Over the years my research activities have been centered around development and clinical implementation of optical methods for minimally invasive diagnosis and treatment of disease. The work comprises the entire track from basic research and development of methodology to clinical validation and implementation.

The optical diagnostic techniques I have been using have changed over the years. Initially work was focussed around imaging and spectroscopy of autofluorescence and fluorescent contrast agents. In later years the emphasis moved to diffuse reflection spectroscopy and nonlinear optical spectroscopy and imaging. My current research focus lies entirely on elastic scattering spectroscopy and imaging.

Elastic Scattering Spectroscopy uses broadband white light and guides it to the tissue through optical fibers. Light entering the tissue will be scattered around before it is being absorbed, or leaves the tissue at the surface. This backscattered light is detected with an optical fiber and then analysed by a spectrograph. Current research activities have been focussed at development of quantitative approaches, i.e. methods to measure the scattering and absorption spectra quantitatively. So far I developed methods to measure absorption quantitatively, translate these into biologically related parameters and evaluated these extensively in clinical studies. Current focus is on developing methods for quantitative scattering information. Here both the absolute amount of scattering is of interest, but also the relation between forward and backward scattering is of particular interest because it is thought to be sensitive to intracellular biology. Light scattering occurs due to spatial variations in refractive index. Based on analysis of the wavelength dependence of scattering observed in measurements of tissue it can be concluded that the size of these scattering entities lies well below the resolution of an optical microscope (i.e. 100nm). Other types of microscopes can visualize much smaller structures, but do not do so on the basis of the refractive index. Hence the nature of these scattering entities is not known, but it is speculated that they relate to aspects of the cellular microarchitecture, such as folds in mitochondrial membranes, the presence and distribution of endosomes etc. At present I am focussing on measurement forward-to-backward ratio of scattering in vivo. This uses different fiber diameters and will shortly be tested clinically for screening of Barrett’s esophagus, prostate cancer and for diagnosing mediastinal lymph nodes. In addition, a setup is being developed to measure the angular dependence of back scattering on ex vivo samples.