope of these fits is proportional to B₀² and the change was still detectable as low as 0.1 T.

Discussion

Our results show the K₀ parameter can be described by Equation 2 for the range of field strengths we measured. This agrees with the theory which predicts the dependence on B₀² and (1-sO₂)². The oxygenation contrast is still detectable at low fields using longer refocusing intervals in the CPMG pulse sequence.

$$K_0 = (7.55\pm0.2)\times10^{-14} B_0^2 (1-sO_2)^2\quad\quad(2)$$

We also found that the Luz-Meiboom equation provides a good fit to the T₂ values measured at different refocusing intervals, which suggests that this model is still a good approximation for this effect at low field. Recently, a method for estimating sO₂ with multiple refocusing intervals and Equation 1 was demonstrated¹⁰. A similar method based on fitting K₀ was tested on the low field data and gives good agreement with the optical tracking (Figure 1, grey trace).

Acknowledgements

The project was funded by the New Zealand Ministry of Business Innovation and Employment

We thank perfusion specialist Amber Blakey (Wellington Regional Hospital, Wellington NZ) for assistance with the blood flow circuit.

References

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