The First Commercial 730 nm Picosecond-Domain Laser is Safe and Effective for Treating Multicolor Tattoos.

BACKGROUND AND OBJECTIVES: Laser-pumped lasers enable driving a secondary wavelength through pumping with a primary device. Here we investigate the first 730 nm laser-pumped laser for efficacy in tattoo removal. STUDY DESIGN/MATERIALS AND METHODS: Fifteen subjects with 20 tattoos were enrolled to investigate the effect of a new 730 nm, titanium-sapphire laser-pumped laser at removing decorative tattoos. A total of four treatments were administered and photographic improvement of pre- and post-treatment cross-polarized digital images was evaluated by four blinded physician observers using an 11-point scale. RESULTS: Blinded assessment of pre- and post-treatment images found 70%, 77%, 83%, 83%, 26%, and 8% clearance from baseline images for black, green, blue, purple, red and yellow pigments, respectively. Side effects were limited to pinpoint bleeding and erythema immediately after treatment and some crusting and scale up to 1-2 weeks following treatment, and a localized allergic reaction in a single subject. There was no scarring or pigmentary alteration visible in any follow-up images. CONCLUSION: The new 730 nm, picosecond-domain, titanium-sapphire, laser-pumped laser is safe and effective for removing multicolored tattoos. Green, blue, and purple pigments cleared the most as expected, but black ink cleared more completely than was predicted. Lasers Surg. Med. © 2020 The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals LLC.

A novel titanium sapphire picosecond-domain laser safely and effectively removes purple, blue, and green tattoo inks.

BACKGROUND: Green, blue, and purple tattoo pigments are often the colors most resistant to laser removal. Recently, the first ever production picosecond-domain laser with a 785 nm wavelength was developed to improve the rate of clearance of green, blue, and purple tattoo inks. METHODS: Twenty-two tattoos from 15 subjects with skin phototypes II-IV were enrolled in the study. A total of four treatments were administered using a single 785 nm picosecond-domain laser wavelength. Blinded assessment of digital, cross-polarized photographs taken approximately 8 weeks following the last treatment was performed using an 11-point clearance scale. RESULTS: Fourteen subjects with 21 tattoos completed all study visits. The 21 tattoos contained the following pigments: black (n = 15), green (n = 13), blue (n = 8), yellow (n = 5), purple (n = 4), and red (n = 3). Treatments were performed with a 2-4-mm beam diameter and fluences ranging from 1.1 to 3.1 J/cm2 . Blinded assessment of photographs found 85%, 81%, 74%, 61%, 11%, and 5% clearance from baseline photos for purple, blue, green, black, red, and yellow pigments, respectively. Treatments were well tolerated with typical erythema, edema and one case of pinpoint bleeding. No scarring was noted. CONCLUSION: This first study of a new 785 nm picosecond-domain laser demonstrates safe and effective removal of multicolor tattoos. Although clearance was shown for a multitude of colors including black, the 785 nm laser wavelength has special affinity to purple, blue and green tattoo pigments. Lasers Surg. Med. 9999:1-7, 2018. © 2018 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.

Treatment of acne scarring with a novel fractionated, dual-wavelength, picosecond-domain laser incorporating a novel holographic beam-splitter.

BACKGROUND AND OBJECTIVES: Fractional treatment with a dual wavelength 1,064 and 532 nm picosecond-domain laser, delivering a 10 × 10 array of highly focused beamlets via a holographic optic, was investigated for the treatment of acne scars. STUDY: Twenty-seven of 31 subjects completed the study, 19 were treated using 1,064 nm and 8 were treated at 532 nm, all having four-monthly treatments. Blinded evaluation of digital images by three physician evaluators comparing pre- and 3-month post-treatment images measured efficacy using a 10-point scale. Subject self-assessment of treatment effects were also recorded. Safety was measured by recording subject discomfort scores and adverse effects. RESULTS: Blinded reviewers correctly identified the baseline image in 61 of the 81 image sets (75%), and baseline acne scar scores were 1.8 ± 0.7 and 1.8 ± 0.5 for the 1,064 and 532 nm cohorts, and decreased to 1.1 ± 0.5 (P < 0.001) and 1.1 ± 0.0 (P < 0.005), respectively. Post-treatment erythema, mild edema, and petechiae were the only side effects noted. CONCLUSION: The 1,064 and 532 nm picosecond-domain laser incorporating a 10 × 10 holographic beam-splitting handpiece was found to be safe and effective for the treatment of facial acne scars. The treatments were well tolerated and the subjects experienced little to no downtime. Lasers Surg. Med. 49:796-802, 2017. © 2017 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.

