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: MP2RAGETR 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.

Contents of Metal(loid)s in a Traditional Ethiopian Flat Bread (Injera), Dietary Intake, and Health Risk Assessment in Addis Ababa, Ethiopia.

The traditional Ethiopian flat bread, injera, is a regular component of daily diets in Ethiopia and Eritrea. This bread is also popular among urban refugees particularly Eritreans in Addis Ababa. The levels of metal(loid)s in 40 composite (120 sub-samples) injera samples, representing 4 types of market establishments in Addis Ababa, were determined using inductively coupled plasma-mass spectrometry (ICP-MS) and portable X-ray fluorescence (PXRF). For ICP-MS analysis, the accuracy of the method was evaluated by the analysis of a certified reference material and recovery experiments. It was found that the correlations between the mean levels of Al and Fe and between Al and Mn in injera were highly significant (p < 0.001). It was also found that 1.5 fresh injeras would cover 48-75% of recommended dietary allowance (RDA) for Mg, 17-21% of RDA for K, 19-23% of RDA for Ca, and 60-72% of RDA for P for an adult group aged between 19 and 50. Daily intakes of Al, Fe, and Mn were found to be above the provisional tolerable daily intake (PTDI)/maximum tolerable daily intake (MTDI) values. The mean target hazard quotient (THQ) values for Fe and Mn were greater than 1. The total THQ values varied from 6.52 to 8.53 among market establishments. Estimating carcinogenic risk due to exposure to As, Cr, and Pb indicated that perennial injera consumers might remain at cancer risk. This would further escalate if other staple food items and spices are considered. Hence, there is a need for home-based strategies to reduce extrinsic soil-Al-Fe-Mn in injera/tef batter.

Advanced MRI of Liver Fibrosis and Treatment Response in a Rat Model of Nonalcoholic Steatohepatitis.

Background Liver biopsy is the reference standard to diagnose nonalcoholic steatohepatitis (NASH) but is invasive with potential complications. Purpose To evaluate molecular MRI with type 1 collagen-specific probe EP-3533 and allysine-targeted fibrogenesis probe Gd-Hyd, MR elastography, and native T1 to characterize fibrosis and to assess treatment response in a rat model of NASH. Materials and Methods MRI was performed prospectively (June-November 2018) in six groups of male Wistar rats (a) age- and (b) weight-matched animals received standard chow (n = 12 per group); (c) received choline-deficient, l-amino acid-defined, high-fat diet (CDAHFD) for 6 weeks or (d) 9 weeks (n = 8 per group); (e) were fed 6 weeks of CDAHFD and switched to standard chow for 3 weeks (n = 12); (f) were fed CDAHFD for 9 weeks with daily treatment of elafibranor beginning at week 6 (n = 14). Differences in imaging measurements and tissue analyses among groups were tested with one-way analysis of variance. The ability of each imaging measurement to stage fibrosis was quantified by using area under the receiver operating characteristic curve (AUC) with quantitative digital pathology (collagen proportionate area [CPA]) as reference standard. Optimal cutoff values for distinguishing advanced fibrosis were used to assess treatment response. Results AUC for distinguishing fibrotic (CPA >4.8%) from nonfibrotic (CPA ≤4.8%) livers was 0.95 (95% confidence interval [CI]: 0.91, 1.00) for EP-3533, followed by native T1, Gd-Hyd, and MR elastography with AUCs of 0.90 (95% CI: 0.83, 0.98), 0.84 (95% CI: 0.74, 0.95), and 0.65 (95% CI: 0.51, 0.79), respectively. AUCs for discriminating advanced fibrosis (CPA >10.3%) were 0.86 (95% CI: 0.76, 0.97), 0.96 (95% CI: 0.90, 1.01), 0.84 (95% CI: 0.70, 0.98), and 0.74 (95% CI: 0.63, 0.86) for EP-3533, Gd-Hyd, MR elastography, and native T1, respectively. Gd-Hyd MRI had the highest accuracy (24 of 26, 92%; 95% CI: 75%, 99%) in identifying responders and nonresponders in the treated groups compared with MR elastography (23 of 26, 88%; 95% CI: 70%, 98%), EP-3533 (20 of 26, 77%; 95% CI: 56%, 91%), and native T1 (14 of 26, 54%; 95% CI: 33%, 73%). Conclusion Collagen-targeted molecular MRI most accurately detected early onset of fibrosis, whereas the fibrogenesis probe Gd-Hyd proved most accurate for detecting treatment response. © RSNA, 2020 Online supplemental material is available for this article.