Ultrasound Biomarkers for Assessing Eligibility and Response to Resmetirom Therapy

This study will consist of 3 phases: 1. Technologist Training: Pre-study training will be conducted for all US (ultrasound) and MRI technologists to ensure standardized image acquisition across study sites. 2. A Pilot Study will be conducted in healthy adult participants to qualify imaging centers to participate in the Main Study. 3. The Main Study will be conducted in adult participants suspected of MASH (metabolic dysfunction-steatohepatitis) (with moderate to advanced fibrosis consistent with F2-F3 to evaluate the diagnostic performance of the combination of 2 US (ultrasound) biomarkers (UDFF and pSWE) for determining MRI-defined eligibility for resmetirom treatment and for monitoring treatment response over time . A Pilot Study will be conducted before the Main Study to verify image acquisition quality and data completeness, and to assess repeatability (US) and reproducibility (US and MRI). The Pilot Study will include 24 adult participants (n=8 participants/site across 3 imaging centers). Each participant in the pilot study will undergo 4 US (ultrasound) scans (2 scans each by 2 Certified US Technologists). All US scans will be performed on SIEMENS ACUSON Sequoia systems using the 5C1 transducer and the same software version throughout the study. Repeated US scans will be separated by ≥5 minutes, with participants repositioned between scans by the Certified US Technologists. Each participant in the pilot study will also undergo 2 MRI scans (1 scan each by 2 Certified MRI Technologists): MR scans will be performed using either the SIEMENS MAGNETOM Skyra 3T or GE SIGNA PIONEER 3T, depending on scheduling and site availability. The MR scanner will be running the same software version throughout the study. Data from participants in the Pilot Study will not be included in the analysis of the Main Study. Data Quality Verification : All pilot data will be reviewed by Siemens to verify image acquisition quality, completeness, and adherence to the imaging protocol. Repeatability and reproducibility will be evaluated in the Pilot Study. Main Study Participants will be recruited from clinical practices in the Houston, Texas area by hepatologists, gastroenterologists, and other referring clinicians. US (ultrasound) and MRI examinations will be performed across 3 Sponsor imaging centers in the Houston area. All participants will undergo Baseline US (ultrasound) biomarkers (UDFF, pSWE) and MRI biomarkers (MRI-PDFF, MRE) on the same day. Blinding * Referring physicians will be blinded to US (ultrasound) (UDFF and pSWE) results, and thus decisions to prescribe resmetirom will be made based solely on MRI biomarkers (ie, MRI-PDFF and MRE) and clinical assessment. * US (ultrasound) operators will be blinded to results from MRI biomarkers (MRI-PDFF and MRE). * MRI operators will be blinded to results from US (ultrasound) biomarkers (UDFF and pSWE). Duration of Study Participation * Pilot Study: 1 day, in addition to the Screening Visit * Main Study : * Participants NOT treated with resmetirom: Screening(consenting)and day 1 baseline MRI and US(2 visits total); * Participants treated with resmetirom (prescribed by their referring physician based on Baseline MRI results and clinical assessment): Screening (consenting), day 1 baseline MRI and US then at months 6, 12 and 24 (5 visits total). Study Assessments * Record demographics * Record medication history since last visit * Record laboratory test results since last visit * Perform US (ultrasound) * Perform MRI * Record/report SAEs