Diagnosis and quantification of the iron overload through magnetic resonance

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Dos miembros de una misma familia, los dos con la mutación C282Y/H63D y ambos con elevación de la ferritina y del índice de saturación de transferrina. Método de RIS con secuencias en densidad protónica (TR 120ms, TE 4ms, Flip angle 20°) y T2* (TR 120ms, TE 14ms, Flip angle 20°). A) Sobrecarga férrica moderada con CHH de 61μmol Fe/g. B) Sin sobrecarga férrica con CHH de 14μmol Fe/g." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "J.M. Alústiza Echeverría, M.C. Barrera Portillo, A. Guisasola Iñiguiz, A. Ugarte Muño" "autores" => array:4 [ 0 => array:2 [ "nombre" => "J.M." "apellidos" => "Alústiza Echeverría" ] 1 => array:2 [ "nombre" => "M.C." "apellidos" => "Barrera Portillo" ] 2 => array:2 [ "nombre" => "A." "apellidos" => "Guisasola Iñiguiz" ] 3 => array:2 [ "nombre" => "A." 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Mellado, C.D. Packer" "autores" => array:2 [ 0 => array:2 [ "nombre" => "J.M." "apellidos" => "Mellado" ] 1 => array:2 [ "nombre" => "C.D." 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Alústiza Echeverría, M.C. Barrera Portillo, A. Guisasola Iñiguiz, A. Ugarte Muño" "autores" => array:4 [ 0 => array:4 [ "nombre" => "J.M." "apellidos" => "Alústiza Echeverría" "email" => array:1 [ 0 => "jmalustiza@osatek.net" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "M.C." "apellidos" => "Barrera Portillo" ] 2 => array:2 [ "nombre" => "A." "apellidos" => "Guisasola Iñiguiz" ] 3 => array:2 [ "nombre" => "A." "apellidos" => "Ugarte Muño" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Radiología, Hospital Universitario Donostia, San Sebastián, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Diagnóstico y cuantificación de la sobrecarga férrica mediante resonancia magnética" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 928 "Ancho" => 2333 "Tamanyo" => 199890 ] ] "descripcion" => array:1 [ "en" => "Negative genetic study. Patient with high levels of ferritin, and a high transferrin saturation index in blood. Negative genetic study for HFE gene mutations. SIR method with proton density sequences (RT 120ms, ET 4ms, flip angle of 20°), and T2* (RT 120ms, ET 14ms, flip angle of 20°). High iron overload with a great signal reduction in both sequences. LIC: CHH 245μmolFe/g." ] ] ] "textoCompleto" => "IntroductionIron is a key element of many chemical reactions. To avoid the toxicity from its free form it should be bound to a certain protein, and since the organism cannot cleanse the excess of iron, the balance between stores and the losses is very important. An excessive amount of iron will eventually cause iron overloads.<a class="elsevierStyleCrossRef" href="#bib0245">1</a>Iron overloads can be due to different causes. Type 1 hereditary hemochromatosis (HH), bound to the HFE gene, is the most prevalent conditions of all and starts with an increased abdominal absorption of iron. The conditions with an increased destruction of red blood cells are called secondary hemochromatosis or hemosiderosis. Included in the category of secondary hemochromatosis, we find those due to hepatopathies that, due to an unknown mechanism, also cause iron overloads.<a class="elsevierStyleCrossRef" href="#bib0245">1</a>In its maintained excess form, the iron stores in its toxic form in different organs (liver, heart, thyroid, gonads, hypophysis, skin, pancreas) to later determine cell death and fibrosis. The most serious complications are hepatic cirrhosis and heart failure.<a class="elsevierStyleCrossRefs" href="#bib0245">1,2</a>In the HH, the treatment prior to the irreversibility of lesions through phlebotomy procedures is highly effective.<a class="elsevierStyleCrossRef" href="#bib0250">2</a> Patients with iron overloads and anemia, as it is the case with many hemosiderosis, cannot be phlebotomized and iron chelators are used. Recently, new chelating drugs have hit the market, and they are highly effective when taken orally, which has dramatically changed our management of these patients.The first step toward diagnosis is measuring the transferrin saturation index (TSI) and the blood ferritin levels. Both are high in presence of iron overloads.<a class="elsevierStyleCrossRef" href="#bib0255">3</a> When on suspicion of HH, and once the elevation of both parameters has been confirmed, a genetic study of C282Y and H63D mutations of the HFE gene is conducted in order to rule out the most common form of HH.<a class="elsevierStyleCrossRefs" href="#bib0260">4,5</a>The standard method for the direct assessment of iron deposits in the organism is measuring the liver iron concentration (LIC), since 70 per cent of iron stores itself in the liver.<a class="elsevierStyleCrossRef" href="#bib0270">6</a> The LIC is >36μmolFe/g in normal concentrations. In primary and secondary hemochromatosis, the LIC is usually >80μmolFe/g, except in overloads secondary to hepatopathies.<a class="elsevierStyleCrossRefs" href="#bib0250">2,5,7</a> The measurement of the LIC is, therefore, the standard method to diagnose hemochromatosis.Typically, measuring the LIC requires the biopsy of the liver, and quantifications using the spectrophotometry of part of the biopsized material. The biopsy of the liver is an invasive procedure with high result variability due to sample errors. All this justifies the interest for having a non-invasive technique for measuring the LIC.Today, due to its availability and results, the resonance magnetic imaging (RMI) is considered the most interesting non-invasive modality for the quantification of the LIC.<a class="elsevierStyleCrossRef" href="#bib0270">6</a>In this paper we will review the different MRI modalities available for the assessment of iron concentrations in the liver and the myocardium, their indications in different clinical scenarios, and the actual challenges we face in order to optimize and include them in the clinical guidelines.Hepatic magnetic resonance imagineThe MRI detects iron overloads due to the paramagnetic effect of iron that translates into shortened T2 relaxation times, and a reduced signal that is proportional to the LIC. This direct correlation between the liver signal in the MRI and the LIC has been confirmed by numerous works.<a class="elsevierStyleCrossRefs" href="#bib0275">7–12</a>There are two (2) different modalities for the quantification of LICs using MRIs:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">•Measurement of relaxation times or relaxometry.</li><li class="elsevierStyleListItem" id="lsti0010">•Measurement of signal intensity ratios (SIR).</li></ul>Measurement of relaxation times or relaxometryTheoretically speaking, the best most direct method<a class="elsevierStyleCrossRef" href="#bib0280">8</a> for measuring LICs is measuring the T relaxation time in order to quantify its shortening. The T2 value is defined as the time required for transverse magnetization to reach 37 per cent of its original magnitude. Its measurement requires multiple echoes that will eventually allow us to draw the exponential decay curve of the signal in the most precise way possible (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). When gradient echo-sequences are used with respect to the relaxation time measured, this is called T2*.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>Various papers published have quantified LICs using T2 relaxometry studies or T2*, with a high correlation when compared to the quantification of the LIC in the liver biopsy.<a class="elsevierStyleCrossRefs" href="#bib0285">9–12</a> Different studies have obtained mathematical formulas to make reliable transformations of T2 values or T2* into the LIC measured in standard units expressed as μmolFe/g. The results from these mathematical models are reproducible in other machines.<a class="elsevierStyleCrossRefs" href="#bib0295">11,13–15</a>Relaxometry methods are considered the best ones because they can discriminate all iron overloads and measure the iron concentrations in the myocardium. They are the most widely used in research papers and clinical trials.The methods of T2 relaxometry are used in spin echo sequences that last for a few minutes. The most important of all is Ferriscan®,<a class="elsevierStyleCrossRef" href="#bib0295">11</a> approved by the U.S. Food and Drug Administration (FDA) and used in numerous clinical trials. They require prior calibration and cost €200 per patient.The most widely used T2* relaxometry methods with shorter acquisition sequences in apnea are Garbowski et al.’s method,<a class="elsevierStyleCrossRef" href="#bib0285">9</a> and Wood et al.’s method.<a class="elsevierStyleCrossRef" href="#bib0300">12</a>Methods of signal intensity ratioIn these methods, the correlation between the liver intensity signal and that of paravertebral musculature is measured (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>), and used as a standard since it is not affected by the iron overload. Various echo gradient sequences are used. The difference between the liver signal intensity and that of the muscle will basically depend on the LIC. When analyzing signal measurements within the same image, the measurements are subtracted from factors other than the LIC, such as the homogeneity of the magnetic field that equally affects both structures. The study needs to be performed without surface antennas and with the antenna mounted on the gantry so that the result is not influenced by the location of the region of interest (ROI) measured by the signal. The iron overload will look like a reduced liver/muscle ratio (<a class="elsevierStyleCrossRefs" href="#fig0015">Figs. 3 and 4</a>).<elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia>Various SIR methods have compared their results with the quantification of LICs in liver biopsies expressed as μmolFe/g with high correlation.<a class="elsevierStyleCrossRefs" href="#bib0275">7,8,16</a>The most widely recognized method is the one developed by Gandon et al.<a class="elsevierStyleCrossRef" href="#bib0280">8</a> at the University of Rennes, France. In Spain, the Osatek-SEDIA model is widely known too, and uses two (2) of the sequences from the Rennes method but measures the LIC using a different mathematical model. Both methods have free websites available to calculate LICs.<a class="elsevierStyleCrossRefs" href="#bib0280">8,17</a>The most significant advantages of RIS methods are that they are easy to use and highly accessible. They are easily reproducible in any 1.5-T machines.Reproducibility and biasesBoth the relaxometry and the SIR are two methods that have proven high reproducibility when the same acquisition and post-process parameters are used.<a class="elsevierStyleCrossRefs" href="#bib0295">11,13–15,17</a> Also it has been confirmed that there is a correlation between both parameters in overloads <350μmol.<a class="elsevierStyleCrossRef" href="#bib0330">18</a> The methods developed by St. Pierre et al.<a class="elsevierStyleCrossRef" href="#bib0295">11</a> and Osatek-SEDIA<a class="elsevierStyleCrossRef" href="#bib0325">17</a> have phantomas that allow reproducibility in different machines.<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0015">1)Relaxometry</li></ul>In relaxometry, the most important acquisition parameter is the first echo time (ET) that should be under 1ms in T2* relaxometry studies<a class="elsevierStyleCrossRef" href="#bib0335">19</a> in order to be able to find higher iron overloads. Many echoes will be necessary,<a class="elsevierStyleCrossRefs" href="#bib0290">10–15</a> with the shortest interval time of all, approximately, 1ms.