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  <front>
    <journal-meta>
      <journal-id journal-id-type="publisher-id">abc</journal-id>
      <journal-title-group>
        <journal-title>Arquivos Brasileiros de Cardiologia</journal-title>
        <abbrev-journal-title abbrev-type="publisher">Arq. Bras. Cardiol.</abbrev-journal-title>
      </journal-title-group>
      <issn pub-type="ppub">0066-782X</issn>
      <issn pub-type="epub">1678-4170</issn>
      <publisher>
        <publisher-name>Sociedade Brasileira de Cardiologia - SBC</publisher-name>
        <publisher-loc>S&#227;o Paulo, SP, Brazil</publisher-loc>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v3">QJT7rfNq45DPbMzSkDQmQ7J</article-id>
      <article-id pub-id-type="other">00003</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2004001400003</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v1">S0066-782X(04)08300203</article-id>
      <article-id pub-id-type="doi">10.1590/S0066-782X2004001400003</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigos Originais</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Quantifica&#231;&#227;o da massa infartada do ventr&#237;culo esquerdo pela resson&#226;ncia magn&#233;tica card&#237;aca: compara&#231;&#227;o entre a planimetria e o m&#233;todo de escore visual semi-quantitativo</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Azevedo Filho</surname>
            <given-names>Clerio Francisco de</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Hadlich</surname>
            <given-names>Marcelo</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Petriz</surname>
            <given-names>Jo&#227;o Luiz Fernandes</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Mendon&#231;a</surname>
            <given-names>Lu&#237;s Antonio</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Moll Filho</surname>
            <given-names>Jorge Neval</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Rochitte</surname>
            <given-names>Carlos Eduardo</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
      </contrib-group>
      <aff id="aff01">
        <addr-line>
          <named-content content-type="state">S&#227;o Paulo</named-content>
        </addr-line>
        <institution content-type="orgname">Universidade de S&#227;o Paulo</institution>
        <institution content-type="orgdiv1">FM </institution>
        <institution content-type="orgdiv2">Hospital das Cl&#237;nicas</institution>
        <country country="BR">Brazil</country>
      </aff>
      <pub-date date-type="collection" publication-format="electronic">
        <month>08</month>
        <year>2004</year>
      </pub-date>
      <volume>83</volume>
      <issue>2</issue>
      <fpage>111</fpage>
      <lpage>117</lpage>
      <history>
        <date date-type="accepted">
          <day>03</day>
          <month>12</month>
          <year>2003</year>
        </date>
        <date date-type="received">
          <day>17</day>
          <month>04</month>
          <year>2003</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc/4.0/" xml:lang="en">
          <license-p>This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.</license-p>
        </license>
      </permissions>
      <abstract>
        <p>OBJETIVO: Validar um novo m&#233;todo de escore visual semi-quantitativo contra a planimetria digital quantitativa para a determina&#231;&#227;o da massa infartada do ventr&#237;culo esquerdo pela resson&#226;ncia magn&#233;tica card&#237;aca com t&#233;cnica de realce tardio. M&#201;TODO: Estudados 77 pacientes com infarto mioc&#225;rdico pr&#233;vio em aparelho de resson&#226;ncia magn&#233;tica de 1,5T utilizando t&#233;cnica de realce tardio para avalia&#231;&#227;o da viabilidade mioc&#225;rdica e c&#225;lculo da massa infartada. Para avalia&#231;&#227;o da fun&#231;&#227;o ventricular esquerda pelo m&#233;todo de Simpson utilizamos t&#233;cnica de cine-resson&#226;ncia. O c&#225;lculo da massa infartada foi realizado nas imagens de realce tardio de duas formas: planimetria e m&#233;todo de escore. Utilizamos m&#233;todos de regress&#227;o linear simples, correla&#231;&#227;o e concord&#226;ncia entre m&#233;todos e observadores segundo a an&#225;lise de Bland-Altman. RESULTADOS: Em todos os 77 pacientes as &#225;reas de infarto foram detectadas pela resson&#226;ncia magn&#233;tica card&#237;aca utilizando a t&#233;cnica de realce tardio. O tamanho do infarto medido pela planimetria foi semelhante ao obtido pelo m&#233;todo de escore, com a m&#233;dia das diferen&#231;as entres as medidas de apenas 1,03% da massa do ventr&#237;culo esquerdo. As variabilidades inter (0,41%) e intra-observador (0,34%) evidenciaram excelente reprodutibilidade do m&#233;todo de escore. A massa infartada apresentou boa correla&#231;&#227;o com a fra&#231;&#227;o de eje&#231;&#227;o e volumes dist&#243;lico e sist&#243;lico finais indexados, r=-0,76, r=0,63 e r=0,67, respectivamente. CONCLUS&#195;O: A avalia&#231;&#227;o de pacientes com infarto agudo do mioc&#225;rdio pr&#233;vio pela resson&#226;ncia magn&#233;tica card&#237;aca, utilizando a t&#233;cnica de realce tardio, permite a determina&#231;&#227;o reprodut&#237;vel do tamanho do infarto, tanto pelo m&#233;todo de planimetria, quanto pelo modelo semi-quantitativo de escore.</p>
      </abstract>
      <kwd-group xml:lang="pt" kwd-group-type="author-generated">
        <kwd>infarto do mioc&#225;rdio</kwd>
        <kwd>resson&#226;ncia magn&#233;tica</kwd>
        <kwd>viabilidade mioc&#225;rdica</kwd>
      </kwd-group>
      <pub-date publication-format="electronic" date-type="pub">
        <day>18</day>
        <month>08</month>
        <year>2004</year>
      </pub-date>
    </article-meta>
  </front>
  <body>
    <p>
      <bold>ARTIGO ORIGINAL</bold>
    </p>
    <p>Quantifica&#231;&#227;o da massa infartada do ventr&#237;culo esquerdo pela resson&#226;ncia magn&#233;tica card&#237;aca. Compara&#231;&#227;o entre a planimetria e o m&#233;todo de escore visual semi-quantitativo </p>
    <p>Clerio Francisco de Azevedo Filho; Marcelo Hadlich; Jo&#227;o Luiz Fernandes Petriz; Lu&#237;s Antonio Mendon&#231;a; Jorge Neval Moll Filho; Carlos Eduardo Rochitte </p>
    <p> Rio de Janeiro, RJ e S&#227;o Paulo, SP  </p>
    <p>Rede de Hospitais D'Or e LABS/RJ e InCor do Hospital das Cl&#237;nicas da FMUSP</p>
    <p>
      <xref ref-type="corresp" rid="end">Endere&#231;o para correspond&#234;ncia</xref>
    </p>
    <p>
      <bold>RESUMO</bold>
    </p>
    <p><bold>OBJETIVO: </bold>Validar um novo m&#233;todo de escore visual semi-quantitativo contra a planimetria digital quantitativa para a determina&#231;&#227;o da massa infartada do ventr&#237;culo esquerdo pela resson&#226;ncia magn&#233;tica card&#237;aca com t&#233;cnica de realce tardio. </p>
    <p><bold>M&#201;TODO: </bold>Estudados 77 pacientes com infarto mioc&#225;rdico pr&#233;vio em aparelho de resson&#226;ncia magn&#233;tica de 1,5T utilizando t&#233;cnica de realce tardio para avalia&#231;&#227;o da viabilidade mioc&#225;rdica e c&#225;lculo da massa infartada. Para avalia&#231;&#227;o da fun&#231;&#227;o ventricular esquerda pelo m&#233;todo de Simpson utilizamos t&#233;cnica de cine-resson&#226;ncia. O c&#225;lculo da massa infartada foi realizado nas imagens de realce tardio de duas formas: planimetria e m&#233;todo de escore. Utilizamos m&#233;todos de regress&#227;o linear simples, correla&#231;&#227;o e concord&#226;ncia entre m&#233;todos e observadores segundo a an&#225;lise de Bland-Altman. </p>
    <p><bold>RESULTADOS: </bold>Em todos os 77 pacientes as &#225;reas de infarto foram detectadas pela resson&#226;ncia magn&#233;tica card&#237;aca utilizando a t&#233;cnica de realce tardio. O tamanho do infarto medido pela planimetria foi semelhante ao obtido pelo m&#233;todo de escore, com a m&#233;dia das diferen&#231;as entres as medidas de apenas 1,03% da massa do ventr&#237;culo esquerdo. As variabilidades inter (0,41%) e intra-observador (0,34%) evidenciaram excelente reprodutibilidade do m&#233;todo de escore. A massa infartada apresentou boa correla&#231;&#227;o com a fra&#231;&#227;o de eje&#231;&#227;o e volumes dist&#243;lico e sist&#243;lico finais indexados, r=-0,76, r=0,63 e r=0,67, respectivamente. </p>
    <p><bold>CONCLUS&#195;O:</bold> A avalia&#231;&#227;o de pacientes com infarto agudo do mioc&#225;rdio pr&#233;vio pela resson&#226;ncia magn&#233;tica card&#237;aca, utilizando a t&#233;cnica de realce tardio, permite a determina&#231;&#227;o reprodut&#237;vel do tamanho do infarto, tanto pelo m&#233;todo de planimetria, quanto pelo modelo semi-quantitativo de escore. </p>
    <p><bold>Palavras-Chave: </bold>infarto do mioc&#225;rdio, resson&#226;ncia magn&#233;tica, viabilidade mioc&#225;rdica </p>
    <p>A resson&#226;ncia magn&#233;tica card&#237;aca apresentou grande desenvolvimento na &#250;ltima d&#233;cada, e suas aplica&#231;&#245;es na avalia&#231;&#227;o dos pacientes com doen&#231;a card&#237;aca isqu&#234;mica s&#227;o cada vez mais abrangentes. As t&#233;cnicas de resson&#226;ncia magn&#233;tica card&#237;aca atuais, especialmente os protocolos baseados na t&#233;cnica do realce tardio, permitem uma precisa delimita&#231;&#227;o das &#225;reas de necrose ou fibrose mioc&#225;rdica nos pacientes com infarto pr&#233;vio<sup>1-7</sup>. Nas imagens de realce tardio, as &#225;reas de infarto apresentam intensidade de sinal muito aumentada (brancas) em compara&#231;&#227;o ao mioc&#225;rdio normal (escuro). O grande contraste entre o tecido necr&#243;tico ou fibr&#243;tico e o tecido mioc&#225;rdico &#237;ntegro (intensidade de sinal at&#233; 10 vezes maior nas regi&#245;es de infarto)<sup>8</sup>, associado &#224; &#243;tima resolu&#231;&#227;o espacial proporcionada pela resson&#226;ncia magn&#233;tica card&#237;aca, permitem a precisa avalia&#231;&#227;o do territ&#243;rio infartado. </p>
    <p>Em estudo publicado em 1998, Wu e cols. demonstraram que o tamanho do infarto, expresso como um percentual da massa do ventr&#237;culo esquerdo, tem importante valor progn&#243;stico nos pacientes com infarto agudo do mioc&#225;rdio<sup>9</sup>. Al&#233;m disso, dois outros estudos recentes demonstraram que a avalia&#231;&#227;o da massa infartada foi preditora da recupera&#231;&#227;o da fun&#231;&#227;o sist&#243;lica global e segmentar nesse grupo de pacientes<sup>10,11</sup>. Sobretudo, um estudo recente de Kim e cols. demonstrou que a presen&#231;a de viabilidade mioc&#225;rdica, definida como recupera&#231;&#227;o funcional regional ap&#243;s revasculariza&#231;&#227;o do mioc&#225;rdio, pode ser determinada atrav&#233;s da quantifica&#231;&#227;o da transmuralidade do infarto<sup>12</sup>. Esse mesmo estudo tamb&#233;m demonstrou que quanto maior a massa de mioc&#225;rdio disfuncional e vi&#225;vel antes da interven&#231;&#227;o, maior a recupera&#231;&#227;o global da fra&#231;&#227;o de eje&#231;&#227;o ap&#243;s a revasculariza&#231;&#227;o. Portanto, a determina&#231;&#227;o da massa infartada nos exames de resson&#226;ncia magn&#233;tica card&#237;aca, pode fornecer informa&#231;&#245;es importantes e muito &#250;teis ao manejo dos pacientes com infarto agudo do mioc&#225;rdio pr&#233;vio. </p>
    <p>Atualmente, a resson&#226;ncia magn&#233;tica card&#237;aca &#233; considerada o melhor m&#233;todo para a avalia&#231;&#227;o da massa infartada do ventr&#237;culo esquerdo, superando inclusive o PET na detec&#231;&#227;o de defeitos subendoc&#225;rdicos<sup>13</sup>. A t&#233;cnica usualmente utilizada &#233; a quantifica&#231;&#227;o direta atrav&#233;s da planimetria das &#225;reas de realce tardio. Entretanto, a planimetria &#233; um m&#233;todo bastante laborioso e que consome consider&#225;vel tempo de p&#243;s-processamento das imagens. Al&#233;m disso, exige a utiliza&#231;&#227;o de <italic>softwares</italic> espec&#237;ficos, muitas vezes n&#227;o dispon&#237;veis facilmente. Por outro lado, o m&#233;todo de escore, que se baseia na avalia&#231;&#227;o semi-quantitativa visual das imagens de realce tardio, constitui uma alternativa muito mais r&#225;pida e pr&#225;tica para a determina&#231;&#227;o da extens&#227;o do infarto. Apresenta ainda a vantagem de depender apenas da visibiliza&#231;&#227;o das imagens em formato digital no pr&#243;prio monitor, ou mesmo em filme radiogr&#225;fico ou foto impressa em papel. O nosso estudo tem o objetivo de apresentar e descrever a quantifica&#231;&#227;o do tamanho do infarto pela resson&#226;ncia magn&#233;tica card&#237;aca utilizando a t&#233;cnica do realce tardio e determinar se o c&#225;lculo da massa infartada pelo m&#233;todo de escore &#233; v&#225;lido e confi&#225;vel quando comparado ao m&#233;todo quantitativo de planimetria digital. </p>
    <p>
      <bold>M&#233;todo</bold>
    </p>
    <p>Casos estudados entre outubro/2001 e outubro/2002, constituindo 77 pacientes (60 homens e 17 mulheres, com idade m&#233;dia de 59,9 &#177;10,6 anos), com diagn&#243;stico de infarto agudo do mioc&#225;rdio pr&#233;vio (subagudos e cr&#244;nicos, <underline>&gt;</underline> 2 semanas p&#243;s-infarto), e encaminhados ao servi&#231;o para serem submetidos a exame de resson&#226;ncia magn&#233;tica card&#237;aca, com objetivo de avaliar a viabilidade mioc&#225;rdica. Quatro pacientes apresentaram 2 epis&#243;dios distintos de infarto agudo do mioc&#225;rdio pr&#233;vio, perfazendo um total de 81 diferentes &#225;reas de infarto identificadas: 35 (43%) de localiza&#231;&#227;o anterior, 29 (36%) inferior e 17 (21%) lateral, dais quais 48 (59%) transmurais e 33 (41%) subendoc&#225;rdicas. </p>
