George M. Peavy

Comparison of cortical bone ablations by using infrared laser wavelengths 2.9 to 9.2 μm

The purpose of this study was to compare the ablation of cortical bone at wavelengths across the near and midinfrared region.

Lasers and laser-tissue interaction.

Light produced by a laser differs from incandescent light in that it is monochromatic, coherent, and intense; and it is these properties that allow lasers to be used as such unique tools in biomedical research and patient care. The effect of a laser beam on tissue is dependent on the optical and mechanical properties of the tissue, and the wavelength, power parameters, and time domains of the laser exposure. Understanding these principles is not only important for the selection of an appropriate laser system for a specific application, but also is essential for that application to be successful.

In vivo three-dimensional imaging of normal tissue and tumors in the rabbit pleural cavity using endoscopic swept source optical coherence tomography with thoracoscopic guidance

The purpose of this study was to develop a dynamic tunable focal distance graded-refractive-index lens rod-based high-speed 3-D swept-source (SS) optical coherence tomography (OCT) endoscopic system and demonstrate real-time in vivo, high-resolution (10-microm) imaging of pleural-based malignancies in an animal model. The GRIN lens-based 3-D SS OCT system, which images at 39 fps with 512 A-lines per frame, was able to capture images of and detect abnormalities during thoracoscopy in the thoracic cavity, including the pleura, chest wall, pericardium, and the lungs. The abnormalities were confirmed by histological evaluation and compared to OCT findings. The dynamic tunable focal distance range and rapid speed of the probe and SS prototype OCT system enabled this first-reported application of in vivo 3-D thoracoscopic imaging of pleural-based malignancies. The imaging probe of the system was found to be easily adaptable to various sites within the thoracic cavity and can be readily adapted to other sites, including rigid airway endoscopic examinations.

Use of polarization-sensitive optical coherence tomography to determine the directional polarization sensitivity of articular cartilage and meniscus

The directional polarization sensitivity of articular cartilage and meniscus is investigated by use of polarization-sensitive optical coherence tomography (PS-OCT) by varying the angle of incident illumination. Experimental results show that when the incident light is perpendicular to the tissue surface, normal articular cartilage demonstrates little polarization sensitivity, while meniscus demonstrates strong polarization sensitivity. Differences in optical phase retardation produced by articular cartilage and meniscus are observed when the incident angle of the scanning light beam is adjusted between 0 and 90 deg relative to the tissue surface. Directional polarization sensitivity of articular cartilage and meniscus as obtained by PS-OCT imaging using variations in the angle of incident illumination can be used to assess the orientation and organization of the collagen matrix of these tissues. The polarization sensitivity as evidenced by the Stokes vector and optical phase retardation images can be explained by the orientation of the angle of illumination relative to the unique structural organization of the collagen fibrils and fibers of articular cartilage and meniscus.

Spectra from 2.5–15 µm of tissue phantom materials, optical clearing agents and ex vivo human skin: implications for depth profiling of human skin

Infrared measurements have been used to profile or image biological tissue, including human skin. Usually, analysis of such measurements has assumed that infrared absorption is due to water and collagen. Such an assumption may be reasonable for soft tissue, but introduction of exogenous agents into skin or the measurement of tissue phantoms has raised the question of their infrared absorption spectrum. We used Fourier transform infrared spectroscopy in attenuated total reflection mode to measure the infrared absorption spectra, in the range of 2-15 microm, of water, polyacrylamide, Intralipid, collagen gels, four hyperosmotic clearing agents (glycerol, 1,3-butylene glycol, trimethylolpropane, Topicare), and ex vivo human stratum corneum and dermis. The absorption spectra of the phantom materials were similar to that of water, although additional structure was noted in the range of 6-10 microm. The absorption spectra of the clearing agents were more complex, with molecular absorption bands dominating between 6 and 12 microm. Dermis was similar to water, with collagen structure evident in the 6-10 microm range. Stratum corneum had a significantly lower absorption than dermis due to a lower content of water. These results suggest that the assumption of water-dominated absorption in the 2.5-6 microm range is valid. At longer wavelengths, clearing agent absorption spectra differ significantly from the water spectrum. This spectral information can be used in pulsed photothermal radiometry or utilized in the interpretation of reconstructions in which a constant mu(ir) is used. In such cases, overestimating mu(ir) will underestimate chromophore depth and vice versa, although the effect is dependent on actual chromophore depth.

Preclinical evaluation of 5-aminolevulinic acid-based photodynamic therapy for canine transitional cell carcinoma

As a prelude to photodynamic therapy, 5-aminolevulinic acid (ALA) was given orally to healthy dogs. ALA-induced protoporphyrin IX (PpIX) fluorescence significantly increased in the mucosa of the urinary bladder in an ALA dose-dependent fashion. Vomiting occurred after ALA administration in 70% of the dogs but did not affect PpIX fluorescence. ALA-based photodynamic therapy (PDT) of the urinary bladder in healthy dogs caused only submucosal oedema within the bladder wall. No haematologic or serum biochemistry abnormalities were observed after ALA administration. Microscopic haematuria was observed in all the dogs after PDT but was mild and self limiting. ALA-based PDT was administered to six dogs with transitional cell carcinoma (TCC) of the lower urinary tract. ALA-based PDT resulted in tumour progression-free intervals from 4 to 34 weeks in five dogs; one dog with pre-existing hydronephrosis died shortly after PDT. Dogs with TCC represent an outbred, spontaneous, tumour model for developing PDT protocols for humans with bladder cancer.

