The goal of this EU FP7 project is the development of a novel multimodal hybrid technology and the construction of a sophisticated non-invasive clinical image tool which combines ultrasound and optical features as well as quantitative technologies to visualize, to image and to detect cancerous tissue and intratissue cancer cells in skin. Our role at Imperial is to develop and apply multiphoton multispectral FLIM microscopy and acoustic imaging technology to the diagnosis of skin cancer.
The incidence of skin cancer in Europe, US, and Australia is rising rapidly. The World Health Organization estimates that skin cancer accounts for one in three cancers worldwide. Melanoma is the skin cancer with the greatest mortality. It is the second most common cancer in young adults (aged 15-34) and twice as common in women in this age group. In the UK, its incidence has risen faster than any other common cancer, quadrupling over the last thirty years. It is estimated that in excess of 80% of skin cancers are caused by the ultraviolet light in sunlight. The use of sunbeds doubles the risk of developing melanoma. Actinic keratosis is a UV induced intraepidermal neoplasia which affects millions of Europeans. Although the prevalence is as high as 25% in Caucasian populations above the age of 60, lesions have a low risk (<0.1%) of transforming into an aggressive invasive squamous cell carcinoma.
The 5 year survival rate for people with skin cancers significantly improves if detected and treated early. However, most medical doctors are still using visual inspection as the only diagnostic method of skin cancer. If suspicious, biopsies are taken invasively from which histological sections are prepared, then stained, and finally analyzed by pathologists with visual inspection under a light microscope. Several 10,000 biopsies are investigated annually in a typical hospital. The direct annual costs of diagnosis and treatment of skin cancer are several billion Euro.
A significant improvement of the current diagnostic tools of dermatologists is required in order to identify dermal disorders at a very early stage as well as to monitor directly the effects of treatment. A first step in this direction was achieved with the introduction of dermoscopy based on digital 2D images using CCD cameras. However, this technology does not provide 3D information and only a relatively low resolution. Furthermore, it is very difficult to distinguish between some innocuous or premalignant conditions (such as ‘dysplastic’ naevi or actinic keratosis) and malignant counterparts.
Non-invasive high-resolution imaging systems with the capability to gain additional information from inside the skin have significant potential to address these problems. Several types of 3D imaging have been proposed for skin diagnosis out of which optical methods and acoustic methods appear to be the most promising. A recent development in high resolution in vivo 3D skin imaging is clinical two-photon tomography, which is able to inspect small sub-mm3 volumes of skin. Currently, the most widely used clinical wide-field 3D imaging tool is based on ultrasound. However, clinical devices lack sufficient resolution to monitor intratissue cancer cell clusters or to provide spectroscopic information. This can be addressed by optoacoustic imaging based on localized near infrared tissue excitation and the generation of ultrasound waves, which can, in principle, provide information on vascularization and melanin content. However, no commercial clinical optoacoustical system exists.
Within this project, we aim to develop a non-invasive multimodal hybrid imaging system with the capability to perform non-invasive high resolution three-dimensional clinical imaging using the following modalities:
(i) Multispectral time-resolved two-photon imaging with time-correlated single photon detection
(ii) autofluorescence lifetime imaging
(iii) high-frequency acoustical imaging with novel miniaturized multiple detector arrays
(iv) optoacoustical imaging using ultrashort near infrared (NIR) laser pulses.
This novel multimodal approach will provide a wide-field “acoustic/optoacoustic” view with depth information of the dermatological lesion as well as a close “optical” look into particular intratissue compartments with subcellular resolution. The user of the novel clinical multimodal apparatus will be able to switch from “low” resolution acoustic to “high” resolution two-photon imaging. In addition, fluorescence lifetime imaging will be implemented to obtain a further method of contrast enhancement, to distinguish between different fluorescent biomolecules and to provide a method of signal quantification by time-correlated single photon counting with picosecond temporal resolution.
For more information, please see the SKINSPECTION project website.