    <p>Os pacientes foram submetidos a exame num aparelho de resson&#226;ncia magn&#233;tica Philips Gyroscan NT Intera de 1,5T equipado com sistema de gradientes de alta performance Powertrack 6000 (<italic>Philips Medical Systems, Best, The Netherlands</italic>). Foi utilizado o contraste endovenoso gadol&#237;nio (Dotaren<sup>&#174;</sup>), espec&#237;fico para resson&#226;ncia magn&#233;tica, na dose de 0,2 mmol/kg. A aquisi&#231;&#227;o das imagens foi feita cerca de 10 a 15min ap&#243;s a administra&#231;&#227;o do contraste, utilizando uma seq&#252;&#234;ncia de pulsos do tipo gradiente-eco r&#225;pida ponderada em T1 (<italic>T1 Turbo Field Echo</italic>), sincronizada &#224; monitoriza&#231;&#227;o vetorcardiogr&#225;fica. Foram realizados, de forma seq&#252;encial, 8 cortes do eixo curto do ventr&#237;culo esquerdo cobrindo toda cavidade ventricular, do &#225;pice ao anel mitral. A aquisi&#231;&#227;o de cada corte teve dura&#231;&#227;o de aproximadamente 8s (cerca de 8 a 12 batimentos card&#237;acos, dependendo da freq&#252;&#234;ncia card&#237;aca), durante os quais o paciente era solicitado a realizar pausa respirat&#243;ria em expira&#231;&#227;o. O retardo de disparo da seq&#252;&#234;ncia (<italic>trigger delay</italic>) foi ajustado para que as imagens fossem adquiridas na di&#225;stole ventricular. A aquisi&#231;&#227;o de cada segmento do espa&#231;o K foi precedida de um pr&#233;-pulso de invers&#227;o-recupera&#231;&#227;o com um tempo de invers&#227;o (TI) ajustado para anular o sinal do mioc&#225;rdio normal, aumentando dessa forma o contraste entre as regi&#245;es de infarto (sinal intenso &#150; branco) e o mioc&#225;rdio normal (sinal muito fraco &#150; escuro)<sup>8</sup>. </p>
    <p>A seq&#252;&#234;ncia de pulsos &#233; chamada de t&#233;cnica de realce tardio (<italic>delayed enhancement</italic>) e um exemplo t&#237;pico &#233; demonstrado na <xref ref-type="fig" rid="fig1">figura 1</xref>. Os par&#226;metros t&#233;cnicos utilizados foram os seguintes (ap&#234;ndice): TR 5,7 ms; TE 2,8 ms; &#226;ngulo de inclina&#231;&#227;o (FA): 20&#186;; campo de vis&#227;o (<italic>FOV)</italic> 350-420 mm; matriz: 192 x 192; campo de vis&#227;o retangular (<italic>RFOV) </italic>75%; tempo de invers&#227;o (TI): 170-300 ms; n&#250;mero de aquisi&#231;&#245;es (<italic>NSA)</italic>: 2, n&#250;mero de cortes: 8-10; espessura de corte: 8 mm; intervalo entre os cortes (gap): 2mm (portanto, 1 corte a cada 10 mm do &#225;pex a base do cora&#231;&#227;o).</p>
    <fig id="fig1">
      <graphic xlink:href="1678-4170-abc-83-02-0111-00003-gf01.jpg"/></fig>
    <p>Al&#233;m da an&#225;lise das &#225;reas de infarto, foi avaliada tamb&#233;m a fun&#231;&#227;o ventricular esquerda de todos os pacientes estudados<sup>14-18</sup>. Para tanto, foram adquiridas imagens de cine-resson&#226;ncia do eixo curto do ventr&#237;culo esquerdo, cobrindo toda a cavidade ventricular (precisamente nas mesmas localiza&#231;&#245;es anat&#244;micas das imagens de realce tardio), utilizando uma seq&#252;&#234;ncia de pulsos do tipo gradiente-eco com magnetiza&#231;&#227;o transversal em estado de equil&#237;brio (<italic>Balanced Fast Field Echo ou B-FFE</italic>)<sup>19-23</sup>, com os seguintes par&#226;metros t&#233;cnicos: TR 3,1 ms; TE 1,55 ms; &#226;ngulo de inclina&#231;&#227;o (FA): 55&#186;; campo de vis&#227;o (<italic>FOV)</italic> 350-420 mm; matriz: 192 x 128; campo de vis&#227;o retangular (<italic>RFOV</italic>) 75%; n&#250;mero de fases card&#237;acas: 24; n&#250;mero de aquisi&#231;&#245;es (<italic>NSA)</italic>: 1, n&#250;mero de cortes: 8-10; espessura de corte: 8 mm; intervalo entre os cortes (gap): 2mm. </p>
    <p>
      <graphic xlink:href="1678-4170-abc-83-02-0111-00003-e01.jpg"/></p>
    <p>Todas as imagens foram armazenadas em discos &#243;pticos e posteriormente processadas na <italic>Workstation Philips Easyvision</italic>. As &#225;reas de infarto, definidas como as regi&#245;es que apresentaram realce tardio, foram ent&#227;o avaliadas de duas formas: 1) m&#233;todo de planimetria digital quantitativa: contorno manual, em <italic>software</italic> espec&#237;fico, das regi&#245;es de realce tardio nos cortes que apresentaram &#225;reas de infarto (<xref ref-type="fig" rid="fig2">fig. 2</xref>). O volume de tecido infartado foi calculado como a soma das &#225;reas planimetradas multiplicada pela espessura de cada corte. Para obtermos o valor da massa infartada em gramas, multiplicamos o volume infartado pela densidade do tecido mioc&#225;rdico (1,05g/ml). A etapa seguinte consistiu no contorno manual das bordas endoc&#225;rdica e epic&#225;rdica do ventr&#237;culo esquerdo nos 8 cortes. O volume do ventr&#237;culo esquerdo foi calculado como a diferen&#231;a entre o volume epic&#225;rdico e endoc&#225;rdico do ventr&#237;culo esquerdo (volume do VE = volume epic&#225;rdico &#150; volume endoc&#225;rdico). A determina&#231;&#227;o dos volumes endoc&#225;rdico e epic&#225;rdico foi efetuada segundo o m&#233;todo de Simpson: soma das &#225;reas endoc&#225;rdica e epic&#225;rdica multiplicada pela espessura de cada corte. A massa do ventr&#237;culo esquerdo foi ent&#227;o definida como o volume do VE multiplicado pela densidade do tecido mioc&#225;rdico (1,05g/ml). O percentual de massa infartada do ventr&#237;culo esquerdo foi calculado como: massa infartada (%VE) = (massa infartada /massa do VE)*100. (equa&#231;&#227;o 1); 2) m&#233;todo de escore: avalia&#231;&#227;o visual dos oito cortes, por dois observadores independentes e alheios aos resultados da planimetria. Os cortes foram divididos num total de 48 segmentos: cortes 1 e 2 (cortes apicais) com 4 segmentos cada, cortes 3 a 6 (cortes m&#233;dios) com 6 segmentos cada e cortes 7 e 8 (cortes basais) com 8 segmentos cada. Essa divis&#227;o foi elaborada de forma a fazer uma pondera&#231;&#227;o entre as massas dos diferentes cortes, tendo em vista que os cortes apicais possuem menor massa e, portanto, t&#234;m menor peso na determina&#231;&#227;o da massa final quando comparados aos cortes basais (<xref ref-type="fig" rid="fig3">fig. 3</xref>).</p>
    <fig id="fig2">
      <graphic xlink:href="1678-4170-abc-83-02-0111-00003-gf02.jpg"/></fig>
    <fig id="fig3">
      <graphic xlink:href="1678-4170-abc-83-02-0111-00003-gf03.jpg"/></fig>
    <p>Cada segmento recebeu uma pontua&#231;&#227;o de acordo com o percentual de envolvimento pelo realce tardio (escore zero, 1, 2 ou 3). O escore zero correspondeu &#224; aus&#234;ncia de realce; o escore 1, realce de 1 a 25% da &#225;rea do segmento; escore 2, realce de 26 a 75% e escore 3, realce de mais de 75% da &#225;rea do segmento. O escore total de cada paciente foi definido como a soma dos escores dos 48 segmentos analisados, sendo o escore m&#225;ximo poss&#237;vel de 144 pontos (3*48 segmentos). O percentual de massa infartada do VE foi ent&#227;o calculado como: massa infartada (%VE) = (escore total do paciente/ 144)*100 (equa&#231;&#227;o 2). </p>
    <p>Para determinarmos a variabilidade intra-observador do m&#233;todo de escore, um dos dois observadores calculou o percentual de massa infartada de cada paciente em duas ocasi&#245;es, separadas por um intervalo de 1 a 4 meses. </p>
    <p>Para a avalia&#231;&#227;o da fun&#231;&#227;o ventricular esquerda de cada paciente, foram calculados quatro par&#226;metros utilizando o m&#233;todo de Simpson: fra&#231;&#227;o de eje&#231;&#227;o (FE), volume diast&#243;lico final (VDF), volume sist&#243;lico final (VSF) e volume sist&#243;lico de eje&#231;&#227;o (VS). Esses par&#226;metros foram obtidos a partir das imagens de cine-resson&#226;ncia magn&#233;tica da seguinte forma: contorno manual, em <italic>software</italic> espec&#237;fico, da borda endoc&#225;rdica do ventr&#237;culo esquerdo nas fases diast&#243;lica (maior &#225;rea) e sist&#243;lica (menor &#225;rea) nos 8 cortes do eixo curto do ventr&#237;culo esquerdo. O VDF foi medido como a soma dos produtos da &#225;rea de cada corte na fase diast&#243;lica vezes a espessura do corte. O VSF foi calculado de forma semelhante, s&#243; que utilizando para o c&#225;lculo a fase sist&#243;lica de cada corte. O VS foi calculado como: VS = VDF-VSF e a FE como: FE = (VS/VDF)*100. Os volumes VDF, VSF e VS foram ent&#227;o normalizados para a &#225;rea de superf&#237;cie corporal, gerando os par&#226;metros IVDF, IVSF e IVS. </p>
    <p>Os dados de todas as vari&#225;veis obtidas foram arquivados e analisados utilizando o programa de an&#225;lise estat&#237;stica STATA, vers&#227;o 7.0. Todas as vari&#225;veis cont&#237;nuas foram expressas como m&#233;dia &#177; desvio padr&#227;o. Foi utilizado o teste 't' de Student pareado bicaudal para comparar as amostras relacionadas. O grau de concord&#226;ncia entre os m&#233;todos, assim como as variabilidades intra e inter-obsevador do m&#233;todo de escore, foram avaliados atrav&#233;s do m&#233;todo de an&#225;lise descrito por Bland e Altman<sup>24</sup>. Foram tamb&#233;m utilizadas a an&#225;lise de regress&#227;o linear e a correla&#231;&#227;o de Pearson para examinar a rela&#231;&#227;o entre os dois m&#233;todos (planimetria versus escore) e a rela&#231;&#227;o entre os dados de fun&#231;&#227;o ventricular e o percentual de massa infartada. Os resultados foram considerados estatisticamente significativos quando P&lt;0,05. </p>
    <p>
      <bold>Resultados</bold>
    </p>
    <p>A resson&#226;ncia magn&#233;tica card&#237;aca com t&#233;cnica de realce tardio foi capaz de detectar necrose ou fibrose mioc&#225;rdica em todos os 77 pacientes com hist&#243;ria de infarto agudo do mioc&#225;rdio pr&#233;vio analisados. As regi&#245;es de infarto foram qualitativamente consideradas analis&#225;veis em todos os casos, tanto do ponto de vista da medida da &#225;rea como da transmuralidade. Um exemplo t&#237;pico deste exame &#233; apresentado na <xref ref-type="fig" rid="fig1">figura 1</xref>. </p>
    <p>O tamanho do infarto, definido como o percentual de massa infartada do ventr&#237;culo esquerdo, foi discretamente maior quando medido pela planimetria (19,94 &#177;11,10%) do que pelo m&#233;todo de escore (18,92 &#177;10,41%). A diferen&#231;a m&#233;dia entre as medidas obtidas pelos dois m&#233;todos foi de 1,03% (intervalo de confian&#231;a de 95% de 0,15 a 1,91%). Apesar de ter atingido signific&#226;ncia estat&#237;stica (P=0,02), essa pequena diferen&#231;a n&#227;o &#233; significativa do ponto de vista cl&#237;nico, uma vez que representa apenas aproximadamente 1% da massa total do ventr&#237;culo esquerdo. Mais importante, o intervalo de concord&#226;ncia de 95% entre os dois m&#233;todos foi de -6,74 a +8,80% (<xref ref-type="fig" rid="fig4">fig. 4</xref> e <xref ref-type="table" rid="tab1">tab. I</xref>).</p>
    <fig id="fig4">
      <graphic xlink:href="1678-4170-abc-83-02-0111-00003-gf04.jpg"/></fig>
    <table-wrap id="tab1">
      <graphic xlink:href="1678-4170-abc-83-02-0111-00003-gt01.jpg"/></table-wrap>
    <p>Assim, do ponto de vista pr&#225;tico e no uso cl&#237;nico rotineiro, o tamanho do infarto medido pela planimetria foi semelhante aos valores do m&#233;todo de escore obtidos pelos dois observadores isoladamente e &#224; m&#233;dia desses valores. </p>
    <p>A expressiva correla&#231;&#227;o entre os dois m&#233;todos foi demonstrada ainda atrav&#233;s da an&#225;lise de regress&#227;o linear, considerando a planimetria como vari&#225;vel dependente e o escore como vari&#225;vel independente. A equa&#231;&#227;o da linha de regress&#227;o foi calculada como y=1,00x + 1,05, com intervalo de confian&#231;a de 95% do coeficiente 'b' de 0,91 a 1,08 e desvio padr&#227;o dos res&#237;duos de 3,91 (P&lt;0,0001) (<xref ref-type="table" rid="a03tab02">tab. II</xref>). O coeficiente de correla&#231;&#227;o de Pearson tamb&#233;m evidenciou rela&#231;&#227;o bastante significativa entre os dois m&#233;todos (r = 0,94, P&lt;0,0001) (<xref ref-type="fig" rid="fig5">fig. 5</xref>).</p>
    <p content-type="asset">
      <table-wrap id="a03tab02">
        <graphic xlink:href="1678-4170-abc-83-02-0111-00003-gt02.jpg"/></table-wrap>
    </p>
    <fig id="fig5">
      <graphic xlink:href="1678-4170-abc-83-02-0111-00003-gf05.jpg"/></fig>
    <p>A avalia&#231;&#227;o da variabilidade inter-observador do m&#233;todo de escore revelou uma diferen&#231;a m&#233;dia de 0,41% (NS) entre as medidas obtidas pelos dois observadores e um coeficiente de repetibilidade de &#177;9,56%. J&#225; a avalia&#231;&#227;o da variabilidade intra-observador evidenciou uma diferen&#231;a m&#233;dia de 0,34% (NS) e um coeficiente de repetibilidade de &#177;8,62% (<xref ref-type="table" rid="tab3">tab. III</xref>).</p>
    <table-wrap id="tab3">
      <graphic xlink:href="1678-4170-abc-83-02-0111-00003-gt03.jpg"/></table-wrap>
    <p>O tamanho do infarto, medido tanto pela planimetria quanto pelo m&#233;todo de escore, apresentou expressiva correla&#231;&#227;o com a fra&#231;&#227;o de eje&#231;&#227;o do ventr&#237;culo esquerdo medida pelo m&#233;todo de Simpson (r = -0,74, P&lt;0,0001 para planimetria e r = -0,76, P&lt;0,0001 para o m&#233;todo de escore) (<xref ref-type="fig" rid="fig6">fig. 6</xref>). Al&#233;m da fra&#231;&#227;o de eje&#231;&#227;o, os &#237;ndices de volume diast&#243;lico final (IVDF) e volume sist&#243;lico final (IVSF) tamb&#233;m apresentaram significativa correla&#231;&#227;o com o tamanho do infarto (IVDF: r = 0,63 e 0,67, P&lt;0,0001 e IVSF: r = 0,73 e 0,75, P&lt;0,0001, respectivamente para planimetria e para o m&#233;todo de escore) (<xref ref-type="fig" rid="fig7">fig. 7</xref>). O &#237;ndice de volume sist&#243;lico (IVS) n&#227;o apresentou correla&#231;&#227;o com o tamanho do infarto medido por nenhum dos dois m&#233;todos (r = -0,27, P=0,03 para planimetria e r = -0,19, NS para o m&#233;todo de escore).</p>
    <fig id="fig6">
      <graphic xlink:href="1678-4170-abc-83-02-0111-00003-gf06.jpg"/></fig>
