Original Report
Dynamic magnetic resonance imaging of the breast: Comparison of gadobutrol vs. Gd-DTPA
Resonancia magnética dinámica de mama: estudio comparativo de gadobutrol y Gd-DTPA
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RM de mama bilateral con contraste. a) Secuencia T1 sin contraste. Se coloca una ROI en el interior de la masa, que muestra el área en cm<span class="elsevierStyleSup">2</span>, la media y la desviación estándar de la intensidad de señal en la región medida por la ROI. b) Secuencia T1 con contraste en el primer tiempo (T<span class="elsevierStyleInf">1</span>) tras la administración de contraste. La ROI se localiza en el área de la lesión con mayor realce. c) Secuencia T1 con contraste en el segundo tiempo (T<span class="elsevierStyleInf">2</span>). d) Secuencia T1 con contraste en T<span class="elsevierStyleInf">3</span>. e) Secuencia T1 con contraste en T<span class="elsevierStyleInf">4</span>. f) Última y quinta secuencia T1 con contraste en T<span class="elsevierStyleInf">5</span>. La ROI se mantiene en la misma localización durante todo el estudio. En este caso se observa una captación intensa y rápida en T<span class="elsevierStyleInf">1</span>, con lavado posterior en el resto de las secuencias.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "F. Escribano, M. Sentís, J.C. Oliva, L. Tortajada, M. Villajos, A. Martín, S. Ganau" "autores" => array:7 [ 0 => array:2 [ "nombre" => "F." "apellidos" => "Escribano" ] 1 => array:2 [ "nombre" => "M." "apellidos" => "Sentís" ] 2 => array:2 [ "nombre" => "J.C." "apellidos" => "Oliva" ] 3 => array:2 [ "nombre" => "L." "apellidos" => "Tortajada" ] 4 => array:2 [ "nombre" => "M." "apellidos" => "Villajos" ] 5 => array:2 [ "nombre" => "A." "apellidos" => "Martín" ] 6 => array:2 [ "nombre" => "S." 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(B) Axial CT scan slices in two patients illustrating the different morphological types of bronchiectases: cylindrical bronchiectasis (arrowheads), varicose bronchiectasis (white arrow) and cystic bronchiectasis (hollow arrow).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "J. Bueno, L. Flors" "autores" => array:2 [ 0 => array:2 [ "nombre" => "J." "apellidos" => "Bueno" ] 1 => array:2 [ "nombre" => "L." 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Escribano, M. Sentís, J.C. Oliva, L. Tortajada, M. Villajos, A. Martín, S. Ganau" "autores" => array:7 [ 0 => array:4 [ "nombre" => "F." "apellidos" => "Escribano" "email" => array:1 [ 0 => "ferescri@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "M." "apellidos" => "Sentís" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "J.C." "apellidos" => "Oliva" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "L." "apellidos" => "Tortajada" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 4 => array:3 [ "nombre" => "M." "apellidos" => "Villajos" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 5 => array:3 [ "nombre" => "A." "apellidos" => "Martín" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 6 => array:3 [ "nombre" => "S." "apellidos" => "Ganau" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Área de Radiología Mamaria y Ginecológica, Hospital Universitari Parc Taulí, UDIAT, Institut Universitari Parc Taulí-UAB, Sabadell, Barcelona, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "MPharm, MStat, Institut d’Investigació i Innovació Parc Taulí (I3PT), Sabadell, Barcelona, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Resonancia magnética dinámica de mama: estudio comparativo de gadobutrol y Gd-DTPA" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2307 "Ancho" => 3000 "Tamanyo" => 492842 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Patient diagnosed of right breast neoplasm through ultrasound-guided biopsy. Bilateral breast MRI with contrast. (a) T1-weighted sequence without contrast. One ROI is placed within the mass showing the area in square centimeters, the mean, and the standard deviation of the signal intensity in the area measured by the ROI. (b) T1-weighted sequence with contrast during the first time of acquisition (<span class="elsevierStyleItalic">T</span><span class="elsevierStyleInf">1</span>) after the administration of contrast. ROI placement in the area of the lesion that has the highest enhancement of all. (c) T1-weighted sequence with contrast during the second time of acquisition (<span class="elsevierStyleItalic">T</span><span class="elsevierStyleInf">2</span>). (d) T1-weighted sequence with contrast during the third time of acquisition <span class="elsevierStyleItalic">T</span><span class="elsevierStyleInf">3</span>. (e) T1-weighted sequence with contrast during the fourth time of acquisition <span class="elsevierStyleItalic">T</span><span class="elsevierStyleInf">4</span>. (f) T1-weighted sequence during the fifth and last time of acquisition T<span class="elsevierStyleInf">5</span>. The ROI is maintained in the same location during the entire study. In this case, there is intense and fast uptake in <span class="elsevierStyleItalic">T</span><span class="elsevierStyleInf">1</span>, with later washout in the remaining sequences.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">The IV dynamic contrast-enhanced MRI (DCE-MRI) of the breast is an imaging modality more and more widely accepted as a diagnostic tool for the detection and staging of breast cancer.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Since it is based on neoangiogenesis, the DCE-MRI allows us to make functional assessments of tumors, unlike conventional modalities (mammograms and ultrasound scans) that are just morphological.</p><p id="par0015" class="elsevierStylePara elsevierViewall">The DCE-MRI is conducted using a T-1 weighted sequence acquired previously and several times after the IV injection of a gadolinium-based contrast agent of low-molecular weight. Each acquisition lasts for approximately 1<span class="elsevierStyleHsp" style=""></span>min and one (1) pre-contrast acquisition and, at least, two (2) post-contrast acquisitions are conducted, one after 2<span class="elsevierStyleHsp" style=""></span>min and the other one later.<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">2</span></a> However, normally five (5) post-contrast acquisitions are usually conducted up to 5–8<span class="elsevierStyleHsp" style=""></span>min.<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">3–5</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The DCE-MRI has a high sensitivity and lower specificity for the identification and characterization of breast focal lesions.<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">6–10</span></a> The time-resolved imaging of contrast kinetics includes one time-signal intensity curve from the manual ROI (region of interest). One early and one late phase can be distinguished, being the early phase rapid or slow based on the signal enhancement during the 2<span class="elsevierStyleHsp" style=""></span>min that follow the contrast injection; based on how the washout curve looks like, it is categorized as persistent enhancing (type 1), plateau (type 2), and washout (type 3). The categorization of the kinetics curve contributes to distinguish benign from malignant lesions.