The known optical properties (absorption, scattering, total attenuation, effective attenuation, and/or anisotropy coefficients) of various biological tissues at a variety of wavelengths are reviewed. The theoretical foundations for most experimental approaches are outlined. Relations between Kubelka-Munk parameters and transport coefficients are listed. The optical properties of aorta, liver, and muscle at 633 nm are discussed in detail. An extensive bibliography is provided. >

A review of the optical properties of biological tissues

Two-photon absorption has important advantages over conventional one-photon absorption, which has led to applications in microscopy, microfabrication, three-dimensional data storage, optical power limiting, up-converted lasing, photodynamic therapy, and for the localized release of bio-active species. These applications have generated a demand for new dyes with high two-photon absorption cross-sections. This Review introduces the theory of two-photon absorption, surveys the wide range of potential applications, and highlights emerging structure-property correlations that can serve as guidelines for the development of efficient two-photon dyes.

Two-photon absorption and the design of two-photon dyes.

The tissue photosensitizer protoporphyrin IX (PpIX) is an immediate precursor of heme in the biosynthetic pathway for heme. In certain types of cells and tissues, the rate of synthesis of PpIX is determined by the rate of synthesis of 5-aminolevulinic acid (ALA), which in turn is regulated via a feedback control mechanism governed by the concentration of free heme. The presence of exogenous ALA bypasses the feedback control, and thus may induce the intracellular accumulation of photosensitizing concentrations of PpIX. However, this occurs only in certain types of cells and tissues. The resulting tissue-specific photosensitization provides a basis for using ALA-induced PpIX for photodynamic therapy. The topical application of ALA to certain malignant and non-malignant lesions of the skin can induce a clinically useful degree of lesion-specific photosensitization. Superficial basal cell carcinomas showed a complete response rate of approximately 79% following a single exposure to light. Recent preclinical studies in experimental animals and human volunteers indicate that ALA can induce a localized tissue-specific photosensitization if administered by intradermal injection. A generalized but still quite tissue-specific photosensitization may be induced if ALA is administered by either subcutaneous or intraperitoneal injection or by mouth. This opens the possibility of using ALA-induced PpIX to treat tumors that are too thick or that lie too deep to be accessible to either topical or locally injected ALA.

Endogenous protoporphyrin IX, a clinically useful photosensitizer for photodynamic therapy.

BACKGROUND
Photodynamic therapy (PDT) for cancer patients has developed into an important new clinical treatment modality in the past 25 years PDT involves administration of a tumor-localizing photosensitizer or photosensitizer prodrug (5-aminolevulinic acid [ALA], a precursor in the heme biosynthetic pathway) and the subsequent activation of the photosensitizer by light Although several photosensitizers other than ALA-derived protoporphyrin IX (PpIX) have been used in clinical PDT, ALA-based PDT has been the most active area of clinical PDT research during the past 5 years Studies have shown that a higher accumulation of ALA-derived PpIX in rapidly proliferating cells may provide a biologic rationale for clinical use of ALA-based PDT and diagnosis However, no review updating the clinical data has appeared so far

METHODS
A review of recently published data on clinical ALA-based PDT and diagnosis was conducted

RESULTS
Several individual studies in which patients with primary nonmelanoma cutaneous tumors received topical ALA-based PDT have reported promising results, including outstanding cosmetic results However, the modality with present protocols does not, in general, appear to be superior to conventional therapies with respect to initial complete response rates and long term recurrence rates, particularly in the treatment of nodular skin tumors Topical ALA-PDT does have the following advantages over conventional treatments: it is noninvasive; it produces excellent cosmetic results; it is well tolerated by patients; it can be used to treat multiple superficial lesions in short treatment sessions; it can be applied to patients who refuse surgery or have pacemakers and bleeding tendency; it can be used to treat lesions in specific locations, such as the oral mucosa or the genital area; it can be used as a palliative treatment; and it can be applied repeatedly without cumulative toxicity Topical ALA-PDT also has potential as a treatment for nonneoplastic skin diseases Systemic administration of ALA does not seem to be severely toxic, but the advantage of using this approach for PDT of superficial lesions of internal hollow organs is still uncertain The ALA-derived porphyrin fluorescence technique would be useful in the diagnosis of superficial lesions of internal hollow organs

