Ultrasound contrast microbubbles in the brain vasculature

Mouse skull is easily penetrated by diagnostic ultrasound at MHz frequencies. Therefore, clinical ultrasound imaging can monitor microbubbles in the murine brain vasculature in real time. While nonspecific binding of microbubbles onto vessel wall is low, molecular targeting can be applied to achieve selective adhesion to the vascular biomarkers of disease, such as markers of endothelial inflammation or tumor neovasculature, enabling contrast-specific imaging. Super-resolution imaging of ultrasound contrast microbubbles implies the computation of particle centroids, which improves spatial resolution of contrast ultrasound well beyond the dimensions of the point-spread function on the scanner screen, and the wavelength of ultrasound. Rapid visualization of moving and adherent bubbles, determination of velocity of the particles in blood flow, and distinguishing targeted bubbles becomes possible. With the advancement of all these approaches, undesired bioeffects of the combination of intravascular microbubbles and ultrasound must be noted. It has been observed that the use of clinical imaging equipment, with clinical imaging transducers, in combination of circulating microbubbles, may induce significant bioeffects, such as blood brain barrier opening, with potential for drug delivery, or unwanted bioeffects. Overall, the use of microbubble contrast agents provides quick and inexpensive tool for the assessment of brain vasculature in small experimental animals.