Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
Ultrasound Med Biol. 2013 Feb;39(2):345-59. doi: 10.1016/j.ultrasmedbio.2012.09.011. Epub 2012 Dec 4.
Targeted microbubble imaging at ultrasound frequencies above 5 MHz has applications in both a preclinical context for a range of disease processes and clinically for the assessment of atherosclerosis and superficial tumors. Although the feasibility of ultrasound molecular imaging has been well demonstrated for a range of target molecules, little work has examined the effects of binding on microbubble oscillations, which is of potential relevance to improving the sensitivity, specificity, and quantification of bound-bubble detection. In this study we investigated the influence of binding on the subharmonic response of bubbles at transmit frequencies of 11 and 25 MHz. Individual bubbles were situated adjacent to a boundary in either a bound or an unbound state, optically sized and acoustically interrogated with pressures ranging from 0.02 to 1.2 MPa. At 11 MHz, unbound bubbles (n = 53) were found to have strong subharmonic activity for sizes between 2.4 and 2.6 μm, whereas bound bubbles (n = 50) were most active from 2.6 to 3.0 μm. Destruction thresholds were found to be lower for bound bubbles. At 25 MHz, bound-bubble (n = 57) activity was found to peak at 1.9 μm as compared to 2.1 μm in the unbound cases (n = 53), with a 20% increase in amplitude. Comparison with simulations indicates that both unbound and bound bubbles undergo compression-only behavior at 11 MHz, and expansion-dominated behavior at 25 MHz. Subharmonic emissions elicited from 0 radian transmit pulses were found to be π/2 radians out of phase with those elicited from a π radian transmit pulse, suggesting inefficient subharmonic preservation from pulse inversion schemes. With the appropriate postprocessed phase correction, an increase in the subharmonic amplitude of up to 60% was shown, depending on the bubble size and transmit frequency.
靶向微泡成像是在高于 5 MHz 的超声频率下进行的，在临床前的多种疾病过程和临床中的动脉粥样硬化和浅表肿瘤评估中都有应用。尽管针对多种靶分子的超声分子成像的可行性已得到充分证明，但对于结合对微泡振动的影响的研究很少，这对于提高结合微泡检测的灵敏度、特异性和定量分析具有潜在的意义。在这项研究中，我们研究了结合对 11 和 25 MHz 发射频率下的微泡亚谐波响应的影响。在结合或未结合状态下，将单个微泡置于边界附近，用光对其进行尺寸测量，并在 0.02 至 1.2 MPa 的压力范围内进行声学检测。在 11 MHz 下，未结合的微泡（n=53）在 2.4 至 2.6 μm 的尺寸范围内具有很强的亚谐波活性，而结合的微泡（n=50）在 2.6 至 3.0 μm 的尺寸范围内最活跃。发现结合微泡的破坏阈值较低。在 25 MHz 下，与未结合的情况（n=53）相比，结合微泡（n=57）的活性在 1.9 μm 处达到峰值，在 2.1 μm 处的活性增加了 20%。与模拟结果的比较表明，在 11 MHz 下，未结合和结合的微泡都经历了仅压缩的行为，而在 25 MHz 下经历了扩展主导的行为。从 0 弧度发射脉冲激发的亚谐波发射与从 π 弧度发射脉冲激发的亚谐波发射相比，相位相差 π/2 弧度，这表明从脉冲反转方案中不能有效地保存亚谐波。通过适当的后处理相位校正，取决于微泡尺寸和发射频率，亚谐波幅度可增加高达 60%。
