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BACKGROUND: T1 mapping of the liver is confounded by the presence of fat. Multiparametric T1 mapping combines fat-water separation with T1-weighting to enable imaging of water-specific T1 (T1Water ), proton density fat fraction (PDFF), and T2* values. However, normative T1Water values in the liver and its dependence on age/sex is unknown. PURPOSE: Determine normative values for T1Water in the liver with comparison to MOLLI and evaluate a T2*-compensation approach to reduce T1 variability. STUDY TYPE: Prospective observational; phantoms. POPULATIONS: One hundred twenty-four controls (56 male, 18-75 years), 50 patients at-risk for liver disease (18 male, 30-76 years). FIELD STRENGTH/SEQUENCE: 2.89 T; Saturation-recovery chemical-shift encoded T1 Mapping (SR-CSE); MOLLI. ASSESSMENT: SR-CSE provided T1Water measurements, PDFF and T2* values in the liver across three slices in 6 seconds. These were compared with MOLLI T1 values. A new T2*-compensation approach to reduce T1 variability was evaluated test/re-test reproducibility. STATISTICAL TESTS: Linear regression, ANCOVA, t-test, Bland and Altman, intraclass correlation coefficient (ICC). P < 0.05 was considered statistically significant. RESULTS: Liver T1 values were significantly higher in healthy females (F) than males (M) for both SR-CSE (F-973 ± 78 msec, M-930 ± 72 msec) and MOLLI (F-802 ± 55 msec, M-759 ± 69 msec). T1 values were negatively correlated with age, with similar sex- and age-dependencies observed in T2*. The T2*-compensation model reduced the variability of T1 values by half and removed sex- and age-differences (SR-CSE: F-946 ± 36 msec, M-941 ± 43 msec; MOLLI: F-775 ± 35 msec, M-770 ± 35 msec). At-risk participants had elevated PDFF and T1 values, which became more distinct from the healthy cohort after T2*-compensation. MOLLI systematically underestimated liver T1 values by ~170 msec with an additional positive T1-bias from fat content (~11 msec/1% in PDFF). Reproducibility ICC values were ≥0.96 for all parameters. DATA CONCLUSION: Liver T1Water values were lower in males and decreased with age, as observed for SR-CSE and MOLLI acquisitions. MOLLI underestimated liver T1 with an additional large positive fat-modulated T1 bias. T2*-compensation removed sex- and age-dependence in liver T1, reduced the range of healthy values and increased T1 group differences between healthy and at-risk groups. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.
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Introduction: Short-term clinical outcomes from SARS-CoV-2 infection are generally favorable. However, 15-20% of patients report persistent symptoms of at least 12 weeks duration, often referred to as long COVID. Population studies have also demonstrated an increased risk of incident diabetes and cardiovascular disease at 12 months following infection. While imaging studies have identified multi-organ injury patterns in patients with recovered COVID-19, their respective contributions to the disability and morbidity of long COVID is unclear. Methods: A multicenter, observational study of 215 vaccine-naïve patients with clinically recovered COVID-19, studied at 3-6 months following infection, and 133 healthy volunteers without prior SARS-CoV-2 infection. Patients with recovered COVID-19 were screened for long COVID related symptoms and their impact on daily living. Multi-organ, multi-parametric magnetic resonance imaging (MRI) and circulating biomarkers were acquired to document sub-clinical organ pathology. All participants underwent pulmonary function, aerobic endurance (6 min walk test), cognition testing and olfaction assessment. Clinical outcomes were collected up to 1 year from infection. The primary objective of this study is to identify associations between organ injury and disability in patients with long-COVID symptoms in comparison to controls. As a secondary objective, imaging and circulating biomarkers with the potential to exacerbate cardiovascular health were characterized. Discussion: Long-term sequelae of COVID-19 are common and can result in significant disability and cardiometabolic disease. The overall goal of this project is to identify novel targets for the treatment of long COVID including mitigating the risk of incident cardiovascular disease. Study registration: clinicaltrials.gov (MOIST late cross-sectional study; NCT04525404).