Photochemotherapy of rheumatoid arthritis: Modeling and Monte Carlo simulations.

Abstract

A new local treatment of rheumatoid arthritis based on intra-articular photochemotherapy is investigated. In this work, two modalities, PUVA phototherapy at 350 nm, and photodynamic therapy (PDT) at 630 nm are compared. In vitro optical properties of rabbit cartilage and ligament were determined at 442 and 630 nm, and those of normal porcine ligament and cartilage were obtained at 351, 365 nm and in the range 440--650 nm. The diffuse reflectance and the lateral spread of light introduced by a fixed optical fiber were measured to yield the absorption coefficient mu_a [cm<super>-1</super>], and reduced scattering coefficient mu_s<super>'</super> = mu_s(1 -- g) [cm<super>--1</super>]. The Mie theory of light scattering by thin infinitely long cylinders was applied to simulate the mean scattering cosine, g, and mu_s<super> '</super> of cartilage and ligament from 300 to 650 nm. Simulations and experimental data are in good agreement for ligament, while cartilage simulations yielded greater values than experiments. Fibrocartilage data were simulated with Rayleigh scattering. Human fibro-fatty aorta data were used for synovium, due to their pathological similarities. One-dimensional and three-dimensional Monte Carlo codes including optical laws at boundaries were developed. Simulations of benchmark problems for semi-infinite and thin samples were in good agreement with published results. Light distribution in ligament, cartilage, fibrocartilage and synovium was evaluated and compared at 350 and 630 nm, based on a semi-infinite geometry with low optical mismatch. This study shows the advantages of PDT over UVA: red light penetrates in tissue significantly deeper than UVA, as expected from their relative mean free paths; porphyrin's absorption coefficient is larger than that of psoralen, and PDT effectiveness can be judged based on tissue necrosis. A simplified geometric model of the knee was reconstructed including the tibia, femur, patella and cavity walls lined by synovial membrane, after segmentation of a 3D MRI dataset of a cadaver knee dilated for arthroscopy. After visualization in a web-based virtual environment, three possible zones of treatment were observed: a main space in the anterior part of the cavity, and two other smaller volumes located around the posterior condyles. A physical model was built by rapid prototyping.