The lifetime and attenuation properties measurements of a US/MR multimodality molecular probe

In our previous studies we explored the potential of using a combined US/magnetic resonance (MR) multimodality contrast agent, albumin-gadolinium-diethylenetriaminepentacetate (Gd-DTPA) MBs, to induce BBB opening and for distinguishing between FUS-induced BBB opening and intracerebral hemorrhage in MR T1-weighted contrast imaging. According to the previous study in the literature, 1-2 μm bubbles have more pronounced acoustic activity at frequencies above 10 MHz. The present study developed a new targeted US/MR multimodality MB and the acoustic properties were compared with two commercial MBs, SonoVue and Targestar SA. The acoustic activities of these 1.15-2.78 μm MBs with different shells at 10 MHz were investigated. The feasibility of designing a new targeted US/MR multimodality MB was investigated. The lifetime (survival of MBs in the liquid suspension) and attenuation properties of lipid MBs (SonoVue and Targestar SA), albumin-(Gd-DTPA) MBs, and avidin-conjugated albumin (avidin-albumin)-(Gd-DTPA) MBs at 10 MHz were investigated with the pulse-echo substitution method. It was found that incorporating avidin into the albumin MBs and avidin-albumin-(Gd-DTPA) MBs affects the size distribution but does not affect the concentration of MBs produced. The avidin-albumin-shelled MBs had more significant nonlinear activity at 4-18 MHz (p=0.025), while the nonlinear activity of the other MBs peaked at 6-24 MHz (p=0.003-0.044). Moreover, the incorporation of paramagnetic metal ions into the MB shells increased their attenuation coefficients. With regard to the lifetime of these agents, the attenuations of the SonoVue and Targestar SA lipid MBs were 87.96% and 8.74%, respectively, while those of albumin MBs, avidin-albumin MBs, albumin-(Gd-DTPA) MBs, and avidin-albumin-(Gd-DTPA) MBs were 49.52%, 41.38%, 74.69%, and 100%, respectively. Avidin conjugation decreased the lifetime of the albumin MBs, but not that of the lipid MBs. The incorporation of paramagnetic metal ions into the shells of albumin MBs did not decrease the lifetime.