1st Supervisor: Kirsten Christensen-Jeffries, King’s College London
2nd Supervisor: Maria Thanou , King’s College London
Clinical Supervisor: Dr. Dean Huang
Aim of the PhD Project:
- Developing advanced ultrasound technology for high spatial and temporal resolution imaging of blood vessels.
- Developing optimised signal and image processing techniques for 3D imaging.
- Preparing and characterising phase change nanodroplets (NDs) and quantifying the effect of changing their composition on imaging.
- Exploring tumour microenvironment features which may provide insight into structural and functional constraints to effective nanomedicine delivery.
Project description/background:
Cancer is among the leading causes of death worldwide. Clinical findings indicate that tumours have variable blood vessel density. This can affect the response to therapies that require the tumour dense vasculature to concentrate in the tumours. Nanomedicine can improve the balance between efficacy and safety of drugs by using drug-loaded nanoparticles specifically targeted to a disease, and is therefore of growing interest for cancer treatment1,2. However, tumour heterogeneity, leads to heterogeneity in treatment effect that can limit its clinical success3. This is caused by a combination of the heterogeneity of the tumour vasculature, and the non-uniform drug distribution which may mean a treatment is ineffective if it is present at insufficient concentrations. There are suggestions to characterise tumours for their suitability for nanomedicine.
USR is a rapidly emerging field in ultrasound (US) imaging due to its ability to image extremely fine details of the blood vessel network, previously unseen with standard US imaging. SR-US maps are created by localizing signals from many individual microbubble (MB) contrast agents 4–6 travelling within the blood stream.
MB imaging methods rely on physiological flow to relocate sparsely distributed MBs inside blood microvessels. This results in long acquisition times (tens of seconds/minutes) to generate a single SR-US image due to slow microvascular flows. This also makes USR susceptible to motion artefacts.
Furthermore, visualisation of complex tumour vasculature requires 3D imaging. Existing 3D SR-US studies 7–10 have demonstrated limitations in resolution and volumetric coverage, while using full 2D array probes produces a huge amount of data (< TB per second) with large computing power required for processing.
Exciting initial work using NDs11,12 has demonstrated huge potential for SR-US since they can be acoustically vapourised and imaged (independent of flow), allowing drastically reduced acquisition times. ND are changing phase when they vaporise and this can be selectively done in the tumour.
This project aims to provide a non-invasive and quantitative means of imaging novel phase change NDs and the 3D tumour environment with a 2D sparse-array probe which could lead to improvements of new nanomedicine, increased understanding of underlying mechanisms of heterogeneous distribution, facilitate patient selection and help assess the effect of treatments that aim to reduce therapy heterogeneity.
Super-resolution ultrasound imaging allows visualisation of vasculature of focal lesion not visible in standard ultrasound imaging.
References
- Shi, J. et al. Nat. Publ. Gr.
- Amrahli, M. et al. 5, (2021)
- Maar, J. S. De et al. 10, 4–10 (2020)
- Cosgrove, D. et al. Eur. J. Nucl. Med. Mol. Imaging 37 Suppl 1, S65-85 (2010)
- Becher, H. et al. (Springer, 2000)
- Pysz, M. A. et al. Invest. Radiol. 46, 187–95 (2011)
- Desailly, Y. et al. Appl. Phys. Lett. 103, (2013)
- Lin, F. et al. Theranostics 7, 196–204 (2017)
- Christensen-Jeffries, K. et al. IEEE Trans. Ultrason. Ferroelectr. Freq. Control 64, 1478–1486 (2017)
- Errico, C. et al. Nature 527, 499–502 (2015)
- Zhang, G. et al. IEEE Trans. Ultrason. Ferroelectr. Freq. Control 66, (2019)
- Zhang, G. et al. Appl. Phys. Lett. 113, 014101 (2018)