Treatment of Photoaging With a Dual-Wavelength, 532 nm and 1,064 nm Picosecond-Domain Laser Producing a Fractionated Treatment Beam Using a Holographic Optic.

BACKGROUND: A dual-wavelength, picosecond-domain, fractionated laser delivering 1,064nm and 532nm laser energy through a holographic optic was investigated for safety and effectiveness at improving the appearance of chronic photoaging. MATERIALS AND METHODS: A total of 27 subjects were enrolled with 24 completing the study, and 14 subjects were treated with 1,064 nm and 10 with 532 nm. The 1,064 nm-treated subjects received 5 monthly treatments while the 532 nm-treated subjects received 4 monthly treatments. Improvement was measured by blinded evaluation of pre- and post-treatment images 12 weeks following the final treatment. Subjects also evaluated treatment effect and side-effects. RESULTS: Blinded reviewers correctly identified the baseline image in 52 of 72 paired images, or 72% of the time, with a mean improvement score of 1.4 using an 11-point rating scale (P less than 0.0001). Post-treatment erythema, mild edema, and petechiae were the only side effects noted. CONCLUSION: The fractionated, picosecond-domain, 532 nm and 1,064 nm laser is safe and effective for improvement of facial photodamage. The laser was well tolerated with mild erythema, edema, and petechiae as the most common side-effects.

J Drugs Dermatol. 2017;16(11):1077-1082.

A novel dual-wavelength, Nd:YAG, picosecond-domain laser safely and effectively removes multicolor tattoos.

BACKGROUND AND OBJECTIVES: Although nanosecond-domain lasers have been the mainstay of laser tattoo removal for decades, recent disruptive innovations in laser design have introduced a new class of commercial Q-switched lasers that generate picosecond-domain pulses. STUDY: A picosecond-domain, Nd:YAG laser with a KTP frequency-doubling crystal was used to treat 31 decorative tattoos in 21 subjects. Safety and effectiveness were determined by blinded evaluation of digital images in this prospective clinical study. RESULTS: The average clearance overall as evaluated by blinded observers evaluating randomized digital photographs was 79 ± 0.9% (mean ± sem) after an average of 6.5 treatments. Of the 31 tattoos completing treatment, 6 had evidence of mild hyper- or hypo-pigmentation by evaluation of photographs. CONCLUSION: The 350 picosecond, 532 nm, and 450 picosecond 1,064 nm Nd:YAG laser is safe and effective for removing decorative tattoos. Lasers Surg. Med. 47:542-548, 2015. © 2015 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.

Novel optical detection system for in vivo identification and localization of cervical intraepithelial neoplasia.

A noncontact optical detection system is developed for the in vivo identification and localization of high-grade cervical intraepithelial neoplasia (CIN 2,3). Diagnostic scans of the entire human cervix are performed following acetic acid application employing three integrated optical measurements: laser-induced fluorescence spectroscopy, white light diffuse reflectance spectroscopy, and video imaging. Full cervical scans comprising 499 interrogation locations at 1-mm spatial resolution are completed in 12 s. Diffuse reflectance and fluorescence spectra with signal-to-noise ratios of better than 100-to-1 are collected between 360 and 720 nm in increments of 1 nm, with an inherent spectral resolution of 8 nm. Glare reduction and optical vignetting are handled with a novel illumination scheme and subsequent spectral arbitration algorithms. The system is designed and found to be well below acceptable safe optical exposure levels. Typical reproducibility across multiple systems is approximately 5%, providing reliable and accurate detection of in vivo cervical neoplasia in normal clinical use.

Efficacy of laser debridement with autologous split-thickness skin grafting in promoting improved healing of deep cutaneous sulfur mustard burns.

