Clinical imaging fluorescence apparatus for the endoscopic photodetection of early cancers by use of Photofrin II.

A fluorescence imaging device applied to the detection of early cancer is described. The apparatus is based on the imaging of laser-induced fluorescence of a dye that localizes in a tumor with a higher concentration than in the surrounding normal tissue after iv injection. Tests carried out in the upper aerodigestive tract, the tracheobronchial tree, and the esophagus with Photofrin II (1 mg/kg of body weight) as the fluorescent agent are reported as examples. The fluorescence is induced by violet (410-nm) light from a continuous-wave (cw) krypton-ion laser. The fluorescence contrast between tumor and surrounding tissue is enhanced by real-time image processing. This is done by the simultaneous recording of the fluorescence image in two spectral domains (470-600 and 600-720 nm), after which these two images are digitized and manipulated with a mathematical operator (look-up table) at video frequency. Among the 7 photodetections performed in the tracheobronchial tree, 6 were successful, whereas it was the case for only 5 of the 15 lesions investigated in squamous mucosa (upper aerodigestive tract and esophagus). The sources of false positives and false negatives are evaluated in terms of the fluorescent dye, tissue optical properties, and illumination optics.

Optimizing light dosimetry in photodynamic therapy of early stage carcinomas of the esophagus using fluorescence spectroscopy.

BACKGROUND AND OBJECTIVE: Under standardized conditions (drug and light dose, timing), the result of the photodynamic therapy (PDT) of carcinomas of the esophagus with tetra(meta-hydroxyphenyl)chlorin (mTHPC) shows large variations between patients. STUDY DESIGN/MATERIALS AND METHODS: Before patients underwent PDT treatment, the mTHPC level was measured in the lesion, the normal surrounding tissue, and the oral cavity, with an apparatus based on fluorescence spectroscopy. RESULTS: The fluctuations in degree of tumor destruction between patients can be explained by individual variations in the mTHPC level in the mucosa of the esophagus. The patients showing the highest mTHPC fluorescence signal had also the highest response to PDT. Also, a correlation between the mTHPC level in the oral cavity and esophagus mucosa has been found. CONCLUSION: PDT can be improved by measuring the mTHPC level in the esophagus or the oral cavity before treatment by fluorescence spectroscopy, and then by adjusting the light dose to be applied to the observed mTHPC level.

Cylindrical fiberoptic light diffuser for medical applications.

BACKGROUND AND OBJECTIVE: A cylindrical light diffuser has been developed mainly for medical applications, including photodynamic therapy (PDT), in particular interstitial PDT, PDT of the bronchi, or intravascular PDT. STUDY DESIGN/MATERIALS AND METHODS: The diffuser is based on a polymer optical fiber. The coupling of the light out of the core is controlled by the roughness mechanically induced on the surface of the core. The light is then isotropically diffused by a thin layer of a scattering medium. The active length can be 100 mm or more, whereas the outer diameter is 1 mm or less. The diffuser is flexible and can be introduced in tissue though a hypodermic needle. RESULTS: The main property of this light diffuser is the homogeneity of the light intensity emitted along its whole active length and around its circumference (360 degrees). Various intensity profiles can be made, including M-shape profiles for a homogeneous irradiance (+/- 10%) at a certain depth in the tissue. Furthermore, the diffuser is essentially isotropic and its optical properties are hardly dependent on wavelength. CONCLUSIONS: A diffuser for interstitial and intraluminal PDT has been developed. It is flexible, homogeneous, independent on wavelength, and can be made with a very high length-to-diameter ratio.

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. METHODS: To study these variables in a clinical context, an apparatus based on a noninvasive optical fiber that detects the dye by light-induced fluorescence (LIF) was constructed. RESULTS: Studies on the pharmacokinetics of the fluorescent fraction of Photofrin in patients with early squamous cell carcinoma in the oral cavity, esophagus or bronchi show a signal contrast ranging from 1.5 to 3.5 a short time after intravenous injection that rapidly decreases and tends to unity (one) about 12 hours later. The magnitude of this contrast appears to correlate with the staging of the cancer, the more invasive tumors showing the highest contrast. The more invasive tumors also show the highest uptake. The oral cavity pharmacokinetics are similar to those found in the esophagus and the bronchi. CONCLUSIONS: The oral cavity appears to be a good model, with easy access for optimizing photodetection and PDT in the esophagus and the bronchi. These pharmacokinetics can be used directly for optimizing photodetection. However, complementary information on the detailed localization of the drug by fluorescence microscopy and a correlation of these data with tumor necrosis efficacy are necessary to optimize PDT timing and therapeutic gain.