Emil A Tanghetti, Rafael Sierra, Michael Estes, Aubrey Eck, Alfred Intintoli, Henrik Hofvander, Joel L Cohen, Daniel P Friedmann, Mitchel P Goldman, Hyemin Pomerantz, Jordan V Wang, Roy G Geronemus, R Rox Anderson, Fernanda H Sakamoto
Objectives: This work highlights the methods used to develop a multi-pulse 1726 nm laser system combined with bulk air-cooling for selective sebaceous gland (SG) photothermolysis using thermal imaging and software algorithms. This approach enables treating to a desired tissue temperature and depth to provide a safe, effective, reproducible, and durable treatment of acne.
Methods: We designed and built a 1726 nm laser system with a 40 W maximum power output, a highly controlled air-cooling device, and a thermal camera in the handpiece, which permits real-time temperature monitoring of the epidermis. IRB-approved safety and efficacy trials demonstrated SG damage at depth, resulting in safe, efficacious, and durable clinical outcomes. Bioheat transfer and light transport modeling confirmed that the pulsing protocols could produce therapeutic temperatures at various SG depths, while protecting the epidermis and dermis with bulk air-cooling. Similarly, we employed clinical observations and photothermal modeling to identify pain mitigation opportunities while maintaining therapeutic efficacy. Biopsies were subsequently taken for histological evaluation.
Results: Clinical and histological data, confirmed with modeling, demonstrated that multi-pulse laser delivery with bulk air-cooling selectively increased SG temperature compared to surrounding dermis and at depths unachievable by a single pulse. Subjects showed an average 71% ILC reduction at 3 months posttreatment. We identified two different pulsing protocols with similar selective photothermolysis (SP) of the SG with very different pain responses. Thus, changing the pulsing protocols allowed for pain mitigation and eliminated the need for injectable anesthetic. Histology confirmed the selective damaging of the SG at depth and the preservation of the surrounding dermis and the epidermis.
Conclusions: The multi-pulse 1726 nm laser with bulk air-cooling, thermal monitoring, treat-to-temperature (and depth) control, and a unique pulsing protocol, is capable of selectively damaging SGs at depth without damage to the surrounding dermis or the epidermis. The system offers two different protocols that were developed with different levels of discomfort allowing for two different methods for pain mitigation (injectable vs. topical anesthesia).
{"title":"Treatment of Acne With a 1726 nm Laser, Air Cooling, and Real-Time Temperature Monitoring, Software-Assisted Power Adjustment to Achieve a Temperature Endpoint With Selective Sebaceous Gland Photothermolysis.","authors":"Emil A Tanghetti, Rafael Sierra, Michael Estes, Aubrey Eck, Alfred Intintoli, Henrik Hofvander, Joel L Cohen, Daniel P Friedmann, Mitchel P Goldman, Hyemin Pomerantz, Jordan V Wang, Roy G Geronemus, R Rox Anderson, Fernanda H Sakamoto","doi":"10.1002/lsm.23872","DOIUrl":"https://doi.org/10.1002/lsm.23872","url":null,"abstract":"<p><strong>Objectives: </strong>This work highlights the methods used to develop a multi-pulse 1726 nm laser system combined with bulk air-cooling for selective sebaceous gland (SG) photothermolysis using thermal imaging and software algorithms. This approach enables treating to a desired tissue temperature and depth to provide a safe, effective, reproducible, and durable treatment of acne.</p><p><strong>Methods: </strong>We designed and built a 1726 nm laser system with a 40 W maximum power output, a highly controlled air-cooling device, and a thermal camera in the handpiece, which permits real-time temperature monitoring of the epidermis. IRB-approved safety and efficacy trials demonstrated SG damage at depth, resulting in safe, efficacious, and durable clinical outcomes. Bioheat transfer and light transport modeling confirmed that the pulsing protocols could produce therapeutic temperatures at various SG depths, while protecting the epidermis and dermis with bulk air-cooling. Similarly, we employed clinical observations and photothermal modeling to identify pain mitigation opportunities while maintaining therapeutic efficacy. Biopsies were subsequently taken for histological evaluation.</p><p><strong>Results: </strong>Clinical and histological data, confirmed with modeling, demonstrated that multi-pulse laser delivery with bulk air-cooling selectively increased SG temperature compared to surrounding dermis and at depths unachievable by a single pulse. Subjects showed an average 71% ILC reduction at 3 months posttreatment. We identified two different pulsing protocols with similar selective photothermolysis (SP) of the SG with very different pain responses. Thus, changing the pulsing protocols allowed for pain mitigation and eliminated the need for injectable anesthetic. Histology confirmed the selective damaging of the SG at depth and the preservation of the surrounding dermis and the epidermis.</p><p><strong>Conclusions: </strong>The multi-pulse 1726 nm laser with bulk air-cooling, thermal monitoring, treat-to-temperature (and depth) control, and a unique pulsing protocol, is capable of selectively damaging SGs at depth without damage to the surrounding dermis or the epidermis. The system offers two different protocols that were developed with different levels of discomfort allowing for two different methods for pain mitigation (injectable vs. topical anesthesia).</p>","PeriodicalId":17961,"journal":{"name":"Lasers in Surgery and Medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142950864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gagik P. Djotyan, Eric R. Mikula, Kinga Kranitz, Zoltan Z. Nagy, Tibor Juhasz
Objectives
Femtosecond laser image guided high precision trabeculotomy (FLigHT) is a novel open-angle glaucoma treatment. The procedure non-invasively creates aqueous humor (AH) drainage channel from the anterior chamber (AC) to Schlemm's canal (SC) through the trabecular meshwork (TM) to decrease intraocular pressure (IOP). The purpose of this study was to develop a 3D finite element model (FEM) of the FLigHT procedure and to simulate clinical results for different drainage channel cross-sectional areas.
Methods
First, a FEM model of the average intact glaucomatous eye was constructed. Biometric data published in the literature were used to construct the geometry of the model, including the AC, TM, SC, and collector channels (CCs). The TM and CCs were modeled as porous material, with given permeability, to approximate the outflow resistance found in these tissues in-vivo. The permeability of the TM and CCs was estimated by comparing iterative FEM simulations with published clinical FLigHT IOP data. For that, the model was modified to simulate the FLigHT treatment of glaucoma by applying a block-like channel connecting the AC to the SC. Channel size was varied from the clinically utilized size of 200 µm × 500 µm down to 50 µm × 50 µm to investigate the effects of channel size on resultant IOP.
Results
The model revealed that the minimum achievable IOP after FLigHT is the preoperative pressure in SC. It is independent of TM permeability; rather, it depends on CC permeability, AH inflow rate, and episcleral venous pressure. In addition, simulations predicted that a channel size of 100 μm × 100 μm is sufficient to obtain the maximum achievable IOP reduction. Beyond this size, no appreciable increase in IOP reduction was achieved.
Conclusions
The 3D FEM developed in this study provided an adequate simulation of the IOP reduction of the FLigHT treatment, demonstrating its predictive power regarding drainage channel geometry and subsequent IOP reduction. The results indicate that the model has the potential to aid the design of clinical FLigHT procedures.