The consequences of receiving a cutaneous sulfur mustard (SM) burn are prolonged wound healing and secondary infection. This study was undertaken to find a treatment that promotes quick healing with few complications and minimal disfigurement. Multiple deep SM burns (4 cm diameter) were generated on the ventrum of weanling pigs and treated at 48 h. Four treatments were compared: (1) full-thickness CO(2) laser debridement followed by skin grafting; (2) full-thickness sharp surgical tangential excision followed by skin grafting, the "Gold Standard" used in deep thermal burns management; (3) partial-thickness laser ablation with no grafting; and (4) partial-thickness sharp excision with no grafting. A computer controlled, raster scanned, high-powered continuous wave (cw) CO(2) laser was utilized. Ulceration, wound geometry, and wound contraction were evaluated during a 36-day healing period. Histopathological evaluations were conducted at the end of the healing period. Engraftment rates were similar between both methods of debridement. Laser debridement followed by skin grafting was as efficacious in improving the wound healing of deep SM burns as the "Gold Standard." Full-thickness laser debridement of these small total body surface area (TBSA) burns was time efficient and provided adequate beds for split-thickness skin grafting. Laser debridement offered additional benefits that included hemostatic control during surgery and minimal debridement of normal perilesional skin. Mid-dermal debridement by sharp excision or laser ablation without grafting produced less desirable results but was better than no treatment.

In vivo acceleration of skin growth using a servo-controlled stretching device.

Tension is a principal force experienced by skin and serves a critical role in growth and development. Optimal tension application regimens may be an important component for skin tissue engineering and dermatogenesis. In this study, we designed and tested a novel servo-controlled skin-stretching device to apply predetermined tension and waveforms in mice. The effects of static and cyclical stretching forces were compared in 48 mice by measuring epidermal proliferation, angiogenesis, cutaneous perfusion, and principal growth factors using immunohistochemistry, real-time reverse transcriptase-polymerase chain reaction, and hyperspectral imaging. All stretched samples had upregulated epidermal proliferation and angiogenesis. Real-time reverse transcriptase-polymerase chain reaction of epidermal growth factor, transforming growth factor beta1, and nerve growth factor demonstrated greater expression in cyclically stretched skin when compared to static stretch. Hypoxia-induced factor 1alpha was significantly upregulated in cyclically stretched skin, but poststretch analysis demonstrated well-oxygenated tissue, collectively suggesting the presence of transient hypoxia. Waveform-specific mechanical loads may accelerate tissue growth by mechanotransduction and as a result of repeated cycles of temporary hypoxia. Further analysis of mechanotransduction signaling pathways may provide additional insight to improve skin tissue engineering methods and optimize our device.

The use of medical hyperspectral technology to evaluate microcirculatory changes in diabetic foot ulcers and to predict clinical outcomes.

OBJECTIVE: Foot ulceration is a serious complication of diabetes, and new techniques that can predict wound healing may prove very helpful. We tested the ability of medical hyperspectral technology (HT), a novel diagnostic scanning technique that can quantify tissue oxy- and deoxyhemoglobin to predict diabetic foot ulcer healing. RESEARCH DESIGN AND METHODS: Ten type 1 diabetic patients with 21 foot ulcer sites, 13 type 1 diabetic patients without ulcers, and 14 nondiabetic control subjects were seen up to 4 times over a 6-month period. HT measurements of oxyhemoglobin (HT-oxy) and deoxyhemoglobin (HT-deoxy) were performed at or near the ulcer area and on the upper and lower extremity distant from the ulcer. An HT healing index for each site was calculated from the HT-oxy and -deoxy values. RESULTS: Hyperspectral tissue oxygenation measurements observed changes in tissue immediately surrounding the ulcer when comparing ulcers that heal and ulcers that do not heal (P < 0.001). The sensitivity, specificity, and positive and negative predictive values of the HT index for predicting healing were 93, 86, 93, and 86%, respectively, when evaluated on images taken at the first visit. Changes in HT-oxy among the three risk groups were noted for the metatarsal area of the foot (P < 0.05) and the palm (P < 0.01). Changes in HT-deoxy and the HT healing index were noted for the palm only (P < 0.05 and P < 0.01, respectively). CONCLUSIONS: HT has the capability to identify microvascular abnormalities and tissue oxygenation in the diabetic foot and predict ulcer healing. HT can assist in the management of foot ulceration.

Optical, real-time monitoring of the glomerular filtration rate.

An easy and accurate assessment of the renal function is a critical requirement for detecting the initial functional decline of the kidney induced by acute or chronic renal disease. A method for measuring the glomerular filtration rate is developed with the accuracy of clearance techniques and the convenience of plasma creatinine. The renal function is measured in rats as the rate of clearance determined from time-resolved transcutaneous fluorescence measurements of a new fluorescent glomerular filtration agent. The agent has a large dose-safety coefficient and the same space distribution and clearance characteristics as iothalamate. This new approach is a convenient and accurate way to perform real-time measurements of the glomerular filtration rate to detect early kidney disease before the renal function becomes severely and irreversibly compromised.

