Clinical trial NCT06373536: Comparison of MRI-PDFF to TAEUS FLIP Device to Estimate Liver Fat Fraction in Adults
Official title: Comparison of Thermoacoustic Enhanced Ultrasound for Estimating Liver Fat Fraction to MRI-PDFF
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Steatosis of Liver
Keywords: MRI-PDFF
Thermoacoustics
Lead sponsor: Endra Lifesciences
Sponsor class: INDUSTRY
First posted: 2024-04-18
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients referred to radiology for abdominal imaging and suspected of having steatotic liver disease.

Brief summary: Primary nonalcoholic fatty Liver disease (NAFLD) is an excess of fat in the liver (steatosis) that is not a result of excessive alcohol consumption or other secondary causes11. NAFLD is defined by the presence of hepatic fat content (steatosis) in ≥ 5% of hepatocytes and is currently the most common liver disease worldwide14 . Non-Alcoholic Fatty Liver Disease (NAFLD) is the world\&#39;s most common liver disease and affects around 33% of the adult population.

Nonalcoholic steatohepatitis (NASH), a progressive form of nonalcoholic fatty liver disease (NAFLD), is a growing clinical concern associated with the increasing prevalence of obesity, type 2 diabetes, and metabolic syndrome. NASH is characterized by the presence of hepatic steatosis, inflammation, and hepatocellular injury and is predicted to be the leading indication for liver transplantation by 20201. Patients with NASH have an increased risk of developing cirrhosis and its complications, such as ascites, variceal hemorrhage, hepatic encephalopathy, hepatocellular carcinoma, and liver failure. The prevalence worldwide of NAFLD in the general population is estimated at 20-35%2 . Around 2-3% of the population have NASH.

In patients with type 2 diabetes, the prevalence is even over 50% (55.5% globally, 68% in Europe). In Germany, the NAFLD prevalence was 23% in 2016 and will be around 26% in 2030. The prevalence of non-alcoholic alcoholic steatohepatitis (NASH), i.e. the progressive form of NAFLD, is estimated at 4% of the adult population in Germany and will increase to 6% by 2030. This means that NAFLD is already the most common chronic liver disease worldwide and one of the leading causes of liver-related complications (cirrhosis, decompensation, hepatocellular carcinoma, liver transplantation) and deaths. NAFLD and NASH are largely underdiagnosed worldwide.

Detailed description: Early detection and surveillance of steatosis hepatis improves the chances of management or even improvement of the disease before irreversible damage occurs12. Liver tissue biopsy is the current reference standard for the diagnosis and severity of steatosis hepatis. However, due to its invasiveness, biopsy collection is not suitable for screening or regular follow-up. The diagnostic techniques of magnetic resonance spectroscopy (MRS) and MRI-PDFF (proton density fat fraction) for the assessment of liver fat content have been shown to correlate well with the results of liver biopsy, but are particularly associated with high costs, low availability, long examination times and exclusion of patients with metal implants. Conventional B-scan ultrasonography is the most commonly used imaging modality for assessing steatosis hepatis based on qualitative image features of the liver. These include an echo-enhanced internal reflex pattern of the liver parenchyma, loss of signal in depth, blurred demarcation of the blood vessels and diaphragm, or areas of focal obesity. The sensitivity and specificity of conventional sonography is high in severe steatosis hepatis. On the other hand, the sensitivity is significantly worse in mild cases. In addition, intra- and interobserver reliability are poor in the assessment of steatosis hepatis of the conventional B-scan.

Quantitative ultrasound-based methods are the current standard of practice for point-of-care, noninvasive liver fat assessment. However, due to low penetration depth and confounding factors, invalid or poor-quality measurements are often encountered in large patients, or patients with liver fibrosis. In contrast to purely ultrasound-based approaches, thermoacoustic (TA) approaches are sensitive to tissue composition chemistry rather than acoustic scattering and/or attenuation, making TA measurements of liver fat content relatively insensitive to liver fibrosis or patient size.

Thermoacoustic (imaging) technology is non-invasive and combines short pulses of radio-frequency energy to create ultrasound signals (acoustic waves) in tissue to create images, or measurements, of fat in body tissues. The radio-frequency energy that is used to create thermoacoustic ultrasound signals is very similar to that used by cell phones and MRI scanners. Thermoacoustic signals are created in proportion to how well tissue is able to conduct electricity. Lean tissues are highly conductive while fatty tissues are not, and thus, thermoacoustics is able to differentiate lean and fatty tissues. A primary interest in detecting, and monitoring metabolic health, is measuring liver fat content. Thermoacoustic approaches to fat measurement in the liver have several unique advantages compared to other currently used technologies, including ultrasound and MRI. Medical ultrasound scanners are widely available but often have difficulty making high-quality images, and reliable measurements, in larger patients or deeper tissues. Thermoacoustic ultrasound signals are formed in the tissue allowing measurements of fat to be made at depths that may not be possible with conventional ultrasound systems. While MRI is the most accurate noninvasive method to estimate fat in tissue, it has limited availability and is very expensive compared to thermoacoustics, and thus impractical for widespread use that is needed to address the growing problem of fatty liver disease and metabolic syndrome.

Thermoacoustic approaches to fat measurement in tissue are exceptionally safe using radio frequency energy levels similar to MRI, with tissue heating that is less than a 0.001 degrees Celsius per pulse in temperature. ENDRA has developed a noninvasive bedside device called the TAEUS®-FLIP system for measuring fat in liver tissue. The TAEUS®-FLIP exam is performed during a routine exam and takes between 5-10 minutes to perform. The TAEUS®-FLIP system has the potential to bring wide access to accurate liver fat measurements to a wide range of patient populations and to address the unmet need for detecting and monitoring patients with fatty liver disease and metabolic syndrome.

In this study, the investigators want to compare TAEUS® FLIP with MRI-PDFF to gain insight into the potential of thermoacoustic methods to assess liver fat content, similar to MRI-PDFF. Unlike conventional quantitative ultrasound methods, the thermoacoustic approach has demonstrated the potential to obtain estimates of liver fat fraction in individuals with high BMI (45), and those with confirmed liver fibrosis.

Eligibility criteria: Inclusion Criteria:

* Study participants are 18-70 years of age
* Existing MRI-PDFF not older than 6 weeks or routine MRI-PDFF in the following 6 weeks
* Be able to understand, read, and provide written informed consent in German
* Tolerant to ultrasound and MRI examinations
* Able to lay flat for 20 minutes

Exclusion Criteria:

* Metal or electronic implants, including, but not limited to: pacemakers, metal clips, drug delivery pumps, hip implants, and neural stimulation devices.
* Known pregnancy the day of consent, or becoming pregnant during study participation
* Liver disease other than NAFLD/NASH including, but not limited to, hepatitis, cirrhosis, hepatocellular carcinoma.
* Patients with broken, or injured skin, in the right upper abdominal quadrant.
* BMI over 43 kg/m2

Primary outcomes:
measure: Thermoacoustic Fat Measurements
timeFrame: May 2024 to September 2025
measure: Estimate Accuracy of Thermoacoustic Fat Fraction
timeFrame: May 2024 to September 2025
Secondary outcomes:
measure: Usability Metric
timeFrame: May 2024 to January 2025
measure: Estimate Operator Variability
timeFrame: May 2024 to January 2025
Other outcomes:
Locations:
city: München
country: Germany
facility: Klinikum der Universität München Großhadern Klinik und Poliklink für Radiologie
Study officials:
References: