Cardiac sympathetic innervation scintigraphy with <span class="elsevierStyleSup">123</span>I-meta-iodobenzylguanidine. Basis, protocols and clinical applications in Cardiology | Revista Española de Medicina Nuclear e Imagen Molecular (English Edition)

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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall"><elsevierMultimedia ident="tb0005"></elsevierMultimedia></p><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Introduction</span><p id="par0055" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleSup">123</span>I-meta-iodobenzylguanidine &#40;<span class="elsevierStyleSup">123</span>I-MIBG&#41; scintigraphy studies demonstrate the integrity and the status of automomic sympathetic innervation of the myocardium&#44; facilitating qualitative and quantitative global and regional evaluation&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">1</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">One of the main indications of this technique is in patients diagnosed with heart failure &#40;HF&#41;&#44; who have risen in number due to the increase in life expectancy and advances in therapeutic options&#44; thereby giving increasingly greater importance to the knowledge of this study in nuclear medicine&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Here we review the physiopathological basis as well as all the aspects that should be taken into account for correct performance and interpretation of this type of study and the principle clinical applications in cardiology patients&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Physiopathological basis</span><p id="par0070" class="elsevierStylePara elsevierViewall">The autonomic nervous system plays a fundamental role in the regulation of cardiovascular function&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">2</span></a> The heart is densely innervated by a network of autonomic nerve fibers which constantly modulate its activity&#44; balancing the predominantly stimulating sympathetic tone and the mainly inhibitor parasympathic tone&#46; The sympathetic nerves travel in the subepicardium parallel to the vascular structures and penetrate the myocardium&#44; being more sensitive to hypoxia than muscle fibers&#46; Stimulation of the sympathetic nervous system produces an increase in heart rate &#40;HR&#41; and myocardial contractility aimed at increasing cardiac output&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">3</span></a> Noradrenaline &#40;NA&#41; is synthetized in the presynaptic nerve terminal where it is stored in vesicles&#46; After sympathetic activation&#44; NA is released to the synaptic cleft where it interacts with postsynaptic receptors &#945; and &#946; of the myocyte membrane&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">2</span></a> &#946;<span class="elsevierStyleInf">1</span> receptors predominate in the heart and their fundamental action is ventricular contraction&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">4</span></a> There are also receptors in the presynaptic nerve terminal such as &#946;<span class="elsevierStyleInf">2</span>&#44; which facilitates the release of NA from the vesicles&#44; or the &#945;<span class="elsevierStyleInf">2</span> receptors which inhibit the release of NA&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">5</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">MIBG is an NA analog and its structure resembles that of the false neurotransmitter guanethidine&#46; After intravenous administration MIBG diffuses toward the synaptic cleft where it is taken up by the presynaptic sympathetic nerve terminals through the transport 1 process which consumes energy&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">1</span></a> In contrast to NA&#44; MIBG is stored for several hours without being metabolized&#44; thereby allowing the acquisition of images&#46; Thus&#44; myocardial uptake of <span class="elsevierStyleSup">123</span>I-MIBG showing good intensity indicates adequate neuronal innervation and correct functioning of the reuptake 1 system&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">2</span></a> Regional heterogeneity of the ventricular uptake of <span class="elsevierStyleSup">123</span>I-MIBG has been described as having less radioactivity in the apex&#44; the inferior side and the base&#44;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">6</span></a> probably related to 1&#46;1&#37; of the photons of 529<span class="elsevierStyleHsp" style=""></span>keV of <span class="elsevierStyleSup">123</span>I&#44; since this is not reported with the PET radiotracers <span class="elsevierStyleSup">11</span>C-hydroxyephedrine and <span class="elsevierStyleSup">18</span>F-fluorodopamine&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">7</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">Following intravenous administration of <span class="elsevierStyleSup">123</span>I-MIBG&#44; the CTR or ratio of radioactivity between the heart and the mediastinum in the delayed images and the percentage of lavage between the early and delayed images show the cardiac activity of the sympathetic nervous system and sympathetic nerve tone&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">4</span></a> That is&#44; the washout shows not only the capacity of the presynaptic neurons to retain the radiotracer but also the competence by the circulating NA&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleSup">123</span>I-MIBG studies show the denervation associated with a variety of diseases&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">6</span></a> Thus&#44; in patients with HF this study has be shown to have independent prognostic value for death and cardiac events&#44;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">8</span></a> and it is useful for predicting arrhythmias&#44;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">9</span></a> as well as for evaluating response to medical treatment and cardiac devices&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">10</span></a> It is also useful in transplantation&#44; in diabetes mellitus&#44; cardiotoxicity due to chemotherapy and cardiac involvement by systemic processes such as Parkinson disease<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">2</span></a> and amyloidosis&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">11</span></a> Approval of <span class="elsevierStyleSup">123</span>I-MIBG for clinical use in the United States was achieved in 2013 after years of experience in Japan&#44; Europe and Brazil&#44;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">12</span></a> and its principal cardiological indication is in patients with class II or III HR according to the New York Heart Association &#40;NYHA&#41; and a left ventricular ejection fraction &#40;FEVI&#41;<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>35&#37; for evaluating risk and helping in the decision as to whether to implant and implantable automatic defibrillator &#40;IAD&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">1</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Performing the study</span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Information for the patient and clinical history</span><p id="par0090" class="elsevierStylePara elsevierViewall">It is important for the patient to have previous knowledge of the methodology of the study in relation to the way it is administered&#44; the chronological sequence and the time of gamma camera image acquisition in order to reduce patient anxiety during the diagnostic study&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">From the point of view of radiological protection&#44; <span class="elsevierStyleSup">123</span>I is a low energy &#40;159<span class="elsevierStyleHsp" style=""></span>keV&#41;&#44; short-life isotope &#40;13&#46;2<span class="elsevierStyleHsp" style=""></span>h&#41; which does not require exceptional isolation measures even in the setting of hospital admission&#46; Nonetheless&#44; due to the radioactive nature of the study the patient should be informed that during 24&#8211;48<span class="elsevierStyleHsp" style=""></span>h after the procedure contact with children and pregnant women should be minimal&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">In the case of a breastfeeding woman&#44; it is recommended to temporarily suspend breastfeeding for 48<span class="elsevierStyleHsp" style=""></span>h&#44; and in the case of a pregnant woman the indication and need for the study should be assessed considering the benefits versus the risks of administering a radiopharmaceutical&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">It is also convenient to have clinical information of the patient including medications and any cardiovascular study undertaken&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Patient preparation</span><p id="par0110" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Thyroid blockade&#46;</span> It is recommendable to block the thyroids to avoid the uptake of <span class="elsevierStyleSup">123</span>I not bound to the radiotracer &#40;free <span class="elsevierStyleSup">123</span>I&#41;&#46; This can be done with oral potassium perchlorate &#40;400<span class="elsevierStyleHsp" style=""></span>mg for adults&#59; according to weight in children&#58; 3&#8211;6<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#41; 30<span class="elsevierStyleHsp" style=""></span>min prior to intravenous injection or with a potassium iodine or Lugol solution &#40;100&#8211;130<span class="elsevierStyleHsp" style=""></span>mg&#47;day in adults&#44; and according to weight and age in children&#41; beginning 1 or 2 days before the procedure