Nanda Navin C, Kitzman Dalane W, Dittrich Howard C, Hall Gail
University of Alabama at Birmingham, Heart Station SW/S102, 619 19th Street, Birmingham, AL 35249, USA.
Echocardiography. 2003 Feb;20(2):151-61. doi: 10.1046/j.1540-8175.2003.03014.x.
This study was conducted to assess the ability of a new echocardiographic contrast agent, Imagent (perflexane lipid microspheres; Alliance Pharmaceutical Corp., San Diego, CA), to improve endocardial border delineation (EBD) and assessment of segmental wall motion (SWM). This was achieved by analysis of inter-reader agreement by echocardiography and comparison with an independent imaging technique, magnetic resonance imaging (MRI).
Two separate, independent, prospective, randomized, controlled, multicenter trials were conducted at 26 centers and included a total of 409 efficacy-evaluable patients. In Study A 206 patients were randomized to receive either Imagent or saline and in Study B, 203 patients received Imagent with a subset imaged by both echocardiography and MRI. All patients were required to have suboptimal baseline images using fundamental imaging. Images were optimized at baseline prior to contrast and the settings maintained post-contrast. Imagent, a suspension of perfluorohexane-filled spheres with flexible lipid shells, was administered as an IV bolus at 0.125 mg/kg body weight. Gated MRI studies were performed within 48 hours of dosing in a subset of 26 subjects. Six expert independent blinded readers reviewed unpaired noncontrast and contrast exams and scored EBD and SWM. Analysis of inter-reader agreement was performed by comparing the SWM score (1 to 5) recorded by each reader pair. In addition, unanimity between readers for SWM was evaluated. For comparison to MRI, the results from echo readers 4, 5, and 6 were each compared with a single independent MRI reader.
The patients enrolled in these clinical trials displayed markedly suboptimal images with 49% and 71% (Study A and Study B) of the segments determined by the readers to be suboptimal prior to contrast administration. All readers recorded statistically significant (P < 0.0001) improvement in total EBD scores following the administration of Imagent. Comparison of noncontrast SWM scores for each pair of echo readers resulted in agreement in an average of 39%, of segments in Study A, and 31% of the segments in Study B. Use of Imagent improved agreement in SWM scores to 65% in Study A, and 48% of segments in Study B (P < 0.0001) for all reader pairs in both studies. Reader unanimity in SWM scores increased from 13% to 41% of the segments with the administration of Imagent. Blinded review of the noncontrast echo examinations resulted in agreement with MRI derived SWM scores in 15% of the segments. The administration of Imagent improved this agreement to 47%, of the segments (P < pr = 0.0005 for each blinded reader).
Use of Imagent during echocardiographic imaging improves EBD, providing a significant improvement in inter-reader agreement in SWM evaluation with echo and greater than a threefold improvement in SWM scoring accuracy with MRI.
本研究旨在评估新型超声心动图造影剂Imagent（全氟己烷脂质微球；Alliance制药公司，加利福尼亚州圣地亚哥）改善心内膜边界勾勒（EBD）及节段性室壁运动（SWM）评估的能力。这通过超声心动图分析阅片者间的一致性并与独立成像技术磁共振成像（MRI）进行比较得以实现。
在26个中心进行了两项独立、前瞻性、随机、对照、多中心试验，共纳入409例可进行疗效评估的患者。在研究A中，206例患者随机接受Imagent或生理盐水；在研究B中，203例患者接受Imagent，其中一部分患者同时接受超声心动图和MRI检查。所有患者使用基础成像时基线图像质量欠佳。在使用造影剂前对图像进行基线优化，造影后保持设置不变。Imagent是一种填充全氟己烷的球体悬浮液，外壳为柔性脂质，以0.125mg/kg体重静脉推注给药。在26名受试者的亚组中，给药后48小时内进行门控MRI研究。六位独立的专家盲法阅片者对未配对的非造影和造影检查进行评估，并对EBD和SWM进行评分。通过比较每对阅片者记录的SWM评分（1至5分）来分析阅片者间的一致性。此外，评估阅片者对SWM的一致性。为了与MRI进行比较，将超声阅片者4、5和6的结果分别与一位独立的MRI阅片者进行比较。
参与这些临床试验的患者基线图像明显欠佳，在使用造影剂前，阅片者确定研究A和研究B中分别有49%和71%的节段图像质量欠佳。所有阅片者均记录到使用Imagent后总EBD评分有统计学显著改善（P<0.0001）。对每对超声阅片者的非造影SWM评分进行比较，结果显示研究A中节段的一致性平均为39%，研究B中为31%。使用Imagent后，研究A中SWM评分的一致性提高到65%，研究B中为48%（两项研究中所有阅片者对P<0.0001）。使用Imagent后，阅片者对SWM评分的一致性从节段的13%提高到41%。对非造影超声检查的盲法评估显示，15%的节段与MRI得出的SWM评分一致。使用Imagent后，这一一致性提高到47%的节段（每位盲法阅片者P<pr=0.0005）。
超声心动图成像时使用Imagent可改善EBD，在超声评估SWM时显著提高阅片者间的一致性，且与MRI相比，SWM评分准确性提高了三倍以上。