    <fig id="fig7">
      <graphic xlink:href="1678-4170-abc-83-02-0111-00003-gf07.jpg"/></fig>
    <p>
      <bold>Discuss&#227;o</bold>
    </p>
    <p>Este estudo demonstrou que a quantifica&#231;&#227;o do tamanho do infarto, assim como sua caracteriza&#231;&#227;o e delineamento, podem ser obtidos atrav&#233;s da resson&#226;ncia magn&#233;tica card&#237;aca utilizando a t&#233;cnica de realce tardio com grande precis&#227;o e reprodutibilidade. O m&#233;todo de escore foi capaz de quantificar a massa infartada de forma r&#225;pida e precisa quando comparado ao m&#233;todo da planimetria. A boa concord&#226;ncia e correla&#231;&#227;o verificada entre os dois m&#233;todos nos permite apresentar o m&#233;todo de escore como alternativa r&#225;pida e pr&#225;tica para o c&#225;lculo da massa infartada, que pode ent&#227;o ser relatada rotineiramente nos laudos de resson&#226;ncia magn&#233;tica card&#237;aca, tornando-se de fundamental import&#226;ncia cl&#237;nica, uma vez que o valor diagn&#243;stico e progn&#243;stico da avalia&#231;&#227;o da massa infartada vem sendo demonstrado sistematicamente em estudos realizados nos &#250;ltimos anos<sup>9-12</sup>. </p>
    <p>A t&#233;cnica de realce tardio se desenvolveu a partir dos estudos pioneiros de Lima e cols. avaliando a detec&#231;&#227;o e caracteriza&#231;&#227;o das &#225;reas de infarto atrav&#233;s da resson&#226;ncia magn&#233;tica card&#237;aca contrastada com gadol&#237;nio<sup>25</sup>. Foi utilizada inicialmente nos trabalhos experimentais e cl&#237;nicos do grupo liderado por Kim e Judd e cols.<sup>1-4,10,12,26,27</sup> e descrita do ponto de vista t&#233;cnico por Simonetti e cols.<sup>8</sup>. A t&#233;cnica de realce tardio se baseia numa seq&#252;&#234;ncia de pulsos do tipo gradiente-eco r&#225;pida ponderada em T1 (<italic>T1 Turbo Field Echo</italic>), com um pr&#233;-pulso de invers&#227;o-recupera&#231;&#227;o e um tempo de invers&#227;o (TI) ajustado para anular o sinal do mioc&#225;rdio normal. Portanto, nas imagens adquiridas com essa t&#233;cnica, o mioc&#225;rdio &#237;ntegro aparece com intensidade de sinal muito baixa (escuro). Outra caracter&#237;stica da t&#233;cnica de realce tardio &#233; a utiliza&#231;&#227;o do contraste endovenoso gadol&#237;nio, que n&#227;o penetra nas membranas celulares &#237;ntegras e, portanto, tem distribui&#231;&#227;o extra-celular. Nas regi&#245;es de infarto ocorre ruptura das membranas dos mi&#243;citos necr&#243;ticos e, portanto, o gadol&#237;nio pode se distribuir livremente (maior volume de distribui&#231;&#227;o)<sup>28-30</sup>. Al&#233;m disso, a necrose dos mi&#243;citos tamb&#233;m causa uma altera&#231;&#227;o da cin&#233;tica de distribui&#231;&#227;o do contraste, de modo que a sa&#237;da do gadol&#237;nio das &#225;reas de infarto ocorre mais lentamente (<italic>delayed washout</italic>)<sup>2</sup>. Estes dois fatores fazem com que a concentra&#231;&#227;o do contraste, cerca de 10 a 15 minutos ap&#243;s a inje&#231;&#227;o, seja muito maior nas regi&#245;es necr&#243;ticas do que no tecido mioc&#225;rdico normal<sup>31</sup>, tornando as &#225;reas de infarto brancas (sinal intenso) nas imagens de realce tardio. Em resumo, ao aumentar a intensidade de sinal do infarto (utilizando o gadol&#237;nio e ponderando as imagens em T1) e diminuir a intensidade de sinal do mioc&#225;rdio normal (com o pr&#233;-pulso de invers&#227;o e TI em torno de 200-300 ms), a t&#233;cnica do realce tardio otimiza o contraste entre os dois tecidos (diferen&#231;a de sinal de at&#233; 1080%) e permite a precisa delimita&#231;&#227;o das &#225;reas de necrose mioc&#225;rdica<sup>8</sup>. </p>
    <p>No caso dos infartos antigos, a fibrose e n&#227;o a necrose, &#233; o fen&#244;meno patol&#243;gico subjacente. Nesses casos, o maior espa&#231;o extracelular verificado no tecido fibr&#243;tico, quando comparado ao mioc&#225;rdio normal, &#233; a causa do maior volume de distribui&#231;&#227;o e da altera&#231;&#227;o da cin&#233;tica do gadol&#237;nio (sa&#237;da lentificada do contraste do tecido fibr&#243;tico)<sup>31</sup>. </p>
    <p>Diversos estudos publicados recentemente validaram a medida do tamanho do infarto pela resson&#226;ncia magn&#233;tica card&#237;aca contra a medida direta da massa infartada pela anatomopatologia<sup>1-3;5</sup>. A t&#233;cnica de mensura&#231;&#227;o da massa infartada utilizada nesses estudos foi a planimetria das &#225;reas de realce tardio e esta demonstrou excelente concord&#226;ncia e correla&#231;&#227;o com os valores obtidos pela anatomopatologia utilizando a colora&#231;&#227;o TTC. Portanto, em nosso estudo consideramos como padr&#227;o-ouro o c&#225;lculo da massa infartada atrav&#233;s da planimetria, contra o qual comparamos o m&#233;todo de escore desenvolvido pelo nosso grupo. </p>
    <p>A correla&#231;&#227;o entre os dois m&#233;todos, medida atrav&#233;s do coeficiente de correla&#231;&#227;o de Pearson, foi bastante expressiva e estatisticamente significativa (r = 0,93; P&lt;0,0001). A an&#225;lise de regress&#227;o linear tamb&#233;m evidenciou resultados bastante consistentes (<xref ref-type="table" rid="a03tab02">tab. II</xref>). Entretanto, como demonstrado por Bland e Altman em seu estudo sobre compara&#231;&#245;es de dois m&#233;todos de mensura&#231;&#227;o<sup>24</sup>, mais importante do que a correla&#231;&#227;o ou a regress&#227;o linear, &#233; a avalia&#231;&#227;o da concord&#226;ncia entre os m&#233;todos. </p>
    <p>Baseados na an&#225;lise descrita por Bland e Altman, demonstramos que a diferen&#231;a m&#233;dia entre os valores de massa infartada obtidos pelos dois m&#233;todos n&#227;o foi significativa do ponto de vista cl&#237;nico: apenas 1,03% (intervalo de confian&#231;a de 95% de 0,15 a 1,91%). Ainda que tenha atingido signific&#226;ncia estat&#237;stica (P&lt;0,02), j&#225; que o n&#250;mero de pacientes estudados foi expressivo (n = 77), essa pequena diferen&#231;a n&#227;o interfere de forma significativa na abordagem dos pacientes avaliados pelo m&#233;todo de escore, j&#225; que representa apenas cerca de 1% da massa total do ventr&#237;culo esquerdo. O intervalo de concord&#226;ncia dos dois m&#233;todos foi de &#150;6,74% a 8,80%, demonstrando que, para um dado paciente, o percentual de massa infartada medido pelo m&#233;todo de escore apresentar&#225;, em 95% das vezes, uma diferen&#231;a inferior a 8,8% do valor que seria obtido se fosse calculado pela planimetria. Isto caracteriza um grau de concord&#226;ncia plenamente aceit&#225;vel do ponto de vista cl&#237;nico, demonstrando que o m&#233;todo semi-quantitativo visual pode substituir com seguran&#231;a o m&#233;todo de planimetria na rotina cl&#237;nica di&#225;ria. Adicionalmente, como evidenciado no gr&#225;fico de Bland-Altman (<xref ref-type="fig" rid="fig4">fig. 4</xref>), a dispers&#227;o das diferen&#231;as individuais em torno da diferen&#231;a m&#233;dia (<italic>bias</italic>) &#233; bastante homog&#234;nea, independentemente da extens&#227;o do infarto. Em outras palavras, a reprodutibilidade do m&#233;todo de escore &#233; boa tanto para os pacientes com pequenos infartos quanto para aqueles com infartos extensos. </p>
    <p>A boa reprodutibilidade do m&#233;todo de escore foi ainda demonstrada atrav&#233;s da an&#225;lise das variabilidades inter e intra-observador. A diferen&#231;a m&#233;dia (<italic>bias</italic>) entre as medidas obtidas pelos dois observadores foi inferior a 0,5% e o coeficiente de repetibilidade inferior a 10%. Este coeficiente representa o grau de varia&#231;&#227;o entre os resultados obtidos pelos dois observadores e &#233; calculado como 2 vezes o desvio padr&#227;o da diferen&#231;a daquelas medidas. O resultado obtido, ao serem comparadas as duas medidas calculadas pelo mesmo observador, em momentos diferentes (variabilidade intra-observador), foi bastante semelhante: <italic>bias</italic> inferior a 0,4% e coeficiente de repetibilidade inferior a 9%. De forma semelhante &#224; compara&#231;&#227;o com a planimetria, a avalia&#231;&#227;o da reprodutibilidade do m&#233;todo de escore demonstrou coeficientes de repetibilidade que atestam graus de variabilidade inter e intra-observador bastante aceit&#225;veis do ponto de vista da aplicabilidade cl&#237;nica. </p>
    <p>Recentemente, Wu e cols. demonstraram que pacientes com infarto agudo do mioc&#225;rdio t&#234;m pior progn&#243;stico &#224; medida que aumenta a quantidade de massa infartada<sup>9</sup>. Posteriormente, Choi e cols. observaram que a determina&#231;&#227;o da transmuralidade do infarto permite predizer a recupera&#231;&#227;o espont&#226;nea da contratilidade segmentar do ventr&#237;culo esquerdo em pacientes com infarto agudo do mioc&#225;rdio<sup>10</sup>. Gerber e cols. tamb&#233;m demonstraram que o potencial de recupera&#231;&#227;o da contratilidade regional, medida quantitativamente pela t&#233;cnica de <italic>tagging</italic>, pode ser definido atrav&#233;s da avalia&#231;&#227;o dos padr&#245;es de realce tardio dos pacientes com infarto agudo do mioc&#225;rdio<sup>11</sup>. Sobretudo, um importante estudo, de grande repercuss&#227;o cl&#237;nica, demonstrando utilidade da t&#233;cnica de realce tardio na avalia&#231;&#227;o dos pacientes coronariopatas, com indica&#231;&#227;o de revasculariza&#231;&#227;o do mioc&#225;rdio, foi desenvolvido por Kim e cols. e publicado recentemente no <italic>New EnglandJournal of Medicine</italic><sup>12</sup>. Nesse estudo demonstrou-se que &#233; poss&#237;vel determinar a viabilidade mioc&#225;rdica regional atrav&#233;s da avalia&#231;&#227;o da transmuralidade das &#225;reas de infarto nas imagens de realce tardio. </p>
    <p>A correla&#231;&#227;o entre o tamanho do infarto e a fun&#231;&#227;o ventricular esquerda &#233; intuitiva e j&#225; foi demonstrada em estudos utilizando t&#233;cnicas de medicina nuclear<sup>32,33</sup>. Entretanto, as determina&#231;&#245;es tanto da extens&#227;o do territ&#243;rio infartado, quanto da fun&#231;&#227;o ventricular esquerda, s&#227;o mais precisas pela resson&#226;ncia magn&#233;tica card&#237;aca do que pela medicina nuclear<sup>4,13</sup>, dada a sua maior resolu&#231;&#227;o espacial. O nosso estudo foi o primeiro a demonstrar, atrav&#233;s da resson&#226;ncia magn&#233;tica card&#237;aca, uma expressiva correla&#231;&#227;o entre o tamanho do infarto medido pela t&#233;cnica do realce tardio e os dados de fun&#231;&#227;o do ventr&#237;culo esquerdo medidos pelo m&#233;todo de Simpson. Em seu estudo sobre o valor progn&#243;stico da obstru&#231;&#227;o microvascular, Wu e cols. n&#227;o observaram correla&#231;&#227;o estatisticamente significativa entre esses par&#226;metros<sup>9</sup>. Por sua vez, Klein e cols. demonstraram correla&#231;&#227;o inversa apenas discreta (r = -0,42) entre o tamanho do infarto e a fra&#231;&#227;o de eje&#231;&#227;o<sup>13</sup>. Estudos futuros de larga escala e desenhados especificamente para esclarecer essa correla&#231;&#227;o ser&#227;o necess&#225;rios para avaliar o valor progn&#243;stico de cada par&#226;metro isoladamente. Uma quest&#227;o importante a ser respondida por esses estudos &#233; se a massa infartada poderia se tornar um fator progn&#243;stico ainda mais importante que a fra&#231;&#227;o de eje&#231;&#227;o do ventr&#237;culo esquerdo nos pacientes com infarto agudo do mioc&#225;rdio. </p>
    <p>Concluindo, a avalia&#231;&#227;o dos pacientes com infarto agudo do mioc&#225;rdio pr&#233;vio pela resson&#226;ncia magn&#233;tica card&#237;aca utilizando a t&#233;cnica de realce tardio, permite a determina&#231;&#227;o reprodut&#237;vel do tamanho do infarto, tanto pelo m&#233;todo de planimetria quanto pelo modelo semi-quantitativo de escore. A planimetria exige que sejam desenhados, manualmente (em <italic>software</italic> espec&#237;fico), os contornos das &#225;reas de infarto e das bordas endoc&#225;rdica e epic&#225;rdica do ventr&#237;culo esquerdo em todos os cortes do eixo curto, tornando-se um m&#233;todo bastante laborioso, que consome consider&#225;vel tempo de p&#243;s-processamento das imagens e, portanto, de dif&#237;cil implementa&#231;&#227;o na rotina cl&#237;nica di&#225;ria. J&#225; o m&#233;todo de escore, baseado na avalia&#231;&#227;o semi-quantitativa visual das imagens de realce tardio, constitui uma alternativa muito mais r&#225;pida e pr&#225;tica para a determina&#231;&#227;o da extens&#227;o do infarto. Nosso estudo foi o primeiro a demonstrar, que um m&#233;todo mais simples de determina&#231;&#227;o da massa infartada, poderia substituir com boa acur&#225;cia e reprodutibilidade o m&#233;todo mais trabalhoso de planimetria. Acreditamos que a utiliza&#231;&#227;o do m&#233;todo de escore possa permitir que o percentual da massa infartada do ventr&#237;culo esquerdo seja calculado de forma mais rotineira nos exames de RMC dos pacientes com infarto do mioc&#225;rdio pr&#233;vio. Dessa forma, este dado objetivo, de grande import&#226;ncia diagn&#243;stica e progn&#243;stica, poderia ser inclu&#237;do regularmente nos relat&#243;rios e laudos de resson&#226;ncia magn&#233;tica card&#237;aca. </p>
    <p>
      <fn id="end" fn-type="corresp">
        <label>
          <bold>Endere&#231;o para correspond&#234;ncia</bold>
        </label>
        <p> Dr. Carlos Eduardo Rochitte </p>
        <p> Av. Dr. En&#233;as de Carvalho Aguiar, 44 </p>
        <p> Cep 05403-000 - S&#227;o Paulo - SP </p>
        <p> E-mail: </p>
        <p>
          <email xlink:href="rochitte@incor.usp.br">rochitte@incor.usp.br</email>
        </p>
      </fn>
    </p>
    <p>Recebido para Publica&#231;&#227;o em 17/4/03 </p>
    <p> Aceito em 3/12/03  </p>
  </body>
  <back>
    <ref-list>
      <ref id="B1">
