In vivo study of microbubbles as an MR susceptibility contrast agent

Abstract

The potential application of gas microbubbles as a unique intravascular susceptibility contrast agent for MRI has not been fully explored. In this study, the MR susceptibility effect of an ultrasound microbubble contrast agent, Optison®, was studied with rat liver imaging at 7 T. Optison® suspension in two different doses (0.15 mL/kg and 0.4 mL/kg) was injected into rats, and induced transverse relaxation rate increases (⌬R 2 *) of 29.1 ؎ 1.6 s -1 (N ‫؍‬ 2) and 61.5 ؎ 12.9 s -1 (N ‫؍‬ 6), respectively, in liver tissue. Liver uptake of intact albumin microbubbles was observed 10 min after injection. Eight of the 16 rats studied showed no susceptibility enhancement. This is probably attributable to the intravascular microbubble growth due to transmural CO 2 supersaturation in the cecum and colon in small animals that causes microbubble aggregation and trapping in the inferior vena cava (IVC). In vitro ⌬R 2 * measurements of Optison® suspension at different concentrations are also reported. Magn Reson Med 52:445-452, 2004.

Air Microbubbles as MR Susceptibility Contrast Agent at 1.5 Tesla

“…Time constants of the decay obtained from monoexponentialˆts were 39 s for 125 mg W mL; 50 for 100 mg W mL; 51 for 76 mg W mL; and 57 for 67 mg W mL. Because R2 * was considered to be proportional to the microbubble volume fraction, [5][6][7] the microbubble concentration was exponentially decreased over time in the syringe phantom. Figure 2 shows the …”

“…7,11,14 This implies that a high magneticˆeld is necessary to measure such weak susceptibility. Thus, previous studies 3,5,6 could be conducted at advantageous high magneticˆelds (2T or greater). Although the availability of high-ˆeld MR systems has increased, in most hospitals, magnetiĉ elds of MR scanners do not exceed 3T.…”

“…Another method to improve susceptibility is to increase the microbubble concentration within the limitations from microbubble toxicity in vivo. [5][6][7]13 Withˆrst-pass bolus delivery, a lower dose would achieve higher microbubble concentration. Microbubble susceptibility can also be enhanced by choice of gas.…”

“…3 Another experimental study on a 4.7T MR scanner explored the potential application of microbubbles as MR pressure sensors based on pressure-induced susceptibility change, 5 and recently, an animal study of Optison } microbubbles at 7T demonstrated their potential application as MR intravascular susceptibility contrast agents in vivo. 6 Microbubbles used in these studies were coated with shells of liposomes or human albumin to improve their stability.…”

Molecular properties of lysozyme-microbubbles: towards the protein and nucleic acid delivery

“…The first in vivo investigation of susceptibility contrast induced by MBs was reported in liver using Optison Ò , MBs with human albumin shell with perfluorocarbon as core gas, at 7 T in rat liver (Wong et al 2004). Moreover, a peculiarity of the albumincoated MBs is the ability to adhere only to the vessel walls in the setting of endothelial dysfunction and not to normally functioning endothelium, thus suggesting also the use of these MBs as markers of endothelial integrity (Villanueva et al 1997).…”