<a class="elsevierStyleCrossRef" href="#bib0340">20</a>The type of mathematical modelization of the T2* curve also influences the final result<a class="elsevierStyleCrossRefs" href="#bib0345">21,22</a> and should be reproduced from the original model in order to be able to reproduce the results. The most widely used one is the monoexponential model and typically one correction factor is added to correct the signal of the last echoes; truncation and constant offset are the most widely used ones. However, most companies measure the T2* using linear models,<a class="elsevierStyleCrossRef" href="#bib0345">21</a> but there is still no consensus on the mathematical modelization or the post-processing method.In practice, various machines cannot reproduce the acquisition and post-processing parameters of the standard methods.<a class="elsevierStyleCrossRefs" href="#bib0305">13–15</a> Several works measure the LIC without reproducing the methodology of the original studies, which translates into an important variability of results.<a class="elsevierStyleCrossRef" href="#bib0355">23</a><ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0020">2)Signal intensity ratio (SIR)</li></ul>The SIR methods are also reproducible in different machines, and the measurement of the LIC is not affected by the presence of steatosis in the method designed by the University Rennes, or in the Osatek-SEDIA method<a class="elsevierStyleCrossRef" href="#bib0280">8</a> (<a class="elsevierStyleCrossRef" href="#fig0025">Fig. 5</a>)<elsevierMultimedia ident="fig0025"></elsevierMultimedia>The most important downside of SIR methods is that with very high overload values they become saturated (>250μmol, approx.) (<a class="elsevierStyleCrossRef" href="#fig0030">Fig. 6</a>). In these cases they always recognize that we are dealing with patients with high overloads, but they do not discriminate values above the LIC. This limitation is more significant in the monitoring of iron overloads secondary to chelating drugs.<elsevierMultimedia ident="fig0030"></elsevierMultimedia>The method designed by the University of Rennes is the most widely used, but several studies have confirmed that it has one important bias with a tendency to overestimating LICs.<a class="elsevierStyleCrossRefs" href="#bib0360">24–27</a> In two (2) different studies that compared both methods, the Osatek-SEDIA method proved to be the most accurate of the two.<a class="elsevierStyleCrossRefs" href="#bib0275">7,28</a>Magnetic resonance imaging of the myocardiumCardiomyopathy due to iron deposits in the myocardium is the most serious complication of patients with hemosiderosis, and its depletion using chelating therapy is a determinant factor to improve the survival of some complications, such as thalassemia major.<a class="elsevierStyleCrossRef" href="#bib0385">29</a> Iron deposits in the myocardium occur progressively and on the clinical level they remain silent for a long time. The functional tests that will detect these deposits in late stages are, therefore, not useful for early diagnosis purposes.<a class="elsevierStyleCrossRef" href="#bib0390">30</a>Although higher risks of cardiomyopathy are associated with higher quantities of iron deposits in an organism, this is not always the case. Iron deposits in the myocardium depend on free iron (unbound transferrin), which is also determined by other factors such as the rhythm of transfusions, the coexistence, or not, of inflammatory processes and prior chelating therapies, since some of these decrease the total load, which is not the case of free iron.<a class="elsevierStyleCrossRefs" href="#bib0385">29,31</a>Monitoring iron concentrations in the myocardium requires specific measurements.<a class="elsevierStyleCrossRefs" href="#bib0385">29,31</a> Since the only technique capable of assessing the iron load of the heart is the magnetic resonance imaging (MRI), this imaging modality has been playing an important role in the management and follow-up of patients with hemosiderosis.TechniqueT2* relaxometry methods are used, and there is an inverse correlation between iron concentrations in the myocardium and the T2* value. Lower T2 values represent higher iron concentrations.Multiple echo gradient echo T2-weighted sequences* in short axis projections on the left ventricle, with cardiac synchronization, and one single slice in the medium ventricular segment are used, acquiring all echoes in one single apnea.<a class="elsevierStyleCrossRef" href="#bib0395">31</a> Usually eight (8) different echoes are used<a class="elsevierStyleCrossRef" href="#bib0395">31</a> (<a class="elsevierStyleCrossRef" href="#fig0030">Fig. 6</a>). From the signal of the different echoes, one T2-weighted parametric map* is obtained, usually in the machine, where the T2* can be measured. Since the iron distribution in the myocardium is arranged in patches, and in order to avoid any issues with the sample, the T2* is measured in the intraventricular septum using one ROI including maximum thickness and excluding endocavitary lumen and areas close to the coronary veins.<a class="elsevierStyleCrossRef" href="#bib0395">31</a>Measuring the T2* has proven reproducible and transferable among different centers.<a class="elsevierStyleCrossRefs" href="#bib0395">31,32</a> The T2* values obtained at 1.5T are, actually, the standard. Studies obtained at 3T, although have a correlation with the results obtained at 1.5T, experience greater difficulties with high overload values, show more artifacts, and measure lower T2* values than 1.5T studies.<a class="elsevierStyleCrossRefs" href="#bib0405">33,34</a>Today, the cardiac T2* is the best parameter to monitor chelating therapies in patients with risk of iron overload in their myocardium, and it is used as the standard system in clinical trials of chelating drugs.<a class="elsevierStyleCrossRef" href="#bib0410">34</a>Thalassemia major is hemosiderosis with a higher risk of overload in the myocardium.<a class="elsevierStyleCrossRef" href="#bib0410">34</a> In other types of hemosiderosis much more prevalent in our setting, such as post-transfusion overloads in the myelodysplastic syndrome (MDS), or bone marrow transplants, the risk of cardiac affectation and its clinical repercussions have not been duly assessed. The very first studies published claim that in the myelodysplastic syndrome, we need to see a high number of transfusions (over 50) to be able to detect myocardial iron overloads in the MRI,<a class="elsevierStyleCrossRef" href="#bib0415">35</a> and that iron overload in the liver is a mandatory requirement in all patients.<a class="elsevierStyleCrossRefs" href="#bib0390">30,35,36</a>Magnetic resonance of the pancreasAlthough not widely used in clinical practice yet, the analysis of the presence or absence of iron overloads in the pancreas (something very easy to do with liver MRIs), it is interesting to assess the presence or absence of iron overloads in the myocardium. The mechanism of iron deposits in the pancreas is similar to that of the myocardium, but occurs earlier in time. This is why it is an early, reliable marker of the risk of myocardial overload. A pancreas free from overload has nearly 100 per cent negative predictive value for cardiac iron deposits,<a class="elsevierStyleCrossRef" href="#bib0425">37</a> and it can significantly reduce the need to conduct cardiac MRIs.<a class="elsevierStyleCrossRef" href="#bib0410">34</a> All the papers published so far on pancreatic iron overloads have been conducted through T2* relaxometries.The role of magnetic resonance imaging in clinical practiceHepatic MRIYet despite all the scientific evidence generated during the last thirty years demonstrating the accuracy of MRIs in the measurement of LICs, there is still no consensus on what the indications should be for the management of the different types of iron overloads.<ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0025">1)Hereditary hemochromatosis</li></ul>In the context of a possible hereditary hemochromatosis we include all patients with high levels of ferritin or transferrin saturation, and without any prior hematological conditions or blood transfusions that may justify hemosiderosis, regardless of the results obtained in the genetic study.There is a series of contradictions among the different clinical guidelines available today. The American Association for the Study of Liver Diseases (AASLD) does not take MRIs into consideration. The AASLD claims that iron overloads should be ruled out (through liver biopsies) in non-C282Y/C282Y patients with high levels of ferritin and transferrin saturation. According to the guidelines elaborated by the AASLD, patients with high levels of ferritin and TSI, and C282Y/C282Y mutations, can be treated without having to measure the actual iron overload deposited in the liver.<a class="elsevierStyleCrossRef" href="#bib0260">4</a>For the European Association for the Study of the Liver (EASL), the MRI can reliably diagnose LICs in ranges of clinical significance. The EASL claims that the LIC needs to be measured in all patients with hyperferritinemia in whom inflammation; alcohol abuse; cellular necrosis; and metabolic syndrome have been ruled out, regardless of the assessment of the TSI, or the results coming from the study of HFE gene mutations. The guidelines elaborated by the EASL claim that patients with C282Y/C282Y mutations and never diagnosed of real iron overloads should not be treated.<a class="elsevierStyleCrossRef" href="#bib0265">5</a> The recent clinical guidelines from the European Molecular Genetics Quality Network also claim that C282Y/C282Y homozygous mutations and altered blood tests are not enough to prove presence of HH.<a class="elsevierStyleCrossRef" href="#bib0430">38</a><ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0030">2)Hemochromatosis secondary to hepatopathy</li></ul>In the late cutaneous porphyria, the beneficial effect of iron overload depletion using phlebotomy procedures is a proven fact.<a class="elsevierStyleCrossRef" href="#bib0260">4</a> In the alcoholic liver disease, no beneficial effect derived from using phlebotomy procedures has been confirmed.<a class="elsevierStyleCrossRef" href="#bib0260">4</a> In hepatitis C, iron overloads <45μmol<a class="elsevierStyleCrossRef" href="#bib0260">4</a> should not be treated. Today different studies are under way to analyze therapies using phlebotomy procedures in patients with non-alcoholic fatty liver disease.<ul class="elsevierStyleList" id="lis0030"><li class="elsevierStyleListItem" id="lsti0035">3)Hemochromatosis secondary to hematologic disorders</li></ul>In hemosiderosis, the LIC is the parameter that is best associated with the total amount of iron deposits and, hence, the most reliable marker to prescribe chelating drugs. In this condition, the liver iron stores in Kupffer cells first, making the degree of iron tolerance higher than that of HH; also the liver structural damage starts with higher levels of iron overload.<a class="elsevierStyleCrossRef" href="#bib0340">20</a> The organ that is most severely damaged due to iron overloads is the heart, that will usually set the bar for the prognosis of this condition.<a class="elsevierStyleCrossRef" href="#bib0395">31</a>In clinical practice, ferritin is still the most widely used parameter to monitor iron overloads yet despite its limitations and thanks to its easy accessibility.<a class="elsevierStyleCrossRef" href="#bib0435">39</a> The risk of cardiac affectation is very low with ferritin values <1000mg/l, and high with values >2500mg/l, so, in general, 1000mg/l is the most widely used cut-off value to assess the need to prescribe chelating therapy.<a class="elsevierStyleCrossRef" href="#bib0435">39</a> Iron overloads in the liver also have a correlation with the number of prior blood transfusions.<a class="elsevierStyleCrossRefs" href="#bib0390">30,35</a>Due to the limitations inherent to ferritin, there is general consensus that in all patients, before prescribing any chelating treatments, doctors should have access to MRIs to be able to measure the LIC and the iron concentrations deposited in the myocardium.<a class="elsevierStyleCrossRefs" href="#bib0410">34,39,40</a>In general, the goal of treatment is to keep the LIC within 125μmolFe/g (7mg).