Background

MR-Linac systems enable concurrent irradiation and imaging.¹ Direct imaging of radiation beam effects could enable more accurate dosimetry and in vivo dose verification, potentially enabling smaller treatment margins. Previous studies found T₁-weighted intensity changes in aqueous dissolved free radical scavenger solutions irradiated on a 0.35T MR-Linac.² It was hypothesized that dissolved oxygen depletion during water radiolysis was the primary mechanism. In this abstract, we investigate the feasibility of using quantitative T₁ mapping and a 1.5T MR-Linac to detect immediate changes in T₁ relaxation during water radiolysis.

Methods

Sample preparation: 50 mL tubes were filled with ultrapure Milli-Q water at atmospheric pressure, sealed using rubber septa to prevent gas exchange (Figure 1A), and placed in a styrofoam box filled with tap water at ambient room temperature (20 °C).

MR acquisition: Imaging used a 1.5T Elekta Unity MR-Linac (Elekta AB, Stockholm, Sweden). Dynamic T₁/B₀ maps were acquired using dual gradient-echo Look-Locker inversion recovery (4x4x8 mm³ resolution, TR/TE1/TE2 = 7.0/1.9/4.8 ms, FA 7°, maximum TI 15846 ms, 40 TIs, inversion spacing 30 s, 8-channel anterior/posterior array). Look-Locker 3-parameter fitting was used to obtain 2D (30 s per dynamic) and 3D (6 slices, 4 min per dynamic) T1 maps.^3,4

Beam-on imaging: The experimental scheme and radiation plan are shown in Figure 1B and 1C. A radiation plan from a single gantry angle (180°, from underneath the bed) was designed using the Monaco treatment planning system (Elekta AB, Stockholm, Sweden) to irradiate one column of a 3x3 grid of tubes with a total of 6000 monitor units delivered in two irradiations lasting 6 min each. Dynamic T₁/B₀ maps were obtained over 70 minutes concurrent with irradiation. Voxelwise univariate t-tests (false discovery rate q=0.05) were used to compare mean T₁s before and after irradiation.

Dissolved oxygen relaxivity measurement: Dissolved O₂ concentrations were varied by bubbling a nitrogen/oxygen gas mixture through water for 10 minutes (total flow rate 300 mL/min, pO₂/pN₂ ratios 0%/100%, 10%/90%, 50%/50%, 100%/0%, 21%/79% [room air]). 2D and 3D T₁ maps of 15 mL samples were obtained for 20 minutes each.

Results

Figure 1D shows T₁ increases within irradiated tubes, with minimal qualitative change in tubes receiving low dose and in the surrounding tap water. Figure 2 shows T₁ dynamics during irradiation. A linear increase is observed during the beam-on periods. Voxelwise changes within the radiation field were observable. Mean T₁ changes between baseline and each post-beam period were used to estimate ΔT₁/Dose of 0.71 ms/Gy and ΔR1/Dose of -9.4x10^-5 s^-1/Gy. Figure 3 shows corresponding post-irradiation 3D T₁ maps, with elevated T₁ within the irradiated field compared to low-dose regions. Figure 4 shows that T₁ increases are visible in single frames.

The dissolved oxygen relaxivity r_1,O2 was estimated to be 0.25x10-3 s^-1/mmHg (Figure 5). The maximum temporal standard deviation in single-echo T₁ across all tubes was 13 ms (max SD/mean 0.57%), with no evidence of non-normality (Kolmogorov-Smirnov; p>0.05) or correlation between T₁s fitted from either echo. T₁ and B₀ drifts over a 20 min period were estimated to be at most 20 ms and 6 Hz, respectively. Using the r_1,O2 value for calibration, the dissolved pO₂/Dose was estimated to be -0.38 mmHg/Gy.

Discussion

Various MRI contrast mechanisms for visualizing ionizing radiation effects exist, including Fricke oxidation of ferrous ions^5,6, gel polymerization^7,8, beam-induced thermal convection⁹, and water radiolysis induced oxygen depletion². In this study, real-time T₁ changes (0.71 ms/Gy) were observed in ultrapure water without any added contrast agent, using a 1.5T MR-Linac.

T₁ measurements were temporally uncorrelated, suggesting that signal averaging could improve the T₁ measurement precision. The current T₁ and dose precision (SEM) for a 10 min scan are estimated to be 2 ms and 3 Gy, respectively.

Calibration experiments supported the working hypothesis that changes in T₁ primarily result from oxygen depletion, although the estimated pO₂/Dose (-0.38 mmHg/Gy) was larger than literature estimates based on simulation² (-0.14 μM/Gy = -0.08 mmHg/Gy, assuming a conversion factor of 0.58 mmHg/μM). Independent dissolved oxygen measurements are needed for validation. The measured r_1,O2 agreed with empirical models for oxygen relaxivity.¹⁰

T₁ changes were observed in ultrapure water but not deionized or tap water. We speculate that trace organic compounds, found in non-ultrapure water, scavenge free radicals produced during radiolysis.

Conclusions

The irradiation of ultrapure water using a 1.5T MR-Linac resulted in measurable real-time T₁ changes (0.71 ms/Gy), which could be imaged in both 2D and 3D. The feasibility of in vivo measurement should be assessed in biological-like phantoms.

Acknowledgements

We thank the following individuals for their assistance: Khang Vo and Danielle Letterio for MR-Linac operation; Brian Keller, Ryan Oglesby and Lingyue Sun for useful discussions; Michael Pozzobon (machine shop). We gratefully acknowledge the Natural Sciences and Engineering Research Council of Canada (NSERC RGPIN-2017-06596) and the Ontario ERA for funding. Brandon Tran and Liam Lawrence contributed equally to this work as first authors.

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