BACKGROUND

Stereotactic MR-guided Adaptive Radiation Therapy (SMART) dose painting for hypoxia has potential to improve treatment outcomes, but clinical implementation on low-field MR-Linac faces substantial challenges due to dramatically lower signal-to-noise ratio (SNR) characteristics. While quantitative MRI and T mapping of hypoxia biomarkers show promise, T-to-noise ratio (TNR) optimization at low fields is paramount, particularly for the clinical implementation of oxygen-enhanced (OE)-MRI. The 3D Magnetization Prepared (2) Rapid Gradient Echo (MP2RAGE) sequence stands out for its ability to acquire homogeneous T-weighted contrast images with simultaneous T mapping.

PURPOSE

To optimize MP2RAGE for low-field T mapping; conduct experimental validation in a ground-truth phantom; establish feasibility and reproducibility of low-field MP2RAGE acquisition and T mapping in healthy volunteers.

METHODS

The MP2RAGE optimization was performed to maximize the contrast-to-noise ratio (CNR) of T values in white matter (WM) and gray matter (GM) brain tissues at 0.35T. Low-field MP2RAGE images were acquired on a 0.35T MR-Linac (ViewRay MRIdian) using a multi-channel head coil. Validation of T mapping was performed with a ground-truth Eurospin phantom, containing inserts of known T values (400-850 ms), with one and two average (1A and 2A) MP2RAGE scans across four acquisition sessions, resulting in eight T maps. Mean (± SD) T relative error, TNR, and intersession coefficient of variation (CV) were determined. Whole-brain MP2RAGE scans were acquired in 5 healthy volunteers across two sessions (A and B) and T maps were generated. Mean (± SD) T values for WM and GM were determined. Whole-brain T histogram analysis was performed, and reproducibility was determined with the CV between sessions. Voxel-by-voxel T difference maps were generated to evaluate 3D spatial variation.

RESULTS

Low-field MP2RAGE optimization resulted in parameters: MP2RAGE of 3250 ms, inversion times (TI/TI) of 500/1200 ms, and flip angles (α/α) of 7/5°. Eurospin T maps exhibited a mean (± SD) relative error of 3.45% ± 1.30%, TNR of 20.13 ± 5.31, and CV of 2.22% ± 0.67% across all inserts. Whole-brain MP2RAGE images showed high anatomical quality with clear tissue differentiation, resulting in mean (± SD) T values: 435.36 ± 10.01 ms for WM and 623.29 ± 14.64 ms for GM across subjects, showing excellent concordance with literature. Whole-brain T histograms showed high intrapatient and intersession reproducibility with characteristic intensity peaks consistent with voxel-level WM and GM T values. Reproducibility analysis revealed a CV of 0.46% ± 0.31% and 0.35% ± 0.18% for WM and GM, respectively. Voxel-by-voxel T difference maps show a normal 3D spatial distribution of noise in WM and GM.

CONCLUSIONS

Low-field MP2RAGE proved effective in generating accurate, reliable, and reproducible T maps with high TNR in phantom studies and in vivo feasibility established in healthy volunteers. While current work is focused on refining the MP2RAGE protocol to enable clinically efficient OE-MRI, this study establishes a foundation for TOLD T mapping for hypoxia biomarkers. This advancement holds the potential to facilitate a paradigm shift toward MR-guided biological adaptation and dose painting by leveraging 3D hypoxic spatial distributions and improving outcomes in conventionally challenging-to-treat cancers.