<a class="elsevierStyleCrossRef" href="#bib0435">39</a> When it comes to thalassemia intermedia, the limit values accepted are 89μmolFe/g (5mg).<a class="elsevierStyleCrossRef" href="#bib0445">41</a> Today, in the thalassemia major, measuring the LIC through MRIs is indicated, and the dose of the chelating drug is titrated upward with higher LICs, never to exceed the maximum dose of 350μmolFe/g (20mg).<a class="elsevierStyleCrossRef" href="#bib0450">42</a>In patients with myelodysplastic syndrome (MDS), the goal is to keep the LIC within the same range as in the thalassemia major. The chelating treatment is indicated in patients in the periodic transfusion stage that for the last six (6) months have been receiving, at least, 10 concentrates of red blood cells, or whose levels of ferritin are>1000mg/l with TSI>60 per cent.<a class="elsevierStyleCrossRef" href="#bib0455">43</a> Monitoring using liver MRIs is indicated at the beginning and, then, annually.<a class="elsevierStyleCrossRef" href="#bib0455">43</a> The studies published so far confirm that 80 per cent of MDS patients studied through MRIs show liver iron overload deposits.<a class="elsevierStyleCrossRefs" href="#bib0415">35,36</a>Various studies have suggested the impact that iron overloads have on the survival of patients with bone marrow transplants, establishing such correlation based on indirect markers such as ferritin.<a class="elsevierStyleCrossRef" href="#bib0460">44</a> However, the studies that have analyzed the correlation between LICs measured through MRIs have obtained contradictory results.<a class="elsevierStyleCrossRef" href="#bib0465">45</a> This is an important question still unanswered, and of great clinical significance if we think that post-transplant mortality rate is somewhere around 25 per cent.Cardiac MRILike we said, the diagnosis of cardiac iron overloads requires specific monitorization in patients with hemosiderosis. MRI studies performed every 1, or 2 years, or every six months are recommended depending on whether the patient is a low, medium, or high-risk patient.<a class="elsevierStyleCrossRef" href="#bib0410">34</a> The patient's level of risk depends on various factors (degree of ineffective erythropoiesis; hemolysis; genotype; transfusion rate; prior compliance to chelation; results obtained in prior liver; cardiac MRIs, or pancreatic MRIs, etc.).<a class="elsevierStyleCrossRef" href="#bib0410">34</a>Although the typical thing to do is annual MRIs, patients with T2*<10ms; a reduced cardiac function; or prior withdrawal of treatment may require MRIs every semester and, on the contrary, patients with T2*>20ms; a good cardiac function; and good compliance to treatment, may require MRIs every 2 or 3 years.<a class="elsevierStyleCrossRef" href="#bib0440">40</a>In the thalassemia major, the monitorization of iron concentrations in the myocardium is indicated every two years as long as the prior values were normal.<a class="elsevierStyleCrossRef" href="#bib0410">34</a>In MDS patients, it is recommended to rule out iron concentrations in the myocardium through one annual cardiac MRI starting at 50 transfusions,<a class="elsevierStyleCrossRef" href="#bib0415">35</a> and whenever there is an iron overload stored in the liver.<a class="elsevierStyleCrossRefs" href="#bib0390">30,35,36</a> In different series published so far, approximately 18 per cent of all MDS patients studied showed iron overloads in their myocardium.<a class="elsevierStyleCrossRefs" href="#bib0415">35,36</a><ul class="elsevierStyleList" id="lis0035"><li class="elsevierStyleListItem" id="lsti0040">1)Interpreting MRI measurements</li></ul>In practice we usually perform a semiquantitative assessment of patients into three (3) different groups of risk of cardiac affectation following a three color scheme:<ul class="elsevierStyleList" id="lis0040"><li class="elsevierStyleListItem" id="lsti0045">•Green: T2*>20ms, low risk, lack of iron overload.</li><li class="elsevierStyleListItem" id="lsti0050">•Yellow: T2* 10–20ms, intermediate risk, moderate iron overload.</li><li class="elsevierStyleListItem" id="lsti0055">•Red: T2*<10ms, high risk, high iron overload.<a class="elsevierStyleCrossRefs" href="#bib0385">29,40,46</a></li></ul>The risk of heart failure is 160 times higher with T2*<10ms, and 260 times higher with T2*<6ms.<a class="elsevierStyleCrossRef" href="#bib0465">45</a> In the most important prospective study conducted so far in patients with thalassemia major and prior MRIs, 98 per cent of the patients who experienced heart failure the first year after the MRI had a T2* value<10ms (6.7±1.8ms). T2* values<10ms predict heart failure with a 97.5 per cent sensitivity (95 per cent confidence interval [95 per cent CI]: 91.3–99.7) and a 85.3 per cent specificity (95 per cent CI: 83.3–87.2).<a class="elsevierStyleCrossRef" href="#bib0470">46</a> T2* values<20ms are associated with left ventricular dysfunction when the MRI is taken<a class="elsevierStyleCrossRef" href="#bib0395">31</a> and with a higher prevalence of arrhythmias. In the aforementioned prospective study,<a class="elsevierStyleCrossRef" href="#bib0470">46</a> the 98 patients who presented with arrhythmia the first year after the MRI showed T2* values of 13.5±9ms. T2* values<20ms predict arrhythmias with a 82.7 per cent sensitivity (95 per cent CI: 73.7–89.6), and a 53.5 per cent specificity (95 per cent CI: 50.8–56.2).<a class="elsevierStyleCrossRef" href="#bib0470">46</a>With T2* values<10ms, modifications in the chelating therapy are introduced, whether intensifying or combining new drugs,<a class="elsevierStyleCrossRef" href="#bib0410">34</a> which leads to an improvement in ejection fraction confirmed after herapy.<a class="elsevierStyleCrossRef" href="#bib0395">31</a>The MRI also allows us to assess the cardiac function. Although the existence of a correlation between the iron overload and ventricular dysfunction measured through MRIs has been confirmed, today it is widely accepted that low levels of T2* pose a high risk of myocardial affectation even with a normal ventricular function.<a class="elsevierStyleCrossRef" href="#bib0395">31</a>3T magnetic resonance imagingThe paramagnetic susceptibility of iron dramatically increases at 3T, which in turn alters dramatically its MRI assessment. Recent studies show that it is also possible to assess iron overloads at 3T, but this still has not been assessed in multicenter studies.<a class="elsevierStyleCrossRefs" href="#bib0475">47,48</a>ConclusionsThe clinical management of iron overloads has changed dramatically ever since the discovery of HFE gene mutations back in 1992. Nevertheless, the diagnostic algorithms of HH still do not solve the main problem: what patients are considered to be really sick?The new chelating therapies available for patients with hemosiderosis require an accurate quantification of the LIC to determine the need for therapy and also for monitoring purposes.Different studies have confirmed the accuracy of the MRI for the assessment of LICs both through SIR and relaxometry. However, the lack of a standard method is an obstacle for its introduction in clinical guidelines about the management of iron overloads. Today's greatest challenge is to have validated, precise, accessible and reproducible methods that will allow us to move forward to a universal standardization. In the liver, relaxometry techniques are accurate and allow us to see the highest values of overloads. However, these methods are not available yet, because, today, most MRI machines cannot perform acquisition, or post-processing techniques of validated models. These will be the methods of the future but they still have not been fully implemented, or completely standardized today to be called a real alternative in 2017.For all these reasons and yet despite their limitations, the SIR methods are the most realistic alternative today for a standardized practice of the technique. Among the different SIR methods available, the method designed by the University of Rennes, that is widely used, accessible and reproducible, is, nevertheless, not very accurate since it has been proven that it has a tendency to overestimate the concentrations of iron.The cardiac MRI should be accessible in patients with hemosiderosis for the early diagnosis of iron overloads, and also to assess the real clinical repercussion of iron overloads in these patients. Pancreatic MRIs will also play a role in the future by reducing the need to perform cardiac MRIs in most of these patients.Authors<ul class="elsevierStyleList" id="lis0045"><li class="elsevierStyleListItem" id="lsti0060">1.Manager of the integrity of the study: J.M.A., M.C.B.</li><li class="elsevierStyleListItem" id="lsti0065">2.Study idea: J.M.A., M.C.B.</li><li class="elsevierStyleListItem" id="lsti0070">3.Study design: J.M.A., M.C.B.</li><li class="elsevierStyleListItem" id="lsti0075">4.Data mining: J.M.A., M.C.B., A.G., A.U.</li><li class="elsevierStyleListItem" id="lsti0080">5.Data analysis and interpretation: J.M.A., M.C.B.</li><li class="elsevierStyleListItem" id="lsti0085">6.Statistical analysis: J.M.A.</li><li class="elsevierStyleListItem" id="lsti0090">7.Reference: J.M.A., M.C.B., A.G., A.U.</li><li class="elsevierStyleListItem" id="lsti0095">8.Writing: J.M.A., M.C.B., A.G., A.U.</li><li class="elsevierStyleListItem" id="lsti0100">9.Critical review of the manuscript with intellectually relevant remarks: J.M.A., M.C.B., A.G., A.U.</li><li class="elsevierStyleListItem" id="lsti0105">10.Approval of final version: J.M.A., M.C.B.</li></ul>Ethical disclosuresProtection of human and animal subjectsThe authors declare that no experiments were performed on humans or animals for this investigation.Confidentiality of dataThe authors declare that no patient data appears in this article.Right to privacy and informed consentThe authors declare that no patient data appear in this article.Conflicts of interestsThe authors declare no conflict of interests associated with this article whatsoever." "textoCompletoSecciones" => array:1 [ "secciones" => array:15 [ 0 => array:3 [ "identificador" => "xres942180" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec915103" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres942179" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec915104" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Hepatic magnetic resonance imagine" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Measurement of relaxation times or relaxometry" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Methods of signal intensity ratio" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Reproducibility and biases" ] ] ] 6 => array:3 [ "identificador" => "sec0030" "titulo" => "Magnetic resonance imaging of the myocardium" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0035" "titulo" => "Technique" ] ] ] 7 => array:2 [ "identificador" => "sec0040" "titulo" => "Magnetic resonance of the pancreas" ] 8 => array:3 [ "identificador" => "sec0045" "titulo" => "The role of magnetic resonance imaging in clinical practice" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0050" "titulo" => "Hepatic MRI" ] 1 => array:2 [ "identificador" => "sec0055" "titulo" => "Cardiac MRI" ] ] ] 9 => array:2 [ "identificador" => "sec0060" "titulo" => "3 T magnetic resonance imaging" ] 10 => array:2 [ "identificador" => "sec0065" "titulo" => "Conclusions" ] 11 => array:2 [ "identificador" => "sec0070" "titulo" => "Authors" ] 12 => array:3 [ "identificador" => "sec0080" "titulo" => "Ethical disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0085" "titulo" => "Protection of human and animal subjects" ] 1 => array:2 [ "identificador" => "sec0090" "titulo" => "Confidentiality of data" ] 2 => array:2 [ "identificador" => "sec0095" "titulo" => "Right to privacy and informed consent" ] ] ] 13 => array:2 [ "identificador" => "sec0075" "titulo" => "Conflicts of interests" ] 14 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-11-08" "fechaAceptado" => "2017-07-13" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec915103" "palabras" => array:3 [ 0 => "Hemochromatosis" 1 => "Iron overload" 2 => "Magnetic resonance imaging" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec915104" "palabras" => array:3 [ 0 => "Hemocromatosis" 1 => "Sobrecarga férrica" 2 => "Resonancia magnética" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "There are different magnetic resonance techniques and models to quantify liver iron concentration. T2 relaxometry methods evaluate the iron concentration in the myocardium, and they are able to discriminate all the levels of iron overload in the liver. Signal intensity ratio methods saturate with high levels of liver overload and cannot assess iron concentration in the myocardium but they are more accessible and are very standardized. This article reviews, in different clinical scenarios, when magnetic resonance must be used to assess iron overload in the liver and myocardium and analyzes the current challenges to optimize the application of the technique and to be it included in the clinical guidelines." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "Existen diferentes técnicas y modelos de resonancia magnética (RM) para cuantificar la concentración de hierro en el hígado. Los métodos de relaxometría T2, además de evaluar la concentración de hierro en el miocardio pueden discriminar todos los niveles de sobrecarga férrica en el hígado. Los métodos de ratio de intensidad de señal saturan con los altos niveles de sobrecarga en el hígado y no pueden evaluar la concentración de hierro en el miocardio. Sin embargo, son más accesibles y están muy estandarizados. En este artículo se revisan las diferentes técnicas de RM para evaluar la concentración de hierro en el hígado y en el miocardio, sus indicaciones en diferentes escenarios clínicos y los retos actuales para lograr su optimización y su inclusión en las guías clínicas." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Alústiza Echeverría JM, Barrera Portillo MC, Guisasola Iñiguiz A, Ugarte Muño A. Diagnóstico y cuantificación de la sobrecarga férrica mediante resonancia magnética. Radiología. 2017;59:487–495." ] ] "multimedia" => array:6 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1802 "Ancho" => 2500 "Tamanyo" => 428974 ] ] "descripcion" => array:1 [ "en" => "T2* relaxometry. (A) Normal patient, no iron overload. Multiple echo sequence, nine (9) first echoes (RT 21ms, flip angle of 35°, first echo 0.9ms, ET interval=1ms). Liver isosignal in all the echoes. T2: 11.5ms (see the T2 curve in graph A). (B) Polytransfused patient with acute myeloblastic leukemia. MRI before bone marrow transplant. Multiple echo sequence. High liver overload with a reduced liver signal visible from the first echoes. T2*: 2.5ms (see the T2 curve in graph B)." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 610 "Ancho" => 750 "Tamanyo" => 63674 ] ] "descripcion" => array:1 [ "en" => "Signal intensity ratio. Proton density sequence. RT 120ms. ET 4ms. Flip angle of 20°. Patient with iron overload. Three (3) ROIs in the liver over 1cm2, avoiding vascular structures, and two (2) ROIs in the paravertebral musculature. LIC: 17μmolFe/g." ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 547 "Ancho" => 2917 "Tamanyo" => 180459 ] ] "descripcion" => array:1 [ "en" => "Positive genetic study. Two (2) family members with the C282Y/H63D mutation, and both with high levels of ferritin, and a high transferrin saturation index. SIR method with proton density sequences (RT 120ms, ET 4ms, flip angle of 20°), and T2* (RT 120ms, ET 14ms, flip angle of 20°). (A) Moderate iron overload with a LIC of 61μmolFe/g. (B) No iron overload with a LIC of 14μmolFe/g." ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 928 "Ancho" => 2333 "Tamanyo" => 199890 ] ] "descripcion" => array:1 [ "en" => "Negative genetic study. Patient with high levels of ferritin, and a high transferrin saturation index in blood. Negative genetic study for HFE gene mutations. SIR method with proton density sequences (RT 120ms, ET 4ms, flip angle of 20°), and T2* (RT 120ms, ET 14ms, flip angle of 20°). High iron overload with a great signal reduction in both sequences. LIC: CHH 245μmolFe/g." ] ] 4 => array:7 [ "identificador" => "fig0025" "etiqueta" => "Figure 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 1042 "Ancho" => 2344 "Tamanyo" => 153118 ] ] "descripcion" => array:1 [ "en" => "SIR method versus liver biopsy. Correlation between the LIC measured in the liver biopsy and the LIC measured through the MRI in a group of 112 patients with two (2) different SIR models. With both methods we see saturation with values >250μmolFe/g, and how the correlation line moves away from the perfection line with these overload values. (A) Model by the University of Rennes. (B) Osatek-SEDIA model. The model by the University of Rennes shows overestimation with respect to the liver biopsy in values <250μmolFe/g." ] ] 5 => array:7 [ "identificador" => "fig0030" "etiqueta" => "Figure 6" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr6.jpeg" "Alto" => 1871 "Ancho" => 2500 "Tamanyo" => 453741 ] ] "descripcion" => array:1 [ "en" => "T2* relaxometry of the myocardium. Polytransfused patient with liver iron overload deposits. MRI of the myocardium. Multiple echo gradient echo sequence in the short axis projection. Normal myocardium without presence of iron overloads: T2* 32ms. 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Diagnóstico y cuantificación de la sobrecarga férrica mediante resonancia magnética

J.M. Alústiza Echeverría

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jmalustiza@osatek.net

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, M.C. Barrera Portillo, A. Guisasola Iñiguiz, A. Ugarte Muño

Servicio de Radiología, Hospital Universitario Donostia, San Sebastián, Spain

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          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Negative genetic study&#46; Patient with high levels of ferritin&#44; and a high transferrin saturation index in blood&#46; Negative genetic study for HFE gene mutations&#46; SIR method with proton density sequences &#40;RT 120<span class="elsevierStyleHsp" style=""></span>ms&#44; ET 4<span class="elsevierStyleHsp" style=""></span>ms&#44; flip angle of 20&#176;&#41;&#44; and T2&#42; &#40;RT 120<span class="elsevierStyleHsp" style=""></span>ms&#44; ET 14<span class="elsevierStyleHsp" style=""></span>ms&#44; flip angle of 20&#176;&#41;&#46; High iron overload with a great signal reduction in both sequences&#46; LIC&#58; CHH 245<span class="elsevierStyleHsp" style=""></span>&#956;mol<span class="elsevierStyleHsp" style=""></span>Fe&#47;g&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Iron is a key element of many chemical reactions&#46; To avoid the toxicity from its free form it should be bound to a certain protein&#44; and since the organism cannot cleanse the excess of iron&#44; the balance between stores and the losses is very important&#46; An excessive amount of iron will eventually cause iron overloads&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Iron overloads can be due to different causes&#46; Type 1 hereditary hemochromatosis &#40;HH&#41;&#44; bound to the HFE gene&#44; is the most prevalent conditions of all and starts with an increased abdominal absorption of iron&#46; The conditions with an increased destruction of red blood cells are called secondary hemochromatosis or hemosiderosis&#46; Included in the category of secondary hemochromatosis&#44; we find those due to hepatopathies that&#44; due to an unknown mechanism&#44; also cause iron overloads&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">1</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">In its maintained excess form&#44; the iron stores in its toxic form in different organs &#40;liver&#44; heart&#44; thyroid&#44; gonads&#44; hypophysis&#44; skin&#44; pancreas&#41; to later determine cell death and fibrosis&#46; The most serious complications are hepatic cirrhosis and heart failure&#46;<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">1&#44;2</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">In the HH&#44; the treatment prior to the irreversibility of lesions through phlebotomy procedures is highly effective&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">2</span></a> Patients with iron overloads and anemia&#44; as it is the case with many hemosiderosis&#44; cannot be phlebotomized and iron chelators are used&#46; Recently&#44; new chelating drugs have hit the market&#44; and they are highly effective when taken orally&#44; which has dramatically changed our management of these patients&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The first step toward diagnosis is measuring the transferrin saturation index &#40;TSI&#41; and the blood ferritin levels&#46; Both are high in presence of iron overloads&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">3</span></a> When on suspicion of HH&#44; and once the elevation of both parameters has been confirmed&#44; a genetic study of C282Y and H63D mutations of the HFE gene is conducted in order to rule out the most common form of HH&#46;<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">4&#44;5</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The standard method for the direct assessment of iron deposits in the organism is measuring the liver iron concentration &#40;LIC&#41;&#44; since 70 per cent of iron stores itself in the liver&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">6</span></a> The LIC is &#62;36<span class="elsevierStyleHsp" style=""></span>&#956;mol<span class="elsevierStyleHsp" style=""></span>Fe&#47;g in normal concentrations&#46; In primary and secondary hemochromatosis&#44; the LIC is usually &#62;80<span class="elsevierStyleHsp" style=""></span>&#956;mol<span class="elsevierStyleHsp" style=""></span>Fe&#47;g&#44; except in overloads secondary to hepatopathies&#46;<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">2&#44;5&#44;7</span></a> The measurement of the LIC is&#44; therefore&#44; the standard method to diagnose hemochromatosis&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Typically&#44; measuring the LIC requires the biopsy of the liver&#44; and quantifications using the spectrophotometry of part of the biopsized material&#46; The biopsy of the liver is an invasive procedure with high result variability due to sample errors&#46; All this justifies the interest for having a non-invasive technique for measuring the LIC&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Today&#44; due to its availability and results&#44; the resonance magnetic imaging &#40;RMI&#41; is considered the most interesting non-invasive modality for the quantification of the LIC&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">6</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">In this paper we will review the different MRI modalities available for the assessment of iron concentrations in the liver and the myocardium&#44; their indications in different clinical scenarios&#44; and the actual challenges we face in order to optimize and include them in the clinical guidelines&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Hepatic magnetic resonance imagine</span><p id="par0050" class="elsevierStylePara elsevierViewall">The MRI detects iron overloads due to the paramagnetic effect of iron that translates into shortened T2 relaxation times&#44; and a reduced signal that is proportional to the LIC&#46; This direct correlation between the liver signal in the MRI and the LIC has been confirmed by numerous works&#46;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">7&#8211;12</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">There are two &#40;2&#41; different modalities for the