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The pharmacokinetics model provides one quantitative approach in the analysis of IV contrast distribution based on the vascularization of breast lesions.<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">11–13</span></a> The simplest model describes two (2) different behaviors: the tissue of interest and the plasma. In the pharmacokinetics model of the DCE-MRI of the breast three (3) pharmacokinetics parameters are normally used: the endothelial transfer constant (<span class="elsevierStyleItalic">K</span><span class="elsevierStyleSup">trans</span>, expressed in min<span class="elsevierStyleSup">−1</span>), the reverse volume transfer constant (<span class="elsevierStyleItalic">K</span><span class="elsevierStyleInf">ep</span>, expressed in min<span class="elsevierStyleSup">−1</span>) and the fraction of tumor volume occupied by the extravascular space (<span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">e</span>).<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">12,14,15</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The pharmacokinetics parameters can help us characterize breast lesions as benign or malignant, since high patency and low extravascular fractions are signs of malignancy.<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">16–20</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The first gadolinium-based contrast agent for MRI-based diagnoses was gadopentetate dimeglumine (Gd-DTPA; Magnevist, Bayer Healthcare, Berlin, Germany).<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">3</span></a> Since then, other contrast agents have been studied with different physical and chemical properties. The T1-relaxivity<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">21,22</span></a> is one important physical property, meaning that a higher T1-relaxivity will imply greater enhancement and better visualization of brain and breast lesions.<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">23–26</span></a> Another property that may have something to say when it comes to spreading among biological tissues is the electric charge of the molecules from the contrast agent. Gadolinium-based contrast agents can be ionic or non-ionic; ionic agents have a negative charge, whereas non-ionic agents have a neutral charge. These differences in the electric charge may alter the contrast uptake in tissues with negatively charged components such as mucopolysaccharides.<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">27,28</span></a> It is widely known that malignant breast lesions have a high content of mucopolysaccharide acids.<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">29–31</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Gadobutrol is a non-ionic contrast agent with a very stable macrocyclic structure, high T1-relaxivity, and twice as much molarity as Gd-DTPA, whereas Gd-DTPA is an ionic contrast agent with a less stable linear structure and lower T1-relaxivity.<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">21,22,32</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">The main goal of this study is to investigate the differences between gadobutrol and Gd-DTPA when it comes to T1-relaxivity-based enhancement peaks, and the time-signal intensity attributed to different electric charges.</p><p id="par0050" class="elsevierStylePara elsevierViewall">The secondary goals of this study are to compare whether there are any differences in the detection of additional malignant lesions that may lead to a better diagnostic accuracy, and also assess the safety profile of both contrast agents.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Patients</span><p id="par0055" class="elsevierStylePara elsevierViewall">Retrospective, observational, single-center study including 400 female patients with a histological diagnosis of breast cancer through percutaneous stereotactic biopsies or ultrasound scans conducted between May 2006 and July 2011. All patients underwent one DCE-MRI after the histological diagnosis (7–15 days after diagnosis). Only lesions with a histological diagnosis of breast cancer and as mass-type uptake in the MRI were included. The patients did not sign any informed consents to participate in the study since the nature of the study was retrospective. The sample included two (2) groups of patients who met the aforementioned criteria: one group of 200 patients consecutively diagnosed between May 2006 and November 2008 who received Gd-DTPA for the DCE-MRI study, and another group of 200 patients diagnosed between November 2009 and July 2011 who received gadobutrol for the DCE-MRI study.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Imaging modality</span><p id="par0060" class="elsevierStylePara elsevierViewall">The MRI study was conducted using the 1.5<span class="elsevierStyleHsp" style=""></span>T Siemens Symphony Maestro Class machine (Siemens Medical System, Erlangen, Germany).</p><p id="par0065" class="elsevierStylePara elsevierViewall">Our protocol consisted of one bilateral study in the coronal plane with an eight-channel surface antenna. One T2-weighted TSE sequence was acquired plus one dynamic study including six T1w3D GRE sequences. After the T1-weighted sequence without contrast, and following a 20<span class="elsevierStyleHsp" style=""></span>s break after the injection of contrast, five (5) acquisitions were obtained. The same dose of gadolinium – 0.1<span class="elsevierStyleHsp" style=""></span>mmol/kg of body weight was injected, with both contrast agents, at a speed of 3<span class="elsevierStyleHsp" style=""></span>ml/s followed by one (1) bolus of physiological saline solution of the same volume of injected contrast.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Study design</span><p id="par0070" class="elsevierStylePara elsevierViewall">Only one radiologist with over 13 years of experience in breast pathology and DCE-MRIs of the breast analyzed all cases. This radiologist knew the contrast agent administered to each patient and had access to the clinical history too.</p><p id="par0075" class="elsevierStylePara elsevierViewall">One 5-pixel ROI was drawn manually in the region of higher and faster lesion enhancement, while avoiding the areas of fat, and following the recommendations suggested by the American College of Radiology on the placement of ROIs.<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">33</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">The placement of the ROI was based on the radiologist's subjective visual assessment. The signal intensity readings, in the same ROI, were obtained for all the post-contrast sequences of the dynamic study (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">On the other hand, the images were analyzed with the Leonardo working station using the Tissue 4D<span class="elsevierStyleSup">®</span> software (Siemens Healthcare, Erlangen, Germany), which is capable of assessing the dynamic uptake of the tumor contrast by assessing the pharmacokinetic values–all based on Tofts et al.’s bicompartmental model.