MRI-Guided Focused Ultrasound as a New Method of Drug Delivery

Ultrasound-mediated drug delivery under the guidance of an imaging modality can improve drug disposition and achieve site-specific drug delivery. The term focal drug delivery has been introduced to describe the focal targeting of drugs in tissues with the help of imaging and focused ultrasound. Focal drug delivery aims to improve the therapeutic profile of drugs by improving their specificity and their permeation in defined areas. Focused-ultrasound- (FUS-) mediated drug delivery has been applied with various molecules to improve their local distribution in tissues. FUS is applied with the aid of microbubbles to enhance the permeability of bioactive molecules across BBB and improve drug distribution in the brain. Recently, FUS has been utilised in combination with MRI-labelled liposomes that respond to temperature increase. This strategy aims to “activate” nanoparticles to release their cargo locally when triggered by hyperthermia induced by FUS. MRI-guided FUS drug delivery provides the opportunity to improve drug bioavailability locally and therefore improve the therapeutic profiles of drugs. This drug delivery strategy can be directly translated to clinic as MRg FUS is a promising clinically therapeutic approach. However, more basic research is required to understand the physiological mechanism of FUS-enhanced drug delivery. 1. Introduction Therapeutic high intensity focused ultrasound (HIFU) or Focused Ultrasound (FUS) is a noninvasive medical treatment that allows the deposition of energy inside the human body. Frequencies of 0.8–3.5？MHz are generally used during the clinical applications of FUS. The energy levels carried in the ultrasound beam are several orders of magnitude greater than those of a standard diagnostic ultrasound beam. In the case of focused ultrasound, the ultrasound waves can be focused at a given point. The high energy levels carried in a HIFU beam can therefore be magnified further and delivered with precision to a small volume, while sparing surrounding tissues. FUS energy can be deposited in small areas providing a substantial advantage for drug targeting. The volume of energy deposition following a single HIFU exposure is small and will vary according to transducer characteristics but is typically cigar shaped with dimensions in the order of 1–3？mm (transverse) 8–15？mm (along beam axis) [1]. HIFU transducers deliver ultrasound with intensities in the range of 100–10,000？W/cm2 to the focal region, with peak compression pressures of up to 30？MPa peak and rarefaction pressures up to 10？MPa [2]. The ultrasound wave propagates