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.

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.