CONCLUSIONS
Promising results of ALA-based clinical PDT and diagnosis have been obtained The modality has advantages over conventional treatments However, some improvements need to be made, such as optimization of parameters of ALA-based PDT and diagnosis; increased tumor selectivity of ALA-derived PpIX; better understanding of light distribution in tissue; improvement of light dosimetry procedure; and development of simpler, cheaper, and more efficient light delivery systems Cancer 1997; 79:2282-308 © 1997 American Cancer Society

5-Aminolevulinic acid-based photodynamic therapy. Clinical research and future challenges.

Knowledge about the optical properties μa,μs, and g of human blood plays an important role for many diagnostic and therapeutic applications in laser medicine and medical diagnostics. They strongly depend on physiological parameters such as oxygen saturation, osmolarity, flow conditions, haematocrit, etc. The integrating sphere technique and inverse Monte Carlo simulations were applied to measure μa,μs, and g of circulating human blood. At 633 nm the optical properties of human blood with a haematocrit of 10% and an oxygen saturation of 98% were found to be 0.210±0.002 mm-1 for μa,77.3±0.5 mm-1 for μs, and 0.994±0.001 for the g factor. An increase of the haematocrit up to 50% lead to a linear increase of absorption and reduced scattering. Variations in osmolarity and wall shear rate led to changes of all three parameters while variations in the oxygen saturation only led to a significant change of the absorption coefficient. A spectrum of all three parameters was measured in the wavelength range 400-2500 nm for oxygenated and deoxygenated blood, showing that blood absorption followed the absorption behavior of haemoglobin and water. The scattering coefficient decreased for wavelengths above 500 nm with approximately λ-1.7; the g factor was higher than 0.9 over the whole wavelength range. © 1999 Society of Photo-Optical Instrumentation Engineers.

https://www.spiedigitallibrary.org/journals/Journal-of-Biomedical-Optics/volume-4/issue-01/0000/Optical-properties-of-circulating-human-blood-in-the-wavelength-range/10.1117/1.429919.pdf

Optical Properties of Circulating Human Blood in the Wavelength Range 400-2500 nm.

Optical properties of different human tissues in vitro have been evaluated by measuring extinction and absorption coefficients at 635- and 515-nm wavelengths and a scattering angular dependence at 635 nm. Extinction was determined by the on-axis attenuation of light transmitted through sliced specimens of various thicknesses. The absorption coefficient was determined by placing samples into an integrating sphere. The Henyey-Greenstein function was used for fitting experimental data of the scattering pattern. The purpose of this work was to contribute to the study of light propagation in mammalian tissues. The results show that, for the investigated tissues, extinction coefficients range from ~200 to 500 cm(-1) whereas absorption coefficients, depending on wavelength, vary from 0.2 to 25 cm(-1). Scattering is forward peaked with an average cosine of ~0.7.

Extinction and absorption coefficients and scattering phase functions of human tissues in vitro

Few data are available about temperature distribution in tissue during Nd:YAG laser irradiation To study the heat distribution that produces tissue coagulation, we used a thermographic camera aimed orthogonally to the laser beam axis to obtain thermal maps Immediately after surgical resection, specimens of human stomach were irradiated near the resected edge, and the heat emitted sideways was detected by an infrared image system A magnifying lens mounted on the camera enabled us to obtain 01 mm spatial resolution of the isothermic curves The thermal analysis showed that the maximum depth where the increase in temperature reached 25 degrees C (corresponding to a coagulation temperature of about 60 degrees C) was never greater than 3 mm, irrespective of the power and exposure time used Moreover, the bidimensional thermal maps showed that the temperature did not decrease in a purely exponential fashion along the beam axis, but reached a maximum at about 1 mm beneath the surface This fact, which confirms the decrepitation theorem, could explain the explosion inside the tissues observed in surgical application of the Nd:YAG laser

