Hemochromatosis Imaging 

Updated: Apr 16, 2018
  • Author: Sandor Joffe, MD; Chief Editor: John Karani, MBBS, FRCR  more...
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Practice Essentials

Hemochromatosis is characterized by a progressive increase in total body iron stores, with abnormal iron deposition in multiple organs. [1] Primary hemochromatosis is a genetic disorder, whereas secondary hemochromatosis can be the result of a variety of disorders, most commonly chronic hemolytic anemias. [1, 2, 3, 4, 5]

Preferred examination

Magnetic resonance imaging (MRI) is the best imaging examination to evaluate abnormal iron deposition in the liver. Computed tomography (CT) scanning is less sensitive than MRI but can demonstrate increased iron if it is severe. Although quantification of iron deposition in the liver is possible with MRI, calibration of each MR scanner is necessary. Therefore, quantitative MRI for iron deposition is not available at many institutions. [6, 7, 8, 9]  Iron deposits in the liver usually do not alter liver echogenicity. If ultrasonographic liver abnormalities are present, they are usually secondary to cirrhosis. An echogenic pancreas has been described with iron deposition.

(See the images below.)

T2-weighted gradient echo axial image in a patient T2-weighted gradient echo axial image in a patient with hemochromatosis demonstrates diffuse abnormal low signal intensity of the liver. The pancreas and spleen appear normal.
Noncontrast CT scan in a 47-year-old man with sick Noncontrast CT scan in a 47-year-old man with sickle cell disease who had undergone multiple transfusions demonstrates diffuse increased attenuation of the liver, representing abnormal iron deposition. The spleen is small and calcified from autosplenectomy.

 

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Computed Tomography

Patients with increased hepatic iron demonstrate diffuse increased attenuation of the liver, usually greater than 75 Hounsfield units on noncontrast examination. The liver vasculature appears particularly prominent because of the increased contrast between the vessels and the high-attenuation liver. Hepatomegaly also may be seen on CT scan. [10] Dual-phase (arterial and venous) CT can help detect hepatocellular carcinoma in patients with cirrhosis. (See the image below.)

Noncontrast CT scan in a 47-year-old man with sick Noncontrast CT scan in a 47-year-old man with sickle cell disease who had undergone multiple transfusions demonstrates diffuse increased attenuation of the liver, representing abnormal iron deposition. The spleen is small and calcified from autosplenectomy.

However, MRI is more sensitive and specific than CT scanning for the detection of abnormal hepatic iron deposition.

Other abnormalities that can cause increased attenuation of the liver on CT scans include amiodarone toxicity, Thorotrast, glycogen storage disease, gold therapy, and Wilson disease.

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Magnetic Resonance Imaging

Increased iron in the liver can be detected and quantified by MRI. Iron causes magnetic susceptibility artifact, which leads to spin dephasing (T2*-related signal loss). This dephasing results in decreased signal intensity on MRI scans. [6, 7, 10, 11, 12, 13, 14, 15, 16, 8, 17] (See the images below.)

T2-weighted gradient echo axial image in a patient T2-weighted gradient echo axial image in a patient with hemochromatosis demonstrates diffuse abnormal low signal intensity of the liver. The pancreas and spleen appear normal.
T2-weighted spin echo axial image in a 4-year-old T2-weighted spin echo axial image in a 4-year-old boy with thalassemia demonstrates abnormal low signal intensity of the liver, spleen, and pancreas.
T2-weighted gradient echo axial image in a 24-year T2-weighted gradient echo axial image in a 24-year-old man with sickle cell disease who had undergone multiple transfusions demonstrates diffuse abnormal low signal intensity of the liver and spleen.
T2-weighted spin echo axial image in the same pati T2-weighted spin echo axial image in the same patient as in the previous image demonstrates diffuse abnormal low signal intensity of the liver and spleen. Signal abnormality is less apparent on this spin echo image, and the liver is only slightly lower in signal intensity than the paraspinal muscles.
T1-weighted spin echo axial image in the same pati T1-weighted spin echo axial image in the same patient as in the previous 2 images fails to demonstrate abnormal low signal intensity of the liver and spleen.
T2-weighted spin echo axial image in a 40-year-old T2-weighted spin echo axial image in a 40-year-old man with alpha-thalassemia demonstrates diffuse, abnormal low signal intensity of the liver, spleen, and pancreas.
T1-weighted spin echo axial image in the same pati T1-weighted spin echo axial image in the same patient as in the previous image demonstrates diffuse abnormal low signal intensity of the liver, spleen, and pancreas. Although T1-weighted images are less sensitive than many other pulse sequences at detecting abnormal iron deposition, they still may demonstrate this abnormality.
T1-weighted spin echo image in a 47-year-old man w T1-weighted spin echo image in a 47-year-old man with sickle cell disease who had undergone multiple transfusions demonstrates diffuse, abnormal low signal intensity of the liver.
T2-weighted spin echo image in a 47-year-old man w T2-weighted spin echo image in a 47-year-old man with sickle cell disease who had undergone multiple transfusions demonstrates diffuse, abnormal low signal intensity of the liver.
T2-weighted gradient echo image in a 47-year-old m T2-weighted gradient echo image in a 47-year-old man with sickle cell disease who had undergone multiple transfusions demonstrates diffuse, abnormal low signal intensity of the liver. Magnetic susceptibility artifact obscures the upper pole of the left kidney because of dense splenic calcification.
MRI demonstrates abnormal low signal intensity of MRI demonstrates abnormal low signal intensity of the liver on this T2-weighted gradient echo image in a 37-year-old male. The spleen and pancreas are normal. These findings indicate abnormal iron deposition in the liver with sparing of the spleen and pancreas. This distribution is typical of hemochromatosis before the onset of cirrhosis.

