Frank P. Bolin

Refractive index of some mammalian tissues using a fiber optic cladding method

The index of refraction n of the many mammalian tissues is an important but somewhat neglected optical constant. Archival and oral papers have quoted the use of values of n for tissue generally ranging from 1.35 to 1.55. However, these values are frequently without experimental basis. They have arbitrarily used values near that of water, which is a major component of mammalian tissue, or have calculated a theoretical n from the weighted elemental composition of tissue. Since these values have not been precise and little information is available on specific indices for each tissue, a study was undertaken to develop a simple, rapid, and reliable method for the experimental determination of n. This was done using the ubiquitous quartz optical fiber. By substituting the usual cladding found on commercial quartz optics by the tissue in question and utilizing the principle of internal reflection, the value of n for the specific tissue can be calculated. This is done by utilizing the known indices for air and quartz and measuring the angle of the emergent cone of light from the output of the optical fiber. A number of indices for mammalian tissue (bovine, porcine, canine, and human) have been determined at 632.8 nm. With few exceptions, for tissues at this wavelength, n was in the 1.38-1.41 range. The species type did not appear to be a factor. Bovine muscle showed normal dispersion characteristics through the visible wavelengths. The denaturation of tissue was shown to alter significantly the refractive index.

OPTIMIZATION OF PHOTODYNAMIC THERAPY LIGHT DOSE DISTRIBUTION and TREATMENT VOLUME BY MULTI‐FIBER INSERTIONS*

Abstract The development of a methodology which optimizes the light dosage in tissue and improves the tailoring of the light with consequent sparing of normal adjacent tissue, will enhance the possibility for routine clinical photodynamic therapy. Specific, important goals for the clinical use of PDT are (a) efficient distribution of light flux to all parts of the tumor at sufficient level to effect eradication. (b) avoidance of the destruction of adjacent normal tissue, and (c) ability to tailor the treatment field, taking into account the varied shapes of tumors. Dividing the available power among several fibers is a promising method of achieving these goals. This is accomplished by (1) extending the volume, and by (2) increasing the flux spatial uniformity. This latter defocussing of the flux field is especially important because it may help to avoid concentrating a high intensity field from an implanted fiber near an essential structure of the normal tissue. The question arises how best to orient these multiple fibers for maximum coverage and uniformity. Hence, theoretical and experimental investigations were made to determine optimal fiber placements. A series of intensity distributions were generated using two and three fibers positioned at various separations within a postulated tumor volume. A criterion for uniformity was defined. Iterative computation produced optimal fiber separation for the given constraints. In the two fiber case, for small values of attenuation coefficient (μ. ≦ 0.2 mm−1), optimal fiber separation ranged from 0.6 to 0.7 times the diameter of the defined volume. For large values of attenuation coefficient (μ. ≧ 0.8), fiber separation was about 0.5 to 0.55 times the region diameter. The effects of fiber separation on volume of treatment were also determined. Maximal treatment volume was found to be dependent on the attenuation coefficient. With μ, = 0.50, a 40% increase in treatment volume over single fiber insertion of equivalent energy input was shown to be obtainable with a dual fiber configuration of 24 mm separation. Experiments using two fibers in vitro in mammalian tissue were performed to substantiate these results. The multiple fiber system is a promising method for delivering optimum light dosage to targeted PDT tissue.

Photodynamic therapy in prostate cancer: optical dosimetry and response of normal tissue

The present study explores the possibility of utilizing photodynamic therapy (PDT) in treating localized prostate carcinoma. Optical properties of ex vivo human prostatectomy specimens, and in vivo and ex vivo dog prostate glands were studied. The size of the PDT induced lesion in dog prostate was pathologically evaluated as a biological endpoint. The data indicate that the human normal and carcinoma prostate tissues have similar optical properties. The average effective attenuation depth is less in vivo than that of ex vivo. The PDT treatment generated a lesion size of up to 16 mm in diameter. The data suggest that PDT is a promising modality in prostate cancer treatment. Multiple fiber system may be required for clinical treatment.

A study of the three-dimensional distribution of light (632.8 nm) in tissue

Effective application of photodynamic therapy requires that light dose to tissue be accurately calculated. Special fiber optic detectors have been constructed, and experimental methods developed, for determining three-dimensional flux patterns of red light instilled into tissue. These methods utilize the insertion and movement of the detecting fibers along fixed coordinates within tissue, and the measurement of light flux values at these positions. Resulting values of bovine skeletal muscle have been interpolated and mapped into two-dimensional graphical patterns. Combinations of two-dimensional patterns allow a reconstruction in three dimensions. Either calculation or geometric construction provides penetration depths. Light dispersion is spherically symmetrical, as predicted by diffusion theory. Penetration depths for bovine muscle ranged from 1.8 to 2.3 mm. Three theoretical formulations were fit to the experimental data and were found to be equally valid at depth.

A dual beam study with isotopic X- and gamma-rays for in vivo lymph pool assay

Abstract Dual beam absorptiometry utilizes differential absorption of X- and gamma rays of differing energy to determine an absorbers component ratio. This principle has been applied to diverse physical and biological problems. Our method, using the 22 and 88 keV emissions from 109 Cd, resolves the lean and non-lean mammalian tissue fractions. Accuracy of 1%, and reproducibility of 1–2% is attainable in in vitro measurements. Techniques have been developed to apply this system to the more complicated applications involved in human studies. A scanning device capable of measuring limbs has been developed. Mathematical treatment provides an integrated value of lean fraction over the scanned area. Lymphedema is a painful malady in which blockage of lymph flow causes swelling and distension of the extremities. Compressive therapy is the preferred medical treatment. There has been no accurate quantitative index of the efficacy of this therapy. Our research program uses dual beam analysis as a unique quantitative measure of the lymph transport. Lymph pool change is equated to change in the lean. Five measurements are made on subjects undergoing a two week regimen of compressive therapy. These absorptiometric results are analyzed for correlation to other indices of treatment effect. Data shows a progressive decrease in the lean tissue component over the treatment period. Changes seen vary with the individual and the severity of involvement. This study showed that the largest transport rate occurs in the first treatment days. Absorptiometry accurately monitors total adipose mass, total non-adipose mass, extremely cross section, and change in lymph pooling.