Topographical variations in the polarization sensitivity of articular cartilage as determined by polarization-sensitive optical coherence tomography and polarized light microscopy

To understand the influence of topographical variations in collagen fibril orientation of articular cartilage on optical phase images of polarization-sensitive optical coherence tomography (PS-OCT), we use polarized light microscopy (PLM) to quantify the orientation and phase retardation of the collagen architecture in cartilage at the same locations imaged by PS-OCT. The PS-OCT experiments demonstrate that articular cartilage has normal variations in polarization sensitivity at different locations over an intact bovine tibial plateau. Articular cartilage is not polarization sensitive along the vertical axis on the medial edge and central areas of the joint surface, but becomes polarization sensitive on the lateral edge of the tibia. This difference in optical phase retardation, as demonstrated by PS-OCT, is verified by PLM to be caused by differences in collagen fibril orientation at different locations of the tibial plateau. This study demonstrates that normal topographical variations in the collagen architecture of articular cartilage within a joint have a profound influence on the optical phase retardation detected by PS-OCT imaging, and therefore must be understood and mapped for specific joints before PS-OCT imaging can be used for the evaluation of the health status of individual joint surfaces.

Imaging of normal and pathologic joint synovium using nonlinear optical microscopy as a potential diagnostic tool

An estimated 1.3 million people in the United States suffer from rheumatoid arthritis (RA). RA causes profound changes in the synovial membrane of joints, and without early diagnosis and intervention, progresses to permanent alterations in joint structure and function. The purpose of this study is to determine if nonlinear optical microscopy (NLOM) can utilize the natural intrinsic fluorescence properties of tissue to generate images that would allow visualization of the structural and cellular composition of fresh, unfixed normal and pathologic synovial tissue. NLOM is performed on rabbit knee joint synovial samples using 730- and 800-nm excitation wavelengths. Less than 30 mW of excitation power delivered with a 40×, 0.8-NA water immersion objective is sufficient for the visualization of synovial structures to a maximum depth of 70 μm without tissue damage. NLOM imaging of normal and pathologic synovial tissue reveals the cellular structure, synoviocytes, adipocytes, collagen, vascular structures, and differential characteristics of inflammatory infiltrates without requiring tissue processing or staining. Further study to evaluate the ability of NLOM to assess the characteristics of pathologic synovial tissue and its potential role for the management of disease is warranted.

Variation in the distribution of a phthalocyanine photosensitizer in naturally occurring tumors of animals

Jcmllldd J J AND PIIOII:il]I:IIK~ Journal of P h o t o c h e m i s t r y and Photobiology n , ~ B: Biology 27 (1995) 271-277 ELSEVIER News and Views Variation in the distribution of a phthalocyanine photosensitizer in naturally occurring tumors of animals George M. Peary, Tatiana B. Krasieva, Bruce J. Tromberg, E. Dave Eusantos, Michael W. Berns Beckman Laser Institute and Medical Clinic, College of Medicine, University of California, Irvine, CA 92715, USA 1. Introduction The biodistribution and cytotoxicity of photosensi- tizers have been shown to vary in tumors, not only between classes of photosensitizer [1-5], but also be- tween differently sulfonated forms of the same parent compound [6-14]. For example, the distribution has been reported to be different for related phthalocyanine compounds when viewed in the same tumor model [14,15]. In addition, the local hypoxia which results from early vascular collapse induced by photodynamic therapy (PDT) has been observed to protect tumor cells from the direct effects of photodynamic cytotoxicity in vivo by limiting the oxygen availability for singlet oxygen generation [16], further suggesting that the distribution of a photosensitizer within a tumor can influence its efficiency for that tumor type. It has been proposed that a variety of tissue factors may be responsible for the preferential uptake and/or retention of hematoporphyrin derivative [17]. It is con- ceivable that these factors could vary substantially be- tween tumor types. When different tumors were im- planted on the chick chorioallantoic membrane (CAM) model, photosensitizer uptake varied with tumor type [18]. Thus the uptake and distribution of a photosen- sitizer are clearly complex functions which may be influenced by both the chemical properties of the pho- tosensitizer and the physiologic behavior of a specific tumor which may vary between tumor types. In this report, we evaluate the intratumor distribution of a phthalocyanine preparation in three different, naturally occurring, domestic dog and cat tumors. Our goal was to determine whether the same intratumor biodistribution could be observed in a variety of naturally occurring tumors. Lack of uniformity would highlight 1011-1344/95/

CO2 laser treatment of traumatic pulpal exposures in dogs

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