Medical Ultrasound: Advanced Imaging and Targeted Therapy

Ultrasound is a widely used medical imaging and therapeutic modality, due to its safety, noninvasiveness, large penetration depth and cost effectiveness compared to other modalities. Ultrasound imaging enables the observation and perturbation of internal anatomy and physiology, however limitations in resolution and contrast restricts the resulting performance.  In the first part of my talk I will present a method that was developed to address these challenges by manipulating the emitted acoustical field using an optically-inspired holographic algorithm. This beam shaping technology was used to achieve ultrasound super-resolution through acoustical structured illumination, and effectively double the spatial resolution of the reconstructed image compared to one-way focusing. Acoustical beam shaping was additionally utilized for imaging of tissues beyond ultrasonically-impenetrable obstacles, in order to bypass the obstacle and place the beam focus beyond the obstruction.

The second part of my talk will focus on therapeutic ultrasound using microbubble contrast agents. Lipid-shelled, gas-filled microbubbles are widely used in ultrasound imaging and therapy, typically with transmission center frequencies that matches their resonance frequency, which is in the MHz range. Upon ultrasound excitation, microbubbles expand and contract, increasing cell membrane permeability and providing a way through which different therapeutics can be delivered into a targeted region. Currently, an ultrasound center frequency near 250 kHz is proposed for clinical human studies in which ultrasound combined with microbubbles is applied to open the blood brain barrier, since at this low frequency focusing through the human skull to a predetermined location can be performed with reduced distortion and attenuation. In the past, it was assumed that encapsulated microbubble expansion is maximized near the resonance frequency and monotonically decreases with decreasing frequency. Our results indicate that at 250 kHz, well below the resonance frequency of these agents, the vibrational response of microbubbles is enhanced, and high amplitude oscillations occur at substantially lower pressures as compared to higher frequencies, contrary to what was previously assumed. Our work was aimed to determine a safe range of parameters for enhanced brain delivery, and the results were implemented in blood brain barrier opening through transcranial ultrasound in mice. Lastly, I will present the combination of low frequency ultrasound and targeted microbubbles for enhanced drug delivery by improving the uptake of DNA and drugs in tumors in vivo.

These advances in ultrasound imaging and therapy open new avenues in early disease diagnosis and evaluation of disease progression, in addition to enhanced therapy for brain and cancer related disease.