        <mixed-citation>1. Judd RM, Lugo-Olivieri    CH, Arai M et al. Physiological basis of myocardial contrast enhancement in    fast magnetic resonance images of 2-day-old reperfused canine infarcts. Circulation    1995; 92: 1902-10. </mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Physiological basis of myocardial contrast enhancement in fast magnetic resonance images of 2-day-old reperfused canine infarcts</article-title>
          <source>Circulation</source>
          <date>
            <year>1995</year>
          </date>
          <fpage>1902</fpage>
          <lpage>10</lpage>
          <volume>92</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Judd</surname>
              <given-names>RM</given-names>
            </name>
            <name>
              <surname>Lugo-Olivieri</surname>
              <given-names>CH</given-names>
            </name>
            <name>
              <surname>Arai</surname>
              <given-names>M</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B2">
        <mixed-citation>2. Kim RJ, Chen    EL, Lima JA, Judd RM. Myocardial Gd-DTPA kinetics determine MRI contrast enhancement    and reflect the extent and severity of myocardial injury after acute reperfused    infarction. Circulation 1996; 94: 3318-26. </mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Myocardial Gd-DTPA kinetics determine MRI contrast enhancement and reflect the extent and severity of myocardial injury after acute reperfused infarction</article-title>
          <source>Circulation</source>
          <date>
            <year>1996</year>
          </date>
          <fpage>3318</fpage>
          <lpage>26</lpage>
          <volume>94</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Kim</surname>
              <given-names>RJ</given-names>
            </name>
            <name>
              <surname>Chen</surname>
              <given-names>EL</given-names>
            </name>
            <name>
              <surname>Lima</surname>
              <given-names>JA</given-names>
            </name>
            <name>
              <surname>Judd</surname>
              <given-names>RM</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B3">
        <mixed-citation>3. Kim RJ, Fieno    DS, Parrish TB et al. Relationship of MRI delayed contrast enhancement to irreversible    injury, infarct age, and contractile function. Circulation 1999; 100: 1992-2002.    </mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Relationship of MRI delayed contrast enhancement to irreversible injury, infarct age, and contractile function</article-title>
          <source>Circulation</source>
          <date>
            <year>1999</year>
          </date>
          <fpage>1992</fpage>
          <lpage>2002</lpage>
          <volume>100</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Kim</surname>
              <given-names>RJ</given-names>
            </name>
            <name>
              <surname>Fieno</surname>
              <given-names>DS</given-names>
            </name>
            <name>
              <surname>Parrish</surname>
              <given-names>TB</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B4">
        <mixed-citation>4. Mahrholdt H,    Wagner A, Holly TA et al. Reproducibility of chronic infarct size measurement    by contrast-enhanced magnetic resonance imaging. Circulation 2002; 106: 2322-7.    </mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Reproducibility of chronic infarct size measurement by contrast-enhanced magnetic resonance imaging</article-title>
          <source>Circulation</source>
          <date>
            <year>2002</year>
          </date>
          <fpage>2322</fpage>
          <lpage>7</lpage>
          <volume>106</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Mahrholdt</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Wagner</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Holly</surname>
              <given-names>TA</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B5">
        <mixed-citation>5. Rochitte CE,    Lima JA, Bluemke DA et al. Magnitude and time course of microvascular obstruction    and tissue injury after acute myocardial infarction. Circulation 1998; 98: 1006-14.    </mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Magnitude and time course of microvascular obstruction and tissue injury after acute myocardial infarction</article-title>
          <source>Circulation</source>
          <date>
            <year>1998</year>
          </date>
          <fpage>1006</fpage>
          <lpage>14</lpage>
          <volume>98</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Rochitte</surname>
              <given-names>CE</given-names>
            </name>
            <name>
              <surname>Lima</surname>
              <given-names>JA</given-names>
            </name>
            <name>
              <surname>Bluemke</surname>
              <given-names>DA</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B6">
        <mixed-citation>6. Schaefer S,    Malloy CR, Katz J et al. Gadolinium-DTPA-enhanced nuclear magnetic resonance    imaging of reperfused myocardium: identification of the myocardial bed at risk.    J Am Coll Cardiol 1988; 12: 1064-72. </mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Gadolinium-DTPA-enhanced nuclear magnetic resonance imaging of reperfused myocardium: identification of the myocardial bed at risk</article-title>
          <source>J Am Coll Cardiol</source>
          <date>
            <year>1988</year>
          </date>
          <fpage>1064</fpage>
          <lpage>72</lpage>
          <volume>12</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Schaefer</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Malloy</surname>
              <given-names>CR</given-names>
            </name>
            <name>
              <surname>Katz</surname>
              <given-names>J</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B7">
        <mixed-citation>7. Wu E, Judd RM,    Vargas JD, Klocke FJ, Bonow RO, Kim RJ. Visualisation of presence, location,    and transmural extent of healed Q-wave and non-Q-wave myocardial infarction.    Lancet 2001; 357: 21-8. </mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Visualisation of presence, location, and transmural extent of healed Q-wave and non-Q-wave myocardial infarction</article-title>
          <source>Lancet</source>
          <date>
            <year>2001</year>
          </date>
          <fpage>21</fpage>
          <lpage>8</lpage>
          <volume>357</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Wu</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Judd</surname>
              <given-names>RM</given-names>
            </name>
            <name>
              <surname>Vargas</surname>
              <given-names>JD</given-names>
            </name>
            <name>
              <surname>Klocke</surname>
              <given-names>FJ</given-names>
            </name>
            <name>
              <surname>Bonow</surname>
              <given-names>RO</given-names>
            </name>
            <name>
              <surname>Kim</surname>
              <given-names>RJ</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B8">
        <mixed-citation>8. Simonetti OP,    Kim RJ, Fieno DS et al. An improved MR imaging technique for the visualization    of myocardial infarction. Radiology 2001; 218: 215-23. </mixed-citation>
        <element-citation publication-type="journal">
          <article-title>An improved MR imaging technique for the visualization of myocardial infarction</article-title>
          <source>Radiology</source>
          <date>
            <year>2001</year>
          </date>
          <fpage>215</fpage>
          <lpage>23</lpage>
          <volume>218</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Simonetti</surname>
              <given-names>OP</given-names>
            </name>
            <name>
              <surname>Kim</surname>
              <given-names>RJ</given-names>
            </name>
            <name>
              <surname>Fieno</surname>
              <given-names>DS</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B9">
        <mixed-citation>9. Wu KC, Zerhouni    EA, Judd RM et al. Prognostic significance of microvascular obstruction by magnetic    resonance imaging in patients with acute myocardial infarction. Circulation    1998; 97: 765-72. </mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Prognostic significance of microvascular obstruction by magnetic resonance imaging in patients with acute myocardial infarction</article-title>
          <source>Circulation</source>
          <date>
            <year>1998</year>
          </date>
          <fpage>765</fpage>
          <lpage>72</lpage>
          <volume>97</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Wu</surname>
              <given-names>KC</given-names>
            </name>
            <name>
              <surname>Zerhouni</surname>
              <given-names>EA</given-names>
            </name>
            <name>
              <surname>Judd</surname>
              <given-names>RM</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B10">
        <mixed-citation>10. Choi KM, Kim    RJ, Gubernikoff G, Vargas JD, Parker M, Judd RM. Transmural extent of acute    myocardial infarction predicts long-term improvement in contractile function.    Circulation 2001; 104: 1101-7. </mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Transmural extent of acute myocardial infarction predicts long-term improvement in contractile function</article-title>
          <source>Circulation</source>
          <date>
            <year>2001</year>
          </date>
          <fpage>1101</fpage>
          <lpage>7</lpage>
          <volume>104</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Choi</surname>
              <given-names>KM</given-names>
            </name>
            <name>
              <surname>Kim</surname>
              <given-names>RJ</given-names>
            </name>
            <name>
              <surname>Gubernikoff</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Vargas</surname>
              <given-names>JD</given-names>
            </name>
            <name>
              <surname>Parker</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Judd</surname>
              <given-names>RM</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B11">
        <mixed-citation>11. Gerber BL,    Garot J, Bluemke DA, Wu KC, Lima JA. Accuracy of contrast-enhanced magnetic    resonance imaging in predicting improvement of regional myocardial function    in patients after acute myocardial infarction. Circulation 2002; 106: 1083-9.    </mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Accuracy of contrast-enhanced magnetic resonance imaging in predicting improvement of regional myocardial function in patients after acute myocardial infarction</article-title>
          <source>Circulation</source>
          <date>
            <year>2002</year>
          </date>
          <fpage>1083</fpage>
          <lpage>9</lpage>
          <volume>106</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Gerber</surname>
              <given-names>BL</given-names>
            </name>
            <name>
              <surname>Garot</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Bluemke</surname>
              <given-names>DA</given-names>
            </name>
            <name>
              <surname>Wu</surname>
              <given-names>KC</given-names>
            </name>
            <name>
              <surname>Lima</surname>
              <given-names>JA</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B12">
        <mixed-citation>12. Kim RJ, Wu    E, Rafael A et al. The use of contrast-enhanced magnetic resonance imaging to    identify reversible myocardial dysfunction. N Engl J Med 2000; 343: 1445-53.    </mixed-citation>
        <element-citation publication-type="journal">
          <article-title>The use of contrast-enhanced magnetic resonance imaging to identify reversible myocardial dysfunction</article-title>
          <source>N Engl J Med</source>
          <date>
            <year>2000</year>
          </date>
          <fpage>1445</fpage>
          <lpage>53</lpage>
          <volume>343</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Kim</surname>
              <given-names>RJ</given-names>
            </name>
            <name>
              <surname>Wu</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Rafael</surname>
              <given-names>A</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B13">
        <mixed-citation>13. Klein C, Nekolla    SG, Bengel FM et al. Assessment of myocardial viability with contrast-enhanced    magnetic resonance imaging: comparison with positron emission tomography. Circulation    2002; 105: 162-7. </mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Assessment of myocardial viability with contrast-enhanced magnetic resonance imaging: comparison with positron emission tomography</article-title>
          <source>Circulation</source>
          <date>
            <year>2002</year>
          </date>
          <fpage>162</fpage>
          <lpage>7</lpage>
          <volume>105</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Klein</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Nekolla</surname>
              <given-names>SG</given-names>
            </name>
            <name>
              <surname>Bengel</surname>
              <given-names>FM</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B14">
