An ultrasound technology for delivering smart imaging probes to the brain
Deadline is 4 March 2019
Project description. Molecular imaging probes have the potential to transform neuroimaging. Whereas CT and conventional MRI provide structural and anatomic information of the brain, molecular probes can identify processes that are specific to a disease and its stage. This could allow doctors to classify the disease earlier and more accurately, and match it with the best therapeutic option (i.e., personalised medicine). Some important unmet needs include locating hidden cancer cells after surgical removal of a glioblastoma tumour; and identifying Alzheimer’s disease early so that the correct treatments can be initiated.
But molecular imaging probes cannot enter the brain, because of the blood-brain barrier, and thus remain impractical. Thus, at the moment, molecular imaging targets are constrained to intravascular targets, such as receptors on endothelial cells.
We would like to open the scope of molecular imaging probes to all extravascular targets –neurons, microglial cells, and disease processes in the extracellular space (e.g., ABeta plaques in Alzheimer’s disease).
Dr. Choi’s lab has developed a short-pulse ultrasound technology that can deliver drugs across the blood-brain barrier. Meanwhile, Prof. Long’s lab specialises in creating molecular imaging probes. In this PhD project, we would like to combine the ultrasound technology with these imaging probes to create a platform for imaging specific disease processes using MRI or other imaging modalities.
To enable the use of molecular imaging probes by ultrasound delivery, it must not damage the blood-brain barrier and brain tissue. We have developed a short-pulse ultrasound sequence for blood-brain barrier opening. In preliminary data that is soon to be published in Radiology, we have shown the following:
Diffuse delivery of drugs to parenchyma
Delivery into cells
Short duration BBB permeability change (< 20 min)
Reduced release of albumin into the brain
Size-selective BBB permeability change
Centre for doctoral training website: http://www.imagingcdt.com
We are seeking the PhD candidate that has the best mind and work ethic. Depending on the student’s background, he or she can work on many different aspects of the proposed work - as an engineer, physicist, or mathematician on the device, acoustics and acoustic bubble activity; as a chemist on the microbubble formulation or imaging probes; as a biologist looking at the mechanisms of blood-brain barrier opening or how to modify the techniques to image neurological diseases with the imaging probes; or as a neuroscientist seeking specific applications for the molecular imaging probes. We recruit the best students with a strong foundational knowledge in their specialty, and then fill in the blanks with training and learning in our laboratory. No acoustics or physics background is necessary.
If you have your own funding support or would like to apply to a funding body yourself, contact Dr. James Choi at email@example.com about which projects are available in the laboratory.
Facilities and Resources
The laboratory is equipped to run experiments at multiple levels:
In vitro (cell cultures, ex vivo human skulls)
We manufacturer or design transducers and microbubbles in-house. Some of the equipment we have include:
Transducers: 16 single-element transducers (0.5, 1, 5, and 7.5 MHz), a linear imaging array
Multi-element array manufacturing setup
Microbubble manufacturing setup
Signal generators, power amplifiers, filters, scopes, etc.
Experimental water tanks
Basic life sciences equipment
We work closely with Dr. Mengxing Tang's Ultrasound Imaging Group who has built state-of-the-art facilities in ultrasound imaging.
We also have access to all shared Department facilities including:
Tissue Culture Room
Microscopy Suite (including confocal microscopy)