<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">15</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">The following pharmacokinetic parameters were analyzed: <span class="elsevierStyleItalic">K</span><span class="elsevierStyleSup">trans</span>–endothelial transfer constant; <span class="elsevierStyleItalic">K</span><span class="elsevierStyleInf">ep</span>–the reverse volume transfer constant; and <span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">e</span>–the fraction of tumor volume occupied by the extravascular space. These parameters are related to one another through the following equation: <span class="elsevierStyleItalic">K</span><span class="elsevierStyleInf">ep</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">K</span><span class="elsevierStyleSup">trans</span>/<span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">e</span>. In order to find this equation, one ROI in the area of higher lesion signal intensity of the first, or second postcontrast acquisition was drawn manually. The number of additional suspicious lesions found on the MRI and histologically confirmed through percutaneous biopsy or surgery was recorded–in cases were the surgical planning was not altered.</p><p id="par0095" class="elsevierStylePara elsevierViewall">Also, all adverse reactions and all gadolinium-based contrast agents were recorded in the patients’ clinical histories.</p><p id="par0100" class="elsevierStylePara elsevierViewall">This work has been approved by our hospital research ethics committee.</p><p id="par0105" class="elsevierStylePara elsevierViewall">The authors declare that they have followed the protocols established in their healthcare center on accessing the patients’ clinical histories, and also abide by the recommendations set out by the Research Committee. Our center routine healthcare protocol is familiar to us and includes the locoregional extension MRI study of all the patients diagnosed of breast cancer.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Imaging analysis</span><p id="par0110" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">(1)</span><p id="par0115" class="elsevierStylePara elsevierViewall">Relative enhancement (RE) of signal intensity</p></li></ul></p><p id="par0120" class="elsevierStylePara elsevierViewall">The relative increase of signal intensity was estimated using the formula 100<span class="elsevierStyleHsp" style=""></span>*<span class="elsevierStyleHsp" style=""></span>([IS<span class="elsevierStyleInf">post</span><span class="elsevierStyleHsp" style=""></span>−<span class="elsevierStyleHsp" style=""></span>IS<span class="elsevierStyleInf">pre</span>]/IS<span class="elsevierStyleInf">pre</span>). This was the study main variable obtained in the post-contrast early phase during the first and second acquisitions of the dynamic study. The peak signal intensity RE and the remaining intensity signals RE of the dynamic study were estimated too. The percentages of the RR values for gadobutrol and Gd-DTPA were compared both during the first (<span class="elsevierStyleItalic">T</span><span class="elsevierStyleInf">1</span>) and second (<span class="elsevierStyleItalic">T</span><span class="elsevierStyleInf">2</span>) times of acquisition after the administration of contrast and in the time to peak signal intensity (<span class="elsevierStyleItalic">T</span><span class="elsevierStyleInf">MAX</span>).<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">(2)</span><p id="par0125" class="elsevierStylePara elsevierViewall">Time to peak signal intensity and post-initial contrast behavior</p></li></ul></p><p id="par0130" class="elsevierStylePara elsevierViewall">The time to peak signal intensity, and the different signal RE in the second post-contrast measurement minus the last measurement (<span class="elsevierStyleItalic">T</span><span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>−<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">T</span><span class="elsevierStyleInf">5</span>) were estimated, and the comparison between both contrast agents was drawn.</p><p id="par0135" class="elsevierStylePara elsevierViewall">The curve time was estimated using the <span class="elsevierStyleItalic">T</span><span class="elsevierStyleInf">2</span> and <span class="elsevierStyleItalic">T</span><span class="elsevierStyleInf">5</span> measurements. The “washout” curve was defined as the relative loss of more than 10% of signal intensity, the “plateau” curve was defined as the relative difference of losing no more than 10%, and the “persistent” curve was defined as the relative increase of more than 10% of signal intensity following the BI-RADS lexicon set out by the European guidelines.<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">2</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Statistical analysis</span><p id="par0140" class="elsevierStylePara elsevierViewall">Initially, an analysis of both groups of patients was conducted to see if they could be compared from the point of view of the tumor, the histological grade, hormone receptors, the Ki-67 index and the Her-2 status (Chi-square test).</p><p id="par0145" class="elsevierStylePara elsevierViewall">The uptake during the first and second times of acquisition, and the maximum uptake are expressed in averages and through the 95% confidence interval (95% CI), and compared using the Student's <span class="elsevierStyleItalic">t</span> test.</p><p id="par0150" class="elsevierStylePara elsevierViewall">The Mann–Whitney test was used to compare the time to peak signal intensity between both contrasts. The contrast behavior in the late phase (washout, plateau, permanent) was compared using the chi-square test.</p><p id="par0155" class="elsevierStylePara elsevierViewall">The pharmacokinetic parameters were measured using the Tissue 4D<span class="elsevierStyleSup">®</span> software (<span class="elsevierStyleItalic">K</span><span class="elsevierStyleSup">trans</span>, <span class="elsevierStyleItalic">K</span><span class="elsevierStyleInf">ep</span> and <span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">e</span>), their means and percentiles 25–75 shown, and later compared using the Mann–Whitney non-parametric test.</p><p id="par0160" class="elsevierStylePara elsevierViewall">All tests were bilateral and were considered statistically significant when <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05. The statistical analysis was conducted using the IBM<span class="elsevierStyleSup">®</span> SPSS<span class="elsevierStyleSup">®</span> v. 21 software.</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Results</span><p id="par0165" class="elsevierStylePara elsevierViewall">The average age of the patients included in the analysis was 58.1 years old (range: 20.9–89.2 years old; standard deviation [SD]: 13.5 years old).</p><p id="par0170" class="elsevierStylePara elsevierViewall">On the histological level, out of the 398 malignant lesions, 315 lesions (79.1%) were infiltrating ductal carcinomas, 35 (8.8%) infiltrating lobular carcinomas, 17 lesions (4.3%) were intraductal carcinomas, and 31 lesions (7.8%) were other unusual kinds of tumors. The average size of the lesions was 27.0<span class="elsevierStyleHsp" style=""></span>mm (range: 4–140<span class="elsevierStyleHsp" style=""></span>mm; SD: 18.2<span class="elsevierStyleHsp" style=""></span>mm).