Room-temperature susceptometry predicts biopsy-determined hepatic iron in patients with elevated serum ferritin

Abstract

Background: There is an ongoing clinical need for novel methods to measure hepatic iron content (HIC) noninvasively. Both magnetic resonance imaging (MRI) and superconducting quantum interference device (SQUID) methods have previously shown promise for estimation of HIC, but these methods can be expensive and are not widely available. Room-temperature susceptometry (RTS) represents an inexpensive alternative and was previously found to be strongly correlated with HIC estimated by SQUID measurements among patients with transfusional iron overload related to thalassemia.

Aim: The goal of the current study was to examine the relationship between RTS and biochemical HIC measured in liver biopsy specimens in a more varied patient cohort.

Material and methods: Susceptometry was performed in a diverse group of patients with hyperferritinemia due to hereditary hemochromatosis (HHC) (n = 2), secondary iron overload (n = 3), nonalcoholic fatty liver disease (NAFLD) (n = 2), and chronic viral hepatitis (n = 3) within one month of liver biopsy in the absence of iron depletion therapy.

Results: The correlation coefficient between HIC estimated by susceptometry and by biochemical iron measurement in liver tissue was 0.71 (p = 0.022). Variance between liver iron measurement and susceptometry measurement was primarily related to reliance on the patient's body-mass index (BMI) to estimate the magnetic susceptibility of tissue overlying the liver.

Conclusions: We believe RTS holds promise for noninvasive measurement of HIC. Improved measurement techniques, including more accurate overlayer correction, may further improve the accuracy of liver susceptometry in patients with liver disease.

Figure 1. Room-temperature susceptometer

Patients lay on their side below the field-producing coils as the susceptometer recorded changes in the magnetic field induced by hepatic iron.

Figure 2. Two-layer model used in liver-iron calculation

In the diagram, z_SS is the distance from the patient’s skin to the bottom of the susceptometer, and z_LS is the liver-skin distance measured by ultrasound. These values are used in Eq. (1) to account for alterations in susceptometry measurements due to increasing distance and changes in the magnetic field from non-hepatic tissue.

Figure 3. Correlation between liver iron concentrations determined by room-temperature susceptometry (HIC_RTS) and biochemical hepatic iron content of biopsy specimens (HIC_biopsy)

The mean of 12 measurements are plotted for HIC_RTS with error bars to display standard deviation. Pearson’s correlation with 95 percent confidence interval band is shown with r-and p-values provided.

Figure 4. Association between the magnitude of susceptometry-HIC difference and liver-skin distance

Liver-skin distance was determined by ultrasound at the chosen point of measurement. Accuracy of RTS measurements was determined by finding the absolute difference between HIC_RTS and HIC_biopsy (i.e. Error = |HIC_RTS − HIC_biopsy|). Pearson’s correlation with 95 percent confidence interval band is shown with r-and p-values provided.