T2-weighted gradient echo images are most sensitive to magnetic susceptibility artifact and thus are the best sequences to detect increased iron in the liver. T2-weighted gradient echo images can be performed as breath-hold images on most scanners. On a 1.5-T scanner, an echo time (TE) of at least 10 milliseconds and a flip angle of less than 30° should be used. The recovery time (TR) is less important and should be chosen based on the number of slices to be obtained and duration of the breath-hold.

Although less sensitive than T2-weighted gradient echo sequences, spin echo sequences also may demonstrate decreased signal intensity of the liver in patients with increased hepatic iron concentration. Spin echo pulse sequences with a long TE (T2-weighted sequences) are more sensitive than those with a short TE.

In determining whether the signal intensity of the liver is abnormally low, skeletal muscle can be used as a control. If the liver demonstrates signal intensity equal to or lower than that of skeletal muscle, such as the paraspinal muscles, on either T2-weighted gradient echo or T2-weighted spin echo images, increased iron accumulation in the liver can be diagnosed.

Most patients with primary hemochromatosis do not have involvement of the spleen; iron deposition in primary hemochromatosis occurs in the parenchymal cells of the liver (hepatocytes) and not in the reticuloendothelial system (Kupffer cells and spleen). Therefore, splenic signal intensity usually is normal in these patients.

In patients with primary hemochromatosis, iron deposition can occur in the pancreas. Pancreatic involvement is uncommon in patients without cirrhosis. Most cirrhotic patients with primary hemochromatosis have pancreatic involvement and may have type 1 diabetes mellitus. These patients with pancreatic involvement usually demonstrate low signal intensity of the pancreas, regardless of whether they have diabetes.

Many types of anemia require multiple blood transfusions, resulting in abnormal iron deposition in the reticuloendothelial system. These patients demonstrate MR evidence of iron overload in the liver and spleen with low signal of both organs, particularly on T2-weighted gradient echo images. If the reticuloendothelial system becomes saturated with iron from too many transfusions, iron may deposit in the parenchymal cells of the liver, pancreas, and heart. Therefore, these patients may demonstrate low signal in the liver, spleen, and pancreas. [1, 3, 11, 18, 19, 20]

Patients with thalassemia who have not undergone transfusions may have increased iron in the liver with a similar appearance to that in patients with primary hemochromatosis. If these patients are transfusion-dependent, they may demonstrate low signal in the liver and spleen and possibly the pancreas.

Bantu siderosis, a condition found in parts of Africa, causes abnormal iron deposition in the liver. The disorder occurs in patients who drink a large amount of locally brewed beer, which is iron-laden. In addition, these patients have a genetic predisposition for increased iron absorption and have abnormal iron deposition in parenchymal cells (hepatocytes) and in the reticuloendothelial system (Kupffer cells). Bantu siderosis may cause decreased signal intensity of the liver and spleen from abnormal iron deposition in these organs. 

Several types of MRI liver iron content (LIC) measurement have been described in the literature. Straightforward gradient echo (GRE) shows signal loss at the later echo time but is only qualitative and easily confounded by the presence of hepatic steatosis. Quantitative approaches include signal intensity ratio (SIR) measurement and spin-echo (SE) relaxometry. [21]

Utilizing the liver-to-muscle SIR on differently weighted MRI-scans allows easy and free calculation of the LIC, by entering regions-of-interest (ROI) values in an online tool. A major limitation is its upper limit detection of 350 µmol/g (equal to 20 mg/g). A significant number of affected patients actually present an LIC above this threshold. [22]  

SE relaxometry relies on the calculation of tissue relaxation rates (R2 and R2*, the inverse of relaxation times T2 and T2*), which increase as iron accumulates and are sensitive to changes in LIC values with an upper limit of 769 µmol/g (43 mg Fe per g dry liver tissue), well above the SIR-threshold. [22] The commercially available St. Pierre method (FerriScan) is based on T2* analysis of spin-echo (SE) data. It is FDA approved and meets the quality requirements for clinical use, but data have to be transferred for data analysis. In addition to cost, other limitations are the need for scanner calibration and long measurement times. Alternative free-of-charge approaches are available for R2 using free-breathing or respiratory triggered SE-MRI and for R2* using single breath-hold GRE MRI. [21]

Quantitative measurement of hepatic iron content by MRI has the advantage of sampling the entire liver, whereas liver biopsy only samples a small area of liver parenchyma. In addition, quantitative measurement of hepatic iron by MRI avoids the risks inherent in percutaneous liver biopsy. However, a meta-analysis found that T2 spin echo and T2* gradient-recalled echo MRI sequences accurately identified patients without liver iron overload (liver iron concentration greater than 7 mg Fe/g dry liver weight) (negative likelihood ratios, 0.10 and 0.05 respectively), but are less accurate in establishing a definite diagnosis of liver iron overload (positive likelihood ratio, 8.85 and 4.86, respectively). [23]

Although MR is sensitive for detecting abnormal hepatic iron, particularly if performed with optimized technique for this purpose, it may not always determine the etiology of the abnormal iron deposition based on its distribution. However, this is typically not a difficult problem clinically, as the patient's history usually confirms the etiology.

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