</p><p id="par0175" class="elsevierStylePara elsevierViewall">There were no statistically significant differences between the two groups of patients when it comes to the type of tumor, the histological grade, hormone receptors, the Ki-67 index and the Her-2 status (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0180" class="elsevierStylePara elsevierViewall">Out of the 400 patients, one was excluded from the gadobutrol group because the tumor volume was not consistent with the values obtained in the remaining patients (diameter 1<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1<span class="elsevierStyleHsp" style=""></span>mm, diameter 2<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1<span class="elsevierStyleHsp" style=""></span>mm, and diameter 3<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1<span class="elsevierStyleHsp" style=""></span>mm). Then another patient was excluded from the Gd-DTPA group because all measurements from the dynamic study could not be obtained, meaning that the time-signal intensity curve could not be estimated either.</p><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Relative enhancement of signal intensity in the early phase</span><p id="par0185" class="elsevierStylePara elsevierViewall">The peak signal intensity in the early phase was higher with gadobutrol than it was with Gd-DTPA. The average peak signal intensity during the first post-contrast measurement was 289.84% (95% CI: 259.64–320.03%) for gadobutrol, and 260.10% (95% CI: 246.02–274.19%) for Gd-DTPA. In most cases, the average values of signal intensity during the second post-contrast acquisition were higher: 311.21% (95% CI: 281.31–341.11%) for gadobutrol, and 274.42% (95% CI: 260.55–288.02%) for Gd-DTPA.</p><p id="par0190" class="elsevierStylePara elsevierViewall">The average of maximum rate of enhancement peak was 337.90% (95% CI: 308.07–367.74%) for gadobutrol and 295.36% (95% CI: 281.24–309.48%) for Gd-DTPA (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Time to peak signal intensity</span><p id="par0195" class="elsevierStylePara elsevierViewall">There were no differences between gadobutrol and Gd-DTPA when it comes to time to peak signal intensity (see Table in the additional material).</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Post-initial contrast behavior</span><p id="par0200" class="elsevierStylePara elsevierViewall">There was a statistically significant higher percentage of washout curves in the Gd-DTPA group compared to the gadobutrol group (58.29% vs. 46.0%; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.032) (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>). <a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a> shows the different contrast uptake over time.</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Pharmacokinetic parameters <span class="elsevierStyleItalic">K</span><span class="elsevierStyleSup">trans</span>, <span class="elsevierStyleItalic">K</span><span class="elsevierStyleInf">ep</span> and <span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">e</span></span><p id="par0205" class="elsevierStylePara elsevierViewall">Higher <span class="elsevierStyleItalic">K</span><span class="elsevierStyleSup">trans</span> and <span class="elsevierStyleItalic">K</span><span class="elsevierStyleInf">ep</span> values for the gadobutrol group compared to the Gd-DTPA group were confirmed, being this difference statistically significant. There were no differences in the <span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">e</span> (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>).</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Number of additional lesions</span><p id="par0210" class="elsevierStylePara elsevierViewall">The number of additional malignant lesions found on the MRI in both groups of patients was compared. There were no statistically significant differences: 31 additional malignant lesions (15.5%) in the Gd-DTPA group, and 25 additional malignant lesions (12.5%) in the gadobutrol group (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.387).</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Safety</span><p id="par0215" class="elsevierStylePara elsevierViewall">Nine (9) patients (2.25%) had adverse events after the administration of IV contrast. Some of these adverse events were nausea and dizziness (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>3 in the Gd-DTPA group and n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>5 for the gadobutrol group), and skin rash (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1) in the gadobutrol group.</p></span></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Discussion</span><p id="par0220" class="elsevierStylePara elsevierViewall">In this study, we analyzed the use of gadobutrol and Gd-DTPA while conducting DCE-MRIs for the assessment of any possible effects on the resulting time-signal intensity curves and pharmacokinetic parameters.</p><p id="par0225" class="elsevierStylePara elsevierViewall">Gd-DTPA and gadobutrol have several different characteristics. The concentration of Gd-DTPA was 0.5<span class="elsevierStyleHsp" style=""></span>M, while the concentration of gadobutrol was 1<span class="elsevierStyleHsp" style=""></span>M, so that in order to obtain equivalent plasmatic concentrations we would need less contrast volume during the same period of time.</p><p id="par0230" class="elsevierStylePara elsevierViewall">Also, gadobutrol has a higher T1-relaxivity than Gd-DTPA (5.3 and 4.3<span class="elsevierStyleHsp" style=""></span>l/mmol<span class="elsevierStyleHsp" style=""></span>s<span class="elsevierStyleSup">−1</span>, respectively at 1.5<span class="elsevierStyleHsp" style=""></span>T in plasma at 37<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleSmallCaps">C</span>).<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">32</span></a> Our results showed higher signal intensity relative enhancement in the gadobutrol group maybe due to the higher T1-relaxivity of the macrocyclic agent. As a matter of fact, it has been confirmed that higher relaxivities are associated with higher enhancement values, which in turn increases sensitivity in the DCE-MRI detection of breast lesions.<a class="elsevierStyleCrossRefs" href="#bib0300"><span class="elsevierStyleSup">24–26</span></a></p><p id="par0235" class="elsevierStylePara elsevierViewall">Gadobutrol and Gd-DTPA have a different electric charge too. While Gd-DTPA is a linear and ionic contrast agent, gadobutrol has more of a macrocyclic structure and a neutral electric charge.<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">34</span></a> Gadolinium-based contrast agents have a different distribution in the cartilage based on their electric charge. The cartilage is rich in negatively charged mucopolysaccharide acids, and there is a lower uptake when a contrast agent with a negative ionic charged is used.<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">28,31</span></a> Our results show higher percentages of washout curves in the Gd-DTPA group. Breast lesions have a higher content of mucopolysaccharide acides,<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">29–31</span></a> which may explain the electrostatic repulsion of the negatively charged Gd-DTPA, that would result in a rapid washout of the lesion.</p><p id="par0240" class="elsevierStylePara elsevierViewall">The aforementioned results are consistent with the results obtained by Fallenberg et al.