quantification of LICs using MRIs&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">&#8226;</span><p id="par0060" class="elsevierStylePara elsevierViewall">Measurement of relaxation times or relaxometry&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">&#8226;</span><p id="par0065" class="elsevierStylePara elsevierViewall">Measurement of signal intensity ratios &#40;SIR&#41;&#46;</p></li></ul></p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Measurement of relaxation times or relaxometry</span><p id="par0070" class="elsevierStylePara elsevierViewall">Theoretically speaking&#44; the best most direct method<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">8</span></a> for measuring LICs is measuring the T relaxation time in order to quantify its shortening&#46; The T2 value is defined as the time required for transverse magnetization to reach 37 per cent of its original magnitude&#46; Its measurement requires multiple echoes that will eventually allow us to draw the exponential decay curve of the signal in the most precise way possible &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; When gradient echo-sequences are used with respect to the relaxation time measured&#44; this is called T2&#42;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">Various papers published have quantified LICs using T2 relaxometry studies or T2&#42;&#44; with a high correlation when compared to the quantification of the LIC in the liver biopsy&#46;<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">9&#8211;12</span></a> Different studies have obtained mathematical formulas to make reliable transformations of T2 values or T2&#42; into the LIC measured in standard units expressed as &#956;mol<span class="elsevierStyleHsp" style=""></span>Fe&#47;g&#46; The results from these mathematical models are reproducible in other machines&#46;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">11&#44;13&#8211;15</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">Relaxometry methods are considered the best ones because they can discriminate all iron overloads and measure the iron concentrations in the myocardium&#46; They are the most widely used in research papers and clinical trials&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">The methods of T2 relaxometry are used in spin echo sequences that last for a few minutes&#46; The most important of all is Ferriscan<span class="elsevierStyleSup">&#174;</span>&#44;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">11</span></a> approved by the U&#46;S&#46; Food and Drug Administration &#40;FDA&#41; and used in numerous clinical trials&#46; They require prior calibration and cost &#8364;200 per patient&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">The most widely used T2&#42; relaxometry methods with shorter acquisition sequences in apnea are Garbowski et al&#46;&#8217;s method&#44;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">9</span></a> and Wood et al&#46;&#8217;s method&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">12</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Methods of signal intensity ratio</span><p id="par0100" class="elsevierStylePara elsevierViewall">In these methods&#44; the correlation between the liver intensity signal and that of paravertebral musculature is measured &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#44; and used as a standard since it is not affected by the iron overload&#46; Various echo gradient sequences are used&#46; The difference between the liver signal intensity and that of the muscle will basically depend on the LIC&#46; When analyzing signal measurements within the same image&#44; the measurements are subtracted from factors other than the LIC&#44; such as the homogeneity of the magnetic field that equally affects both structures&#46; The study needs to be performed without surface antennas and with the antenna mounted on the gantry so that the result is not influenced by the location of the region of interest &#40;ROI&#41; measured by the signal&#46; The iron overload will look like a reduced liver&#47;muscle ratio &#40;<a class="elsevierStyleCrossRefs" href="#fig0015">Figs&#46; 3 and 4</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0105" class="elsevierStylePara elsevierViewall">Various SIR methods have compared their results with the quantification of LICs in liver biopsies expressed as &#956;mol<span class="elsevierStyleHsp" style=""></span>Fe&#47;g with high correlation&#46;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">7&#44;8&#44;16</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">The most widely recognized method is the one developed by Gandon et al&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">8</span></a> at the University of Rennes&#44; France&#46; In Spain&#44; the Osatek-SEDIA model is widely known too&#44; and uses two &#40;2&#41; of the sequences from the Rennes method but measures the LIC using a different mathematical model&#46; Both methods have free websites available to calculate LICs&#46;<a class="elsevierStyleCrossRefs" href="#bib0280"><span class="elsevierStyleSup">8&#44;17</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">The most significant advantages of RIS methods are that they are easy to use and highly accessible&#46; They are easily reproducible in any 1&#46;5-T machines&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Reproducibility and biases</span><p id="par0120" class="elsevierStylePara elsevierViewall">Both the relaxometry and the SIR are two methods that have proven high reproducibility when the same acquisition and post-process parameters are used&#46;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">11&#44;13&#8211;15&#44;17</span></a> Also it has been confirmed that there is a correlation between both parameters in overloads &#60;350<span class="elsevierStyleHsp" style=""></span>&#956;mol&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">18</span></a> The methods developed by St&#46; Pierre et al&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">11</span></a> and Osatek-SEDIA<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">17</span></a> have phantomas that allow reproducibility in different machines&#46;<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">1&#41;</span><p id="par0125" class="elsevierStylePara elsevierViewall">Relaxometry</p></li></ul></p><p id="par0130" class="elsevierStylePara elsevierViewall">In relaxometry&#44; the most important acquisition parameter is the first echo time &#40;ET&#41; that should be under 1<span class="elsevierStyleHsp" style=""></span>ms in T2&#42; relaxometry studies<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">19</span></a> in order to be able to find higher iron overloads&#46; Many echoes will be necessary&#44;<a class="elsevierStyleCrossRefs" href="#bib0290"><span class="elsevierStyleSup">10&#8211;15</span></a> with the shortest interval time of all&#44; approximately&#44; 1<span class="elsevierStyleHsp" style=""></span>ms&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">20</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">The type of mathematical modelization of the T2&#42; curve also influences the final result<a class="elsevierStyleCrossRefs" href="#bib0345"><span class="elsevierStyleSup">21&#44;22</span></a> and should be reproduced from the original model in order to be able to reproduce the results&#46; The most widely used one is the monoexponential model and typically one correction factor is added to correct the signal of the last echoes&#59; truncation and constant offset are the most widely used ones&#46; However&#44; most companies measure the T2&#42; using linear models&#44;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">21</span></a> but there is still no consensus on the mathematical modelization or the post-processing method&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">In practice&#44; various machines cannot reproduce the acquisition and post-processing parameters of the standard methods&#46;<a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">13&#8211;15</span></a> Several works measure the LIC without reproducing the methodology of the original studies&#44; which translates into an important variability of results&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">23</span></a><ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">2&#41;</span><p id="par0145" class="elsevierStylePara elsevierViewall">Signal intensity ratio &#40;SIR&#41;</p></li></ul></p><p id="par0150" class="elsevierStylePara elsevierViewall">The SIR methods are also reproducible in different machines&#44; and the measurement of the LIC is not affected by the presence of steatosis in the method designed by the University Rennes&#44; or in the Osatek-SEDIA method<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">8</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0025">Fig&#46; 5</a>&#41;</p><elsevierMultimedia ident="fig0025"></elsevierMultimedia><p id="par0155" class="elsevierStylePara elsevierViewall">The most important downside of SIR methods is that with very high overload values they become saturated &#40;&#62;250<span class="elsevierStyleHsp" style=""></span>&#956;mol&#44; approx&#46;&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0030">Fig&#46; 6</a>&#41;&#46; In these cases they always recognize that we are dealing with patients with high overloads&#44; but they do not discriminate values above the LIC&#46; This limitation is more significant in the monitoring of iron overloads secondary to chelating drugs&#46;</p><elsevierMultimedia ident="fig0030"></elsevierMultimedia><p id="par0165" class="elsevierStylePara elsevierViewall">The method designed by the University of Rennes is the most widely used&#44; but several studies have confirmed that it has one important bias with a tendency to overestimating LICs&#46;<a class="elsevierStyleCrossRefs" href="#bib0360"><span class="elsevierStyleSup">24&#8211;27</span></a> In two &#40;2&#41; different studies that compared both methods&#44; the Osatek-SEDIA method proved to be the most accurate of the two&#46;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">7&#44;28</span></a></p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Magnetic resonance imaging of the myocardium</span><p id="par0170" class="elsevierStylePara elsevierViewall">Cardiomyopathy due to iron deposits in the myocardium is the most serious complication of patients with hemosiderosis&#44; and its depletion using chelating therapy is a determinant factor to improve the survival of some complications&#44; such as thalassemia major&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">29</span></a> Iron deposits in the myocardium occur progressively and on the clinical level they remain silent for a long time&#46; The functional tests that will detect these deposits in late stages are&#44; therefore&#44; not useful for early diagnosis purposes&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">30</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">Although higher risks of cardiomyopathy are associated with higher quantities of iron deposits in an organism&#44; this is not always the case&#46; Iron deposits in the myocardium depend on free iron &#40;unbound transferrin&#41;&#44; which is also determined by other factors such as the rhythm of transfusions&#44; the coexistence&#44; or not&#44; of inflammatory processes and prior chelating therapies&#44; since some of these decrease the total load&#44; which is not the case of free iron&#46;<a class="elsevierStyleCrossRefs" href="#bib0385"><span class="elsevierStyleSup">29&#44;31</span></a></p><p id="par0180" class="elsevierStylePara elsevierViewall">Monitoring iron concentrations in the myocardium requires specific measurements&#46;<a class="elsevierStyleCrossRefs" href="#bib0385"><span class="elsevierStyleSup">29&#44;31</span></a> Since the only technique capable of