Temperature rise in biological tissue during Nd:YAG laser irradiation

We report our preliminary clinical experience with hematoporphyrin derivative (HpD) injection and argon or dye laser irradiation for the treatment of 61 surface neoplastic lesions in 7 patients. Forty-three sites were multiple basal cell carcinoma in 5 patients, and the remaining 18 were cutaneous and subcutaneous recurrent breast carcinoma after mastectomy in the thoracic wall. The patients were selected on the basis of the lack of indication for conventional therapeutic modalities. The selection of irradiation procedures and laser source was based on the thickness of the lesion and extension of the disease. The photochemical reaction between HpD injected i.v. at a dose of 3 mg/kg body weight and the laser beam at a dose of 60 to 120 J/cm2 resulted in 75% favorable responses at the treated sites. Optimal therapeutic effects appeared to be critically dependent on total light dose and tumor infiltration patterns. The phototherapeutic technique proved to be effective in selected cases of neoplastic lesions, especially when conventional treatment modalities were poorly indicated or contraindicated.

Laser phototherapy following HpD administration in superficial neoplastic lesions.

Cutaneous photosensitization by topical administration of a porphyrin derivative has been previously reported from experimental studies. Preliminary clinical trials performed at the National Cancer Institute of Milan in the last six months have confirmed the feasibility of treating skin lesions by topical application of photosensitizers. Fourteen cases of basal cell carcinoma were treated by local administration of tetraphenylporphinesulphonate (TPPS), vehicled by azone. Later, the tumor was exposed to a wavelength of 630 nm from a dye laser.



We noted complete remission, as documented by biopsies, in all tumors, with clinical thickness less than 2 mm, whereas partial remission was obtained in tumors with clinical thickness more than 2 mm. Our experience suggests the possibility of a routine treatment by this method for flat basal cell carcinoma and pre-malignant lesions, with remarkable advantages to conventional therapies. Our results have to be confirmed by increasing the number of cases and length of follow up; our short follow up does not allow us to make definitive claims regarding this therapy.

Preliminary clinical studies with PDT by topical TPPS administration in neoplastic skin lesions

Fibroblasts and lymphocytes are the most widely used cells for studying the so-called biostimulative effect of low-power laser in vitro. In contrast, stimulation of cancer cells by laser light has not been investigated extensively. The present study attempted to evaluate whether or not human tumor cells could exhibit an increase in colony-forming capability following low-watt laser irradiation. LoVo and HT29 (colon carcinoma), MCF7 (breast carcinoma), M14 and JR1 (malignant melanoma) cell lines were irradiated at different doses of light delivered from an argon or an argon-dye laser. Radiant exposures between 4.2 and 150 kJ/m2 at irradiances ranging from 35 to 500 W/m2 were delivered. Results were mixed. Of the 41 experiments performed, five showed a significant statistical increase in the number of colonies (P less than 0.05), whereas three showed a decrease (P less than 0.05). Nevertheless, the trend of most data was toward an increase in colony formation, and Wilcoxon's signed-ranks test suggested that light increases tumor cell culture growth (P less than 0.03).

Elsa Melloni

Papers

Extinction and absorption coefficients and scattering phase functions of human tissues in vitro

Temperature rise in biological tissue during Nd:YAG laser irradiation

Laser phototherapy following HpD administration in superficial neoplastic lesions.

Preliminary clinical studies with PDT by topical TPPS administration in neoplastic skin lesions

Effect of low-energy laser irradiation on colony formation capability in different human tumor cells in vitro.