        <mixed-citation>14. Buser PT, Auffermann    W, Holt WW et al. Noninvasive evaluation of global left ventricular function    with use of cine nuclear magnetic resonance. J Am Coll Cardiol 1989; 13: 1294-300.    </mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Noninvasive evaluation of global left ventricular function with use of cine nuclear magnetic resonance</article-title>
          <source>J Am Coll Cardiol</source>
          <date>
            <year>1989</year>
          </date>
          <fpage>1294</fpage>
          <lpage>300</lpage>
          <volume>13</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Buser</surname>
              <given-names>PT</given-names>
            </name>
            <name>
              <surname>Auffermann</surname>
              <given-names>W</given-names>
            </name>
            <name>
              <surname>Holt</surname>
              <given-names>WW</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B15">
        <mixed-citation>15. Lorenz CH,    Walker ES, Morgan VL, Klein SS, Graham TP, Jr. Normal human right and left ventricular    mass, systolic function, and gender differences by cine magnetic resonance imaging.    J Cardiovasc Magn Reson 1999; 1: 7-21. </mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Normal human right and left ventricular mass, systolic function, and gender differences by cine magnetic resonance imaging</article-title>
          <source>J Cardiovasc Magn Reson</source>
          <date>
            <year>1999</year>
          </date>
          <fpage>7</fpage>
          <lpage>21</lpage>
          <volume>1</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Lorenz</surname>
              <given-names>CH</given-names>
            </name>
            <name>
              <surname>Walker</surname>
              <given-names>ES</given-names>
            </name>
            <name>
              <surname>Morgan</surname>
              <given-names>VL</given-names>
            </name>
            <name>
              <surname>Klein</surname>
              <given-names>SS</given-names>
            </name>
            <name>
              <surname>Graham</surname>
              <given-names>TP, Jr</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B16">
        <mixed-citation>16. Sakuma H, Fujita    N, Foo TK et al. Evaluation of left ventricular volume and mass with breath-hold    cine MR imaging. Radiology 1993; 188: 377-80. </mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Evaluation of left ventricular volume and mass with breath-hold cine MR imaging</article-title>
          <source>Radiology</source>
          <date>
            <year>1993</year>
          </date>
          <fpage>377</fpage>
          <lpage>80</lpage>
          <volume>188</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Sakuma</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Fujita</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Foo</surname>
              <given-names>TK</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B17">
        <mixed-citation>17. Semelka RC,    Tomei E, Wagner S et al. Interstudy reproducibility of dimensional and functional    measurements between cine magnetic resonance studies in the morphologically    abnormal left ventricle. Am Heart J 1990; 119: 1367-73. </mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Interstudy reproducibility of dimensional and functional measurements between cine magnetic resonance studies in the morphologically abnormal left ventricle</article-title>
          <source>Am Heart J</source>
          <date>
            <year>1990</year>
          </date>
          <fpage>1367</fpage>
          <lpage>73</lpage>
          <volume>119</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Semelka</surname>
              <given-names>RC</given-names>
            </name>
            <name>
              <surname>Tomei</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Wagner</surname>
              <given-names>S</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B18">
        <mixed-citation>18. Semelka RC,    Tomei E, Wagner S et al. Normal left ventricular dimensions and function: interstudy    reproducibility of measurements with cine MR imaging. Radiology 1990; 174: 763-8.    </mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Normal left ventricular dimensions and function: interstudy reproducibility of measurements with cine MR imaging</article-title>
          <source>Radiology</source>
          <date>
            <year>1990</year>
          </date>
          <fpage>763</fpage>
          <lpage>8</lpage>
          <volume>174</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Semelka</surname>
              <given-names>RC</given-names>
            </name>
            <name>
              <surname>Tomei</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Wagner</surname>
              <given-names>S</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B19">
        <mixed-citation>19. Carr JC, Simonetti    O, Bundy J, Li D, Pereles S, Finn JP. Cine MR angiography of the heart with    segmented true fast imaging with steady-state precession. Radiology 2001; 219:    828-34. </mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Cine MR angiography of the heart with segmented true fast imaging with steady-state precession</article-title>
          <source>Radiology</source>
          <date>
            <year>2001</year>
          </date>
          <fpage>828</fpage>
          <lpage>34</lpage>
          <volume>219</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Carr</surname>
              <given-names>JC</given-names>
            </name>
            <name>
              <surname>Simonetti</surname>
              <given-names>O</given-names>
            </name>
            <name>
              <surname>Bundy</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Li</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Pereles</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Finn</surname>
              <given-names>JP</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B20">
        <mixed-citation>20. Haacke EM,    Tkach JA. Fast MR imaging: techniques and clinical applications. AJR Am J Roentgenol    1990; 155: 951-64. </mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Fast MR imaging: techniques and clinical applications</article-title>
          <source>AJR Am J Roentgenol</source>
          <date>
            <year>1990</year>
          </date>
          <fpage>951</fpage>
          <lpage>64</lpage>
          <volume>155</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Haacke</surname>
              <given-names>EM</given-names>
            </name>
            <name>
              <surname>Tkach</surname>
              <given-names>JA</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B21">
        <mixed-citation>21. Lee VS, Resnick    D, Bundy JM, Simonetti OP, Lee P, Weinreb JC. Cardiac function: MR evaluation    in one breath hold with real-time true fast imaging with steady-state precession.    Radiology 2002; 222: 835-42. </mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Cardiac function: MR evaluation in one breath hold with real-time true fast imaging with steady-state precession</article-title>
          <source>Radiology</source>
          <date>
            <year>2002</year>
          </date>
          <fpage>835</fpage>
          <lpage>42</lpage>
          <volume>222</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Lee</surname>
              <given-names>VS</given-names>
            </name>
            <name>
              <surname>Resnick</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Bundy</surname>
              <given-names>JM</given-names>
            </name>
            <name>
              <surname>Simonetti</surname>
              <given-names>OP</given-names>
            </name>
            <name>
              <surname>Lee</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Weinreb</surname>
              <given-names>JC</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B22">
        <mixed-citation>22. Miller S, Simonetti    OP, Carr J, Kramer U, Finn JP. MR Imaging of the heart with cine true fast imaging    with steady-state precession: influence of spatial and temporal resolutions    on left ventricular functional parameters. Radiology 2002; 223: 263-9. </mixed-citation>
        <element-citation publication-type="journal">
          <article-title>MR Imaging of the heart with cine true fast imaging with steady-state precession: influence of spatial and temporal resolutions on left ventricular functional parameters</article-title>
          <source>Radiology</source>
          <date>
            <year>2002</year>
          </date>
          <fpage>263</fpage>
          <lpage>9</lpage>
          <volume>223</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Miller</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Simonetti</surname>
              <given-names>OP</given-names>
            </name>
            <name>
              <surname>Carr</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Kramer</surname>
              <given-names>U</given-names>
            </name>
            <name>
              <surname>Finn</surname>
              <given-names>JP</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B23">
        <mixed-citation>23. Rehwald WG,    Kim RJ, Simonetti OP, Laub G, Judd RM. Theory of high-speed MR imaging of the    human heart with the selective line acquisition mode. Radiology 2001; 220: 540-7.    </mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Theory of high-speed MR imaging of the human heart with the selective line acquisition mode</article-title>
          <source>Radiology</source>
          <date>
            <year>2001</year>
          </date>
          <fpage>540</fpage>
          <lpage>7</lpage>
          <volume>220</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Rehwald</surname>
              <given-names>WG</given-names>
            </name>
            <name>
              <surname>Kim</surname>
              <given-names>RJ</given-names>
            </name>
            <name>
              <surname>Simonetti</surname>
              <given-names>OP</given-names>
            </name>
            <name>
              <surname>Laub</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Judd</surname>
              <given-names>RM</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B24">
        <mixed-citation>24. Bland JM, Altman    DG. Statistical methods for assessing agreement between two methods of clinical    measurement. Lancet 1986; 1: 307-10. </mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Statistical methods for assessing agreement between two methods of clinical measurement</article-title>
          <source>Lancet</source>
          <date>
            <year>1986</year>
          </date>
          <fpage>307</fpage>
          <lpage>10</lpage>
          <volume>1</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Bland</surname>
              <given-names>JM</given-names>
            </name>
            <name>
              <surname>Altman</surname>
              <given-names>DG</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B25">
        <mixed-citation>25. Lima JA, Judd    RM, Bazille A, Schulman SP, Atalar E, Zerhouni EA. Regional heterogeneity of    human myocardial infarcts demonstrated by contrast-enhanced MRI. Potential mechanisms.    Circulation 1995; 92: 1117-25. </mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Regional heterogeneity of human myocardial infarcts demonstrated by contrast-enhanced MRI: Potential mechanisms</article-title>
          <source>Circulation</source>
          <date>
            <year>1995</year>
          </date>
          <fpage>1117</fpage>
          <lpage>25</lpage>
          <volume>92</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Lima</surname>
              <given-names>JA</given-names>
            </name>
            <name>
              <surname>Judd</surname>
              <given-names>RM</given-names>
            </name>
            <name>
              <surname>Bazille</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Schulman</surname>
              <given-names>SP</given-names>
            </name>
            <name>
              <surname>Atalar</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Zerhouni</surname>
              <given-names>EA</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B26">
        <mixed-citation>26. Fieno DS, Kim    RJ, Chen EL, Lomasney JW, Klocke FJ, Judd RM. Contrast-enhanced magnetic resonance    imaging of myocardium at risk: distinction between reversible and irreversible    injury throughout infarct healing. J Am Coll Cardiol 2000; 36: 1985-91. </mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Contrast-enhanced magnetic resonance imaging of myocardium at risk: distinction between reversible and irreversible injury throughout infarct healing</article-title>
          <source>J Am Coll Cardiol</source>
          <date>
            <year>2000</year>
          </date>
          <fpage>1985</fpage>
          <lpage>91</lpage>
          <volume>36</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Fieno</surname>
              <given-names>DS</given-names>
            </name>
            <name>
              <surname>Kim</surname>
              <given-names>RJ</given-names>
            </name>
            <name>
              <surname>Chen</surname>
              <given-names>EL</given-names>
            </name>
            <name>
              <surname>Lomasney</surname>
              <given-names>JW</given-names>
            </name>
            <name>
