Development and Application of Fibre-Laser Based Excitation Sources for Biomedical Photoacoustic Imaging

The aim of this research is to develop a range of novel fibre based laser systems for use in a promising new medical and biological imaging technique. The technique, called photoacoustic imaging, works by forming an image from acoustic waves generated by the absorption of pulsed laser light in anatomical structures such as blood vessels. Its key advantage is that it overcomes the limited penetration depth/spatial resolution that purely optical imaging techniques suffer from due to the strong optical scattering exhibited by tissue. At the same time it retains their high contrast and spectral specificity enabling visualisation of anatomical features indistinguishable with other modalities such as ultrasound imaging. Potential clinical applications include imaging breast, oral and skin cancers, cardiovascular disease and skin abnormalities. It can also be used for imaging small animals such as mice which are used extensively in research to study a wide range of human diseases, especially cancer, and evaluate new drugs and other treatments.

Laboratory based photoacoustic scanners have produced exquisite images of tissue structure and function and in doing so excited a great deal of interest in the biomedical imaging community. However, these studies have generally been proof-of-concept experiments aimed at showcasing feasibility rather than addressing a real clinical need or scientific question. The challenge that now lies ahead is to translate the technique to a practical imaging tool that can be used routinely for clinical applications or basic research in the life sciences. However, meeting this challenge is seriously compromised by the limitations of existing lasers used in photoacoustic imaging. These are typically too bulky, unreliable, often require specialist personnel for their operation and provide insufficient control over their temporal output. To overcome these shortcomings, a new generation of tunable excitation laser systems based on fibre laser and OPO technology will be developed and evaluated. This approach offers important advantages over existing photoacoustic excitation laser technology. These include compact size, high reliability and efficiency, high pulse repetition frequencies and the unique ability to arbitrarily modulate the laser output over a wide range of timescales (sub ns-ms). The latter offers the prospect of investigating a wide range of new time and frequency domain excitation methods which can be exploited to optimise SNR and spatial resolution and implement new methods for measuring blood flow.

The project will entail developing a range of tunable laser systems based on novel high energy pulsed fibre lasers and custom designed OPOs. Two systems will be developed. One will be a high energy (mJ) fibre laser pumped OPO with an output in the 650-1050nm spectral range designed for full field photoacoustic tomography. The other will be a lower energy (uJ) system operating in the 450-750nm spectral range and designed to provide a diffraction limited beam for optical resolution photoacoustic microscopy. Both will be table-top, self-contained systems that are roughly the size of a desktop PC allowing them incorporated into a compact portable photoacoustic scanner for practical clinical or preclinical use. An integral part of the project will be the application of the technology. As well as in vivo imaging studies, this will involve developing novel signal processing techniques that exploit the unique diversity of temporal output that fibre lasers support in order to optimise imaging performance and functionality.

By removing the principal technical translational bottleneck in photoacoustic imaging and thereby advancing it to practical application in the clinical and life sciences, this research is expected to have a transformative effect on this rapidly emerging field.

Realising the clinical impact of photoacoustic imaging requires the development of portable, reliable high speed photoacoustic scanners that can be used within a hospital environment. This in turn requires laser sources that are significantly more compact and robust than existing lasers used in photoacoustic imaging. Fibre laser based systems have the potential to meet this need and in doing so could lead to new imaging tools for clinicians that provide improved detection, diagnosis and treatment monitoring of conditions such as breast and skin cancers, atherosclerosis, eye disease and skin abnormalities with consequent healthcare benefits for the patients they treat. Photoacoustic imaging also has significant potential as a preclinical tool for researchers in the life sciences studying the above mentioned conditions both to provide insight into the underlying disease mechanisms and evaluate new drugs and other therapies. By facilitating the development of practical preclinical photoacoustic scanners with improved imaging performance and functionality, the proposed research will both help translate the technique to widespread preclinical use. The laser technology developed within the project may also be applicable to a range of other biomedical applications and thus be of interest to researchers developing multiphoton microscopy and Coherent Anti-Stokes Raman Spectroscopy.

There are also a number of potential non medical applications. The higher pulse energy sources and greater wavelength coverage provided by the frequency conversion modules we develop are likely to be of interest for a range of materials processing applications, including marking, fine surface polishing and fibre drilling amongst others, providing a whole further host of opportunities for new manufacturing processes as well as of course the improvement of existing manufacturing techniques and systems. The fibre laser research also has potential to impact the UK energy theme since nanosecond pulsed fibre lasers are used as precision seed sources to drive the high power laser systems being used to investigate laser driven fusion.

In common with other medical imaging modalities, commercial exploitation of PA imaging is key to making it widely available to end users, achieving widespread uptake and realising its biomedical impact. Effective commercialisation requires lasers sources that are more compact, reliable and user friendly than existing laser technology and fibre lasers offer the prospect of achieving this. By removing the bottleneck that current lasers represent, fibre laser technology could lead to rapid growth in the commercialisation of PA imaging as a pre-clinical imaging tool within 3-5 years ($300m pa global market) and within a decade for clinical use ($10bn global market). Fibre lasers are also displacing the incumbent technology in a diverse range of application sectors, spanning defence, through manufacturing, through medical, to fundamental science and are enjoying an ever increasing share (currently ~10%) of the $8bn/pa global laser market.