Combined functional MRI and super-resolution ultrasound for non-invasive monitoring of tumour blood delivery during breast cancer radiotherapy.
Prof M Tang
Dr N Somaiah
Dr M Blackledge
Friday, November 22, 2019
Funded PhD Project (European/UK Students Only)
Combined super-resolution ultrasound and functional MRI for non-invasive monitoring of tumour blood delivery during breast cancer radiotherapy.
Success of targeted radiotherapy (RT) is strongly related to oxygenation levels within tumour tissues. Poor oxygen status (hypoxia) is associated with resistance to RT, and is linked to the chaotic capillary architecture observed within tumours as they grow uncontrollably; such disordered angiogenesis is one of the key hallmarks of cancer. As RT technology has improved, highly conformal radiation delivery has become possible, and may allow increased healthy-tissue sparing and higher therapeutic ratios. However, in order to achieve maximum benefit from these technologies it is essential that accurate, non-invasive image monitoring techniques be developed that can (i) spatially map the biology of the tumour (including hypoxic status) in order to boost the therapeutic dose to more aggressive regions, and (ii) quantify tumour response during treatment so that RT plans can be adapted appropriately.
Dynamic contrast-enhanced (DCE-), and diffusion-weighted (DW-) MRI provide non-invasive mapping of the properties of tumour vasculature and cellularity respectively. Both techniques have shown considerable power as response biomarkers for a wide variety of tumour types and therapeutic interventions, and there is increasing hope that these techniques might provide potent biomarkers of response for RT. Although MRI provides excellent anatomical coverage within a clinically feasible time-frame, it still suffers from (i) a relatively low spatial resolution (order of millimetres), (ii) increasing safety concerns on the use of Gadolinium contrast agents used in DCE studies, and (iii) lack of validation of MR-derived biomarkers, which only act as surrogate measures of the underlying biology that occurs at much smaller length-scales. Contrast-enhanced ultrasound (CEUS) imaging employs intravenously administered microbubbles that enhance ultrasound signals by two or more orders of magnitude within blood vessels. By pinpointing individual microbubbles and tracking their paths over time, SRUS allows us to characterise the structure and dynamics of the tumour microvascular system with much higher spatial resolutions than available using clinical systems such as MRI.
The convergent solution
We propose to combine a recent breakthrough in medical ultrasound imaging, super-resolution ultrasound (SRUS) pioneered at ICL and Kings College London, with clinical functional MRI to monitor RT response at multiple spatial (~20 microns to tens of centimetres) and temporal (sub-millisecond to tens of seconds) scales. We will validate these images with histopathological findings in breast cancer and identify the most relevant image features and imaging approach for adaptive and personalised RT therapy.
Keywords /Subject Areas
1. Quantitative Imaging Biomarkers
2. Super-Resolution Ultrasound
3. Breast Cancer Radiotherapy
4. Therapy Response Monitoring
5. Multi-Parametric MRI
6. Functional Image Modelling
Convergence Science PhDs cover tuition fees for UK/EU students only