In Vivo Destruction of Ultrasound Contrast Microbubbles Is Independent of the Mechanical Index

ers2,3 have shown in vitro that the mechanical index (MI) displayed on the ultrasound scanner monitor does not predict the degree of contrast microbubble destruction. This is an important finding because most clinical investigators (including ourselves) report the value of the MI displayed on clinical ultrasound scanners as an indicator of exposure conditions related to the destruction of microbubble contrast agents during in vivo contrast studies.4,5 However, in vitro results do not always carry over to in vivo situations. Hence, we have investigated the relationship between the MI and in vivo microbubble destruction (assessed indirectly as the duration of contrast enhancement). As part of 2 clinical trials of contrast-enhanced ultrasound for diagnosing breast lesions,6,7 112 women older than 21 years were studied after palpation and/or x-ray mammography identified a solid mass or a suggestive area (eg, microcalcifications). The study was approved by the university’s Institutional Review Board, and all patients provided written informed consent. First, a baseline gray scale scan, which identified the mass or abnormality seen on x-ray mammography, was performed with an HDI 3000 scanner (Philips Medical Systems, Bothell, WA) and an L10-5 broad-bandwidth linear array transducer. Second, power Doppler images of the target region were obtained. Image parameters such as MI, field of view, gain, pulse repetition frequency (PRF), and filter settings were adjusted for each individual patient to optimize flow visualization and then kept constant (ie, for the individual patient but not between patients). Next, an ultrasound contrast agent was administered intravenously via a peripheral vein, preferably the antecubital vein. The agent used was either Levovist (Berlex Laboratories, Montville, NJ) or Optison (GE Healthcare, Princeton, NJ) in 10 and 1.0 mL dosages, respectively. The first 79 patients studied received Levovist, whereas Optison was administrated to the remaining 33 women. The system gain and power Doppler settings were unaltered from the precontrast settings. The precontrast and postcontrast scans of the mass or area of abnormality were videotaped for documentation and subsequent analysis. Apart from diagnostic assessments, the duration of contrast enhancement was recorded in each case as the time from initial arrival of the contrast to return to baseline conditions. For this investigation, changes in enhancement duration were assumed to provide an indirect measure of in vivo bubble destruction (ie, we assumed that as more destruction occurred there would be a shorter duration of contrast enhancement). Finally, linear regression analysis was performed for each contrast agent to compare the time of enhancement (in seconds) to the corresponding MI values, with P < . 05 considered significant. The displayed MI varied between 0.3 and 1.2 for the patients receiving Levovist, whereas MI values between 0.3 and 0.6 were recorded for patients imaged with Optison. The duration of contrast enhancement obtained with Levovist as a function of MI is shown in Figure 1. The extent of enhancement (ie, the degree of bubble destruction) varied widely for identical MI values. At a displayed MI of 1.0, the duration of enhancement observed for Levovist ranged from 35 to 432 seconds. The regression analysis found no statistically significant, linear relationship between MI and bubble destruction (r2 = 0.014; P = .32). Similar results were obtained with Optison (r2 = 0.002; P = .82), albeit based on less data. These are not completely surprising results