Multiple-fiber probe design for fluorescence spectroscopy in tissue.

The fiber-optic probe is an essential component of many quantitative fluorescence spectroscopy systems, enabling delivery of excitation light and collection of remitted fluorescence in a wide variety of clinical and laboratory situations. However, there is little information available on the role of illumination--collection geometry to guide the design of these components. Therefore we used a Monte Carlo model to investigate the effect of multifiber probe design parameters--numerical aperture, fiber diameter, source--collection fiber separation distance, and fiber-tissue spacer thickness--on light propagation and the origin of detected fluorescence. An excitation wavelength of 400 nm and an emission wavelength of 630 nm were simulated. Noteworthy effects included an increase in axial selectivity with decreasing fiber size and a transition with increasing fiber-tissue spacer size from a subsurface peak in fluorophore sensitivity to a nearly monotonic decrease typical of single-fiber probes. We provide theoretical evidence that probe design strongly affects tissue interrogation. Therefore application-specific customization of probe design may lead to improvements in the efficacy of fluorescence-based diagnostic devices.

Bioengineering methods employed in the study of wound healing of sulphur mustard burns.

BACKGROUND/PURPOSE: Sulphur mustard (SM) is a potent incapacitating chemical warfare agent that remains a threat to war fighters and civilians worldwide. SM lesions may require weeks or months to heal, depending upon their severity. This study was undertaken to find a treatment regimen that promotes speedier healing of deep cutaneous SM burns in a weanling pig model. The principal objective of the study was to compare four treatment regimens and establish which achieved the shortest healing time. METHODS: Twelve Yorkshire Cross weanling pigs were exposed to SM liquid for 2h, generating six large deep dermal/full thickness burns on the ventrum of each animal. Three additional animals served as sham-exposed controls. Surgical intervention occurred at 48 h postexposure. Treatments included: (i) full-thickness debridement of the burns with a computer controlled, raster scanned continuous wave CO2 laser followed by autologous split-thickness skin grafting; (ii) full-thickness sharp surgical tangential excision followed by skin grafting, the 'Gold Standard' used in human deep dermal/full-thickness thermal burns management; (iii) partial-thickness laser ablation with no grafting; and (iv) partial-thickness sharp surgical excision with no grafting. Several non-invasive bioengineering methods were used to monitor the progress of wound healing throughout a 36-day healing period: reflectance colourimetry, evaporimetry, laser Doppler perfusion imaging and ballistometry. RESULTS: Bioengineering methods indicated that laser debridement followed by autologous split-thickness skin grafting was as efficacious in improving the wound healing of deep SM burns in weanling swine as the 'Gold Standard.' Regardless of the method of debridement, barrier function, skin colour and mechanical properties returned to near-normal levels within 15 days of treatment in the grafted sites. Regardless of surgical approach, blood flux levels remained approximately 50-60% of normal tissue throughout the 36-day postsurgical observation period. Mid-dermal debridement by sharp surgical tangential excision or laser ablation without the use of skin grafts did not produce as good a result as those attained through the use of grafts, but was better than no surgical treatment of the wounds. CONCLUSION: Bioengineering methods were useful in evaluating multiple characteristics during wound healing: (i) reflectance colourimetry for skin colour, (ii) evaporimetry to measure transepidermal water loss as an indicator of barrier function, (iii) laser Doppler perfusion imaging to assess cutaneous blood flow, and (iv) ballistometry to measure the mechanical properties of skin hardness and elasticity. Perhaps the most useful method was evaporimetry, as a restored barrier function was the best indicator of healed wounds. The use of reflectance colourimetry and ballistometry will continue in future wound healing studies for their contributions in judging cosmetic and functional outcomes. While useful, laser Doppler perfusion imaging was found to be rather time consuming. This methodology will be limited in the future to burn depth estimation prior to treatment, and for evaluation of pharmaceuticals specifically designed to improve or sustain blood flow into damaged areas.

Temporally and spectrally resolved fluorescence spectroscopy for the detection of high grade dysplasia in Barrett's esophagus.