and continuing for 2 days afterwards&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Drug withdrawal&#46;</span> Pharmacological interaction with the cardiac uptake of <span class="elsevierStyleSup">123</span>I-MIBG has been described&#46; Therefore&#44; it is necessary to suspend the following drugs&#58; tricyclic antidepressants&#44; sympathetic mimetic drugs&#44; antipsychotics&#44; specific antihypertensive drugs&#44; opioids&#44; cocaine and tramadol &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; In contrast to oncological studies with <span class="elsevierStyleSup">123</span>I-MIBG&#44; there is scientific evidence showing that it is not necessary to withdraw beta-blockers&#44; angiotensin converting enzyme inhibitors and angiotensin receptor blockers for cardiac studies&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">13</span></a> In addition&#44; according to a subanalysis of the ADMIRE study&#44; neither is it necessary to withdraw calcium channel blockers nor beta-agonist bronchodilator medications used in patients with respiratory disease&#46;<a class="elsevierStyleCrossRefs" href="#bib0350"><span class="elsevierStyleSup">14&#44;15</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0120" class="elsevierStylePara elsevierViewall">With regard to foods&#44; it is recommended to avoid the intake of compounds containing vanilla extract &#40;the principal element of the vanilla flavor used in the preparation of different food products&#41;&#44; chocolate&#44; and blue cheese due to their content of substances similar to catecholamines&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">1</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Radiotracer administration</span><p id="par0125" class="elsevierStylePara elsevierViewall">An intravenous line is placed and after 5&#8211;15<span class="elsevierStyleHsp" style=""></span>min of rest in supine the patient is slowly administered the radiotracer over 1&#8211;2<span class="elsevierStyleHsp" style=""></span>min followed by lavage with saline solution&#46; Although lower radioactivities of 3&#8211;5<span class="elsevierStyleHsp" style=""></span>mCi &#40;111&#8211;185<span class="elsevierStyleHsp" style=""></span>MBq&#41; were initially used&#44; the radioactivity recommended<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">1</span></a> for a patient of 70<span class="elsevierStyleHsp" style=""></span>kg is 10<span class="elsevierStyleHsp" style=""></span>mCi &#40;370<span class="elsevierStyleHsp" style=""></span>MBq&#41; in order to obtain adequate image quality for both planar and SPECT taking into account that many of these patients have severe sympathetic impairment&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">It is infrequent for adverse reactions to appear after the administration of <span class="elsevierStyleSup">123</span>I-MIBG&#46; However&#44; in cases in which the radiotracer is administered rapidly&#44; the patient may present palpitations&#44; the sensation of heat&#44; dyspnea or transitory hypertension&#46; The presentation of an anaphylactic reaction is exceptional&#46; <span class="elsevierStyleSup">123</span>I-MIBG is contraindicated in patients showing hypersensitivity to this compound in previous studies&#46; Allergy to iodine contrast is not a contraindication&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Image acquisition</span><p id="par0135" class="elsevierStylePara elsevierViewall">Following intravenous administration of the radiotracer static planar images of the thorax are obtained at 15&#8211;20<span class="elsevierStyleHsp" style=""></span>min and at 4<span class="elsevierStyleHsp" style=""></span>h&#46; These images allow evaluation of the binding of the radiotracer to the myocardium and the remaining surrounding organs&#46; The image in anterior projection is essential to assess myocardial uptake both visually and semiquantitatively by obtaining the CTR which is the quantitative value used in practice to express global cardiac sympathetic activity&#46; However&#44; it is recommended to additionally perform single photon emission computed tomography &#40;SPECT&#41;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">1</span></a> to evaluate the regional distribution of the sympathetic radioactivity which could have greater value for predicting arrhythmias than global evaluation&#46; <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> shows the parameters recommended<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">1&#44;13</span></a> for obtaining these planar and SPECT images&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0140" class="elsevierStylePara elsevierViewall">Review of all the images obtained is essential to confirm adequate technical quality and the absence of patient movement during image acquisition&#44; among other aspects&#44; prior to image processing&#46; An important aspect is the choice of the type of collimator to be used since although in most studies low energy high resolution &#40;LEHR&#41; collimators have been used from the beginning and CTR limits of normality were established with these collimators&#44; decay in the quality of the image has been described &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41; due to septal penetration of other less abundant&#44; albeit high energy&#44; photons which also emit <span class="elsevierStyleSup">123</span>I&#44; together with its principal photopeak of 159<span class="elsevierStyleHsp" style=""></span>keV which leads to underestimation of the CTR&#46; The quality of the image improves and higher CTR values are obtained with medium energy general purpose &#40;MEGP&#41; collimators&#44; and in order to carry out comparative evaluation of the results&#44; Nakajima and Nakata<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">16</span></a> proposed the application of a correction factor derived by calibration with phantom&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0145" class="elsevierStylePara elsevierViewall">The use of solid-state gamma cameras provides greater image resolution and greater quality SPECT and can allow better evaluation of the regional cardiac sympathetic activity while also establishing the CTR values of normality with this type of equipment&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">1</span></a></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Semiquantitative evaluation</span><p id="par0150" class="elsevierStylePara elsevierViewall">For correct quantification of the CTR regions of interest must be created in the cardiac and mediastinal area to determine the ratio &#40;mean count&#41; between the two in both the early and delayed images while also determining the variation of the myocardial washout rate between the two Images&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">17</span></a> Due to the scarce physiological sympathetic activity of the mediastinum&#44; it is considered the most appropriate zone for background radioactivity to establish this assessment&#46; Myocardial uptake is normally rapid after radiotracer administration&#44; slightly decreasing during the following hours&#44; reflecting neuronal integrity&#46; When there is decay in the cardiac sympathetic activity in addition to a reduction in the initial uptake&#44; more rapid washout can be observed&#44; being associated with a worse prognosis&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">17</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">It is recommended to create an area which covers the whole myocardium&#44; carefully avoiding the inclusion of adjacent pulmonary and hepatic activity&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">18</span></a> The area could be ellipsoidal&#44; circular or better adapted manually to the shape of the myocardium &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>A&#41; since these patients usually present ventricular dilatation&#44; but care should be taken to use the same area in both the early and delayed Images&#46;<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">1&#44;13</span></a> It may even be helpful to create the myocardial area over the planar image obtained with a perfusion radiotracer &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>B&#41;&#44; especially in cases with severe innervation deterioration&#44; since it is sometimes useful to obtain a planar myocardial perfusion and SPECT study which provides complementary information for correct assessment of the defects of innervation and perfusion together&#46; It is recommended that the mediastinal area be rectangular in the central zone of the upper mediastinum and below the thyroid radioactivity which can be weakly observed if thyroid blockade is correct &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>A&#41;&#46; It is essential to process the early and delayed images at the same time always using the same myocardial and mediastinal area in both Images&#46;<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">1&#44;17&#44;18</span></a> The myocardial washout rate is obtained according to the formula shown in <a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>C in which correction for decay is applied for <span class="elsevierStyleSup">123</span>I in the delayed Image&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">13</span></a></p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Processing of SPECT</span><p id="par0160" class="elsevierStylePara elsevierViewall">The SPECT images can be processed as if they were a myocardial SPECT&#44; obtaining the tomographic slices to evaluate the localization and extension of the alterations of sympathetic innervation&#46; It is of interest to represent the perfusion and innvervation