<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">35</span></a></p><p id="par0245" class="elsevierStylePara elsevierViewall">Unlike other studies, we could not find any differences in the number of additional malignant lesions histologically confirmed in the two groups.<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">25</span></a> In Martincich et al.’s study,<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">25</span></a> Gd-DTPA was compared to gadobenate dimeglumine in a group of patients. Gadobenate dimeglumine was found to be superior to Gd-DTPA for cancer diagnosis. Gadobenate dimeglumine has a higher T1-relaxivity<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">21</span></a> of 6.7<span class="elsevierStyleHsp" style=""></span>l/mmol<span class="elsevierStyleHsp" style=""></span>s<span class="elsevierStyleSup">−1</span> (at 1.5<span class="elsevierStyleHsp" style=""></span>T in plasma at 37<span class="elsevierStyleHsp" style=""></span>°C) – higher than gadobutrol, which would facilitate the characterization of lesions and the higher detection of malignant lesions. The results obtain show significantly higher <span class="elsevierStyleItalic">K</span><span class="elsevierStyleSup">trans</span> and <span class="elsevierStyleItalic">K</span><span class="elsevierStyleInf">ep</span> values in the gadobutrol group. One simple analysis of Tofts’ bicompartmental model would put the <span class="elsevierStyleItalic">K</span><span class="elsevierStyleSup">trans</span> parameter on the same level of the early uptake pattern, whereas <span class="elsevierStyleItalic">K</span><span class="elsevierStyleInf">ep</span> would be associated with the late uptake pattern, since <span class="elsevierStyleItalic">K</span><span class="elsevierStyleSup">trans</span> is the contrast patency constant from plasma up to the interstitial space, while <span class="elsevierStyleItalic">K</span><span class="elsevierStyleInf">ep</span> is the extraction coefficient from the tumor up to the vascular space.</p><p id="par0250" class="elsevierStylePara elsevierViewall">Based on this hypothesis, the <span class="elsevierStyleItalic">K</span><span class="elsevierStyleInf">ep</span> values should be higher in the Gd-DTPA group, since it has a significantly higher percentage of washout curves.</p><p id="par0255" class="elsevierStylePara elsevierViewall">In the medical literature, there is variability in the results coming from the pharmacokinetic parameters.<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">13</span></a> The pharmacokinetic analysis needs a 9–19<span class="elsevierStyleHsp" style=""></span>s temporal resolution, but our acquisitions lasted for about 60<span class="elsevierStyleHsp" style=""></span>s. Maybe this is why there are different results in studies that use protocols with very fast sequences.</p><p id="par0260" class="elsevierStylePara elsevierViewall">Our work has some limitations. The first one is that it is an interindividual study, although both groups are not comparable from the histological point of view, or on the basis of the radiological pattern. The second limitation is that only one radiologist took care of the analysis, which is why interobserver variability could not be analyzed; also, this radiologist knew about the histological diagnosis. The MRIs were always conducted after the biopsy, which may affect the assessment of signal intensity; however, when placing the ROI, both the swollen areas and the artifact of susceptibility of the marking clip were avoided–during the biopsy, the lesions that were deep, small or difficult to locate were marked. Nonetheless, conducting MRIs after the biopsy to assess the extension and multicentricity of the lesion is the daily practice of many centers. For the study of breast lesions, the usual histological staining procedures were used. No specific staining procedures for the mucopolysaccharide acids<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">29–31</span></a> were used, which is why the signal enhancement patterns cannot be directly associated with histology.</p><p id="par0265" class="elsevierStylePara elsevierViewall">Thanks to the large multicenter, prospective studies published so far, we have come to know that the MRIs of the breast that use gadobutrol have high percentages of sensitivity and specificity, which is consistent with the data published on other contrast agents.<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">36</span></a> However, this is the first study that compared gadobutrol with Gd-DTPA when conducting DCE-MRIs, and it is one of the largest series ever published, with 200 patients in each group. Also, the objective measurement of the pharmacokinetic parameters and the signal intensity allows the study to be reproduced. Gadobutrol has higher values of relative enhancement compared to Gd-DTPA, but the Gd-DTPA washout is more significant.</p><p id="par0270" class="elsevierStylePara elsevierViewall">El gadobutrol is not inferior to Gd-DTPA when it comes to the number of additional malignant lesions found on the MRI.</p><p id="par0275" class="elsevierStylePara elsevierViewall">Both contrast agents are safe, and not a single case of systemic nephrogenic fibrosis has occurred.</p><p id="par0280" class="elsevierStylePara elsevierViewall">We need more studies comparing the pharmacokinetic parameters of the contrast agents used when conducting MRIs of the breast in order to determine what contrast agents increase the detection of malignant lesions and, therefore, improve the performance of this imaging modality.</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Authors</span><p id="par0285" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">•</span><p id="par0290" class="elsevierStylePara elsevierViewall">Manager of the integrity of the study: MS and FE.</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">•</span><p id="par0295" class="elsevierStylePara elsevierViewall">Study Idea: MS and FE.</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">•</span><p id="par0300" class="elsevierStylePara elsevierViewall">Study Design: MS and FE.</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">•</span><p id="par0305" class="elsevierStylePara elsevierViewall">Data Mining: FE, LT, MV and AM.</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">•</span><p id="par0310" class="elsevierStylePara elsevierViewall">Data Analysis and Interpretation: JCO and FE.</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">•</span><p id="par0315" class="elsevierStylePara elsevierViewall">Statistical Analysis: JCO and FE.</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">•</span><p id="par0320" class="elsevierStylePara elsevierViewall">Reference: FE and SG.</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">•</span><p id="par0325" class="elsevierStylePara elsevierViewall">Writing: FE.</p></li><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">•</span><p id="par0330" class="elsevierStylePara elsevierViewall">Critical review of the manuscript with intellectually relevant remarks: MS, JCO, LT, MV, AM, SG and FE.</p></li><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">•</span><p id="par0335" class="elsevierStylePara elsevierViewall">Approval of final version: MS, JCO, LT, MV, AM, SG and FE.