Clinical multi-color fluorescence imaging of malignant tumors— initial experience—review article

Purpose: The detection of malignant tumors relies on a variety of diagnostic procedures including X-ray images and, for hollow organs, endoscopy. The purpose of this study was to present a new technique for noninvasive tumor detection based on tissue fluorescence imaging. Material and Methods: A clinically adapted multi-color fluorescence system was employed in the real-time imaging of malignant tumors of the skin, breast, head and neck region, and urinary bladder. Tumor detection was based on the contrast displayed in fluorescence between normal and malignant tissue, related to the selective uptake of tumor-making agents, such as hematoporphyrin derivative (HPD) and δ-amino levulinic acid (ALA), and natural chromophore differences between various tissues. In order to demarcate basal cell carcinomas of the skin, ALA was applied topically 4–6 hours before the fluorescence investigation. For urinary bladder tumor visualization (transitional cell carcinoma of different stages including carcinoma in situ), ALA was instilled into the bladder 1–2 hours prior to the study. Malignant and premalignant lesions in the head and neck region were imaged after i.v. injection of HPD (Photofrin). Finally, the extent of in situ and invasive carcinomas of the breast was investigated in surgically excised specimens from patients that received a low-dose injection of HPD 24 hours prior to the study. The tumor imaging system was coupled to an endoscope. Fluorescence light emission from the tissue surface was induced with 100-ns-long optical pulses at 390 nm, generated from a frequency-doubled alexandrite laser. With the use of special image-splitting optics, the tumor fluorescence, intensified in a micro-channel plate, was imaged in three selected wavelength bands. These three images were processed together to form a new optimized-contrast image of the tumor. This image, updated at a rate of about three frames/s, was mixed with a normal color video image of the tissue. Results: A clear demarcation from normal surrounding tissue was found during in vivo measurements of superficial bladder carcinoma, basal cell carcinoma of the skin, and leukoplakia with dysplasia of the lip, and in in vitro investigations of resected breast cancer. Conclusion: The initial clinical experience of using multi-color fluorescence imaging has shown that the technique has the potential to reveal malignant tumor tissue, including noninvasive early carcinoma and also precancerous tissue. Further investigations are needed to fully develop the method.