3D radiation force enhanced ultrasonic molecular imaging with a clinical system

For over a decade, acoustic radiation force (ARF) has been proposed as a method to enhance microbubble contrast agent (MCA) retention in ultrasonic molecular imaging (USMI), since ARF can push microbubbles in contact with the vessel endothelium. However, to date, the application of ARF-enhanced targeted imaging in-vivo has not been demonstrated. 3D ARF-enhanced MI was performed on 7 rat fibrosarcoma tumors using size selected MCAs fitted with a cyclic RGD peptide targeted to α_vβ₃ and non-targeted MCAs. 3 different low-amplitude ARF pulse sequences, previously shown to produce non-destructive bubble translation in-vitro, (4.4, 13.4 and 20.6 kPa; Duty Cycle: 25%, Freq: 7MHz) were tested and compared to passive targeting studies in the same animal. The maximum increase in targeting was achieved using the ARF-13.4 kPa setting. On average, ARF at 13.4 kPa yielded 80% greater targeting than with no ARF (13.4 kPa: 1.8 ± 1.1 vs No ARF: 1.0 ± 0.7; p <; 0.05). This in-vivo study demonstrates the enhancement of USMI with ARF, as assessed by 3D imaging with a clinical US system. Results show a significant improvement in sensitivity over traditional non-ARF-enhanced targeted imaging without a corresponding loss in specificity.