assessing the iron load of the heart is the magnetic resonance imaging &#40;MRI&#41;&#44; this imaging modality has been playing an important role in the management and follow-up of patients with hemosiderosis&#46;</p><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Technique</span><p id="par0185" class="elsevierStylePara elsevierViewall">T2&#42; relaxometry methods are used&#44; and there is an inverse correlation between iron concentrations in the myocardium and the T2&#42; value&#46; Lower T2 values represent higher iron concentrations&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">Multiple echo gradient echo T2-weighted sequences&#42; in short axis projections on the left ventricle&#44; with cardiac synchronization&#44; and one single slice in the medium ventricular segment are used&#44; acquiring all echoes in one single apnea&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">31</span></a> Usually eight &#40;8&#41; different echoes are used<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">31</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0030">Fig&#46; 6</a>&#41;&#46; From the signal of the different echoes&#44; one T2-weighted parametric map&#42; is obtained&#44; usually in the machine&#44; where the T2&#42; can be measured&#46; Since the iron distribution in the myocardium is arranged in patches&#44; and in order to avoid any issues with the sample&#44; the T2&#42; is measured in the intraventricular septum using one ROI including maximum thickness and excluding endocavitary lumen and areas close to the coronary veins&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">31</span></a></p><p id="par0195" class="elsevierStylePara elsevierViewall">Measuring the T2&#42; has proven reproducible and transferable among different centers&#46;<a class="elsevierStyleCrossRefs" href="#bib0395"><span class="elsevierStyleSup">31&#44;32</span></a> The T2&#42; values obtained at 1&#46;5<span class="elsevierStyleHsp" style=""></span>T are&#44; actually&#44; the standard&#46; Studies obtained at 3<span class="elsevierStyleHsp" style=""></span>T&#44; although have a correlation with the results obtained at 1&#46;5<span class="elsevierStyleHsp" style=""></span>T&#44; experience greater difficulties with high overload values&#44; show more artifacts&#44; and measure lower T2&#42; values than 1&#46;5<span class="elsevierStyleHsp" style=""></span>T studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0405"><span class="elsevierStyleSup">33&#44;34</span></a></p><p id="par0200" class="elsevierStylePara elsevierViewall">Today&#44; the cardiac T2&#42; is the best parameter to monitor chelating therapies in patients with risk of iron overload in their myocardium&#44; and it is used as the standard system in clinical trials of chelating drugs&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">34</span></a></p><p id="par0205" class="elsevierStylePara elsevierViewall">Thalassemia major is hemosiderosis with a higher risk of overload in the myocardium&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">34</span></a> In other types of hemosiderosis much more prevalent in our setting&#44; such as post-transfusion overloads in the myelodysplastic syndrome &#40;MDS&#41;&#44; or bone marrow transplants&#44; the risk of cardiac affectation and its clinical repercussions have not been duly assessed&#46; The very first studies published claim that in the myelodysplastic syndrome&#44; we need to see a high number of transfusions &#40;over 50&#41; to be able to detect myocardial iron overloads in the MRI&#44;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">35</span></a> and that iron overload in the liver is a mandatory requirement in all patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0390"><span class="elsevierStyleSup">30&#44;35&#44;36</span></a></p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Magnetic resonance of the pancreas</span><p id="par0210" class="elsevierStylePara elsevierViewall">Although not widely used in clinical practice yet&#44; the analysis of the presence or absence of iron overloads in the pancreas &#40;something very easy to do with liver MRIs&#41;&#44; it is interesting to assess the presence or absence of iron overloads in the myocardium&#46; The mechanism of iron deposits in the pancreas is similar to that of the myocardium&#44; but occurs earlier in time&#46; This is why it is an early&#44; reliable marker of the risk of myocardial overload&#46; A pancreas free from overload has nearly 100 per cent negative predictive value for cardiac iron deposits&#44;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">37</span></a> and it can significantly reduce the need to conduct cardiac MRIs&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">34</span></a> All the papers published so far on pancreatic iron overloads have been conducted through T2&#42; relaxometries&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">The role of magnetic resonance imaging in clinical practice</span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Hepatic MRI</span><p id="par0215" class="elsevierStylePara elsevierViewall">Yet despite all the scientific evidence generated during the last thirty years demonstrating the accuracy of MRIs in the measurement of LICs&#44; there is still no consensus on what the indications should be for the management of the different types of iron overloads&#46;<ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">1&#41;</span><p id="par0220" class="elsevierStylePara elsevierViewall">Hereditary hemochromatosis</p></li></ul></p><p id="par0225" class="elsevierStylePara elsevierViewall">In the context of a possible hereditary hemochromatosis we include all patients with high levels of ferritin or transferrin saturation&#44; and without any prior hematological conditions or blood transfusions that may justify hemosiderosis&#44; regardless of the results obtained in the genetic study&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall">There is a series of contradictions among the different clinical guidelines available today&#46; The American Association for the Study of Liver Diseases &#40;AASLD&#41; does not take MRIs into consideration&#46; The AASLD claims that iron overloads should be ruled out &#40;through liver biopsies&#41; in non-C282Y&#47;C282Y patients with high levels of ferritin and transferrin saturation&#46; According to the guidelines elaborated by the AASLD&#44; patients with high levels of ferritin and TSI&#44; and C282Y&#47;C282Y mutations&#44; can be treated without having to measure the actual iron overload deposited in the liver&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">4</span></a></p><p id="par0240" class="elsevierStylePara elsevierViewall">For the European Association for the Study of the Liver &#40;EASL&#41;&#44; the MRI can reliably diagnose LICs in ranges of clinical significance&#46; The EASL claims that the LIC needs to be measured in all patients with hyperferritinemia in whom inflammation&#59; alcohol abuse&#59; cellular necrosis&#59; and metabolic syndrome have been ruled out&#44; regardless of the assessment of the TSI&#44; or the results coming from the study of HFE gene mutations&#46; The guidelines elaborated by the EASL claim that patients with C282Y&#47;C282Y mutations and never diagnosed of real iron overloads should not be treated&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">5</span></a> The recent clinical guidelines from the European Molecular Genetics Quality Network also claim that C282Y&#47;C282Y homozygous mutations and altered blood tests are not enough to prove presence of HH&#46;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">38</span></a><ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">2&#41;</span><p id="par0245" class="elsevierStylePara elsevierViewall">Hemochromatosis secondary to hepatopathy</p></li></ul></p><p id="par0250" class="elsevierStylePara elsevierViewall">In the late cutaneous porphyria&#44; the beneficial effect of iron overload depletion using phlebotomy procedures is a proven fact&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">4</span></a> In the alcoholic liver disease&#44; no beneficial effect derived from using phlebotomy procedures has been confirmed&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">4</span></a> In hepatitis <span class="elsevierStyleSmallCaps">C&#44;</span> iron overloads &#60;45<span class="elsevierStyleHsp" style=""></span>&#956;mol<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">4</span></a> should not be treated&#46; Today different studies are under way to analyze therapies using phlebotomy procedures in patients with non-alcoholic fatty liver disease&#46;<ul class="elsevierStyleList" id="lis0030"><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">3&#41;</span><p id="par0255" class="elsevierStylePara elsevierViewall">Hemochromatosis secondary to hematologic disorders</p></li></ul></p><p id="par0260" class="elsevierStylePara elsevierViewall">In hemosiderosis&#44; the LIC is the parameter that is best associated with the total amount of iron deposits and&#44; hence&#44; the most reliable marker to prescribe chelating drugs&#46; In this condition&#44; the liver iron stores in Kupffer cells first&#44; making the degree of iron tolerance higher than that of HH&#59; also the liver structural damage starts with higher levels of iron overload&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">20</span></a> The organ that is most severely damaged due to iron overloads is the heart&#44; that will usually set the bar for the prognosis of this condition&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">31</span></a></p><p id="par0265" class="elsevierStylePara elsevierViewall">In clinical practice&#44; ferritin is still the most widely used parameter to monitor iron overloads yet despite its limitations and thanks to its easy accessibility&#46;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">39</span></a> The risk of cardiac affectation is very low with ferritin values &#60;1000<span class="elsevierStyleHsp" style=""></span>mg&#47;l&#44; and high with values &#62;2500<span class="elsevierStyleHsp" style=""></span>mg&#47;l&#44; so&#44; in general&#44; 1000<span class="elsevierStyleHsp" style=""></span>mg&#47;l is the most widely used cut-off value to assess the need to prescribe chelating therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">39</span></a> Iron overloads in the liver also have a correlation with the number of prior blood transfusions&#46;<a class="elsevierStyleCrossRefs" href="#bib0390"><span class="elsevierStyleSup">30&#44;35</span></a></p><p id="par0270" class="elsevierStylePara elsevierViewall">Due to the limitations inherent to ferritin&#44; there is general consensus that in all patients&#44; before prescribing any chelating treatments&#44; doctors should have access to MRIs to be able to measure the LIC and the iron concentrations deposited in the myocardium&#46;<a class="elsevierStyleCrossRefs" href="#bib0410"><span class="elsevierStyleSup">34&#44;39&#44;40</span></a></p><p id="par0275" class="elsevierStylePara elsevierViewall">In general&#44; the goal of treatment is to keep the LIC within 125<span class="elsevierStyleHsp" style=""></span>&#956;mol<span class="elsevierStyleHsp" style=""></span>Fe&#47;g &#40;7<span class="elsevierStyleHsp" style=""></span>mg&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">39</span></a> When it comes to thalassemia intermedia&#44; the limit values accepted are 89<span class="elsevierStyleHsp" style=""></span>&#956;mol<span class="elsevierStyleHsp" style=""></span>Fe&#47;g &#40;5<span class="elsevierStyleHsp" style=""></span>mg&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">41</span></a> Today&#44; in the thalassemia major&#44; measuring the LIC through MRIs is indicated&#44; and the dose of the chelating drug is titrated upward with higher LICs&#44; never to exceed the maximum