Dermatologic history of the ruby laser: the long story of short pulses.
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History, 20th Century↗
Biomedical subjects
R Rox Anderson
Publications and source records attributed to R Rox Anderson.
Selective cell targeting with light-absorbing microparticles and nanoparticles.
We describe a new method for selective cell targeting based on the use of light-absorbing microparticles and nanoparticles that are heated by short laser pulses to create highly localized cell damage. The method is closely related to chromophore-assisted laser inactivation and photodynamic therapy, but is driven solely by light absorption, without the need for photochemical intermediates (particularly singlet oxygen). The mechanism of light-particle interaction was investigated by nanosecond time-resolved microscopy and by thermal modeling. The extent of light-induced damage was investigated by cell lethality, by cell membrane permeability, and by protein inactivation. Strong particle size dependence was found for these interactions. A technique based on light to target endogenous particles is already being exploited to treat pigmented cells in dermatology and ophthalmology. With exogenous particles, phamacokinetics and biodistribution studies are needed before the method can be evaluated against photodynamic therapy for cancer treatment. However, particles are unique, unlike photosensitizers, in that they can remain stable and inert in cells for extended periods. Thus they may be particularly useful for prelabeling cells in engineered tissue before implantation. Subsequent irradiation with laser pulses will allow control of the implanted cells (inactivation or modulation) in a noninvasive manner.
Apoptosis↗
Demarcation of nonmelanoma skin cancer margins in thick excisions using multispectral polarized light imaging.
More than a million cases of nonmelanoma skin cancers are diagnosed every year. Treatment of cancer patients could benefit greatly if a real-time, noninvasive, reliable, and cost-effective technique for delineating tumor margins were available. A novel multispectral dye-enhanced polarized light imaging technique that enables rapid imaging of large tumor fields is described. A tunable monochromatic light source and a CCD camera were employed as the imaging device. Linear polarizers were introduced into both the incident and collected light pathways in order to limit the measurement volume to the superficial tissue layers. To enhance the tumor contrast in the image, aqueous solutions of toluidine blue or methylene blue were topically applied to fresh thick skin excisions for several minutes. Then the specimens were rinsed in saline solution. Images were acquired before and after staining at the selected wavelengths. The two sets of wavelengths corresponding to the hemoglobin Soret absorption band and to the absorption bands of the dyes were used to demarcate the areas of enhanced hemoglobin and dye absorption, respectively. The resulting images demonstrate that staining significantly enhances contrast of the tumor in the image and enables reliable delineation of cancer. Locations and shapes of tumor lobules revealed by polarized light images closely correspond to those found in Mohs frozen sections for 41 specimens out of 45. The study demonstrates that the suggested technique has significant potential as a guidance tool in tumor excision surgery.
Basal Cell Carcinoma↗
Photodynamic therapy for cutaneous proliferative vascular tumors in a mouse model.
Photodynamic therapy with benzoporphyrin derivative monoacid ring A and red light (PDT-BPD) has been used to treat human choroidal hemangiomas, and may be useful for cutaneous vascular lesions. The potential for PDT-BPD to inhibit selectively vascular tumor growth was tested in a mouse angiosarcoma model, of which the tumor growth mimics the proliferative phase of hemangiomas. Vascular tumors arising after intradermal injection of immortalized murine endothelial cells were exposed to 50 to 150 J per cm2 of 690 nm laser light 15 min after intravenous injection of 1 mg per kg BPD. Tumor volume and gross response were followed after PDT-BPD and compared with control tumors receiving no treatment, light alone, or BPD alone. At 2 wk, hematoxylin-eosin and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling stained tumor sections was performed. There was a selective, fluence-dependent inhibition of tumor growth after PDT-BPD (p< or =0.05), typically with eradication of tumors exposed to higher fluences. A common effect was the replacement of tumor by small scar. Surrounding PDT-BPD exposed normal skin showed no changes. Based on these results, we conclude that PDT-BPD can lead to selective eradication of these tumors. Further studies investigating the efficacy of PDT-BPD for human hemangiomas are warranted.
Animals↗
Q-switched laser-induced chrysiasis treated with long-pulsed laser.
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Aged↗
Magnetite tattoos.
BACKGROUND AND OBJECTIVES: Tattoo removal is a significant problem. The extraction of magnetite (Fe(3)O(4)) ink tattoos by a magnetic field was investigated, with and without Q-switched laser treatment. STUDY DESIGN/MATERIALS AND METHODS: Magnetite particles (1.4 microm) were used to make mature, black skin tattoos on hairless albino rats. A Q-switched ruby laser (QSRL) 3.5 J/cm(2), 6.5-mm spot size, 40-nanosecond pulse width was used for treatment. Permanent magnets (1.4 T, 6-mm diameter) were tested to extract the magnetite particles, alone and after QSRL. Lightening of treated tattoos was measured from digital photographs, and the amount and distribution of magnetite in skin biopsies was scored blindly. RESULTS: External application of magnets on mature magnetite tattoos without prior QSRL treatment, did not significantly extract, lighten, darken, or change their histologic appearance. A magnetic field applied immediately after QSRL treatment extracted some ink when epidermal injury was present, and caused significant redistribution of magnetite into the upper dermis with vertical banding along magnetic field lines. When applied for 3 weeks following QSRL, magnets caused darkening of tattoos. CONCLUSIONS: Magnetite skin tattoos can be manipulated by external magnets, especially after Q-switched laser treatment. Magnetically-extractable tattoos may be feasible.
