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Iron, liver and MRI.
Yves Gandon - Medical Imaging, Rennes, France.
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Introduction |
This document explains the way to detect/quantify liver iron overload
using MR imaging.
It allows you:
- to become familiar with the principle of the MR quantification
of liver iron content and to discover the best indications,
- to perform a study using your MR equipment by chosing the appropriate
MR protocol depending on the field strength of your magnet,
- and to estimate subjectively, or even calculate on-line, the
liver iron content by running a java applet. The calculation algorithm
is also depending on the the magnetic field strength of your MR-scan:
0.5T, 1.0T or 1.5T.
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Context |
Iron is integrated in the hemoglobin cycle. Iron in excess is predominantly
stored in the liver. There is a homeostatic regulation mechanism.
A constant small quantity of iron is daily eliminated by the bile.
The intestinal absorption is regulated in order to keep the iron store
constant.
Two different mechanisms can produce iron overload:
- Non-transfusional iron overload is due to an increase of intestinal
iron absorption and iron is predominantly stored in the liver,
within the hepatocytes where it can exert direct toxicity. This
is typically the mechanism occurring in genetic hemochromatosis,
by genetic dysregulation of intestinal uptake. This can be also
observed in anemia in case of ineffective erythropoïesis.
- Iron overload can also be a consequence of multiple transfusions
needed to treat severe anemias like ß-thalassemia. Iron
is then predominantly deposited in the spleen and in the Kupffer
cells where it is less toxic.
Non-transfusional iron overload is frequent, probably underestimated,
and mainly due in western countries to genetic hemochromatosis or
dysmetabolic hepatosiderosis. Vital risks, such as cirrhosis and
hepatocellular carcinoma can be reduced by an early treatment which
consist on repeated phlebotomies (1).
Iron overload is rarely evoked on specific clinical signs (melanodermia...)
but must often by discovering an elevation of serum iron, transferrin
saturation or ferritinemia or by doing family studies (2).
The diagnosis of genetic hemochromatosis is now based on the specific
genetic test (3). In that case
the level of iron overload is well correlated to the ferritinemia.
In the other diseases, serum tests are not a good reflect of the
liver iron overload (5).
On CT-scan images, liver density increases in case of liver iron
overload. However this is not enough sensitive, particularly in
case of associated steatosis (6).
On the other hand, a liver density greater than 80 HU can of course
be due to a major overload but also to a long term treatment by
amiodarone, a glycogenosis, a Wilson disease… So, CT-scan has no
place for the diagnosis or quantification of iron in the liver.
The gold standard was, up to now, the biopsy with semi-quantitative
assessment by histopathology and quantification of liver iron concentration
(LIC) by biochemical analysis. Now, MRI is able to replace liver
biopsy for this purpose.
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Quantification by MR |
The best non-invasive technique to assess the iron liver content
is MRI. The superparamagnetic properties of iron stored in the liver
explain the decrease of the T2 relaxation times of the liver, which
leads to a decrease of the signal intensity of the hepatic parenchyma
(7).
Previous quantitative studies have tried to quantify major overload
using spin-echo sequences(7-17).
The assessment of liver iron content was one by using liver to muscle
ratio (10, 11,
13, 14,
16, 19,
23-27) or by liver T2 relaxation
time calculation(12, 16,
18, 20,
26). This parameter is more
difficult to obtain and results are probably different from one
equipment to another. This T2 calculation gave less sensitive result
than liver to fat or liver to muscle ratio obtained from T2-weighted
gradient echo sequences (26).
This is easy to understand knowing that gradient echo sequences
are more sensitive to magnetic susceptibility. The use of T2-weighted
gradient echo sequences has permitted to decrease the detection
threshold of liver iron overload (26,
27) by comparison to T2-weighted spin echo gradient sequence
(14) cancelling previous limitations
(22). The use of T2-weighted
gradient echo sequence is necessary to detect a slight iron overload
(28).
Using this type of sequences, the liver is usually hyperintense
to the muscle. A liver hypointense to the muscle indicates a liver
iron overload.
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Normal liver (LIC=20µmol/g, Signa
1.5T)
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GRE "T2+"
TR=120 ms, TE=14 ms, PA=20° |
GRE "PD"
TR=120 ms, TE=4 ms, PA=20° |
GRE "T1"
TR=120 ms, TE=4 ms, PA=90° |
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In case of slight overload, liver signal intensity decrease can only
be seen on T2-weighted gradient echo sequences. The liver is then
hypointense to the muscle.
Slight overload (lic=50µmol/g,
Signa 1.5T)
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GRE "T2+"
TR=120 ms, TE=14 ms, PA=20° |
GRE "PD"
TR=120 ms, TE=4 ms, PA=20° |
GRE "T1"
TR=120 ms, TE=4 ms, PA=90° |
In case of moderate overload the decrease of the liver signal intensity
is depicted on all sequence..
Moderate overload (LIC=120µmol/g,
Signa 1.5T)
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GRE "T2+"
TR=120 ms, TE=14 ms, PA=20° |
GRE "PD"
TR=120 ms, TE=4 ms, PA=20° |
GRE "T1"
TR=120 ms, TE=4 ms, PA=90° |
Major overload cannot be estimated using gradient echo sequences.
Above 300µmol/g, liver signal intensity is at the same level
that the background noise. A less sensitive sequence (a spin echo
sequence with a very short TE around 12 ms) could be used.
Major overload (LIC=350µmol/g,
Signa 1.5T)
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GRE "PD"
TR=120 ms, TE=4 ms, PA=20° |
GRE "T1"
TR=120 ms, TE=4 ms, PA=90° |
GRE "SE "T1"
TR=120 ms, TE=14 ms, PA=20° |
To get a quantitative data we proposed (as many authors 26,
27) to calculate the ratio of the liver signal intensity obtained
by means of ROIs and the signal intensity of paraspinous muscles.
A multicentric study which has enrolled 510 patients had permitted
to define a simple technique available on all types of equipement.
Results obtained allowed to design a calculation software available
on this web site.
If you have the opportunity to check the algorithm proposed in
this site by comparison of MR results and biochemical assessment
of liver iron concentration (LIC) do not hesitate to contact
me.
Details on MR protocol...
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