              <surname>Klocke</surname>
              <given-names>FJ</given-names>
            </name>
            <name>
              <surname>Judd</surname>
              <given-names>RM</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B27">
        <mixed-citation>27. Ricciardi MJ,    Wu E, Davidson CJ et al. Visualization of discrete microinfarction after percutaneous    coronary intervention associated with mild creatine kinase-MB elevation. Circulation    2001; 103: 2780-3. </mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Visualization of discrete microinfarction after percutaneous coronary intervention associated with mild creatine kinase-MB elevation</article-title>
          <source>Circulation</source>
          <date>
            <year>2001</year>
          </date>
          <fpage>2780</fpage>
          <lpage>3</lpage>
          <volume>103</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Ricciardi</surname>
              <given-names>MJ</given-names>
            </name>
            <name>
              <surname>Wu</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Davidson</surname>
              <given-names>CJ</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B28">
        <mixed-citation>28. Diesbourg LD,    Prato FS, Wisenberg G et al. Quantification of myocardial blood flow and extracellular    volumes using a bolus injection of Gd-DTPA: kinetic modeling in canine ischemic    disease. Magn Reson Med 1992; 23: 239-53. </mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Quantification of myocardial blood flow and extracellular volumes using a bolus injection of Gd-DTPA: kinetic modeling in canine ischemic disease</article-title>
          <source>Magn Reson Med</source>
          <date>
            <year>1992</year>
          </date>
          <fpage>239</fpage>
          <lpage>53</lpage>
          <volume>23</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Diesbourg</surname>
              <given-names>LD</given-names>
            </name>
            <name>
              <surname>Prato</surname>
              <given-names>FS</given-names>
            </name>
            <name>
              <surname>Wisenberg</surname>
              <given-names>G</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B29">
        <mixed-citation>29. Saeed M, Wendland    MF, Masui T, Higgins CB. Reperfused myocardial infarctions on T1- and susceptibility-enhanced    MRI: evidence for loss of compartmentalization of contrast media. Magn Reson    Med 1994; 31: 31-9. </mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Reperfused myocardial infarctions on T1- and susceptibility-enhanced MRI: evidence for loss of compartmentalization of contrast media</article-title>
          <source>Magn Reson Med</source>
          <date>
            <year>1994</year>
          </date>
          <fpage>31</fpage>
          <lpage>9</lpage>
          <volume>31</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Saeed</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Wendland</surname>
              <given-names>MF</given-names>
            </name>
            <name>
              <surname>Masui</surname>
              <given-names>T</given-names>
            </name>
            <name>
              <surname>Higgins</surname>
              <given-names>CB</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B30">
        <mixed-citation>30. Schwitter J,    Saeed M, Wendland MF et al. Influence of severity of myocardial injury on distribution    of macromolecules: extravascular versus intravascular gadolinium-based magnetic    resonance contrast agents. J Am Coll Cardiol 1997; 30: 1086-94. </mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Influence of severity of myocardial injury on distribution of macromolecules: extravascular versus intravascular gadolinium-based magnetic resonance contrast agents</article-title>
          <source>J Am Coll Cardiol</source>
          <date>
            <year>1997</year>
          </date>
          <fpage>1086</fpage>
          <lpage>94</lpage>
          <volume>30</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Schwitter</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Saeed</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Wendland</surname>
              <given-names>MF</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B31">
        <mixed-citation>31. Rehwald WG,    Fieno DS, Chen EL, Kim RJ, Judd RM. Myocardial magnetic resonance imaging contrast    agent concentrations after reversible and irreversible ischemic injury. Circulation    2002; 105: 224-9. </mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Myocardial magnetic resonance imaging contrast agent concentrations after reversible and irreversible ischemic injury</article-title>
          <source>Circulation</source>
          <date>
            <year>2002</year>
          </date>
          <fpage>224</fpage>
          <lpage>9</lpage>
          <volume>105</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Rehwald</surname>
              <given-names>WG</given-names>
            </name>
            <name>
              <surname>Fieno</surname>
              <given-names>DS</given-names>
            </name>
            <name>
              <surname>Chen</surname>
              <given-names>EL</given-names>
            </name>
            <name>
              <surname>Kim</surname>
              <given-names>RJ</given-names>
            </name>
            <name>
              <surname>Judd</surname>
              <given-names>RM</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B32">
        <mixed-citation>32. Gibbons RJ,    Miller TD, Christian TF. Infarct size measured by single photon emission computed    tomographic imaging with (99m)Tc-sestamibi: A measure of the efficacy of therapy    in acute myocardial infarction. Circulation 2000; 101: 101-8. </mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Infarct size measured by single photon emission computed tomographic imaging with (99m)Tc-sestamibi: A measure of the efficacy of therapy in acute myocardial infarction</article-title>
          <source>Circulation</source>
          <date>
            <year>2000</year>
          </date>
          <fpage>101</fpage>
          <lpage>8</lpage>
          <volume>101</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Gibbons</surname>
              <given-names>RJ</given-names>
            </name>
            <name>
              <surname>Miller</surname>
              <given-names>TD</given-names>
            </name>
            <name>
              <surname>Christian</surname>
              <given-names>TF</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B33">
        <mixed-citation>33. Kang X, Berman    DS, Van Train KF et al. Clinical validation of automatic quantitative defect    size in rest technetium-99m-sestamibi myocardial perfusion SPECT. J Nucl Med    1997; 38: 1441-6. </mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Clinical validation of automatic quantitative defect size in rest technetium-99m-sestamibi myocardial perfusion SPECT</article-title>
          <source>J Nucl Med</source>
          <date>
            <year>1997</year>
          </date>
          <fpage>1441</fpage>
          <lpage>6</lpage>
          <volume>38</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Kang</surname>
              <given-names>X</given-names>
            </name>
            <name>
              <surname>Berman</surname>
              <given-names>DS</given-names>
            </name>
            <name>
              <surname>Van Train</surname>
              <given-names>KF</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
    </ref-list>
  </back>
  <sub-article article-type="translation" id="TRen" xml:lang="en">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original Articles</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title xml:lang="en">Quantification of left ventricular infarcted mass on cardiac magnetic resonance imaging: comparison between planimetry and the semiquantitative visual scoring method</article-title>
      </title-group>
      <abstract xml:lang="en">
        <p>OBJECTIVE: To compare a new semiquantitative visual scoring method with quantitative digital planimetry for determining left ventricular infarcted mass by use of cardiac delayed contrast-enhanced magnetic resonance imaging. METHOD: Seventy-seven patients with previous myocardial infarction underwent delayed contrast-enhanced magnetic resonance imaging using a 1.5T device for assessing myocardial viability and calculating the infarcted mass. Cine magnetic resonance imaging was used for assessing left ventricular function with the Simpson method. The infarcted mass was calculated on the delayed contrast-enhanced images according to the following 2 methods: planimetry and the scoring method. Simple linear regression and correlation and agreement between the methods and observers according to the Bland-Altman plot were used. RESULTS: The infarcted areas in all 77 patients were detected by use of cardiac delayed contrast-enhanced magnetic resonance imaging. The size of the infarction measured by planimetry was similar to that obtained with the scoring method, with a mean difference between measurements of only 1.03% of the left ventricular mass. Inter- (0.41%) and intraobserver (0.34%) variabilities indicated an excellent reproducibility of the scoring method. Infarcted mass showed a good correlation with ejection fraction and indexed end-diastolic and end-systolic volumes, r=-0.76, r=0.63, and r=0.67, respectively. CONCLUSION: In patients with previous myocardial infarction, delayed-enhanced magnetic resonance imaging provides accurate infarct size quantification by planimetry and by semiquantitative score.</p>
      </abstract>
      <kwd-group xml:lang="en">
        <kwd>myocardial infarction</kwd>
        <kwd>magnetic resonance imaging</kwd>
        <kwd>myocardial viability</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>
        <bold>ORIGINAL ARTICLE</bold>
      </p>
      <p>Quantification of left ventricular infarcted mass on cardiac magnetic resonance imaging. Comparison between planimetry and the semiquantitative visual scoring method </p>
      <p>Clerio Francisco de Azevedo Filho; Marcelo Hadlich; Jo&#227;o Luiz Fernandes Petriz; Lu&#237;s Antonio Mendon&#231;a; Jorge Neval Moll Filho; Carlos Eduardo Rochitte</p>
      <p> Rio de Janeiro, RJ and S&#227;o Paulo, SP - Brazil </p>
      <p>Rede de Hospitais D'Or, LABS/RJ, and InCor of the Hospital das Cl&#237;nicas of the FMUSP</p>
      <p>
        <xref ref-type="corresp" rid="end-body2">Correspondence</xref>
      </p>
      <p>
        <bold>ABSTRACT</bold>
      </p>
      <p><bold>OBJECTIVE: </bold>To compare a new semiquantitative visual scoring method with quantitative digital planimetry for determining left ventricular infarcted mass by use of cardiac delayed contrast-enhanced magnetic resonance imaging.</p>
      <p><bold>METHOD:</bold> Seventy-seven patients with previous myocardial infarction underwent delayed contrast-enhanced magnetic resonance imaging using a 1.5T device for assessing myocardial viability and calculating the infarcted mass. Cine magnetic resonance imaging was used for assessing left ventricular function with the Simpson method. The infarcted mass was calculated on the delayed contrast-enhanced images according to the following 2 methods: planimetry and the scoring method. Simple linear regression and correlation and agreement between the methods and observers according to the Bland-Altman plot were used. </p>
      <p><bold>RESULTS: </bold>The infarcted areas in all 77 patients were detected by use of cardiac delayed contrast-enhanced magnetic resonance imaging. The size of the infarction measured by planimetry was similar to that obtained with the scoring method, with a mean difference between measurements of only 1.03% of the left ventricular mass. Inter- (0.41%) and intraobserver (0.34%) variabilities indicated an excellent reproducibility of the scoring method. Infarcted mass showed a good correlation with ejection fraction and indexed end-diastolic and end-systolic volumes, r=-0.76, r=0.63, and r=0.67, respectively.</p>
      <p><bold>CONCLUSION: </bold>In patients with previous myocardial infarction, delayed-enhanced magnetic resonance imaging provides accurate infarct size quantification by planimetry and by semiquantitative score. </p>
      <p><bold>Key words:</bold> myocardial infarction, magnetic resonance imaging, myocardial viability </p>
      <p>Cardiac magnetic resonance imaging has undergone great development in the last decade, and its applications for assessing patients with cardiac ischemic disease are increasingly comprehensive. Current cardiac magnetic resonance imaging techniques, especially the protocols based on delayed contrast enhancement, provide precise delimitation of the areas of myocardial necrosis or fibrosis in patients with previous infarction <sup>1-7</sup>. On delayed contrast-enhanced images, the infarcted areas had a very increased signal intensity (white areas) as compared with those of healthy myocardium (dark areas). The marked contrast between the necrotic or fibrotic tissue and the intact myocardium (signal intensity may be up to 10 times greater in infarcted areas) <sup>8</sup>, in addition to the excellent spatial resolution provided by cardiac magnetic resonance imaging, allow a precise evaluation of the infarcted area. </p>