slices together &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41; in cases in which both studies are performed in order to optimize the orientation of the slices&#44; especially in cases with severe denervation and to improve the interpretation of the findings&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">17</span></a> Correction of attenuation&#44; compensation of dispersion and iterative reconstruction methods may be performed to improve the SPECT images depending on the technical options available in each case and always comparing the corrected with the non corrected Images&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">13</span></a> Semiquantitative evaluation of the SPECT images can also be made&#44; while also performing a similar analysis of perfusion&#44; the grades of reduced radioactivity &#40;score 0&#8211;4&#41; and its localization in the model of 17 usual segments&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">17</span></a> The possibility of obtaining cardiac <span class="elsevierStyleSup">123</span>I-MIBG SPECT&#47;CT has even been described&#44; which could improve the localization and quantification of the areas of denervation&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">19</span></a></p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Study report</span><p id="par0165" class="elsevierStylePara elsevierViewall">With regard to published recommendations related to preparing the report of this exploration&#44;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">20</span></a> visual evaluation of the global myocardial uptake and quantification of the CTR are requisites in addition to the usual data on the clinical manifestations of the patient&#44; the indication for the study and the description of the technique used&#46; It is recommended to include the pattern of uptake&#44; whether it is homogeneous or presents diffuse or localized reduced uptake&#44; calculation of the myocardial washout rate as well as assess the extension&#44; severity and the localization of the defects by SPECT&#46;</p></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Reproducibility and normal values</span><p id="par0170" class="elsevierStylePara elsevierViewall">The main quantitative parameters derived from the images with <span class="elsevierStyleSup">123</span>I-MIBG are&#44; as mentioned previously&#44; the CTR in the images at 4<span class="elsevierStyleHsp" style=""></span>h and the washout rate&#46; It is important to standardize the obtainment of the quantitative parameters to establish the normal values for correct stratification of risk since&#44; depending on the methods used for attainment&#44; important variations many be found&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">The values obtained can be influenced by the type of gamma camera &#40;solid-state Anger&#41; used&#44; the time of image acquisition&#44; the size and localization of the areas of interest of the heart and mediastinum&#44;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">21</span></a> as well as the experience in delimiting these&#44; especially in patients with severe heart failure&#46; Moreover&#44; the type and even different trademarks of collimator used can have an impact on these values&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">22</span></a> In general&#44; from the technical point of view&#44; the CTR is higher in the images obtained with MEGP collimators compared with those obtained with LEHR collimators as mentioned previously&#46; Based on these differences in the CTR&#44; different cut-off values have been proposed for the different collimators as well as conversion algorithms among the different apparatus&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">23</span></a></p><p id="par0180" class="elsevierStylePara elsevierViewall">Many of the studies published to date are based on the obtainment of images using LEHR collimators with a energy window centered at 20&#37; around the photopeak of the principal isotope which is of 159<span class="elsevierStyleHsp" style=""></span>keV&#46; The differences between collimators are also related to the different energy of <span class="elsevierStyleSup">123</span>I emission&#44; some being of high energy&#46; Although the proportion of this emission is small in relation to the principal peak&#44; LEHR collimators allow the penetration of more energetic photons which decay the quality of the image and affect the quantitative values such as CTR&#46; There are some promising recently published studies on the image of <span class="elsevierStyleSup">123</span>I-MIBG in solid-state gamma cameras&#44; but considering what was previously mentioned&#44; the quantitative values obtained could be somewhat different from those of a conventional gamma camera&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">1</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">Based on the data from the Working Group of the Japanese Society of Nuclear Medicine&#44; the normal early and delayed CTR values are 2&#46;39<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;21 &#40;mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#41;&#44; 2&#46;49<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;25 for the LEHR collimator and 2&#46;76<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;31 and 3&#46;01<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;35 for the MEGP collimator&#44; respectively&#46; Similarly&#44; in 11 studies carried out in Europe and the United States&#44; the mean delayed CTR varied from 1&#46;77 to 2&#46;50&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">16</span></a></p><p id="par0190" class="elsevierStylePara elsevierViewall">The normal myocardial washout value is considered to be 10<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#37;&#44; with values higher than 27&#37; being associated with a worse prognosis&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">2</span></a> However&#44; there is no full consensus for this cut-off value&#44;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">17</span></a> and therefore more studies with a larger number of patients and using standardized techniques are needed&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">The effect of advanced age on <span class="elsevierStyleSup">123</span>I-MIBG uptake is controversial&#46; In healthy subjects an increase in cardiac uptake of <span class="elsevierStyleSup">123</span>I-MIBG has been described&#44; reflecting the increase in sympathatetic tone with age but with CTR stability&#44; since uptake in the mediastinum is also increased&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">24</span></a> However&#44; in patients with HF a reduction has been observed in early and delayed CTR ratios with a progressive increase in <span class="elsevierStyleSup">123</span>I-MIBG washout&#44; making it necessary to adjust the cut-off level for correct evaluation of risk in these patients&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">25</span></a></p><p id="par0200" class="elsevierStylePara elsevierViewall">Finally&#44; it is important to mention that within the context of the same methodology&#44; some studies have shown intra- and interobserver variability of less than 5&#37; in these parameters&#44; and it has recently been reported that the CTR of <span class="elsevierStyleSup">123</span>I-MIBG is a consistent and highly reproducible measurement in patients with class II-III HF&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">26</span></a></p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Dosimetry</span><p id="par0205" class="elsevierStylePara elsevierViewall">The summary of product characteristics of the radiopharmaceutical<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">27</span></a> describes the internal dosimetry &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41; of the radiation calculated according to Publication no&#46; 80 of the International Commission of Radiological Protection &#40;ICRP&#41;&#46; For 370<span class="elsevierStyleHsp" style=""></span>MBq of radioactivity administered&#44; the typical radiation dose in the target organ &#40;heart&#41; is 6&#46;7<span class="elsevierStyleHsp" style=""></span>mGy&#44; being 24&#46;6<span class="elsevierStyleHsp" style=""></span>mGy in the liver&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0210" class="elsevierStylePara elsevierViewall">For an adult of 70<span class="elsevierStyleHsp" style=""></span>kg the effective dose resulting from the administration of radioactivity of 370 MBq &#40;maximum recommended&#41; is 4&#46;8<span class="elsevierStyleHsp" style=""></span>mSv&#44; which is a much lower dose than the 16<span class="elsevierStyleHsp" style=""></span>mSv used in a thoracic CT with contrast for the study of coronary arteries&#46;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">28</span></a></p><p id="par0215" class="elsevierStylePara elsevierViewall">Hydratation prior to and after administration of the radiotracer is important to ensure rapid elimination&#46; The recommendations of radiological protection should also be taken into account to avoid close contact of the patient with small children or pregnant women&#44; as stated previously in the section on patient information&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Clinical applications</span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Heart failure</span><p id="par0220" class="elsevierStylePara elsevierViewall">It is possible to maintain blood flow to vital organs during states of low cardiac output thanks to the activation of the sympathetic nervous&#44; renin&#8211;angiotensin&#8211;aldosterone and antidiuretic hormone