Roland Bays

Noninvasive determination of the optical properties of two-layered turbid media

Light propagation in two-layered turbid media having an infinitely thick second layer is investigated in the steady-state, frequency, and time domains. A solution of the diffusion approximation to the transport equation is derived by employing the extrapolated boundary condition. We compare the reflectance calculated from this solution with that computed with Monte Carlo simulations and show good agreement. To investigate if it is possible to determine the optical coefficients of the two layers and the thickness of the first layer, the solution of the diffusion equation is fitted to reflectance data obtained from both the diffusion equation and the Monte Carlo simulations. Although it is found that it is, in principle, possible to derive the optical coefficients of the two layers and the thickness of the first layer, we concentrate on the determination of the optical coefficients, knowing the thickness of the first layer. In the frequency domain, for example, it is shown that it is sufficient to make relative measurements of the phase and the steady-state reflectance at three distances from the illumination point to obtain useful estimates of the optical coefficients. Measurements of the absolute steady-state spatially resolved reflectance performed on two-layered solid phantoms confirm the theoretical results.

Clinical pharmacokinetic studies of photofrin by fluorescence spectroscopy in the oral cavity, the esophagus, and the bronchi

Background. To optimize photodynamic therapy (PDT) and photodetection of cancer, two important variables that must be considered are the uptake of the dye and the dye contrast between normal and neoplastic tissue after injection.

Clinical determination of tissue optical properties by endoscopic spatially resolved reflectometry

A noninvasive method to measure the optical properties of a diffusing and absorbing medium is described. Based on the spatially resolved measurement of diffuse reflectance at the sample surface, this method is particularly suitable for investigating the in vivo optical properties of biological tissues endoscopically in a clinical context. The sensitivity of the measurement is discussed, and two optical probes for two different clinical applications are presented. Preliminary measurements are performed on a nonbiological medium, which illustrate the possibilities of the proposed method. Finally, we report on in vivo measurements of the optical properties of the human esophageal wall at 630 nm.

Three-dimensional optical phantom and its application in photodynamic therapy

A technique to manufacture a stable, reproducible three‐dimensional optical phantom is presented. This phantom reproduces the tissues optical properties as well as the geometry and, to some extent, the mechanical properties of the organ concerned. Easy to make and to handle, this phantom is a useful tool for numerous medical applications involving light interaction with biological tissues.

Light dosimetry for photodynamic therapy in the esophagus

Photodynamic therapy (PDT) is an efficient technique to treat superficial early cancers in the pharynx, esophagus, and tracheo‐bronchial tree. However, the lack of selectivity of some of the clinically used photosensitizers can result in significant damage to the healthy tissue during the treatment. In the esophagus, this may lead to medical complications such as stenosis and fistula. Insufficient selectivity may be compensated to some extent by accurate light dosimetry. Here, we present an approach to safer and more efficient PDT by improved light dosimetry in the esophagus.

Clinical optical dose measurement for PDT: invasive and noninvasive techniques

Two methods for clinical optical light dosimetry are developed. In the first method, which is invasive, a fluorescent probe attached to an optical fiber is inserted by means of a thin hypodermic needle and measures light transmitted through the cheek as a function of the penetration depth. In the second noninvasive method, the diffusely reflected light intensity, from a small illuminated spot on the surface of the tissue to be investigated, is measured as a function of the radial distance along the surface. Preliminary results with both methods are presented. Simulations of the second measurements, which allow for a simplified extraction procedure of the relevant optical data from such measurements, are also shown.

Endoscopic tissue autofluorescence measurements in the upper aerodigestive tract and the bronchi

A single multimode optical fiber is used to excite and collect tissue autofluorescence as well as the fluorescence of an IV-injected fluorescent tumor marker. Measurements of the relative fluorescence intensity of a tumor marker as a function of the time after IV injection permit measurement of the kinetics of this substance in tumor, normal tissue, and skin. The authors believe that these are the first measurements of this kind in patients. Furthermore, the autofluorescence spectrum generated at several excitation wavelengths in different tissues is compared, for instance in the oesophagus, the bronchi, and the tongue. The measuring system is based on an optical multichannel analyzer which measures the fluorescence excited by monochromatic radiation from a spectrally filtered Xe lamp. A correlation between the observed pharmacokinetics and tumor properties like the degree of vascularization is of fundamental importance for each selected tumor marker. Also, the results of these measurements are used for the optical detection of tumors.

Clinical measurements of tissue optical properties in the esophagus

A noninvasive probe has been devised and clinically used to perform in vivo measurements of the optical properties of the esophageal wall. The absorption coefficient and the effective scattering coefficient are determined from the observation of the spatial distribution of the diffuse reflectance at the tissue surface. Results, obtained at 514 and 630 nm, i.e. wavelengths of interest in photodynamic therapy with actual clinically used photosensitizers are summarized. An efficient and easily-built isotropic microprobe is also presented which is suitable to measure in situ the radiant energy fluence rate distribution in tissue.

Clinical LIF pharmacokinetic measurements with Photofrin II for optimizing the photodetection of early cancer

New results are presented on the pharmacokinetics of the fluorescing fraction of Photofrin II in patients with an early cancer in the oesophagus or the buccal cavity. The light-induced fluorescence signal shows a relatively high contrast between tumor and surrounding normal tissue at short times after i.v. injection. The magnitude of this contrast appears to correlate with the staging of the cancer, the more invasive tumors showing the highest contrast. Some early results on the ex vivo fluorescence analysis of biopsies taken on patients injected with the new sensitizer meta-tetra(hydroxyphenyl)chlorin (mTHPC) demonstrate the selectivity of this efficient second generation photosensitizer for advanced lung cancer. mTHPC appears to have good properties for photodetection and has a rather high rate of photobleaching. The significant of the latter is discussed in relation to simplifying light application in PDT.

New distributors for homogeneous and monitorable light delivery in photodynamic therapy

Novel light distributors for interstitial and esophageal photodynamic therapy are presented. A cylindrical light diffuser has been developed mainly for medical applications like interstitial photodynamic therapy, treatment of the bronchi and arterisclerosis. It can be made with a diameter as small as 1 mm or even less. For interstitial therapy, it can be introduced via a hypodermic needle. The main property of this light diffuser is the homogeneity of the light intensity emitted along its whole length which can be 100 mm or more, as well as its excellent radial homogeneity (360 degree(s)) and flexibility. Furthermore, its optical properties are hardly dependent on wavelength used for treatment (500 - 700 nm). Light distributors for esophageal treatment with homogeneity better than +/- 10% have been built and successfully used clinically. A measuring optical fiber allows the control of the dosimetry during the irradiation. Some other properties like the photosensitizer uptake in the tissue or the photobleaching can also be measured in situ and in real time during the treatment.