      <p>In a study published in 1998, Wu et al <sup>9</sup> reported that infarction size, expressed as a percentage of left ventricular mass, has a significant prognostic value in patients with acute myocardial infarction. In addition, 2 other recent studies <sup>10,11</sup> showed that infarcted mass evaluation was predictive of the recovery of overall and segmentary systolic function in that group of patients. Furthermore, a recent study by Kim et al <sup>12</sup> reported that the presence of myocardial viability, defined as the regional functional recovery after myocardial revascularization, may be determined through quantification of the transmural extent of the infarction. That same study also reported that the greater the dysfunctional myocardial mass that was viable prior to the intervention, the greater the overall recovery of the ejection fraction after revascularization. Therefore, determination of the infarcted mass on cardiac magnetic resonance imaging may provide important and very useful information for the management of patients with previous acute myocardial infarction. </p>
      <p>Currently, cardiac magnetic resonance imaging is considered the best method for assessing left ventricular infarcted mass, surpassing the PET technique for detecting subendocardial defects <sup>13</sup>. The technique usually used is direct quantification through planimetry of the delayed contrast-enhanced areas. However, planimetry is a very laborious method that requires a considerable amount of time after image processing. In addition, it requires the use of specific software, which is not always easily available. On the other hand, the scoring method, which is based on the semiquantitative visual assessment of delayed contrast-enhanced images, is a much faster and more practical alternative for determining infarction extension. It also has the advantage of depending only on the visualization of images in 3 different forms: digitalized on a monitor, developed on radiographic film, or printed on photographic paper. Our study aimed at introducing and describing the infarction size quantification on cardiac magnetic resonance imaging using the delayed contrast-enhanced technique, and at determining whether the calculation of the infarcted mass by use of the scoring method is valid and reliable when compared with that by use of the quantitative method of digital planimetry. </p>
      <p>
        <bold>Method</bold>
      </p>
      <p>This study comprised 77 patients (60 males and 17 females, with a mean age of 59.9&#177;10.6 years) diagnosed with previous acute myocardial infarction (subacute and chronic, <underline>&gt;</underline> 2 weeks after infarction) and referred to our service to undergo cardiac magnetic resonance imaging for assessing myocardial viability from October 2001 to October 2002. Four patients had 2 distinct episodes of previous acute myocardial infarction, adding up to 81 different infarcted areas identified as follows: anterior, 35 (43%); inferior, 29 (36%); and lateral, 17 (21%); of which, 48 (59%) were transmural, and 33 (41%) were subendocardial. </p>
      <p>The patients underwent magnetic resonance imaging with a Philips Gyroscan NT Intera device of 1.5T equipped with the Powertrack 6000 high-performance gradient system (Philips Medical Systems, Best, The Netherlands). The gadolinium intravenous contrast medium (Dotaren<sup>&#174;</sup>), specific for magnetic resonance imaging, was used at the dosage of 0.2 mmol/kg. Image acquisition was performed approximately 10 to 15 minutes after contrast administration, using a sequence of pulses of the T1 turbo field echo type, synchronous with vectorcardiographic monitoring. Eight cuts of the left ventricular short axis were sequentially performed covering the length of the entire ventricular cavity, from the apex to the mitral ring. Acquisition of each cut lasted approximately 8 seconds (around 8 to 12 heart beats, depending on heart rate), during which the patient was requested to perform a respiratory pause when expiring. The trigger delay of the sequence was adjusted so that the images were acquired during ventricular diastole. The acquisition of each segment of the K space was preceded by an inversion-recovery prepulse with an inversion time (IT) adjusted to neutralize the signal of the healthy myocardium, therefore, increasing the contrast between the infarcted regions (intense signal &#150; white) and the healthy myocardium (very weak signal &#150; dark) <sup>8</sup>. </p>
      <p>The pulse sequence is called the delayed contrast enhancement technique, and <xref ref-type="fig" rid="fig1-body2">figure 1</xref> depicts a typical example. The technical parameters used were as follows (appendix): TR, 5.7 ms; TE, 2.8 ms; flip angle (FA), 20&#186;; field of view (FOV), 350-420 mm; matrix, 192 x 192; rectangular field of view (RFOV), 75%; inversion time (IT), 170-300 ms; number of signals averaged or acquired (NSA), 2; number of cuts, 8-10; cut thickness, 8 mm; interval between the cuts (gap), 2 mm (therefore, 1 cut every 10 mm from the heart apex to the base).</p>
      <fig id="fig1-body2">
        <graphic xlink:href="1678-4170-abc-83-02-0111-00003-gf01-en.jpg"/></fig>
      <p>In addition to analyzing the infarcted areas, the left ventricular function of all patients studied was also assessed <sup>14-18</sup>. For this purpose, cine magnetic resonance imaging of the left ventricular short axis was performed, covering the entire ventricular cavity (precisely at the same anatomical locations of the delayed contrast enhancement images), using a sequence of pulses of the T1 turbo field echo type with transverse magnetization in the steady state condition (Balanced Fast Field Echo or B-FFE) <sup>19-23</sup> with the following technical parameters: TR, 3.1 ms; TE, 1.55 ms; flip angle (FA), 55&#186;; field of view (FOV), 350-420 mm; matrix, 192 x 128; rectangular field of view (RFOV), 75%; number of cardiac phases, 24; number of signals averaged or acquired (NSA), 1; number of cuts, 8-10; thickness of the cut, 8 mm; interval between the cuts (gap), 2 mm.</p>
      <p>
        <graphic xlink:href="1678-4170-abc-83-02-0111-00003-e01-en.jpg"/></p>
      <p>All images were stored on optical disks and later processed in the Philips Easyvision Workstation. The infarcted areas, defined as the regions that showed delayed contrast enhancement, were then assessed in the 2 following manners: 1) the quantitative digital planimetry method, and 2) the scoring method. </p>
      <p>The quantitative digital planimetry method required specific software and consisted of manually designing the contour of the delayed contrast-enhanced regions in the cuts with infarcted areas (<xref ref-type="fig" rid="fig2-body2">fig. 2</xref>). The infarcted tissue volume was calculated as the sum of the areas undergoing planimetry multiplied by the thickness of each cut. So that the value of the infarcted mass could be calculated in grams, the infarcted volume was multiplied by the density of the myocardial tissue (1.05g/mL). The next step consisted of manually designing the contour of the left ventricular endocardial and epicardial borders in 8 cuts. The left ventricular volume was calculated as the difference between the left ventricular epicardial and endocardial volumes (LV volume = epicardial volume &#150; endocardial volume). The endocardial and epicardial volumes were determined according to the Simpson method as follows: the sum of the endocardial and epicardial areas multiplied by the thickness of each cut. The left ventricular mass was then defined as the LV volume multiplied by the density of the myocardial tissue (1.05 g/mL). The percentage of left ventricular infarcted mass was calculated as follows: infarcted mass (%LV) = (infarcted mass/LV mass)*100 (equation 1).</p>
      <fig id="fig2-body2">
        <graphic xlink:href="1678-4170-abc-83-02-0111-00003-gf02-en.jpg"/></fig>
      <p>The scoring method consisted of the visual evaluation of 8 cuts performed by 2 independent observers, who ignored the results of planimetry. The cuts were divided into 48 segments as follows: cuts 1 and 2 (apical cuts) with 4 segments each; cuts 3 to 6 (middle cuts) with 6 segments each; and cuts 7 and 8 (basal cuts) with 8 segments each. This division was elaborated in a way to provide weight between the masses of different cuts, considering that apical cuts have smaller mass, and, therefore, have a smaller participation (weight) in determining the final mass when compared with basal cuts (<xref ref-type="fig" rid="fig3-body2">fig. 3</xref>).</p>
      <fig id="fig3-body2">
        <graphic xlink:href="1678-4170-abc-83-02-0111-00003-gf03-en.jpg"/></fig>
      <p>Each segment received a score according to the percentage of involvement obtained on delayed contrast enhancement (score zero, 1, 2, or 3). Score zero corresponded to the absence of contrast enhancement; score 1 corresponded to a contrast enhancement of 1 to 25% of the area of the segment; score 2 corresponded to a contrast enhancement of 26 to 75%; and score 3 corresponded to a contrast enhancement greater than 75% of the area of the segment. The total score of each patient was defined as the sum of the scores of the 48 segments analyzed, 144 being the maximum score possible (3*48 segments). The percentage of LV infarcted mass was then calculated as follows: infarcted mass (%LV) = (total score of the patient/144)*100. (equation 2). </p>
      <p>For determining the intraobserver variability of the scoring method, 1 of the 2 observers calculated the percentage of infarcted mass of each patient on 2 occasions, separated by an interval of 1 to 4 months. </p>
      <p>For assessing the left ventricular function in each patient, the following 4 parameters were calculated using the Simpson method: ejection fraction (EF); end-diastolic volume (EDV); end-systolic volume (ESV); and systolic ejection volume (SEV). These parameters were obtained from the images of cine magnetic resonance imaging as follows: manual contour, in specific software, of the left ventricular border in the diastolic (greater area) and systolic (smaller area) phases in the 8 cuts of the left ventricular short axis. The EDV was measured as the sum of the products of the area of each cut in the diastolic phase multiplied by the thickness of the cut. The ESV was calculated similarly, but using the systolic phase of each cut for calculation. The SEV was calculated as follows: SEV = EDV-ESV; and the EF was calculated as follows: EF = (SEV/EDV)*100. The volumes EDV, ESV, and SEV were then normalized for the body surface area, generating the parameters IEDV, IESV, and ISEV. </p>
      <p>Data of all variables obtained were filed and analyzed using the STATA statistical program, version 7.0. All continuous variables were expressed as mean &#177; standard deviation. The 2-tailed paired Student <italic>t</italic> test was used to compare the related samples. The degree of agreement between the methods, as well as the intra- and interobserver variabilities of the scoring method, were assessed by use of the analysis method reported by Bland and Altman <sup>24</sup>. The linear regression analysis and Pearson correlation were also used for assessing the relation between both methods (planimetry versus scoring) and the relation between the ventricular function data and the percentage of infarcted mass. The results were considered statistically significant when P&lt;0.05. </p>
      <p>
        <bold>Results</bold>
      </p>
      <p>Cardiac delayed contrast-enhanced magnetic resonance could detect myocardial necrosis or fibrosis in all 77 patients studied with a history of previous acute myocardial infarction. The infarcted regions were qualitatively considered analyzable in all cases, both from the point of view of area of measurement and transmural extent. A typical example of this examination is depicted in <xref ref-type="fig" rid="fig1-body2">figure 1</xref>. </p>
      <p>Infarction size, defined as the percentage of the left ventricular infarcted mass, was slightly greater when measured using planimetry (19.94&#177;11.10%) than when measured using the scoring method (18.92&#177;10.41%). The mean difference between the measurements obtained using both methods was 1.03% (95% confidence interval of 0.15 to 1.91%). Despite reaching statistical significance (P=0.02), this small difference is not significant from the clinical point of view, because it represents only approximately 1% of the total left ventricular mass. More important, the 95% agreement limit between the 2 methods was -6.74 to +8.80% (<xref ref-type="fig" rid="fig4-body2">fig. 4</xref> and <xref ref-type="table" rid="tab1-body2">tab. I</xref>).</p>
      <fig id="fig4-body2">
        <graphic xlink:href="1678-4170-abc-83-02-0111-00003-gf04-en.jpg"/></fig>
      <table-wrap id="tab1-body2">
        <graphic xlink:href="1678-4170-abc-83-02-0111-00003-gt01-en.jpg"/></table-wrap>
      <p>Therefore, from the practical point of view and in routine clinical use, the size of the infarction measured through planimetry was similar to the values of the scoring method obtained by the 2 independent observers and to the mean of these values. </p>
      <p>The significant correlation between the 2 methods was also demonstrated through the linear regression analysis, considering planimetry as the dependent variable and the score as the independent variable. The equation of the regression line was calculated as y=1.00x + 1.05, with a 95% confidence interval of the 'b' coefficient of 0.91 to 1.08, and a standard deviation of the residues of 3.91 (P&lt;0.0001) (<xref ref-type="table" rid="en_a03tab02-body2">tab. II</xref>). The Pearson correlation coefficient also showed an extremely significant relation between both methods (r = 0.94; P&lt;0.0001) (<xref ref-type="fig" rid="fig5-body2">fig. 5</xref>).</p>
      <p content-type="asset">