systems&#46; An increase in myocardial contractility and HR&#44; vasoconstriction with maintenance of systemic pressure and expansion of extracelullar volume are basic compensatory mechanisms<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">29</span></a> which are initially favorable but produce neurohormonal alterations and structural changes in the myocardium in the long term and increase the probability of arrhythmias and cardiac death&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">10</span></a> Thus&#44; in initial phases of ventricular failure&#44; the levels of NA in blood are slightly raised&#44; but as the disease progresses&#44; the transport 1 system is not able to take up NA in the synaptic cleft&#44; producing excessive stimulation of the postsynaptic receptors in myocytes and a loss of sensitivity of these receptors&#46; The excess NA in the synaptic cleft activates the presynaptic &#946;2 receptors&#44; facilitating the release and gradual depletion of NA stored in the vesicles&#46; In cases of severe HF&#44; the presynaptic nerve terminals are damaged and become fibrotic&#44; leading to reduced MIBG uptake and retention&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">5</span></a></p><p id="par0225" class="elsevierStylePara elsevierViewall">Continued activation of the sympathetic system leads to hypertrophy and fibrosis with ventricular remodeling&#44; attenuation of cardiovascular reflexes and sympathetic denervation&#44; which directly contributes to disease progression and a worse prognosis&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">10</span></a></p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Prognostic value</span><p id="par0230" class="elsevierStylePara elsevierViewall">The AdreView Myocardial Imaging for Risk Evaluation in Heart Failure &#40;ADMIRE HF&#41; and HFX studies<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">8&#44;30</span></a> have consistently shown an inverse relation between myocardial uptake of <span class="elsevierStyleSup">123</span>I-MIBG and the risk of cardiac events and sudden death&#44; with CTR values<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>1&#46;6 being associated with increased risk of these events&#46; This relation is independent of the origin of HF&#44; being valid in both HF of ischemic and non ischemic origin<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">16</span></a> and notably valid in HF with forced expiratory volume in one second &#40;FEVI&#41;<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>35&#37;&#44; although it has also been shown with FEVI<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>35&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">2</span></a></p><p id="par0235" class="elsevierStylePara elsevierViewall">CTR values<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>1&#46;6&#8211;1&#46;8 and elevated washout rates are considered indicators of high risk of death due to ventricular failure&#44; sudden cardiac death and malignant arrhythmias and have an independent prognostic value additionally to the clinical parameters&#44; including the NYHA functional class&#44; FEV1&#44; cerebral natriuretic peptide and age&#46;<a class="elsevierStyleCrossRefs" href="#bib0290"><span class="elsevierStyleSup">2&#44;16</span></a></p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Prediction of arrhythmias</span><p id="par0240" class="elsevierStylePara elsevierViewall">Primary prevention with an implantable automatic defibrillator &#40;IAD&#41; has a level IA indication in patients with HF with a NYHA functional class II-III and FEVI<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>35&#37;&#46; However&#44; most patients with these criteria never require an IAD shock&#44;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">31</span></a> while there are deaths due to arrhythmia in patients without an indication for IAD&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">9</span></a> Regional myocardial uptake of <span class="elsevierStyleSup">123</span>I-MIBG by SPECT may be of value for predicting sudden cardiac death in patients with chronic HR&#44;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">31</span></a> improving the prediction based only on the FEVI&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Response to treatment</span><p id="par0245" class="elsevierStylePara elsevierViewall">Studies with <span class="elsevierStyleSup">123</span>I-MIBG are useful for the evaluation of response to medical treatment with beta-blockers&#44; renin&#8211;angiotensin&#8211;aldosterone system &#40;RAAS&#41; inhibitors and the combination of both&#44; showing a relationship between an increase in CTR and a reduction in washout with improvement in the NYHA functional class&#44; FEV1 or tolerance to exercise&#44; and some data suggest that these studies can predict the response to treatment before its initiation&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">16</span></a> An increase in <span class="elsevierStyleSup">123</span>I-MIBG has been reported after treatment with beta-blockers&#44; RAAS inhibitors&#44; angiotensin receptors blockers and mineralcorticoides as well as diuretics&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">7</span></a></p><p id="par0250" class="elsevierStylePara elsevierViewall">With regard to cardiac devices&#44; IAD and cardiac resynchronization therapy &#40;CRT&#41; prevent sudden cardiac death by arrhythmias and delay progressive ventricular failure&#44; respectively&#46; Myocardial denervation is associated with appropriate IAD shocks&#44; and myocardial uptake of <span class="elsevierStyleSup">123</span>I-MIBG improves with symptomatic and functional response to CRT&#46; It is interesting to note that basal uptake &#40;CTR<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>1&#46;6&#41; predicts a positive response to CRT in patients with dyssynchrony&#44; with the frequency of response to CRT being lower in patients with a CTR<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>1&#46;6&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">16</span></a></p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Coronary diseases</span><p id="par0255" class="elsevierStylePara elsevierViewall">The indications of <span class="elsevierStyleSup">123</span>I-MIBG in the study of coronary diseases include the study of HF of ischemic origin and evaluation of cardiac innervation in the presence of ischemic heart disease&#44; including situations of myocardial hibernation and postinfarction&#46;</p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Ischemic heart failure</span><p id="par0260" class="elsevierStylePara elsevierViewall">In patients with ischemic HF&#44; <span class="elsevierStyleSup">123</span>I-MIBG cardiac innervation scintigraphy has the same independent prognostic value as that in patients with non ischemic HF&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">32</span></a></p><p id="par0265" class="elsevierStylePara elsevierViewall">The group of Matsuo et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">32</span></a> followed 1322 patients with HF&#44; including a subgroup of 362 patients with ischemic HF&#44; for 10 years and found that the CTR in the delayed image was an independent predictive factor of lethal events&#46; Thus&#44; 88&#46;2&#37; of the patients who died in the context of ischemic HF presented a CTR<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>2&#46;0&#46; In this subgroup there was a higher proportion of deaths by myocardial infarction or sudden death than in the subgroup of patients with non ischemic HF&#46; These authors concluded that measurement of sympathetic innervation of the heart by <span class="elsevierStyleSup">123</span>I-MIBG scintigraphy can therefore stratify the risk of patients with ischemic HF as well as that of those with non ischemic HF&#46;</p><p id="par0270" class="elsevierStylePara elsevierViewall">The mechanism by which a reduction in <span class="elsevierStyleSup">123</span>I-MIBG uptake is produced in these patients with HF is derived from sympathetic impairment which induces a situation of ischemia&#46; It is thought that the nerve fibers are more sensitive than the heart muscle when there is ischemic damage&#44; and therefore&#44; these fibers may undergo functional changes with repeated episodes of ischemia&#46; This is why sympathetic denervation usually extends beyond the zone of necrosis and covers a larger territory&#46;<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">33</span></a></p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Acute coronary syndrome&#58; acute myocardial infarction with elevation of the ST segment&#46;</span><p id="par0275" class="elsevierStylePara elsevierViewall">In a situation of acute myocardial infarction &#40;AMI&#41; a structural and functional alteration is produced which also involves non infarcted tissue&#46; This alteration is associated with modifications in regional sympathetic tone which may lead to progressive dysfunction of the left ventricle&#46; In patients who have had an infarction&#44; perfusion and innervation scintigraphy techniques have shown that sympathetic impairment is more extensive than perfusion alterations and that it is even associated with myocardial edema assessed by cardiac resonance&#46;<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">34</span></a></p><p id="par0280" class="elsevierStylePara elsevierViewall">It is crucial to demonstrate the area of risk associated with AMI in order to develop adequate prevention and revascularization strategies&#46;</p><p id="par0285" class="elsevierStylePara elsevierViewall">The 2017 European Society of Cardiology guidelines have now included the