Noninvasive Technologies

Our vital organs – our heart, brain, and liver – are protected by the skin, skull, and rib cage. But when a man's liver is invaded by cancer or an elderly lady's brain accumulates toxic Alzheimer's disease plaques, these protective structures inadvertently help the diseases, allowing them to grow unnoticed and without a means of direct intervention. Our laboratory is developing the next generation of noninvasive microsurgical devices that physicians can use to operate on vital organs without having to perform an incision. For patients, this implies accessible, pain-less, and infection-free techniques; and therapeutic and diagnostic capabilities never achieved before. Using a bottom-up research strategy, we develop very early stage noninvasive devices and find exciting and high impact uses for them.

A Noninvasive Capillary Permeabilisier for Drug Delivery

We are developing a noninvasive technology that can noninvasively and locally deliver drugs to diseased regions. This is achieved by using ultrasound and sonosensitive particles to locally alter the permeability of capillaries in different organs. We have performed initial proof of concept studies in vitro and in vivo; and are now pushing this technology towards clinical trials. If successful, we'll sort through a decade of powerful drugs that have been shelved due to poor permeability, and deliver them noninvasively and locally to where they are needed. This technology is being developed for the treatment of cancer and Alzheimer's disease.

A Noninvasive Acoustic Micropump for Drug Enhancement

By using ultrasound alone, we can enhance the distribution of drugs through tissue microenvironments. We are developing methods to enhance the distribution of molecules and nanoparticles. This technology is being developed for a range of diseases that includes cancer.

A Noninvasive Acoustic Particle Palpator for Measuring Tissue Elasticity

Devices and methods are also being developed to push tissue and track its displacement and relaxation to determine stiffness. This elasticity imaging technique provides a quantitative measure of a property, which has been linked to the progression of several diseases. This technology is being developed for early detection of liver diseases, such as liver fibrosis and hepatocellular carcinoma.

How it Works

Ultrasound applied outside of our body can travel through several layers of tissue and converge to a small tissue volume. This focal volume is where all the action happens and we're here to develop innovative ways to probe and modify tissue so that we can diagnose and treat diseases.

Focused Ultrasound

Sound has the unique property of traveling through materials, which is the reason you can often hear your neighbour through opaque walls. Higher sound frequencies attenuate through the wall more so than lower frequencies. This is why you can hear lower tones from sources such as subwoofers.

In biomedical acoustics, very high frequencies known as ultrasound (0.25 to 10 MHz) are focused through several layers of tissue to converge to a small focal volume. This limits ultrasound-induced effects to a confined area while not affecting the surrounding healthy tissue. Ultrasound has unique properties when compared to other kinds of energy (e.g., light, magnetism):

  • Noninvasive
  • Deep penetration (several centimetres)
  • Non-ionising
  • Localisation (safety below certain intensities has been established)

Ultrasonically Generated Forces --> Novel Bioeffects

The focus of our laboratory is to functionally alter or probe biological tissue in a way that (1) is safe and temporary and (2) controllable at the micron- and nano-scale. We do NOT research high-intensity focused ultrasound (HIFU) or lithotripsy, which both use ultrasound to destroy tissue. In fact, we use pulse sequences, which more closely resemble ultrasound imaging pulses, which have an established safety profile. By carefully designing ultrasonic pulse sequences, we generate a wide range of ultrasonic phenomena within the focal volume:

  • Pushing
  • Expansion
  • Contraction
  • Heating (mild levels)

Our laboratory has an in-depth understanding of how the physics and biology are interacting with each other. We have the necessary balance of engineering, physics, and biology. Thus our manipulation and probing techniques are not limited to the size of the focal volume, but can be refined down to molecular and cellular behaviours through compartmentalisation of the phenomena (e.g., vascular, interstitial, and cellular compartments) and the use of sono-sensitive nano- and micro-particles (e.g., expansion and contraction of a microbubble). We can produce a range of safe and reversible bioeffects:

  • Increased vascular permeability
  • Increased cell membrane permeability
  • Displacement of fluid
  • Displacement of tissue

Examples of Our Research

If you'd like a better understanding of the research we perform, read the following two papers by Dr. Choi. The paper published in the Journal of the Acoustical Society of America (JASA) has a Electrical Engineering, Computer Engineering, and Physics focus while the paper published in the Proceedings of the National Academy of Science USA (PNAS) has a Biology and Biomedical Engineering focus. For a full list of outputs, visit the Publications Page.

Imaging ultrasonically-generated phenomena in real-time. Choi et al, JASA 2012

Imaging ultrasonically-generated phenomena in real-time. Choi et al, JASA 2012

Delivery of large molecules across the blood-brain barrier and to neurons. Choi et al, PNAS 2011

Delivery of large molecules across the blood-brain barrier and to neurons. Choi et al, PNAS 2011