</p></li></ul></p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Funding</span><p id="par0340" class="elsevierStylePara elsevierViewall">This paper has been funded by <span class="elsevierStyleGrantSponsor" id="gs1">Bayer Hispania S.L.</span></p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Conflict of interests</span><p id="par0345" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interests.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:3 [ "identificador" => "xres976647" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec946420" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres976648" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec946421" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Material and methods" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Patients" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Imaging modality" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Study design" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Imaging analysis" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Statistical analysis" ] ] ] 6 => array:3 [ "identificador" => "sec0040" "titulo" => "Results" "secciones" => array:6 [ 0 => array:2 [ "identificador" => "sec0045" "titulo" => "Relative enhancement of signal intensity in the early phase" ] 1 => array:2 [ "identificador" => "sec0050" "titulo" => "Time to peak signal intensity" ] 2 => array:2 [ "identificador" => "sec0055" "titulo" => "Post-initial contrast behavior" ] 3 => array:2 [ "identificador" => "sec0060" "titulo" => "Pharmacokinetic parameters K, K and V" ] 4 => array:2 [ "identificador" => "sec0065" "titulo" => "Number of additional lesions" ] 5 => array:2 [ "identificador" => "sec0070" "titulo" => "Safety" ] ] ] 7 => array:2 [ "identificador" => "sec0075" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0080" "titulo" => "Authors" ] 9 => array:2 [ "identificador" => "sec0085" "titulo" => "Funding" ] 10 => array:2 [ "identificador" => "sec0090" "titulo" => "Conflict of interests" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2017-06-24" "fechaAceptado" => "2017-10-27" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec946420" "palabras" => array:4 [ 0 => "Breast cancer" 1 => "Magnetic resonance imaging" 2 => "Contrast agents" 3 => "Gadolinium" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec946421" "palabras" => array:4 [ 0 => "Cáncer de mama" 1 => "Resonancia magnética" 2 => "Agentes de contraste" 3 => "Gadolinio" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To compare the pharmacokinetic profile of gadobutrol versus Gd-DTPA in dynamic contrast-enhanced MRI (DCE-MRI) in patients with breast cancer. Secondary objectives included comparing the safety profiles and diagnostic efficacy of the two contrast agents for detecting additional malignant lesions.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Material and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">This retrospective observational study included 400 patients with histologically confirmed breast cancer; 200 underwent DCE-MRI with Gd-DTPA (Magnevist<span class="elsevierStyleSup">®</span>) and 200 underwent DCE-MRI with gadobutrol (Gadovist<span class="elsevierStyleSup">®</span>). Pharmacokinetic parameters and signal intensity were analyzed in a region of interest placed in the area within the lesion that had greatest signal intensity in postcontrast sequences. We compared the two groups on pharmacokinetic variables (<span class="elsevierStyleItalic">K</span><span class="elsevierStyleSup">trans</span>, <span class="elsevierStyleItalic">K</span><span class="elsevierStyleInf">ep</span>, and <span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">e</span>), time-signal intensity curves, and the number of additional malignant lesions detected.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The relative signal intensity (enhancement) was higher with gadobutrol than with Gd-DTPA. Washout was lower with gadobutrol than with Gd-DTPA (46% vs. 58.29%, respectively; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.0323). Values for <span class="elsevierStyleItalic">K</span><span class="elsevierStyleSup">trans</span> and <span class="elsevierStyleItalic">K</span><span class="elsevierStyleInf">ep</span> were higher for gadobutrol (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.001). There were no differences in the number of histologically confirmed additional malignant lesions detected (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.387).</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Relative enhancement is greater with gadobutrol, but washout is more pronounced with Gd-DTPA. The number of additional malignant lesions detected did not differ between the two contrast agents. Both contrasts are safe.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Evaluar el perfil farmacocinético del gadobutrol en comparación con el Gd-DTPA, en resonancia magnética de mama con contraste (RM-DC). El objetivo secundario es valorar la eficacia diagnóstica en la detección de lesiones adicionales tumorales en RM-DC, y el perfil de seguridad de ambos contrastes.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material y métodos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudio retrospectivo y observacional que incluyó 400 pacientes con diagnóstico histológico de cáncer mamario. A 200 pacientes se les realizó RM-DC con contraste Gd-DTPA (Magnevist<span class="elsevierStyleSup">®</span>) y a las otras 200 con gadobutrol (Gadovist<span class="elsevierStyleSup">®</span>). Se analizaron los parámetros farmacocinéticos y la intensidad de señal mediante una ROI <span class="elsevierStyleItalic">(region of interest)</span> en el área intralesional con mayor intensidad de señal en las secuencias poscontraste. Se compararon las variables farmacocinéticas (K<span class="elsevierStyleSup">trans</span>, K<span class="elsevierStyleInf">ep</span> y V<span class="elsevierStyleInf">e</span>) y las curvas de intensidad de señal-tiempo de ambos grupos, así como el número de lesiones adicionales tumorales detectadas con ambos contrastes.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">El realce relativo de intensidad de señal es más alto con gadobutrol que con Gd-DTPA. El gadobutrol muestra significativamente menos lavado (46%) que el Gd-DTPA (58,29%) (p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,0323). Se observan valores más altos de K<span class="elsevierStyleSup">trans</span>, K<span class="elsevierStyleInf">ep</span> y V<span class="elsevierStyleInf">e</span> para el gadobutrol, siendo la diferencia estadísticamente significativa para los dos primeros parámetros (p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,001). No se encuentran diferencias en el número de lesiones adicionales malignas confirmadas histológicamente (p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,387).</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">El gadobutrol tiene valores más altos de realce, mientras que el Gd-DTPA muestra un lavado más marcado. El gadobutrol no es inferior en cuanto a número de lesiones adicionales malignas detectadas. Ambos contrastes son seguros.