use of myocardial perfusion SPECT or PET for evaluating ischemia and myocardial viability&#44; with a grade IIb recommendation &#40;can be recommended&#41; and level C evidence&#46; Specifically&#44; it is focused on patients in whom only the artery responsible for the infarction has been treated or patients who present late and may benefit from an additional evaluation to detect residual ischemia or viability&#46;<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">35</span></a></p><p id="par0290" class="elsevierStylePara elsevierViewall">However&#44; there is no mention of the possible utility of cardiac innervation studies&#46; In this context there is scientific evidence of the possible incorporation of <span class="elsevierStyleSup">123</span>I-MIBG scintigraphy for the detection of the area of risk in patients who have had an infarction&#46;</p><p id="par0295" class="elsevierStylePara elsevierViewall">In a study by Vauchot et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">36</span></a> 70 patients with AMI and elevation of the ST segment &#40;AMIESTS&#41; and a primary percutaneous coronary intervention underwent myocardial innervation with <span class="elsevierStyleSup">123</span>I-MIBG within the first month after infarction&#46; Based on a system of 17 segments&#44; they found that the <span class="elsevierStyleSup">123</span>I-MIBG score obtained provided similar results to the angiographic score &#40;APPROACH score&#41; in the cases with complete obstruction of a coronary artery&#46; They therefore proposed that this tool be used to quantify the area at risk after AMIESTS&#46; The same group also compared <span class="elsevierStyleSup">123</span>I-MIBG with cardiac magnetic resonance &#40;with delayed gadolinium enhancement&#41;&#44; demonstrating the utility of <span class="elsevierStyleSup">123</span>I-MIBG scintigraphy for detecting the myocardial area at risk and proposed this technique as a possible alternative to cardiac magnetic resonance&#46;<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">37</span></a></p><p id="par0300" class="elsevierStylePara elsevierViewall">The strategy of combining perfusion and innervation studies in patients who have had an infarction seems to be able to evaluate parameters correlated with the early appearance of structural and functional abnormalities&#46; The group of Gimelli et al&#46;<a class="elsevierStyleCrossRefs" href="#bib0470"><span class="elsevierStyleSup">38&#44;39</span></a> described the relationship between regional alterations of cardiac innervation and diastolic dysfunction of the left ventricle&#46; With the use of both techniques this group found that together with the abnormalities of left ventricular perfusion and those of contractility and thickening&#44; alterations of innervation were also related to an alteration of ventricular filling as a measure of diastolic ventricular dysfunction&#46; Indeed&#44; the presence and extension of a discordant pattern between perfusion and innervation was also a predictive factor of the presence of relevant diastolic dysfunction&#46; In this context of a discordant pattern with altered areas of innervation and preserved perfusion&#44; in a recent study the same authors reported the relationship with dyssynchrony of the left ventricle&#46; Using the analysis of the phase of myocardial perfusion and the SPECT and identifying the ventricular wall presenting delayed mechanical activation&#44; these authors concluded that extension of the discordant innervation&#47;perfusion pattern was the only predictor of a delay in the mechanical activation of the ventricle&#46; Thus&#44; this pattern allowed the localization of the wall of the ventricle with greatest ventricular dyssynchrony independently of left ventricular function and extension of the infarction scar&#46;</p></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Evaluation of hibernating myocardium</span><p id="par0305" class="elsevierStylePara elsevierViewall">Evaluation of a myocardium hibernating because of chronic repeated ischemia without previous infarction is also associated with sympathetic dysfunction which may lead to a fatal arrhythmogenic event&#46; In the context of hibernating myocardium&#44; animal models have shown a partial anatomical loss of the sympathetic nerves and not transitory stunning as occurs with myocardial cells in situations of acute ischemia&#46; In partial denervation a compensatory phenomenon is produced with the aim of producing a neuronal remodeling effect in the hibernating zone&#46; This effect&#44; which is also present in patients who have had an infarction&#44; causes areas of hyperinnervation which are very sensitive to norepinephrine&#46; Therefore&#44; in the absence of treatment with beta-blockers&#44; this hibernating territory is converted into a very favorable substrate for triggering arrhythmogenic alterations which can produce a fatal cardiac event&#46;<a class="elsevierStyleCrossRefs" href="#bib0480"><span class="elsevierStyleSup">40&#44;41</span></a></p><p id="par0310" class="elsevierStylePara elsevierViewall">In this sense&#44; in situations of hibernating myocardium without previous infarction&#44; perfusion and innervation studies have also been proposed to detect not only the areas of less perfused myocardium &#40;and less innervated&#41; but also to detect the areas in which there is discordance between innervation&#47;perfusion&#46; The objective is to detect the greatest quantity of hibernating myocardium&#44; while also identifying the myocardial zones with innervation deficit and preserved perfusion&#44; since these areas are also susceptible to originating potentially fatal ventricular arrhythmias&#46; The incorporation of SPECT images to the planar images in <span class="elsevierStyleSup">123</span>I-MIBG studies provides the possibility of evaluating these images together with the SPECT images of myocardial perfusion&#46; As Travin et al&#46;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">42</span></a> stated in a recent study&#44; future studies are needed to determine the relevance of this discordance besides the already established potential of <span class="elsevierStyleSup">123</span>I-MIBG scintigraphy to predict the risk of fatal events in patients with ischemic heart disease&#46;</p></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Evaluation of response to therapy with drugs and intracardiac devices</span><p id="par0315" class="elsevierStylePara elsevierViewall">Cardiac <span class="elsevierStyleSup">123</span>I-MIBG can evaluate response to drugs commonly used in patients with HF such as beta-blockers and RAAS&#46; In a study by Cohen-Solal et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">43</span></a> including 858 patients with HF in the ADMIRE-HF study&#44; the CTR of <span class="elsevierStyleSup">123</span>I-MIBG was the best predictor of mortality in HF patients receiving beta-blocker treatment&#46; Other studies have also shown the CTR and the myocardial washout rate to be useful parameters to demonstrate response to treatment with carvedilol&#44; with an improvement in sympathetic activity&#44;<a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">44</span></a> demonstrating the value of cardiac <span class="elsevierStyleSup">123</span>I-MIBG scintigraphy for monitoring response to treatment in patients with HF&#46;<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">45</span></a></p><p id="par0320" class="elsevierStylePara elsevierViewall">On the other hand&#44; there has been a progressive increase in the incidence of HF associated with longer survival after AMI&#44; an increase in life expectancy and the better medical treatment available&#44; leading to a greater number of patients who are candidates to undergo the implantation of intracardiac devices &#40;IAD&#44; CRT&#41;&#46; However&#44; with the criteria usually used to establish their indication &#40;basically FEV1 and QRS&#41;&#44; 30&#37; of patients do not respond to this type of therapy&#46; The elevated cost of implantation as well as possible complications due to inappropriate shocks or infections of these devices should be taken into account since these can also lead to hospitalizations&#44; patient risk and high health care costs&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">17</span></a></p><p id="par0325" class="elsevierStylePara elsevierViewall">Following approval of the use of cardiac <span class="elsevierStyleSup">123</span>I-MIBG by the Food and Drug Administration &#40;FDA&#41; in 2013&#44; it has been proposed as a recommended indication by the 2015 Society of Nuclear Medicine and Molecular Imaging &#40;SNMMI&#41; and the American Society of Nuclear Cardiology &#40;ASNC&#41; joint expert consensus<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">46</span></a> for the evaluation of prognosis and decision making related to IAD implantation in patients with NYHA II-III and FEV1<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>35&#37;&#44; and is a potential indication in the decision of IAD reimplantation in patients in whom the device has been removed due to infection&#46;</p><p id="par0330" class="elsevierStylePara elsevierViewall">In patients undergoing CRT a significant reduction in the washout rate has been detected 6 months after CRT in responder patients with no changes among non responders&#44; indicating an improvement in sympathetic function associated with improved left ventricular function which may reduce the risk of arrhythmias and sudden death&#46;<a class="elsevierStyleCrossRef" href="#bib0515"><span class="elsevierStyleSup">47</span></a> Less basal uptake of <span class="elsevierStyleSup">123</span>I-MIBG has also been detected in non responder