About the Project
The student will split his or her time approximately 50:50 between Imperial College London & ICR.
Ultrasound drug delivery across the blood-brain barrier for the treatment paediatric brain cancer.
Project Summary
Children diagnosed with diffuse intrinsic pontine gliomas (DIPGs) have an 18-month survival rate of only 10%. Over time, nearly every one of these children will die from their cancer. This devastating prognosis comes from the diffuse spread through healthy tissue, reducing the impact of localised surgery and radiotherapy. In such a diffuse cancer, chemotherapy would normally be the better treatment option; but DIPG spreads behind an intact blood-brain barrier (BBB), where drugs are unable to reach.
We have shown that short pulses of ultrasound can produce controlled, temporary changes to BBB permeability. This project will develop and test the first short-pulse drug delivery method for DIPG. By allowing drugs to cross the BBB, it has the potential to revive previously abandoned therapies that showed great promise for the treatment of DIPG.
We are developing a new ultrasound emission sequence – rapid short pulses (RaSP) – that delivers drugs across the BBB. RaSP gives exceptional control over the microbubbles flowing through the vasculature, gently stimulating them into oscillation, and transporting co-injected drugs across the BBB. RaSP sequences have unique safety & performance features.
Programme of Work
This project will develop and test RaSP ultrasound delivery of a drug for the effective treatment of DIPG modelled in a mouse.
Aim 1: Optimisation of RaSP sequences for safe drug delivery (ICL) - We will maximise the drug payload delivered to the brain without damage by optimising RaSP parameters in vitro and in vivo.
Aim 2: Optimisation of MRI sequences to monitor BBB permeability changes and cancer progression (ICL & ICR).
Aim 3: DIPG treatment in a mouse model (ICR) - We aim to reduce cancer progression in a DIPG mouse model using ultrasound enhanced drug delivery.
The proposed PhD project will translate the use of our ultrasound technology to cancer; and, more specifically, to novel paediatric high grade glioma models which exist at the ICR.
Our Team’s Vision
The proposed PhD project transports a world-unique technology – RaSP ultrasound drug delivery – developed at Imperial College London (ICL) to world-leading experts in clinical therapeutic ultrasound, MR imaging, and paediatric glioma at the Institute of Cancer Research (ICR). The proposed work develops novel noninvasive devices at the Noninvasive Surgery & Biopsy Laboratory (PI: Dr. Choi) at ICL and uses these technologies to treat cancers with experts at ICR. Our long-term vision is to make noninvasive microsurgery one of the top 4 cancer treatment options (amongst drugs, surgery, and radiotherapy).
The PhD student will receive convergent training to become a Biomedical Acoustician & pre-clinical cancer scientist, and will develop the following expertise:
• Mastery of biomedical acoustics: a deep understanding of physical acoustics, microbubbles, pulse sequences, and bioeffects; skills in programming, signal processing, calibration, instrumentation, tissue phantoms, and microbubbles.
• Expertise in general biology: a deep understanding of the BBB and neuroscience; skills in sectioning, staining, western blotting, ELISA, microscopy, safety and toxicity assessment.
• Expertise in animal handling and care: A good understanding of animal health and behaviour; skills in animal handling, injections, isoflurane, and stereotactic frames.
• Expertise in MR imaging: A good understanding of MRI sequences and contrast agents; skills in pre-clinical MRI, contrast agents, and image processing.
• Expertise in paediatric brain cancer: a deep understanding of DIPG and chemotherapeutic agents; skills in cancer implantation, tumour growth monitoring, and drug efficacy assessment.
The successful candidate will have 1h meetings supervisory meetings1st year of the PhD, and as required in subsequent years. In the first 6 months, tutorials will be held weekly at ICL and monthly at ICR. The student will be required to attend courses, seminars, and workshops held at ICL and ICR.
Project Timeline
The student will split his or her time approximately 50:50 between ICL & ICR. The student will begin at ICL for Aim 1, developing the delivery technology, and then progressively increasingly work at ICR for Aims 2 and 3, characterising the delivery pattern using MRI and testing whether ultrasound delivery of a chemotherapeutic agent will produce a response in DIPG in an animal model.
Candidate profile
Candidates must have a first class or upper second class honours BSc Honours/MSc or equivalent in Physics or Engineering (with particular emphasis on biological or medical applications) or Biology (with strength in physics).
How to apply
Full details about these studentship projects, and the online application form, are available on our website, at: http://www.icr.ac.uk/phds and on Dr Choi’s website at www.nsblab.org/ . Applications for all projects should be made online. Please ensure that you read and follow the application instructions very carefully.
Closing date: Monday 20th November 2017
Applicants should be available for interview 29h and 30th January 2018.
Please apply via the ICR vacancies web portal https://studentapps.icr.ac.uk/
Download a PDF of the complete project proposal:
https://d1ijoxngr27nfi.cloudfront.net/default-document-library/ter-haar-amp-choi-crce-icr-icl-phd---updated.pdf?sfvrsn=2
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