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0025">Please cite this article as: Escribano F, Sentís M, Oliva JC, Tortajada L, Villajos M, Martín A, et al. Resonancia magnética dinámica de mama: estudio comparativo de gadobutrol y Gd-DTPA. Radiología. 2018:60;49–56.</p>" ] ] "multimedia" => array:6 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2307 "Ancho" => 3000 "Tamanyo" => 492842 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Patient diagnosed of right breast neoplasm through ultrasound-guided biopsy. Bilateral breast MRI with contrast. (a) T1-weighted sequence without contrast. One ROI is placed within the mass showing the area in square centimeters, the mean, and the standard deviation of the signal intensity in the area measured by the ROI. (b) T1-weighted sequence with contrast during the first time of acquisition (<span class="elsevierStyleItalic">T</span><span class="elsevierStyleInf">1</span>) after the administration of contrast. ROI placement in the area of the lesion that has the highest enhancement of all. (c) T1-weighted sequence with contrast during the second time of acquisition (<span class="elsevierStyleItalic">T</span><span class="elsevierStyleInf">2</span>). (d) T1-weighted sequence with contrast during the third time of acquisition <span class="elsevierStyleItalic">T</span><span class="elsevierStyleInf">3</span>. (e) T1-weighted sequence with contrast during the fourth time of acquisition <span class="elsevierStyleItalic">T</span><span class="elsevierStyleInf">4</span>. (f) T1-weighted sequence during the fifth and last time of acquisition T<span class="elsevierStyleInf">5</span>. The ROI is maintained in the same location during the entire study. In this case, there is intense and fast uptake in <span class="elsevierStyleItalic">T</span><span class="elsevierStyleInf">1</span>, with later washout in the remaining sequences.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1479 "Ancho" => 1506 "Tamanyo" => 100876 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Time-signal intensity curves gadobutrol and Gd-DTPA. The uptake curve profile for both contrasts is shown. With a higher percentage of rapid washout curves, the Gd-DTPA shows average uptakes that are inferior to gadobutrol in all times of acquisition.</p>" ] ] 2 => 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:3 [ "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">IDC: infiltrating ductal carcinoma; IdC: intraductal carcinoma; ILC: infiltrating lobular carcinoma.</p>" "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="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Gd-DTPA (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>200)</th><th class="td" title="table-head " colspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Gadobutrol (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>199)</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span><a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " colspan="6" align="left" valign="top"><span class="elsevierStyleBold">Type of tumor</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">IDC</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">152 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">76.00% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">164 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">82.40% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.197 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">IdC</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.00% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.50% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">ILC</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">19 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9.50% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8.00% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Other</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">21 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10.50% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.00% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="6" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="6" align="left" valign="top"><span class="elsevierStyleBold">Histological grade</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">1</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">57 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">28.80% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">63 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">32.10% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.305 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">2</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">69 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">34.80% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">76 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">38.80% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">3</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">72 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">36.40% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">57 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">29.10% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="6" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="6" align="left" valign="top"><span class="elsevierStyleBold">Hormonal receptors</span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="6" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Estrogen receptor</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Positive \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">160 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">80.00% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">155 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">78.70% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.745 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Negative \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">40 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">20.00% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">42 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">21.30% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="6" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="6" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Progesterone receptor</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Positive \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">149 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">74.50% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">139 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">70.60% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.379 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Negative \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">51 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">25.50% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">58 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">29.40% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="6" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="6" align="left" valign="top"><span class="elsevierStyleBold">Ki-67 index</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><15% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">88 