patients&#44; and their improvement is associated with response to CRT expressed as a reduction in functional grade&#46;</p><p id="par0335" class="elsevierStylePara elsevierViewall">In a recent study in 122 patients who underwent CRT&#44; the delayed basal CTR was the best independent predictor of response to this therapy&#44; after having also detected improvement in sympathetic activity after CRT with an increase in the delayed CTR value at 6 months in patients who responded to CRT&#46;<a class="elsevierStyleCrossRef" href="#bib0520"><span class="elsevierStyleSup">48</span></a></p><p id="par0340" class="elsevierStylePara elsevierViewall">In patients with HF the mechanisms of compensation produce a reduction in the uptake of norepinephrine to attempt to generate an increase of the same in the synapsis&#46; A reduction in delayed CRT and an increase in myocardial washout are therefore produced&#44; thereby indicating the presence of increased sympathetic activity in these patients&#44; and both are associated with an increase in the incidence of fatal arrhythmias and cardiac mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">17</span></a> They are even considered as intermediate abnormalities in the uptake of <span class="elsevierStyleSup">123</span>I-MIBG&#44; and not the most severe&#44; which are those susceptible to generating greater potential arrhythmia&#46;<a class="elsevierStyleCrossRef" href="#bib0525"><span class="elsevierStyleSup">49</span></a></p><p id="par0345" class="elsevierStylePara elsevierViewall">Joint evaluation of the usual criteria for indicating intracardiac devices&#44; together with assessment of cardiac sympathetic innervation by <span class="elsevierStyleSup">123</span>I-MIBG&#44; could more accurately establish in which patients its use would be more useful and those in whom implantation would not be necessary&#46;<a class="elsevierStyleCrossRef" href="#bib0530"><span class="elsevierStyleSup">50</span></a> Thus&#44; cardiac sympathetic activity&#44; in close relationship with the risk of potentially fatal arrhythmias&#44; could better determine the benefits expected from the implantation of these devices and could also contribute to a reduction in costs&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">17</span></a></p><p id="par0350" class="elsevierStylePara elsevierViewall">According to Werner&#44;<a class="elsevierStyleCrossRef" href="#bib0535"><span class="elsevierStyleSup">51</span></a> the results on cardiac <span class="elsevierStyleSup">123</span>I-MIBG published to date and even better evaluation of cardiac sympathetic activity by <span class="elsevierStyleSup">123</span>I-MIBG SPECT and new PET radiotracers&#44; especially <span class="elsevierStyleSup">18</span>F-LMI1195&#44; herald a promising future for better selecting patients who are candidates for intracardiac devices&#46;</p></span><span id="sec0120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Heart transplant</span><p id="par0355" class="elsevierStylePara elsevierViewall">Heart transplant in patients with terminal HF improves the 1- and 5-year survival rates by up to 90 and 70&#37;&#44; respectively&#46; However&#44; due to the limited number of heart donors&#44; the precise indication&#44; the order of priority and the most adequate time for surgery are crucial clinical questions&#46; Images with <span class="elsevierStyleSup">123</span>I-MIBG can contribute to determining the optimum time for transplantation by identifying the patients with a worse prognosis and taking into account that&#44; at present&#44; therapy with advanced devices is available as well as optimal pharmacological treatments&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">16</span></a></p><p id="par0360" class="elsevierStylePara elsevierViewall">Cardiac images with <span class="elsevierStyleSup">123</span>I-MIBG can also be useful for evaluating reinnervation in transplanted hearts&#46; Cardiac neuroimaging with <span class="elsevierStyleSup">123</span>I-MIBG identifies sympathetic ventricular reinnervation which develops slowly after surgery&#46; This reinnervation begins in the anterobasal regions of the heart and spreads apically and is observed in 40&#37; of heart transplant patients one year after surgery&#46;</p><p id="par0365" class="elsevierStylePara elsevierViewall">Although the clinical implications and the mechanisms of the cardiac innervation process are not fully known&#44; it is likely that restoration of sympathetic cardiac innvervation increases the exercise capacity of the patients by improving the physiological responses of the HR and contractile function to exercise which are attenuated in patients with a transplanted heart&#46; Evaluation of cardiac reinnervation with <span class="elsevierStyleSup">123</span>I-MIBG may be useful in the follow-up of transplanted patients in rehabilitation units by allowing the prescription of adequate exercise and to assess the effect of exercise training&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">16</span></a></p></span><span id="sec0125" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Amyloidosis</span><p id="par0370" class="elsevierStylePara elsevierViewall">Cardiac innervation images in patients with amyloidosis is mainly focused on visualizing the effects of amyloidotic involvement in the sympathetic nervous system&#46;</p><p id="par0375" class="elsevierStylePara elsevierViewall">Patients with amyloidosis are prone to developing autonomic innvervation disorders due to infiltration of the myocardium and conduction tissue&#46; This infiltration is more frequent in the transthyretin variant of amyloidosis&#44; and neuropathy and dysautonomy are more usual in the hereditary form&#46; The CTR in <span class="elsevierStyleSup">123</span>I-MIBG scintigraphy provides information of amyloid infiltration in the sympathetic nervous system&#46; In patients with amyloidosis a decrease in CTR to less than 1&#46;6 has an independent prognostic value of mortality&#46; In the hereditary form of amyloidosis the CTR is more decreased&#44; although this parameter does not allow distinguishing the different types of amyloidosis&#46;<a class="elsevierStyleCrossRef" href="#bib0540"><span class="elsevierStyleSup">52</span></a> However&#44; according to a recent study&#44;<a class="elsevierStyleCrossRef" href="#bib0545"><span class="elsevierStyleSup">53</span></a> cardiac innvervation with <span class="elsevierStyleSup">123</span>I-MIBG could be abnormal even before detecting abnormal myocardial uptake of <span class="elsevierStyleSup">99m</span>Tc-diphosphonate in these patients&#46;</p></span></span><span id="sec0130" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Cardiotoxicity by chemotherapy</span><p id="par0380" class="elsevierStylePara elsevierViewall">There is evidence of the utility of adrenergic quantification for the evaluation of cardiotoxicity by chemotherapy drugs&#46; Anthracyclines are used in the adjuvant and neoadjuvant treatment of breast cancer and have shown to have an important role in the reduction in mortality by this disease&#46; However&#44; these treatments may produce acute cardiac toxicity&#44; which is usually reversible&#44; but when the toxicity is produced one year after its administration&#44; the toxicity is usually irreversible&#46; It is&#44; therefore&#44; important to have techniques which can detect myocardial damage and its physiopathology as early as possible&#46; One of these techniques is isotopic ventriculography&#44; which is the most accurate and reproducible method for calculating the ejection fraction&#46; Recently&#44; a relationship was found between the decrease in CTR and echocardiographic parameters indicative of cardiotoxicity in patients with breast cancer who had received anthracyclines&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">2</span></a></p><p id="par0385" class="elsevierStylePara elsevierViewall">Trastuzumab is a monoclonal antibody which is very effective in the treatment of tumors of the breast&#44; esophagus and stomach&#59; it expresses a cellular surface receptor called the human epidermal growth factor receptor 2 &#40;HER<span class="elsevierStyleInf">2</span>&#41;&#46; This drug can produce reversible&#44; dose-dependent cardiotoxicity&#46; In the evaluation of cardiotoxicity related to trastuzumab&#44; and in patients with a persistent decrease in the left ventricular ejection fraction&#44; <span class="elsevierStyleSup">123</span>I-MIBG scintigraphy can indicate whether recovery will be achieved&#44; and thus&#44; whether the treatment can be continued&#44; since a reduction in the CTR is associated with the absence of recovery of the left ventricular ejection fraction in successive controls&#46;<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">54</span></a></p><p id="par0390" class="elsevierStylePara elsevierViewall">Nuclear cardiology can detect and quantify abnormalities in underlying sympathetic function in determined heart diseases which are not accessible by other diagnostic methods&#46; Although the present review is devoted to cardiac <span class="elsevierStyleSup">123</span>I-MIBG scintigraphy&#44; we also have to take into account positron emitting radiotracers which are being used in the study of cardiac sympathetic innervation&#46; Indeed&#44; <span class="elsevierStyleSup">11</span>C-HED<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">55</span></a> or&#44; more recently <span class="elsevierStyleSup">18</span>F-LMI1195<a class="elsevierStyleCrossRef" href="#bib0560"><span class="elsevierStyleSup">56</span></a> have shown promising results&#44; especially considering their greater availability due to their labeling with <span class="elsevierStyleSup">18</span>F&#44; and which undoubtedly represent great possibilities in the future thanks to their qualities and greater resolution and sensitivity of PET equipment&#46;</p></span><span id="sec0135" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Conflict of interests</span><p id="par0395" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interests&#46;</p></span></span>"
