Optoacoustic Imaging

Optoacoustic imaging harnesses the optoacoustic effect, whereby absorption of pulsed laser light gives rise to thermoelastic expansion, producing a broadband ultrasound wave. Reconstructing these sound waves produces images of the absorbed optical energy density, combining the high contrast of optical imaging with the high spatial resolution and penetration depths of ultrasound. The optoacoustic effect can be generated using both endogenous and exogenous molecules. Moreover, the hybrid nature of optoacoustic imaging means it is possible to implement at multiple length scales, from microscopy, to small animal imaging, through to the clinic. This level of flexibility and scalability in terms of instrumentation for a single contrast mechanism is unprecedented. Optoacoustic imaging provides a unique opportunity to link microscopy studies in single cells to preclinical studies in small animals and connect these results with clinical practice.

Optoacoustic imaging has advanced rapidly in the past decade and a wide range of applications in cancer imaging are now possible, from characterisation of the tumour microenvironment and biopsy guidance at diagnosis, through to therapy monitoring. Our work will complement existing programmes at other Comprehensive Cancer Imaging Centres, including the preclinical optoacoustic research at University College London and the clinical instrumentation development at the Institute of Cancer Research, and will focus on the assessment of tumour hypoxia in preclinical models using functional optoacoustic imaging, subsequent translation to the clinic and the development of an optoacoustic imaging contrast agent targeted to cell death.

Blood haemoglobin oxygenation image acquired using MultiSpectral Optoacoustic Tomography (MSOT). MSOT excites the distinct optical absorption profile of haemoglobin using a pulsed multi wavelength laser source and detects the acoustic wave resulting from the transient expansion of the tissue. MSOT is an emerging tool for clinical imaging that is low cost and does not require injected contrast. Scale bar 5mm. (Unpublished data).

Further work is still required to establish the technique for pre-clinical studies of cancer biology as well as for clinical cancer imaging. Within our Cancer Imaging Centre, two key applications will be developed. Firstly, using pre-clinical models, the technique will be applied to the quantitative assessment of tumour hypoxia and compared with both oxygen-enhanced MRI and gold-standard histological methods. Secondly, we will develop a targeted optoacoustic contrast agent to detect treatment response by providing a sensitive readout of tumour cell death.

The strong optical absorption of haemoglobin enables visualisation of tumour vasculature in optoacoustic imaging with exquisite anatomical resolution. Taking this one step further, we are using MultiSpectral Optoacoustic Tomography (MSOT) to enable quantification of the major blood chromophores, oxyhaemoglobin and deoxyhaemoglobin, based on their markedly different absorption spectra. MSOT acquires optoacoustic data at multiple wavelengths, which allows functional parametric maps of oxygen saturation and total haemoglobin concentration to be reconstructed. Based on the emerging literature in this area, we will implement our data handling on a GPU to enable high-speed imaging. We will also develop segmentation algorithms to allow specific analysis of tumour vasculature and oxygen saturation compared to surrounding tissue. These methods will then be translated into a clinical study of hypoxia in breast cancer.

By tuning the wavelength of the contrast agent to absorb in the near-infrared, it is possible using multi-wavelength imaging to simultaneously resolve signals from both the optoacoustic molecular imaging agent and endogenous chromophores. Previous studies using near-infrared imaging have already demonstrated the utility of an agent known as C2Am-AF750 for detecting cell death in tumour-bearing mice. AF750 displays favourable properties for optoacoustic imaging and has already been demonstrated in vivo. We will evaluate C2Am-AF750 as an optoacoustic imaging probe of tumour cell death. Optoacoustic imaging will provide high-resolution maps of the binding of this agent in tumours, which has not been possible with the optical and SPECT imaging employed previously. We will also test alternative near-infrared dyes that give higher optoacoustic signal and better spectral separation from endogenous chromophores, in order to maximize contrast. We will then explore activatable approaches to enable a positive readout of tumour cell death following treatment, without the confounding issues of probe delivery and clearance.

Dr Sarah Bohndiek

Leader of the Imaging Oxygen and Oxidative Stress group at the University of Cambridge.

Professor Kevin Brindle

Chair in Biomedical Magnetic Resonance at the University of Cambridge.

Professor Fiona Gilbert

Consultant Radiologist at Cambridge University Hospitals NHS Foundation Trust.

Dr James O'Connor

Cancer Research UK Clinician Scientist Fellow at The University of Manchester and Honorary Consultant Radiologist at The Christie NHS Foundation Trust.