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">45.65% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">101 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">51.50% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.242 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>>15% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">105 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">54.40% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">95 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">48.50% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="6" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="6" align="left" valign="top"><span class="elsevierStyleBold">Her-2 status</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Positive \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10.30% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9.00% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.675 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Negative \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">175 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">89.70% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">172 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">91.00% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1654394.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Chi-square test.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Tumor histological characteristics in both groups of patients.</p>" ] ] 3 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">95% CI: 95% confidence interval.</p>" "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="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Time of acquisition \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Contrast agent \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Signal intensity relative enhancement (%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">95% CI \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " rowspan="2" align="left" valign="top">T1</td><td class="td" title="table-entry " align="left" valign="top">Gadobutrol \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">289.84 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">259.64–320.03 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " rowspan="2" align="left" valign="top">0.081</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gd-DTPA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">260.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">246.02–274.19 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="2" align="left" valign="top">T2</td><td class="td" title="table-entry " align="left" valign="top">Gadobutrol \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">311.21 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">281.31–341.11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " rowspan="2" align="left" valign="top">0.029</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gd-DTPA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">274.42 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">260.55–288.02 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="2" align="left" valign="top">Peak signal intensity</td><td class="td" title="table-entry " align="left" valign="top">Gadobutrol \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">337.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">308.07–367.74 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " rowspan="2" align="left" valign="top">0.001</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gd-DTPA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">295.36 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">281.24–309.48 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1654395.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Student's <span class="elsevierStyleItalic">t</span> test.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Signal intensity relative enhancement for gadobutrol and Gd-DTPA.</p>" ] ] 4 => 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" ] ] "tabla" => array:2 [ "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="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Washout, n (per cent) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Plateau, n (%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Permanent, n (%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span><a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gd-DTPA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">116 (58.29) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">59 (29.65) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">24 (12.06) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.032 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gadobutrol \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">92 (46.00) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">70 (35.00) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">38 (19.00) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1654396.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Chi-square test.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Type of curve 2<span class="elsevierStyleHsp" style=""></span>min after the injection of contrast.</p>" ] ] 5 => array:8 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at4" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "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="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Gd-DTPA (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>199) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Gadobutrol (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>199) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span><a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">K</span><span class="elsevierStyleSup">trans</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Median [P25–P75] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.523 [0.333–0.826] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.681 [0.396–1.057] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">K</span><span class="elsevierStyleInf">ep</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Median [P25–P75] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.084 [0.715–1.920] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.475 [0.867–2.572] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">e</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Median [P25–P75] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.480 [0.400–0.604] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.508 [0.396–0.640] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1654397.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0020" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Mann–Whitney test.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Pharmacokinetic parameters of both contrast agents.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:36 [ 0 => array:3 [ "identificador" => "bib0185" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Magnetic resonance imaging of the breast: recommendations from the EUSOMA working group" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "I. 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