        <table-wrap id="en_a03tab02-body2">
          <graphic xlink:href="1678-4170-abc-83-02-0111-00003-gt02-en.jpg"/></table-wrap>
      </p>
      <fig id="fig5-body2">
        <graphic xlink:href="1678-4170-abc-83-02-0111-00003-gf05-en.jpg"/></fig>
      <p>Assessment of the interobserver variability of the scoring method showed a mean difference of 0.41% (NS) between the measurements obtained by the 2 observers and a &#177;9.56% repeatability coefficient. On the other hand, assessment of the intraobserver variability showed a mean difference of 0.34% (NS) and a repeatability coefficient of &#177;8.62% (<xref ref-type="table" rid="tab3-body2">tab. III</xref>).</p>
      <table-wrap id="tab3-body2">
        <graphic xlink:href="1678-4170-abc-83-02-0111-00003-gt03-en.jpg"/></table-wrap>
      <p>The size of the infarction, measured both through planimetry and the scoring method, showed a significant correlation with the left ventricular ejection fraction measured through the Simpson method (r= -0.74; P&lt;0.0001 for planimetry; and r= -0.76; P&lt;0.0001 for the scoring method) (<xref ref-type="fig" rid="fig6-body2">fig. 6</xref>). In addition to the ejection fraction, the indices of end-diastolic volume (IEDV) and end-systolic volume (IESV) also had a significant correlation with the size of the infarction (IEDV: r= 0.63 and 0.67; P&lt;0.0001; and IESV: r= 0.73 and 0.75; P&lt;0.0001, respectively, for planimetry and the scoring method) (<xref ref-type="fig" rid="fig7-body2">fig. 7</xref>). The indexed systolic volume (ISEV) showed no correlation with infarction size measured through the 2 methods (r= -0.27; P=0.03 for planimetry; and r=-0.19, NS for the scoring method). </p>
      <fig id="fig6-body2">
        <graphic xlink:href="1678-4170-abc-83-02-0111-00003-gf06-en.jpg"/></fig>
      <fig id="fig7-body2">
        <graphic xlink:href="1678-4170-abc-83-02-0111-00003-gf07-en.jpg"/></fig>
      <p>
        <bold>Discussion</bold>
      </p>
      <p>This study showed that quantification of the size of the infarction, as well as its characterization and delineation, may be obtained through cardiac magnetic resonance imaging using the delayed contrast-enhanced technique with great precision and reproducibility. The scoring method rapidly and accurately quantified the infarcted mass compared with the planimetry method. The good agreement and correlation observed between the 2 methods allow us to indicate the scoring method as a rapid and practical alternative for the calculation of infarcted mass, which may then be incorporated into the routine of cardiac magnetic resonance imaging reports, becoming of fundamental clinical importance, because the diagnostic and prognostic value of assessing the infarcted mass has been systematically reported in recent studies <sup>9-12</sup>. </p>
      <p>The delayed contrast-enhanced technique was developed from the pioneering studies by Lima et al <sup>25</sup>, assessing the detection and characterization of the infarcted areas through cardiac gadolinium-enhanced magnetic resonance imaging. The delayed contrast-enhanced technique was initially used in the experimental and clinical studies of the group led by Kim and Judd <sup>1-4,10,12,26,27</sup> and described from the technical point of view by Simonetti et al <sup>8</sup>. The delayed contrast-enhanced technique is based on a sequence of pulses of the T1 turbo field echo type (T1 Turbo Field Echo), with an inversion-recovery prepulse and an inversion time (IT) adjusted to neutralize the healthy myocardium signal. Therefore, in the images acquired with this technique, the intact myocardium appears as a signal of very low intensity (dark). Another characteristic of the delayed contrast-enhanced technique is the use of the intravenous contrast gadolinium, which does not penetrate intact cell membranes, and, therefore, has an extracellular distribution. In the infarcted regions, rupture of the membranes of necrotic myocytes occurs, and, therefore, gadolinium may be freely distributed (greater distribution volume) <sup>28-30</sup>. In addition, as the necrosis of myocytes also causes an alteration in the kinetics of contrast distribution, gadolinium leaves the infarcted areas more slowly (delayed washout) <sup>2</sup>. These 2 factors cause the concentration of the contrast medium in the necrotic regions, approximately 10 to 15 minutes after its injection, to be much greater than that in the healthy myocardial tissue <sup>31</sup>. As a consequence, the infarcted areas are white (intense signal) in delayed contrast-enhanced images. Briefly, by increasing the intensity of the signal in the infarcted area (using gadolinium and weighed images in T1) and decreasing the intensity of the signal of the healthy myocardium (with inversion prepulse and IT around 200-300 ms), the delayed contrast-enhanced technique optimizes the contrast between the 2 tissues (signal difference of up to 1080%), allowing precise delimitation of the necrotic myocardial areas <sup>8</sup>. </p>
      <p>In the case of old infarctions, fibrosis, and not necrosis, is the underlying pathological phenomenon. In these cases, the larger extracellular space observed in the fibrotic tissue as compared with that in the healthy myocardium is the cause of the greater distribution volume and the alteration in the kinetics of gadolinium (delayed washout of the contrast medium from the fibrotic tissue) <sup>31</sup>. </p>
      <p>Several recent studies have validated the measurement of the infarction size through cardiac magnetic resonance imaging as compared with the direct measurement of the infarcted mass on pathological anatomy <sup>1-3,5</sup>. The technique for measuring the infarcted mass used in these studies was planimetry of the delayed contrast-enhanced areas, which showed excellent agreement and correlation with the values obtained on pathological anatomy using TTC staining. Therefore, in our study, calculation of the infarcted mass through planimetry was considered the gold standard as compared with the scoring method developed by our group. </p>
      <p>Correlation between the 2 methods, measured through the Pearson correlation coefficient, was very expressive and statistically significant (r=0.93; P&lt;0.0001). The linear regression analysis also showed very consistent results (<xref ref-type="table" rid="en_a03tab02-body2">tab. II</xref>). However, as reported by Bland and Altman in their study on the comparison of the 2 measurement methods <sup>24</sup>, assessment of the agreement between methods is more important than the correlation or linear regression. </p>
      <p>Based on the analysis reported by Bland and Altman, we showed that the mean difference between the values of infarcted mass obtained through the 2 methods was not significant from the clinical point of view: only 1.03% (95% confidence interval of 0.15 to 1.91%). Although statistically significant (P&lt;0.02), because the number of patients studied was expressive (n=77), this small difference does not significantly interfere with the approach of patients assessed through the scoring method, because it represents only 1% of the total left ventricular mass. The agreement limit of the 2 methods was &#150;6.74% to 8.80%, showing that, for a certain patient, the percentage of the infarcted mass measured using the scoring method, 95% of the time, will have a difference lower than 8.8% of the value that would be obtained if it were calculated with planimetry. This characterizes a fully acceptable degree of agreement from the clinical point of view, showing that the semiquantitative visual method may safely replace the planimetry method in daily clinical routine. In addition, as shown in the Bland-Altman plot (<xref ref-type="fig" rid="fig4-body2">fig. 4</xref>), the dispersion of the individual differences around the mean difference (bias) is very homogeneous, independent of the extension of the infarction. In other words, the reproducibility of the scoring method is good for patients with both small and extensive infarctions. </p>
      <p>The good reproducibility of the scoring method was also demonstrated through the analysis of inter- and intraobserver variabilities. The mean difference (bias) between the measurements obtained by the 2 observers was lower than 0.5%, and the repeatability coefficient was lower than 10%. This coefficient represents the degree of variation between the results obtained by the 2 observers and is calculated as twice the standard deviation of the difference between those measurements. The results obtained when comparing the 2 measurements calculated by the same observer at different times (intraobserver variability) were very similar: bias lower than 0.4% and repeatability coefficient lower than 9%. Similarly to the comparison with planimetry, assessment of scoring method reproducibility showed repeatability coefficients confirming very acceptable degrees of inter- and intraobserver variability from the point of view of clinical applicability. </p>
      <p>Recently, Wu et al <sup>9</sup> reported that patients with acute myocardial infarction have a poorer prognosis as the amount of infarcted mass increases. Later, Choi et al <sup>10</sup> reported that the determination of the transmural extent of the infarction allows prediction of the spontaneous recovery of left ventricular segmentary contractility in patients with acute myocardial infarction. Gerber et al <sup>11</sup> also reported that the potential of recovery of regional contractility, quantitatively measured by using the tagging technique, may be defined through the evaluation of delayed contrast-enhanced patterns in patients with acute myocardial infarction. Moreover, an important study with great clinical repercussions, showing the usefulness of the delayed contrast-enhanced technique for assessing patients with coronary heart disease indicated for myocardial revascularization, was developed by Kim et al <sup>12</sup> and recently published in <italic>The New England Journal of Medicine</italic>. These authors reported that regional myocardial viability might be determined through the evaluation of the transmural extent of infarcted areas in delayed contrast-enhanced images. </p>
      <p>Correlation between infarction size and left ventricular function is intuitive and has already been shown in studies using nuclear medicine techniques <sup>32,33</sup>. However, extension of the infarcted area and left ventricular function are more precisely determined on cardiac magnetic resonance imaging than by the use of nuclear medicine techniques <sup>4,13</sup>, due to its greater spatial resolution. Our study was the first to show through cardiac magnetic resonance imaging an expressive correlation between the size of the infarction measured through the delayed contrast-enhanced technique and the data of left ventricular function measured using the Simpson method. In their study on the prognostic value of microvascular obstruction, Wu et al <sup>9</sup> reported no statistically significant correlation between these parameters. In turn, Klein et al <sup>13</sup> reported only a discrete inverse correlation (r= -0.42) between infarction size and ejection fraction. Future large-scale studies specifically designed to clarify this correlation are required to assess the prognostic value of each parameter in isolation. An important question to be answered by these studies is whether the infarcted mass could become an even more important prognostic factor than left ventricular ejection fraction in patients with acute myocardial infarction. </p>
      <p>In conclusion, the assessment of patients with previous acute myocardial infarction on cardiac magnetic resonance imaging using the delayed contrast-enhanced technique allows the reproducible determination of the size of the infarction both through the planimetry method and the semiquantitative scoring model. Planimetry requires that the contours of the infarcted areas and the left ventricular endocardial and epicardial borders in all cuts of the short axis be manually designed in specific software. This makes it an extremely laborious method that requires a considerable amount of time after image processing, being, therefore, difficult to implement into a daily clinical routine. On the other hand, the scoring method based on semiquantitative visual assessment of the delayed contrast-enhanced images is a much faster and more practical alternative for determining the extension of the infarction. Our study was the first to show that a simpler method for determining the infarcted mass could replace with good accuracy and reproducibility the more laborious method of planimetry. We believe that the use of the scoring method may allow the percentage of left ventricular infarcted mass to be more routinely calculated on cardiac magnetic resonance imaging in patients with previous myocardial infarction. Thus, these objective data of great diagnostic and prognostic importance may be regularly included in cardiac magnetic resonance imaging reports. </p>
      <p>
        <bold>References</bold>
      </p>
      <p>
        <fn id="end-body2" fn-type="corresp">
          <label>
            <bold>Correspondence to</bold>
          </label>
          <p> Carlos Eduardo Rochitte</p>
          <p> Av. Dr. Eneas de Carvalho Aguiar, 44</p>
          <p> Cep 05403-000 - S&#227;o Paulo, SP, Brazil</p>
          <p> E-mail: </p>
          <p>
            <email xlink:href="rochitte@incor.usp.br">rochitte@incor.usp.br</email>
          </p>
        </fn>
      </p>
      <p>Received: 4/17/03</p>
      <p> Accepted: 12/3/03</p>
      <p>English version by Stela Maris Costalonga </p>
    </body>
  </sub-article>
</article>