BACKGROUND AND OBJECTIVES: Temporal and spectral fluorescence spectroscopy can identify adenomatous colonic polyps accurately. In this study, these techniques were examined as a potential means of improving the surveillance of high grade dysplasia (HGD) in Barrett's esophagus (BE). STUDY DESIGN/MATERIALS AND METHODS: Using excitation wavelengths of 337 and 400 nm, 148 fluorescence spectra, and 108 transient decay profiles (at 550 +/- 20 nm) were obtained endoscopically in 37 patients. Corresponding biopsies were collected and classified as carcinoma, HGD, or low risk tissue (LRT) [non-dysplastic BE, indefinite for dysplasia (IFD), and low grade dysplasia (LGD)]. Diagnostic algorithms were developed retrospectively using linear discriminant analysis (LDA) to separate LRT from HGD. RESULTS: LDA produced diagnostic algorithms based solely on spectral data. Moderate levels of sensitivity (Se) and specificity (Sp) were obtained for both 337 nm (Se = 74%, Sp = 67%) and 400 nm (Se = 74%, Sp = 85%) excitation. CONCLUSIONS: In the diagnosis of HGD in BE, steady-state fluorescence was more effective than time-resolved data, and excitation at 400 nm excitation was more effective than 337 nm. While fluorescence-targeted biopsy is approaching clinical usefulness, increased sensitivity to dysplastic changes-possibly through modification of system parameters-is needed to improve accuracy levels.

Localization of rose bengal, aluminum phthalocyanine tetrasulfonate, and chlorin e6 in the rabbit eye.

PURPOSE: The localization and site of action of photosensitizers in the eye may be important for photodynamic therapy for fundus disorders but remain poorly understood for most agents. We investigated the intraocular localization of xanthene, phthalocyanine, and chlorin photosensitizers by using fluorescence microscopy and digital fundus fluorescence angiography. METHODS: Rose bengal (40 mg/kg), aluminum phthalocyanine tetrasulfonate (CASPc) (5 mg/kg), or chlorin e6 (2 mg/kg) was intravenously administered to albino rabbits. The eyes were enucleated and examined by means of fluorescence microscopy 5, 20, 60, and 120 minutes and 24 hours after dye injection. In vivo digital fundus fluorescence angiography with use of rose bengal (2-4 mg/kg), CASPc (2 mg/kg), and chlorin e6 (2 mg/kg) was performed. RESULTS: For all agents studied pathologically, there was moderate fluorescence from the choroid and retinal pigment epithelium 5 minutes after dye injection. Mild fluorescence detected from the photoreceptor outer segments at 5 minutes was increased at 20 minutes. Angiographic studies with use of rose bengal, CASPc, and chlorin e6 revealed differences in the pattern and rate of photosensitizer accumulation. CONCLUSIONS: Rose bengal, CASPc, and chlorin e6 accumulate rapidly in the choroid and retinal pigment epithelium and less rapidly in the outer retina. Differences in ocular localization of these photosensitizers were demonstrated. The significance of these findings for potential photodynamic therapy with these agents requires further investigation.

Detection of high-grade dysplasia in Barrett's esophagus by spectroscopy measurement of 5-aminolevulinic acid-induced protoporphyrin IX fluorescence.

BACKGROUND: Preliminary studies with qualitative detection methods suggest that 5-aminolevulinic acid-induced protoporphyrin IX fluorescence might improve the detection of dysplastic Barrett's epithelium. This study used quantitative methods to determine whether aminolevulinic acid-induced protoporphyrin IX fluorescence can differentiate between Barrett's mucosa with and without dysplasia. METHODS: Patients were given 10 mg/kg of aminolevulinic acid orally 3 hours before endoscopy. Quantitative fluorescence spectra were acquired by using a nitrogen-pumped dye laser (l 400 nm) spectrograph system. The protoporphyrin IX fluorescence intensity at 635 nm was compared with the histopathologic diagnosis for mucosal biopsy specimens taken immediately after the fluorescence measurements. RESULTS: Ninety-seven spectra were obtained from 20 patients. The mean (+/- standard error) standardized protoporphyrin IX fluorescence intensity was significantly greater (p < 0.05) for high-grade dysplastic Barrett's epithelium (0.29 +/- 0.07, n = 13) than for nondysplastic Barrett's epithelium (0.11 +/- 0.02, n = 43). By using protoporphyrin IX fluorescence alone, high-grade dysplasia was distinguished from nondysplastic tissue types with 77% sensitivity and 71% specificity. Decreased autofluorescence was particularly found in nodular high-grade dysplasia. By using the fluorescence intensity ratio of 635 nm/480 nm, nodular high-grade dysplasia could be differentiated from nondysplastic tissue with 100% sensitivity and 100% specificity. CONCLUSION: Protoporphyrin IX fluorescence may be useful for identifying areas of high-grade dysplasia in Barrett's esophagus and for targeting of biopsies.