Article highlights:

• Proton density fat fraction MRI (MRI-PDFF) quantifies fat content of the entire liver
• MRI-PDFF is non-invasive and decreases sampling errors of invasive tests such as needle biopsy
• Risk factors alone, such as BMI, do not always correlate to fat content in the liver
• MRI-PDFF provides a non-invasive, objective, and accurate measurement of hepatic fat content that meets the rigorous standards of clinical trials

A variety of conditions such as excessive alcohol consumption, metabolic abnormalities like non-alcoholic fatty liver disease (NAFLD), infections, and obesity can cause excess fat to be stored within liver cells. Conventional MRI images of the liver (fig. A) provide exquisite soft-tissue contrast between liver, muscle, vertebral body and subcutaneous fat. However, it does not provide information about fat content within the liver.

Comparatively, proton density fat fraction MRI (MRI-PDFF), fig. B) provides quantitative information about the percentage of fat within each pixel. For example, the fat pad below the skin (subcutaneous fat) has the highest fat content (> 90%), whereas the spleen has negligible fat content.

Liver fat deposition can be heterogenous: Biopsy results depend on sampling location

Although liver biopsy is considered the “gold standard” for evaluating fat content, it is worth noting that a biopsy is not only invasive, expensive, and poses a non-negligible risk, it only measures fat content from a very small region of the liver (1/50,000 volume of the liver).

In contrast, MRI-PDFF provides fat content information across the entire liver.  For example, the liver fat content near the anterior portion of the liver is about 15% whereas the fat content in the rest of the liver is twice as high (>30%) (fig. C). MRI-PDFF is non-invasive and can avoid sampling errors.

Liver fat does not equate to body size

While obesity is a risk factor for fatty liver disease, surrogates such as waist circumference or BMI are imperfect metrics for evaluating fatty liver disease.

Two patients with roughly the same body size can have different amounts of fat content. The patient on the left (patient A) has more subcutaneous fat but fat deposition in the liver is minimal. On the other hand, the patient on the right (Patient B) has elevated fat content in the liver although the amount of subcutaneous fat is minimal.

MRI-PDFF can monitor treatment effectiveness of fatty liver disease

MRI-PDFF quantifies hepatic fat content with a high degree of accuracy and reproducibility. Due to this, it is increasingly used as a tool to measure the effectiveness of various treatment options for non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) in clinical trials¹.

For example, in a clinical research study, the effectiveness of a treatment for non-alcoholic fatty liver disease (NAFLD) was evaluated by measuring the hepatic fat content before and after treatment.  One of the treatment arms showed a significant reduction in hepatic fat content (see figure below) and the other arms did not.

In summary, MRI-PDFF provides a non-invasive, simple to use, objective method for measuring liver fat content with a high degree of accuracy and reproducibility to be considered as the modality of choice in rigorous clinical trials.

¹Caussy C, Reeder SB, Sirlin CB, Loomba R. Non-invasive, quantitative assessment of liver fat by MRI-PDFF as an endpoint in NASH trials. Hepatol Baltim Md. 2018;68(2):763-772. doi:10.1002/hep.29797