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Smart Imaging Probes, Emerging Imaging

An acoustic wavelet technology for delivering smart imaging probes to the brain

Project ID: 2020_037

1st Supervisor: James Choi, Imperial College London
2nd Supervisor: Nicholas Long, Imperial College London
Clinical Champions: Paul Edison, Imperial College London and Wladyslaw Gedroyc, Imperial College London

Aim of the PhD Project:

Create an acoustic wavelet technology that delivers imaging probes across the blood-brain barrier.

Synthesise new and existing single- and dual-modality imaging probes.

Image the delivered imaging probes using MRI and fluorescence experiments.

Project Description / Background:

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.

However, 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, which are unlikely to be direct indicators of the disease. We would like to widen 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 an acoustic wavelet technology that can deliver drugs across the blood-brain barrier. Acoustic wavelets are short, low-pressure ultrasound pulses. Meanwhile, Prof. Long’s lab specialises in creating molecular imaging probes. In this PhD project, we would like to combine the wavelet 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 wavelet delivery, it must not damage the blood-brain barrier and brain tissue. We have developed an acoustic wavelet sequence for blood-brain barrier opening (Fig. 1). In a recent publication Radiology (2019), we have shown the following:

  • Diffuse delivery of drugs to parenchyma
  • Delivery into cells
  • Short duration BBB permeability change (< 20 min)
  • Size-selective BBB permeability change

We are seeking candidates who can either focus on the physics and engineering (acoustics) or chemistry (smart imaging probes) aspects of the research. However, we are not seeking a single student with all of the academic background. Instead, students with a specific background will be taught the other areas of research needed for the PhD project. The student should be willing to conduct animal experiments.

Figure 1. Our acoustic wavelets delivered drugs throughout the parenchyma & into neurons [white box in Fig 1]. Fluorescently-tagged molecules (3-kDa dextran) were delivered throughout the parenchyma (grey background), and into neurons (white arrows).

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