Albinism↗
Efficacy of erbium:yttrium-aluminum-garnet laser-assisted delivery of topical anesthetic.
BACKGROUND: Penetration through the stratum corneum limits effectiveness of topical anesthetics. OBJECTIVE: Our aim was to evaluate the effectiveness of 5% lidocaine (ELA-Max) cream applied after erbium:yttrium-aluminum-garnet (Er:YAG) laser ablation of the stratum corneum. METHODS: Randomized, controlled, split-face comparison of anesthesia was performed on 12 volunteers. The stratum corneum was painlessly ablated with a low-fluence Er:YAG laser on half of the face, then the whole face was covered with ELA-Max cream for 60 minutes. Full-face laser resurfacing was performed, and visual analog pain scores (0 to 10) were recorded during each of 2 passes. RESULTS: Laser-assisted topical anesthesia demonstrated significantly lower mean pain scores than topical anesthesia alone. This was more pronounced during the more painful second pass. Resurfacing after laser-assisted topical anesthesia was well tolerated by 72% of subjects in pass 1 and 58% in pass 2. CONCLUSION: Laser-assisted topical anesthesia is fast, painless, and substantially more effective than conventional topical anesthesia but does not provide adequate anesthesia for full-face resurfacing in all subjects.
Adult↗
In vivo confocal imaging of pigmented eccrine poroma.
BACKGROUND: Near-infrared reflectance confocal microscopy (CM) imaging is a noninvasive technique that can be utilized to evaluate histologic features of cutaneous lesions in vivo. OBJECTIVE: A case of pigmented eccrine poroma was examined with CM. METHODS: Confocal images were taken to define the features of the lesion and correlated with transverse hematoxylin-eosin (HE)-stained sections. RESULTS: In CM imaging, a well-demarcated homogeneous nest consisting of small uniform cells was seen. The nest contained nonrefractile dark spaces that may represent cuticuli. Many dendritic melanocytes containing melanin were intermingled with the tumor cells, and numerous melanophages were present in the upper dermis. A marked prominence of surrounding vessels was also demonstrated. CONCLUSIONS: CM could well demonstrate the features of a pigmented eccrine poroma, as correlated with transverse HE-stained sections. However, high reflectance signals from melanin had to be carefully considered before a definitive diagnosis could be made.
Acrospiroma↗
585-nm pulsed dye laser treatment of glottal papillomatosis.
Treatment of recurrent respiratory papillomatosis of the glottis is often challenging. The surgeon and patient must cooperatively balance decisions regarding airway safety, effects of multiple general anesthesias, employment disturbance, and vocal dysfunction. A pilot study was done in 41 adult cases (23 patients; 78 vocal folds) without complication to evaluate the effectiveness of a 585-nm pulsed dye laser (PDL; 450-micros pulse width; fluence of 38 to 255 J/cm2; 1- to 2-mm spot size) in the treatment of this disorder. Thirty-seven of the 41 cases (90%) were bilateral disease. Twenty-six of the 41 cases (63%; including 20 cases with involvement of the anterior commissure) were treated by bilateral photocoagulation of the lesions' microcirculation without microflap resection of tissue. Clinical observation revealed that irradiated but unresected disease involuted without development of an anterior commissure web. In the initial 13 of the 41 cases (32%), PDL treatment was followed by cold instrument microflap resection. The PDL enhanced the epithelial excision by improving hemostasis and by creating an optimal dissection plane between the basement membrane and the underlying superficial lamina propria. The PDL at 585 nm was less effective in the management of exophytic lesions because of its limited depth of penetration (approximately 2 mm). In this initial trial, the PDL was a relatively safe and efficacious treatment for glottal recurrent respiratory papillomatosis. Since the lesions involute without complete resection of the diseased epithelium, the anterior commissure can be treated to minimize the number of procedures. To study patterns of recurrence will require longer follow-up.
Female↗
Laser-beam-triggered microcavitation: a novel method for selective cell destruction.
We describe a new method of cell destruction that may have potential for use in antitumor therapy. Cells are loaded by phagocytosis with microparticles (<1 microm) and irradiated with short laser pulses. Absorption of laser energy by the microparticles causes localized vaporization of the fluid surrounding the microparticles, leading to the generation of transient vapor bubbles (microcavitation) around the microparticles. Using cultures of bovine aortic endothelial cells, we demonstrate that induction of intralysosomal microcavitation is an efficient, rapid and selective method of cell killing that is dependent on the number of microparticles, the number of laser pulses, and the fluence of the laser pulses. Cell killing by microcavitation is a very selective process that is restricted to cells containing microparticles, leaving other cells unaffected. Intracytoplasmic release of lysosomal hydrolases is, in part, responsible for cell death, because the protease inhibitors E64d and TLCK diminished cell killing. Using the broad-specificity caspase inhibitor Z-VAD-fmk, we determined that lysosomal hydrolases could induce apoptosis in a caspase-independent manner. We also examined the possibility of microcavitation-induced delayed effects in the cells that survived the treatment. Using flow cytometry, we determined that there was no delayed cell death between 1 and 4 days after microcavitation. Moreover, we did not observe changes in the cell cycle, in expression of the proteins BCL2, HSP70 and HSP27, or in PARP degradation. In conclusion, microcavitation induces rapid and specific cells death (limited only to cells containing microparticles), without producing delayed effects among the surviving cells.
Animals↗