dose of 350<span class="elsevierStyleHsp" style=""></span>&#956;mol<span class="elsevierStyleHsp" style=""></span>Fe&#47;g &#40;20<span class="elsevierStyleHsp" style=""></span>mg&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">42</span></a></p><p id="par0280" class="elsevierStylePara elsevierViewall">In patients with myelodysplastic syndrome &#40;MDS&#41;&#44; the goal is to keep the LIC within the same range as in the thalassemia major&#46; The chelating treatment is indicated in patients in the periodic transfusion stage that for the last six &#40;6&#41; months have been receiving&#44; at least&#44; 10 concentrates of red blood cells&#44; or whose levels of ferritin are<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>1000<span class="elsevierStyleHsp" style=""></span>mg&#47;l with TSI<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>60 per cent&#46;<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">43</span></a> Monitoring using liver MRIs is indicated at the beginning and&#44; then&#44; annually&#46;<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">43</span></a> The studies published so far confirm that 80 per cent of MDS patients studied through MRIs show liver iron overload deposits&#46;<a class="elsevierStyleCrossRefs" href="#bib0415"><span class="elsevierStyleSup">35&#44;36</span></a></p><p id="par0285" class="elsevierStylePara elsevierViewall">Various studies have suggested the impact that iron overloads have on the survival of patients with bone marrow transplants&#44; establishing such correlation based on indirect markers such as ferritin&#46;<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">44</span></a> However&#44; the studies that have analyzed the correlation between LICs measured through MRIs have obtained contradictory results&#46;<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">45</span></a> This is an important question still unanswered&#44; and of great clinical significance if we think that post-transplant mortality rate is somewhere around 25 per cent&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Cardiac MRI</span><p id="par0290" class="elsevierStylePara elsevierViewall">Like we said&#44; the diagnosis of cardiac iron overloads requires specific monitorization in patients with hemosiderosis&#46; MRI studies performed every 1&#44; or 2 years&#44; or every six months are recommended depending on whether the patient is a low&#44; medium&#44; or high-risk patient&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">34</span></a> The patient&#39;s level of risk depends on various factors &#40;degree of ineffective erythropoiesis&#59; hemolysis&#59; genotype&#59; transfusion rate&#59; prior compliance to chelation&#59; results obtained in prior liver&#59; cardiac MRIs&#44; or pancreatic MRIs&#44; etc&#46;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">34</span></a></p><p id="par0295" class="elsevierStylePara elsevierViewall">Although the typical thing to do is annual MRIs&#44; patients with T2&#42;<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleHsp" style=""></span>ms&#59; a reduced cardiac function&#59; or prior withdrawal of treatment may require MRIs every semester and&#44; on the contrary&#44; patients with T2&#42;<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>20<span class="elsevierStyleHsp" style=""></span>ms&#59; a good cardiac function&#59; and good compliance to treatment&#44; may require MRIs every 2 or 3 years&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">40</span></a></p><p id="par0300" class="elsevierStylePara elsevierViewall">In the thalassemia major&#44; the monitorization of iron concentrations in the myocardium is indicated every two years as long as the prior values were normal&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">34</span></a></p><p id="par0305" class="elsevierStylePara elsevierViewall">In MDS patients&#44; it is recommended to rule out iron concentrations in the myocardium through one annual cardiac MRI starting at 50 transfusions&#44;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">35</span></a> and whenever there is an iron overload stored in the liver&#46;<a class="elsevierStyleCrossRefs" href="#bib0390"><span class="elsevierStyleSup">30&#44;35&#44;36</span></a> In different series published so far&#44; approximately 18 per cent of all MDS patients studied showed iron overloads in their myocardium&#46;<a class="elsevierStyleCrossRefs" href="#bib0415"><span class="elsevierStyleSup">35&#44;36</span></a><ul class="elsevierStyleList" id="lis0035"><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">1&#41;</span><p id="par0310" class="elsevierStylePara elsevierViewall">Interpreting MRI measurements</p></li></ul></p><p id="par0315" class="elsevierStylePara elsevierViewall">In practice we usually perform a semiquantitative assessment of patients into three &#40;3&#41; different groups of risk of cardiac affectation following a three color scheme&#58;<ul class="elsevierStyleList" id="lis0040"><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">&#8226;</span><p id="par0320" class="elsevierStylePara elsevierViewall">Green&#58; T2&#42;<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>20<span class="elsevierStyleHsp" style=""></span>ms&#44; low risk&#44; lack of iron overload&#46;</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">&#8226;</span><p id="par0325" class="elsevierStylePara elsevierViewall">Yellow&#58; T2&#42; 10&#8211;20<span class="elsevierStyleHsp" style=""></span>ms&#44; intermediate risk&#44; moderate iron overload&#46;</p></li><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">&#8226;</span><p id="par0330" class="elsevierStylePara elsevierViewall">Red&#58; T2&#42;<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleHsp" style=""></span>ms&#44; high risk&#44; high iron overload&#46;<a class="elsevierStyleCrossRefs" href="#bib0385"><span class="elsevierStyleSup">29&#44;40&#44;46</span></a></p></li></ul></p><p id="par0335" class="elsevierStylePara elsevierViewall">The risk of heart failure is 160 times higher with T2&#42;<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleHsp" style=""></span>ms&#44; and 260 times higher with T2&#42;<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>6<span class="elsevierStyleHsp" style=""></span>ms&#46;<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">45</span></a> In the most important prospective study conducted so far in patients with thalassemia major and prior MRIs&#44; 98 per cent of the patients who experienced heart failure the first year after the MRI had a T2&#42; value<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleHsp" style=""></span>ms &#40;6&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;8<span class="elsevierStyleHsp" style=""></span>ms&#41;&#46; T2&#42; values<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleHsp" style=""></span>ms predict heart failure with a 97&#46;5 per cent sensitivity &#40;95 per cent confidence interval &#91;95 per cent CI&#93;&#58; 91&#46;3&#8211;99&#46;7&#41; and a 85&#46;3 per cent specificity &#40;95 per cent CI&#58; 83&#46;3&#8211;87&#46;2&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">46</span></a> T2&#42; values<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>20<span class="elsevierStyleHsp" style=""></span>ms are associated with left ventricular dysfunction when the MRI is taken<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">31</span></a> and with a higher prevalence of arrhythmias&#46; In the aforementioned prospective study&#44;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">46</span></a> the 98 patients who presented with arrhythmia the first year after the MRI showed T2&#42; values of 13&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9<span class="elsevierStyleHsp" style=""></span>ms&#46; T2&#42; values<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>20<span class="elsevierStyleHsp" style=""></span>ms predict arrhythmias with a 82&#46;7 per cent sensitivity &#40;95 per cent CI&#58; 73&#46;7&#8211;89&#46;6&#41;&#44; and a 53&#46;5 per cent specificity &#40;95 per cent CI&#58; 50&#46;8&#8211;56&#46;2&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">46</span></a></p><p id="par0340" class="elsevierStylePara elsevierViewall">With T2&#42; values<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleHsp" style=""></span>ms&#44; modifications in the chelating therapy are introduced&#44; whether intensifying or combining new drugs&#44;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">34</span></a> which leads to an improvement in ejection fraction confirmed after herapy&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">31</span></a></p><p id="par0345" class="elsevierStylePara elsevierViewall">The MRI also allows us to assess the cardiac function&#46; Although the existence of a correlation between the iron overload and ventricular dysfunction measured through MRIs has been confirmed&#44; today it is widely accepted that low levels of T2&#42; pose a high risk of myocardial affectation even with a normal ventricular function&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">31</span></a></p></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">3<span class="elsevierStyleHsp" style=""></span>T magnetic resonance imaging</span><p id="par0350" class="elsevierStylePara elsevierViewall">The paramagnetic susceptibility of iron dramatically increases at 3<span class="elsevierStyleHsp" style=""></span>T&#44; which in turn alters dramatically its MRI assessment&#46; Recent studies show that it is also possible to assess iron overloads at 3<span class="elsevierStyleHsp" style=""></span>T&#44; but this still has not been assessed in multicenter studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0475"><span class="elsevierStyleSup">47&#44;48</span></a></p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conclusions</span><p id="par0355" class="elsevierStylePara elsevierViewall">The clinical management of iron overloads has changed dramatically ever since the discovery of HFE gene mutations back in 1992&#46; Nevertheless&#44; the diagnostic algorithms of HH still do not solve the main problem&#58; what patients are considered to be really sick&#63;</p><p id="par0360" class="elsevierStylePara elsevierViewall">The new chelating therapies available for patients with hemosiderosis require an accurate quantification of the LIC to determine the need for therapy and also for monitoring purposes&#46;</p><p id="par0365" class="elsevierStylePara elsevierViewall">Different studies have confirmed the accuracy of the MRI for the assessment of LICs both through SIR and relaxometry&#46; However&#44; the lack of a standard method is an obstacle for its introduction in clinical guidelines about the management of iron overloads&#46; Today&#39;s greatest challenge is to have validated&#44; precise&#44; accessible and reproducible methods that will allow us to move forward to a universal standardization&#46; In the liver&#44; relaxometry techniques are accurate and allow us to see the highest values of overloads&#46; However&#44; these methods are not available yet&#44; because&#44; today&#44; most MRI machines cannot perform acquisition&#44; or post-processing techniques of validated models&#46; These will be the methods of the future but they still have not been fully implemented&#44; or completely standardized today to be called a real alternative in 2017&#46;</p><p id="par0370" class="elsevierStylePara elsevierViewall">For all these reasons and yet despite their limitations&#44; the SIR methods are the most realistic alternative today for a standardized practice of the technique&#46; Among the different SIR methods available&#44; the method designed by the University of Rennes&#44; that is widely used&#44; accessible and reproducible&#44; is&#44; nevertheless&#44; not very accurate since it has been proven that it has a tendency to overestimate the