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              "titulo" => "Prediction of arrhythmias"
            ]
            3 => array:2 [
              "identificador" => "sec0090"
              "titulo" => "Response to treatment"
            ]
            4 => array:2 [
              "identificador" => "sec0095"
              "titulo" => "Coronary diseases"
            ]
            5 => array:2 [
              "identificador" => "sec0100"
              "titulo" => "Ischemic heart failure"
            ]
            6 => array:2 [
              "identificador" => "sec0105"
              "titulo" => "Acute coronary syndrome&#58; acute myocardial infarction with elevation of the ST segment&#46;"
            ]
            7 => array:2 [
              "identificador" => "sec0110"
              "titulo" => "Evaluation of hibernating myocardium"
            ]
            8 => array:2 [
              "identificador" => "sec0115"
              "titulo" => "Evaluation of response to therapy with drugs and intracardiac devices"
            ]
            9 => array:2 [
              "identificador" => "sec0120"
              "titulo" => "Heart transplant"
            ]
            10 => array:2 [
              "identificador" => "sec0125"
              "titulo" => "Amyloidosis"
            ]
          ]
        ]
        10 => array:2 [
          "identificador" => "sec0130"
          "titulo" => "Cardiotoxicity by chemotherapy"
        ]
        11 => array:2 [
          "identificador" => "sec0135"
          "titulo" => "Conflict of interests"
        ]
        12 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2018-12-30"
    "fechaAceptado" => "2019-01-21"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1130589"
          "palabras" => array:6 [
            0 => "Cardiac sympathetic innervation"
            1 => "<span class="elsevierStyleSup">123</span>I-MIBG"
            2 => "Cardiac scintigraphy"
            3 => "Nuclear cardiology"
            4 => "Heart failure"
            5 => "Arrhythmia"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1130590"
          "palabras" => array:6 [
            0 => "Inervaci&#243;n simp&#225;tica cardiaca"
            1 => "<span class="elsevierStyleSup">123</span>I-MIBG"
            2 => "Gammagraf&#237;a cardiaca"
            3 => "Cardiolog&#237;a nuclear"
            4 => "Insuficiencia cardiaca"
            5 => "Arritmia"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Imaging of cardiac sympathetic innervation is only possible by nuclear cardiology techniques and its assessment is key in the evaluation of and decision-making for patients with cardiac sympathetic impairment&#46; This review includes the basis of cardiac sympathetic scintigraphy with <span class="elsevierStyleSup">123</span>I-meta-iodobenzylguanidine &#40;<span class="elsevierStyleSup">123</span>I-MIBG&#41;&#44; recommended protocols&#44; patient preparation&#44; image acquisition and quantification&#44; reproducibility&#44; dosimetry&#44; etc&#46;&#44; and also the clinical indications for cardiac patients&#44; mainly with regard to heart failure&#44; arrhythmia&#44; coronary artery disease&#44; cardiotoxicity&#44; including its contribution to establishing the indication for and monitoring the response to implantable cardiac devices&#44; pharmacological treatment&#44; heart transplantation and other&#46;</p></span>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La obtenci&#243;n de im&#225;genes de la inervaci&#243;n simp&#225;tica cardiaca solo es posible mediante t&#233;cnicas de cardiolog&#237;a nuclear&#44; y su valoraci&#243;n es de importancia decisiva en la evaluaci&#243;n y en la toma de decisiones en pacientes en los que exista deterioro de inervaci&#243;n simp&#225;tica&#46; Se revisa el fundamento de la gammagraf&#237;a de inervaci&#243;n simp&#225;tica cardiaca con <span class="elsevierStyleSup">123</span>I-metayodobencilguanidina &#40;<span class="elsevierStyleSup">123</span>I-MIBG&#41;&#44; los protocolos recomendados para su realizaci&#243;n&#44; incluyendo preparaci&#243;n del paciente&#44; t&#233;cnicas de obtenci&#243;n y cuantificaci&#243;n de im&#225;genes&#44; reproducibilidad&#44; consideraciones dosim&#233;tricas&#44; etc&#46;&#44; analizando las indicaciones cl&#237;nicas de esta exploraci&#243;n en pacientes cardiol&#243;gicos&#44; principalmente en insuficiencia cardiaca&#44; arritmias&#44; coronariopat&#237;a&#44; cardiotoxicidad&#44; contribuci&#243;n a la indicaci&#243;n y seguimiento de respuesta a dispositivos de estimulaci&#243;n cardiaca&#44; tratamiento farmacol&#243;gico&#44; trasplante cardiaco y otros&#46;</p></span>"
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Cas&#225;ns-Tormo I&#44; Jim&#233;nez-Heffernan A&#44; Pubul-N&#250;&#241;ez V&#44; Ruano-P&#233;rez R&#46; Gammagraf&#237;a de inervaci&#243;n simp&#225;tica cardiaca con <span class="elsevierStyleSup">123</span>I-metayodobencilguanidina&#46; Fundamento&#44; protocolos y aplicaciones cl&#237;nicas en Cardiolog&#237;a&#46; Rev Esp Med Nucl Imagen Mol&#46; 2019&#59;38&#58;262&#8211;271&#46;</p>"
      ]
    ]
    "multimedia" => array:7 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 805
            "Ancho" => 1000
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          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">123</span>I-MIBG cardiac scintigraphy&#46; Anterior planar image of two patients &#40;A and B&#41; obtained with MEGP &#40;left&#41; and LEHR collimators &#40;right&#41;&#46; The first shows greater image quality&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Figure 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
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            "Tamanyo" => 134740
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Semiquantitative evaluation of myocardial uptake of <span class="elsevierStyleSup">123</span>I-MIBG in the planar image&#46; &#40;A&#41; Areas of cardiac and mediastinal interest&#46; &#40;B&#41; Cardiac area created over planar image obtained with perfusion radiotracer labeled with <span class="elsevierStyleSup">99m</span>Tc &#40;left&#41; to be applied to the planar image obtained with <span class="elsevierStyleSup">123</span>I-MIBG &#40;right&#41; of the same patient&#46; &#40;C&#41; Formula for calculating the myocardial washout rate between the early and delayed image&#46; EHR&#58; early heart ratio&#59; EMR&#58; early mediastinal ratio&#59; DHR&#58; delayed heart ratio&#59; DMR&#58; delayed mediastinal ratio&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "fig0015"
        "etiqueta" => "Figure 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr3.jpeg"
            "Alto" => 937
            "Ancho" => 1500
            "Tamanyo" => 235851
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">123</span>I-MIBG cardiac SPECT&#46; Joint representation of the tomographic slices of <span class="elsevierStyleSup">99m</span>Tc-MIBI myocardial perfusion SPECT &#40;A&#41; and <span class="elsevierStyleSup">123</span>I-MIBG cardiac innvervation SPECT &#40;B&#41; in the same patient with idiopathic dilated myocardiopathy&#44; presenting severe denervation on the inferior&#44; apical and inferior septum of the left ventricle&#46;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Drugs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Mechanism of interference&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Withdrawal time&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Opioides&#44; cocaine&#44; tramadol</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Inhibition of uptake&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#8211;14 days&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Tricyclic antidepressants&#58; amitriptyline and derivatives&#44; imipramine&#44; amoxapine and doxepin</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Inhibition of uptake&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#8211;21 days&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Sympathetic mimetic drugs&#58; phenylpropanolamine&#44; pseudoephedrine&#44; phenylephrine&#44; amphetamine&#44; dopamine&#44; isoproterenol&#44; salbutamol&#44; terbutaline&#44; fenoterol&#44; xylometazoline</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Granule depletion&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#8211;14 days&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Antihipertensive agents</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Labetalol&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Inhibition of uptake and granule depletion&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21 days&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Reserpin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Granule depletion and inhibition of transport&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14 days&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Bretylium&#44; guanethidine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Granule depletion and inhibition of transport&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14 days&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Antipsychotic drugs&#58; phenothiazines &#40;chlorpromazine&#8230;&#41;&#44; thioxantines &#40;maprotyline&#44; trazolone&#41;&#44; butyrophenone &#40;droperidol&#44; haloperidol&#41;&#44; loxapine</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Inhibition of uptake&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21&#8211;28 days&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab2073716.png"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Drugs which should be withdrawn before performing a cardiac <span class="elsevierStyleSup">123</span>I-MIBG study&#46;</p>"
