Optimization and validation of low-field MP2RAGE T1 mapping on 0.35T MR-Linac: Toward adaptive dose painting with hypoxia biomarkers

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 T₁ mapping of hypoxia biomarkers show promise, T₁-to-noise ratio (T₁NR) 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 T₁-weighted contrast images with simultaneous T₁ mapping.

Purpose

To optimize MP2RAGE for low-field T₁ mapping; conduct experimental validation in a ground-truth phantom; establish feasibility and reproducibility of low-field MP2RAGE acquisition and T₁ mapping in healthy volunteers.

Methods

The MP2RAGE optimization was performed to maximize the contrast-to-noise ratio (CNR) of T₁ 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 T₁ mapping was performed with a ground-truth Eurospin phantom, containing inserts of known T₁ values (400–850 ms), with one and two average (1A and 2A) MP2RAGE scans across four acquisition sessions, resulting in eight T₁ maps. Mean (± SD) T₁ relative error, T₁NR, 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 T₁ maps were generated. Mean (± SD) T₁ values for WM and GM were determined. Whole-brain T₁ histogram analysis was performed, and reproducibility was determined with the CV between sessions. Voxel-by-voxel T₁ difference maps were generated to evaluate 3D spatial variation.

Results

Low-field MP2RAGE optimization resulted in parameters: MP2RAGE_TR of 3250 ms, inversion times (TI₁/TI₂) of 500/1200 ms, and flip angles (α₁/α₂) of 7/5°. Eurospin T₁ maps exhibited a mean (± SD) relative error of 3.45% ± 1.30%, T₁NR 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) T₁ 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 T₁ histograms showed high intrapatient and intersession reproducibility with characteristic intensity peaks consistent with voxel-level WM and GM T₁ values. Reproducibility analysis revealed a CV of 0.46% ± 0.31% and 0.35% ± 0.18% for WM and GM, respectively. Voxel-by-voxel T₁ 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 T₁ maps with high T₁NR 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 T₁ 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.