Multi-modal, Multi-parametric Liver Imaging for Ultrasound-based Stratification of Patients With MAFLD

1. Purpose The main purpose of this study is to develop ultrasound methods that can identify the stages of metabolic dysfunction-associated steatotic liver disease (MASLD) with Magnetic Resonance Elastography (MRE), MRI Proton Density Fat Fraction (PDFF) and biopsy as the ground truth.
2. Hypothesis Ultrasound can replace MRI in staging steatosis and fibrosis. Ultrasound can improve the staging of inflammation.
3. Justification A wide range of pathologies can cause changes in the mechanical properties of human tissue. For this reason, finding a way to non-invasively evaluate tissue stiffness is proving clinically useful. Many liver diseases of varying etiologies including hepatitis, fatty liver disease, alcoholism, and others, present with increased liver stiffness from fibrosis. Fibrosis can lead to various cancers of the liver or cirrhosis, sometimes causing death. It has been estimated that the prevalence of cirrhosis is 4.5% to 9.5% of the general population, indicating a much larger group is inflicted with the varying stages of fibrosis. If dramatic increases in liver stiffness from fibrosis can be caught at an early stage, treatment can be tailored for the patient, and results can be monitored to increase the likelihood of reversal and slow damaging effects.

Biopsy is traditionally the standard method to diagnose and monitor liver conditions, being widely used since 1958. Some advantages of biopsy include the visualization of fat and iron deposits. Unfortunately, biopsies are not able to show heterogeneity of fibrosis as the reading is often taken from the same location, and consists of only 1/50,000th of the liver volume. Studies have shown discordance in biopsy results from the left to the right lobes in 33% of cases, and 30% misclassification of cirrhotic cases. As well, studies have shown significant inter-observer and intra-observer variation. Finally, a drawback of biopsy that has spurred the transition to non-invasive diagnostic measures, such as elastography, is the associated risk of pain, bleeding, and mortality.

Various elastography methods have been developed and applied to the liver. Transient elastography, FibroScan (EchoSens, Paris) is the most common type of elastography currently applied to the liver for the measurement of stiffness, indicating fibrotic activity. It uses ultrasound technology with a unidimensional probe to measure the velocity of shear waves. It has become the standard of care in some clinics worldwide as an affordable device that is diagnostically reliable. Although it is pain-free, quick, and convenient, it is only able to collect a very small sample from the right lobe of the liver so cannot capture any heterogeneity and may misrepresent the state of the whole organ. As well, to the best of the investigators' knowledge, stiffness values obtained from FibroScan readings have not been correlated with Magnetic Resonance Elastography values in any direct comparison in the literature, and they result in less reliable results for earlier stages of fibrosis.

Magnetic Resonance Elastography is another type of elastography applied to the liver. It has shown very high diagnostic accuracy in the staging of patients into fibrotic stages, and is used in some private clinics, primarily in the United States. It allows flexibility in its application and in the protocols used to acquire the data. It has shown great repeatability and reproducibility, and is often effective in patients with higher BMIs. The high costs and complexity associated with MRI scans restricts its usefulness in many areas affected by liver disease.

The investigators' S-WAVE method is an ultrasound method that will produce two and three-dimensional images, allowing for full visualization of the liver. It is an adjustable multi-frequency technique, which can show large areas of the organ as volumetric elasticity maps. It is affordable and feasible in widespread clinical settings due to the simple hardware needs of an ultrasound device.