What is optical or photo diagnostics?

This short article has been written as a brief overview of the field of optical or photodiagnostics, with a focus on cancer detection. There are a number of competing or complimentary techniques currently being investigated. These include fluorescence, Raman and infrared spectroscopies, elastic scattering and diffuse reflectance spectroscopy. They each have their pros and cons and depending on the application some may be selected above others.

The primary requirement for successful treatment of any malignancy is early detection. Although the pathogenesis of most malignancies is not fully understood, some cancers are known to develop through a pre-malignant state. Current methods of detecting early malignancies rely upon surveillance of at risk populations or diagnostic investigations following presentation with suspicious symptoms. By the time symptoms are present tumours are usually of a significant size, and it is often too late to facilitate a full cure.

Biochemical changes within tissue may either initiate disease or occur as the result of the disease process. The qualitative analysis of such changes provides important clues in the search for a specific diagnosis. Quantitative analysis of biochemical abnormalities is important in measuring the extent of the disease process, designing therapy and evaluating the efficacy of treatment. The conventional method for detection of malignancy is histopathological examination of biopsy samples. This relies upon the subjective assessment of tissue architecture, which is likely to demonstrate abnormal changes at a later stage than analysis of biochemistry. Furthermore, histopathological analysis requires tissue to be removed with possibly undesirable consequences. Evidently, the development of a rapid, non-invasive, qualitative histochemical analysis technique, enabling objective biochemical analysis of tissue, would be of great value. This may be possible with a variety of optical techniques.

Over the past few years a number of groups have been working towards real-time, non-invasive techniques that utilise light to study abnormalities in tissue. Recent technological developments have made it possible to obtain significant amounts of biochemical or architectural data from extremely complex biological tissue in very short time scales (milliseconds to seconds). Optical diagnosis relies upon measurement of the interaction of light with the constituents of biological tissue. The resultant data can provide an evaluation of histochemistry or morphology. This information can aid with the deduction of the pathological state of the tissue, and hence lead to a diagnosis.

Light can interact with tissue in a number of ways, including elastic and inelastic scattering; reflection off boundary layers; and absorption, leading to fluorescence and phosphorescence. All of these can be utilised in some way to measure abnormal changes in tissue. Many authors have used the term ‘Optical Biopsy’ when describing these techniques. Optical biopsy is a misnomer because no tissue is removed in the analysis, however it does help to convey to the lay-person the general principle of using light to detect cancerous transformations in tissue.

Initial optical biopsy systems, utilising tissue fluorescence, have been used as an adjunct to current investigative techniques, mainly to improve targeting of blind biopsy. Future prospects utilising molecular-specific techniques may enable complete replacement of biopsy with objective optical detection providing a real-time, highly sensitive and specific measurement of the tissue histological state. However until its efficacy is proven it is most likely that optical detection will be used as a complimentary technique to improve targeting of biopsy selection.

The clinical requirements for an objective, non-invasive real time probe for the accurate and repeatable measurement of tissue pathological states are overwhelming. There is a clinical need for optical diagnosis in a number of important areas:

Techniques such as Raman spectroscopy (RS) and Fourier-Transform Infra-red absorption spectroscopy (FTIR) have recently provided evidence of discrimination between multiple pathology groups within each organ. Raman spectroscopy, which can be performed endoscopically at any excitation wavelength, is most likely to provide in vivo diagnosis. FTIR currently shows the greatest promise for rapid in vitro diagnosis and spectral imaging, where water content of tissues does not prove problematic.

Other techniques such as optical coherence tomography and optoacoustic imaging are demonstrating potential for high spatial resolution in vivo imaging which may one day provide similar information to histology, although in real time. Whereas imaging techniques are always eye-catching, it should be noted that these techniques still provide information only about structure and cellular morphology. To provide real information about early molecular changes and disease prognosis those techniques that provide extra-value information on tissue biochemistry associated with disease will be the way forward.

A number of recent reviews on this area have been published. These include: -