concentrations of iron&#46;</p><p id="par0375" class="elsevierStylePara elsevierViewall">The cardiac MRI should be accessible in patients with hemosiderosis for the early diagnosis of iron overloads&#44; and also to assess the real clinical repercussion of iron overloads in these patients&#46; Pancreatic MRIs will also play a role in the future by reducing the need to perform cardiac MRIs in most of these patients&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Authors</span><p id="par0380" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0045"><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">1&#46;</span><p id="par0385" class="elsevierStylePara elsevierViewall">Manager of the integrity of the study&#58; J&#46;M&#46;A&#46;&#44; M&#46;C&#46;B&#46;</p></li><li class="elsevierStyleListItem" id="lsti0065"><span class="elsevierStyleLabel">2&#46;</span><p id="par0390" class="elsevierStylePara elsevierViewall">Study idea&#58; J&#46;M&#46;A&#46;&#44; M&#46;C&#46;B&#46;</p></li><li class="elsevierStyleListItem" id="lsti0070"><span class="elsevierStyleLabel">3&#46;</span><p id="par0395" class="elsevierStylePara elsevierViewall">Study design&#58; J&#46;M&#46;A&#46;&#44; M&#46;C&#46;B&#46;</p></li><li class="elsevierStyleListItem" id="lsti0075"><span class="elsevierStyleLabel">4&#46;</span><p id="par0400" class="elsevierStylePara elsevierViewall">Data mining&#58; J&#46;M&#46;A&#46;&#44; M&#46;C&#46;B&#46;&#44; A&#46;G&#46;&#44; A&#46;U&#46;</p></li><li class="elsevierStyleListItem" id="lsti0080"><span class="elsevierStyleLabel">5&#46;</span><p id="par0405" class="elsevierStylePara elsevierViewall">Data analysis and interpretation&#58; J&#46;M&#46;A&#46;&#44; M&#46;C&#46;B&#46;</p></li><li class="elsevierStyleListItem" id="lsti0085"><span class="elsevierStyleLabel">6&#46;</span><p id="par0410" class="elsevierStylePara elsevierViewall">Statistical analysis&#58; J&#46;M&#46;A&#46;</p></li><li class="elsevierStyleListItem" id="lsti0090"><span class="elsevierStyleLabel">7&#46;</span><p id="par0415" class="elsevierStylePara elsevierViewall">Reference&#58; J&#46;M&#46;A&#46;&#44; M&#46;C&#46;B&#46;&#44; A&#46;G&#46;&#44; A&#46;U&#46;</p></li><li class="elsevierStyleListItem" id="lsti0095"><span class="elsevierStyleLabel">8&#46;</span><p id="par0420" class="elsevierStylePara elsevierViewall">Writing&#58; J&#46;M&#46;A&#46;&#44; M&#46;C&#46;B&#46;&#44; A&#46;G&#46;&#44; A&#46;U&#46;</p></li><li class="elsevierStyleListItem" id="lsti0100"><span class="elsevierStyleLabel">9&#46;</span><p id="par0425" class="elsevierStylePara elsevierViewall">Critical review of the manuscript with intellectually relevant remarks&#58; J&#46;M&#46;A&#46;&#44; M&#46;C&#46;B&#46;&#44; A&#46;G&#46;&#44; A&#46;U&#46;</p></li><li class="elsevierStyleListItem" id="lsti0105"><span class="elsevierStyleLabel">10&#46;</span><p id="par0430" class="elsevierStylePara elsevierViewall">Approval of final version&#58; J&#46;M&#46;A&#46;&#44; M&#46;C&#46;B&#46;</p></li></ul></p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Ethical disclosures</span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Protection of human and animal subjects</span><p id="par0440" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this investigation&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Confidentiality of data</span><p id="par0445" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appears in this article&#46;</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Right to privacy and informed consent</span><p id="par0450" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appear in this article&#46;</p></span></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conflicts of interests</span><p id="par0435" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interests associated with this article whatsoever&#46;</p></span></span>"
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          "identificador" => "sec0005"
          "titulo" => "Introduction"
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          "identificador" => "sec0010"
          "titulo" => "Hepatic magnetic resonance imagine"
          "secciones" => array:3 [
            0 => array:2 [
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              "titulo" => "Measurement of relaxation times or relaxometry"
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              "titulo" => "Reproducibility and biases"
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          "titulo" => "Magnetic resonance imaging of the myocardium"
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          "identificador" => "sec0040"
          "titulo" => "Magnetic resonance of the pancreas"
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          "titulo" => "The role of magnetic resonance imaging in clinical practice"
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              "titulo" => "Hepatic MRI"
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    "fechaRecibido" => "2016-11-08"
    "fechaAceptado" => "2017-07-13"
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            0 => "Hemochromatosis"
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            2 => "Magnetic resonance imaging"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">There are different magnetic resonance techniques and models to quantify liver iron concentration&#46; T2 relaxometry methods evaluate the iron concentration in the myocardium&#44; and they are able to discriminate all the levels of iron overload in the liver&#46; Signal intensity ratio methods saturate with high levels of liver overload and cannot assess iron concentration in the myocardium but they are more accessible and are very standardized&#46; This article reviews&#44; in different clinical scenarios&#44; when magnetic resonance must be used to assess iron overload in the liver and myocardium and analyzes the current challenges to optimize the application of the technique and to be it included in the clinical guidelines&#46;</p></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Existen diferentes t&#233;cnicas y modelos de resonancia magn&#233;tica &#40;RM&#41; para cuantificar la concentraci&#243;n de hierro en el h&#237;gado&#46; Los m&#233;todos de relaxometr&#237;a T2&#44; adem&#225;s de evaluar la concentraci&#243;n de hierro en el miocardio pueden discriminar todos los niveles de sobrecarga f&#233;rrica en el h&#237;gado&#46; Los m&#233;todos de ratio de intensidad de se&#241;al saturan con los altos niveles de sobrecarga en el h&#237;gado y no pueden evaluar la concentraci&#243;n de hierro en el miocardio&#46; Sin embargo&#44; son m&#225;s accesibles y est&#225;n muy estandarizados&#46; En este art&#237;culo se revisan las diferentes t&#233;cnicas de RM para evaluar la concentraci&#243;n de hierro en el h&#237;gado y en el miocardio&#44; sus indicaciones en diferentes escenarios cl&#237;nicos y los retos actuales para lograr su optimizaci&#243;n y su inclusi&#243;n en las gu&#237;as cl&#237;nicas&#46;</p></span>"
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        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Al&#250;stiza Echeverr&#237;a JM&#44; Barrera Portillo MC&#44; Guisasola I&#241;iguiz A&#44; Ugarte Mu&#241;o A&#46; Diagn&#243;stico y cuantificaci&#243;n de la sobrecarga f&#233;rrica mediante resonancia magn&#233;tica&#46; Radiolog&#237;a&#46; 2017&#59;59&#58;487&#8211;495&#46;</p>"
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">T2&#42; relaxometry&#46; &#40;A&#41; Normal patient&#44; no iron overload&#46; Multiple echo sequence&#44; nine &#40;9&#41; first echoes &#40;RT 21<span class="elsevierStyleHsp" style=""></span>ms&#44; flip angle of 35&#176;&#44; first echo 0&#46;9<span class="elsevierStyleHsp" style=""></span>ms&#44; ET interval<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1<span class="elsevierStyleHsp" style=""></span>ms&#41;&#46; Liver isosignal in all the echoes&#46; T2&#58; 11&#46;5<span class="elsevierStyleHsp" style=""></span>ms &#40;see the T2 curve in graph A&#41;&#46; &#40;B&#41; Polytransfused patient with acute myeloblastic leukemia&#46; MRI before bone marrow transplant&#46; Multiple echo sequence&#46; High liver overload with a reduced liver signal visible from the first echoes&#46; T2&#42;&#58; 2&#46;5<span class="elsevierStyleHsp" style=""></span>ms &#40;see the T2 curve in graph B&#41;&#46;</p>"
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          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Signal intensity ratio&#46; Proton density sequence&#46; RT 120<span class="elsevierStyleHsp" style=""></span>ms&#46; ET 4<span class="elsevierStyleHsp" style=""></span>ms&#46; Flip angle of 20&#176;&#46; Patient with iron overload&#46; Three &#40;3&#41; ROIs in the liver over 1<span class="elsevierStyleHsp" style=""></span>cm<span class="elsevierStyleSup">2</span>&#44; avoiding vascular structures&#44; and two &#40;2&#41; ROIs in the paravertebral musculature&#46; LIC&#58; 17<span class="elsevierStyleHsp" style=""></span>&#956;mol<span class="elsevierStyleHsp" style=""></span>Fe&#47;g&#46;</p>"
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          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Positive genetic study&#46; Two &#40;2&#41; family members with the C282Y&#47;H63D mutation&#44; and both with high levels of ferritin&#44; and a high transferrin saturation index&#46; SIR method with proton density sequences &#40;RT 120<span class="elsevierStyleHsp" style=""></span>ms&#44; ET 4<span class="elsevierStyleHsp" style=""></span>ms&#44; flip angle of 20&#176;&#41;&#44; and T2&#42; &#40;RT 120<span class="elsevierStyleHsp" style=""></span>ms&#44; ET 14<span class="elsevierStyleHsp" style=""></span>ms&#44; flip angle of 20&#176;&#41;&#46; &#40;A&#41; Moderate iron overload with a LIC of 61<span class="elsevierStyleHsp" style=""></span>&#956;mol<span class="elsevierStyleHsp" style=""></span>Fe&#47;g&#46; &#40;B&#41; No iron overload with a LIC of 14<span class="elsevierStyleHsp" style=""></span>&#956;mol<span class="elsevierStyleHsp" style=""></span>Fe&#47;g&#46;</p>"
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          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Negative genetic study&#46; Patient with high levels of ferritin&#44; and a high transferrin saturation index in blood&#46; Negative genetic study for HFE gene mutations&#46; SIR method with proton density sequences &#40;RT 120<span class="elsevierStyleHsp" style=""></span>ms&#44; ET 4<span class="elsevierStyleHsp" style=""></span>ms&#44; flip angle of 20&#176;&#41;&#44; and T2&#42; &#40;RT 120<span class="elsevierStyleHsp" style=""></span>ms&#44; ET 14<span class="elsevierStyleHsp" style=""></span>ms&#44; flip angle of 20&#176;&#41;&#46; High iron overload with a great signal reduction in both sequences&#46; LIC&#58; CHH 245<span class="elsevierStyleHsp" style=""></span>&#956;mol<span class="elsevierStyleHsp" style=""></span>Fe&#47;g&#46;</p>"
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          "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">T2&#42; relaxometry of the myocardium&#46; Polytransfused patient with liver iron overload deposits&#46; MRI of the myocardium&#46; Multiple echo gradient echo sequence in the short axis projection&#46; Normal myocardium without presence of iron overloads&#58; T2&#42; 32<span class="elsevierStyleHsp" style=""></span>ms&#46; T2&#42; of the liver&#58; 1&#46;3<span class="elsevierStyleHsp" style=""></span>ms&#46;</p>"
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Article information

ISSN: 21735107
Original language: English

DOI:10.1016/j.rxeng.2017.10.003

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2024 April	2	0	2
2024 March	1	0	1
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2024 January	1	0	1
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2017 November	1	0	1

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