        ]
      ]
      4 => array:8 [
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        "etiqueta" => "Table 2"
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          0 => array:3 [
            "identificador" => "at2"
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        "tabla" => array:1 [
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            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Early images&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">At 15<span class="elsevierStyleHsp" style=""></span>min after i&#46;v&#46; administration&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Delayed images&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">At 4<span class="elsevierStyleHsp" style=""></span>h after i&#46;v&#46; administration&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Energy window&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">159<span class="elsevierStyleHsp" style=""></span>keV&#44; 20&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Collimator&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">LEHR&#44; MEGP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Planar&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anterior projectionMatrix 128<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>128&#44; 256<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>256Duration 10<span class="elsevierStyleHsp" style=""></span>min&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SPECT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dual head angle 90180 &#40;45 OAD-45 OPI&#41;Matrix 64<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>64Zoom &#40;pixel size 6&#46;4<span class="elsevierStyleHsp" style=""></span>mm&#41;64 images&#44; 25&#8211;30<span class="elsevierStyleHsp" style=""></span>s&#47;imageDuration 14&#8211;16<span class="elsevierStyleHsp" style=""></span>min with dual head&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2073717.png"
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      5 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at3"
            "detalle" => "Table "
            "rol" => "short"
          ]
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        "tabla" => array:1 [
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            0 => array:2 [
              "tabla" => array:1 [
                0 => """
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">15 years&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">5 years&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">1 year&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;017&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;022&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#46;032&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">0&#46;045&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#46;071&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#46;048&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#46;061&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#46;078&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#46;084&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#46;15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Bone surfaces</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#46;011&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;014&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#46;022&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#46;034&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;068&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Brain</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;0047&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;006&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;0099&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;016&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;029&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Breasts</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;0053&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;0068&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;011&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;017&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;032&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Gall bladder</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;021&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;025&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;036&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;054&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;01&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Gastointestinal tract</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Stomach&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;0084&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;011&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;019&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;03&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;056&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Small intestine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;0084&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;011&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;018&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;028&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;051&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Colon&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;0086&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;011&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;018&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;029&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;052&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Ascending large intestine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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          "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Key points</span><p id="par0010" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1&#46;</span><p id="par0015" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleSup">123</span>I-MIBG shows the sympathetic innervation of the myocardium making qualitative&#44; quantitative&#44; global and regional evaluation possible&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2&#46;</span><p id="par0020" class="elsevierStylePara elsevierViewall">In contrast to oncological studies with <span class="elsevierStyleSup">123</span>I-MIBG&#44; cardiac studies do not require the withdrawal of beta-blockers&#44; angiotensin converting enzyme inhibitors&#44; or angiotensin receptor blockers&#46; Neither is it necessary to withdraw calcium channel blockers or bronchodilator beta agonists&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">3&#46;</span><p id="par0025" class="elsevierStylePara elsevierViewall">For correct quantification of the cardiothoracic ratio &#40;CTR&#41;&#44; regions of interest covering the whole myocardium should be created in the cardiac area while carefully avoiding adjacent pulmonary or hepatic radioactivity and the upper mediastinal area below the thyroid radioactivity&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">4&#46;</span><p id="par0030" class="elsevierStylePara elsevierViewall">The most useful prognostic parameter derived from images with <span class="elsevierStyleSup">123</span>I-MIBG is delayed CTR&#44; but it is important to standardize their acquisition always using the same equipment and the same conditions for reducing variability&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">5&#46;</span><p id="par0035" class="elsevierStylePara elsevierViewall">In heart failure continued activation of the sympathetic system results in hypertrophy and fibrosis with ventricular remodeling&#44; attenuation of cardiovascular reflexes and sympathetic denervation&#46; This cardiac denervation contributes directly to disease progression and a worse prognosis&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">6&#46;</span><p id="par0040" class="elsevierStylePara elsevierViewall">In situations of myocardial hibernation without a previous infarction it is recommended to perform perfusion and innervation studies to detect discordances between innvervation&#47;perfusion&#46; Myocardial areas with a deficit in innvervation and preservation of perfusion are susceptible to causing potentially fatal ventricular arrhythmias&#46;</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">7&#46;</span><p id="par0045" class="elsevierStylePara elsevierViewall">Joint evaluation of the usual criteria for indicating intracardiac devices together with assessment of cardiac sympathetic innervation by <span class="elsevierStyleSup">123</span>I-MIBG can more accurately establish the patients in whom these devices would be more useful and those in whom implantation is not necessary&#46;</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">8&#46;</span><p id="par0050" class="elsevierStylePara elsevierViewall">Quantification of cardiac innervation has shown to be useful for the determination of the optimal time for heart transplant&#44; the possibility of graft rejection&#44; the prognosis of amyloidosis and the cardiotoxicity induced by chemotherapy in the treatment of cancer&#46;</p></li></ul></p></span></span>"
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