{"title":"3D Finite Element Modeling of Femtosecond Laser Trabeculotomy","authors":"Gagik P. Djotyan, Eric R. Mikula, Kinga Kranitz, Zoltan Z. Nagy, Tibor Juhasz","doi":"10.1002/lsm.23873","DOIUrl":"10.1002/lsm.23873","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Femtosecond laser image guided high precision trabeculotomy (FLigHT) is a novel open-angle glaucoma treatment. The procedure non-invasively creates aqueous humor (AH) drainage channel from the anterior chamber (AC) to Schlemm's canal (SC) through the trabecular meshwork (TM) to decrease intraocular pressure (IOP). The purpose of this study was to develop a 3D finite element model (FEM) of the FLigHT procedure and to simulate clinical results for different drainage channel cross-sectional areas.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>First, a FEM model of the average intact glaucomatous eye was constructed. Biometric data published in the literature were used to construct the geometry of the model, including the AC, TM, SC, and collector channels (CCs). The TM and CCs were modeled as porous material, with given permeability, to approximate the outflow resistance found in these tissues in-vivo. The permeability of the TM and CCs was estimated by comparing iterative FEM simulations with published clinical FLigHT IOP data. For that, the model was modified to simulate the FLigHT treatment of glaucoma by applying a block-like channel connecting the AC to the SC. Channel size was varied from the clinically utilized size of 200 µm × 500 µm down to 50 µm × 50 µm to investigate the effects of channel size on resultant IOP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The model revealed that the minimum achievable IOP after FLigHT is the preoperative pressure in SC. It is independent of TM permeability; rather, it depends on CC permeability, AH inflow rate, and episcleral venous pressure. In addition, simulations predicted that a channel size of 100 μm × 100 μm is sufficient to obtain the maximum achievable IOP reduction. Beyond this size, no appreciable increase in IOP reduction was achieved.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The 3D FEM developed in this study provided an adequate simulation of the IOP reduction of the FLigHT treatment, demonstrating its predictive power regarding drainage channel geometry and subsequent IOP reduction. The results indicate that the model has the potential to aid the design of clinical FLigHT procedures.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17961,"journal":{"name":"Lasers in Surgery and Medicine","volume":"57 2","pages":"219-228"},"PeriodicalIF":2.2,"publicationDate":"2025-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Final Letter From the Editor 2015–2025","authors":"Brian J. F. Wong","doi":"10.1002/lsm.23875","DOIUrl":"10.1002/lsm.23875","url":null,"abstract":"","PeriodicalId":17961,"journal":{"name":"Lasers in Surgery and Medicine","volume":"57 1","pages":"5-6"},"PeriodicalIF":2.2,"publicationDate":"2024-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Craig Fisher, Mary Beth Gadarowski, Jared Roberts, Chad Hivnor
Objectives
Glomangiomas are benign vascular malformations that exist within the spectrum of glomuvenous malformations which consist of varying amounts of glomus cells, vascular spaces, and smooth muscle. Glomangiomas are often treated due to associated pain, particularly when located on pressure areas such as the back or extensor surfaces, which can cause difficulty with certain activities and occupational functions. Histologically glomangiomas consist of prominent dilated vascular spaces lined by glomus cells typically situated in the deep-dermis to subcutaneous fat which limits treatment to modalities capable of reaching the depth of the tumor including excision, sclerotherapy, and laser therapy. To our knowledge laser treatment of glomangiomas has been reported with Nd:YAG (neodymium-doped yttrium aluminum garnet), long-pulsed KTP (potassium-titanyl-phosphate), and PDL (pulsed-dye laser). The objective of our case is to compare the clinical and histologic treatment response of glomangiomas to the 595 nm PDL, 755 nm Alexandrite, and 1064 nm Nd:YAG lasers.
Materials and Methods
Two different laser sessions were performed consisting of PDL (Vbeam Prima Pulsed Dye Laser, Candela), Nd: YAG and Alexandrite (GentleMax Pro, Candela) laser pulses. The GentleMax Pro was utilized for both Nd:YAG and Alexandrite laser pulses as it is capable of functioning in both modalities to deliver 1064 nm and 755 nm wavelengths, respectively. Settings were selected to minimize any risk of potential scarring. Punch biopsies were performed following the second session to assess the histologic response to each laser modality.
Results
Treatment response, as measured by clinical flattening, clearance of obvious blue-red vascular coloration, and resolution of pain, was noted to be most effective for the Alexandrite and Nd:YAG lasers. Procedural and post-procedural pain was noted to be the lowest with Alexandrite. Anatomically, greatest degree of clinical flattening, color normalization with surrounding skin, and sustained clearance was noted for glomangiomas located on acral sites and the trunk.
Conlusions
Optimal treatment of glomulovenous malformation while minimizing patient discomfort may best be achieved with Alexandrite. The exception would be palmar glomangiomas which appeared to respond better to Nd:YAG.
{"title":"Successful Multi-Modal Laser Intervention and Histopathological Evaluation of Multiple Glomangiomas","authors":"Craig Fisher, Mary Beth Gadarowski, Jared Roberts, Chad Hivnor","doi":"10.1002/lsm.23867","DOIUrl":"10.1002/lsm.23867","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Glomangiomas are benign vascular malformations that exist within the spectrum of glomuvenous malformations which consist of varying amounts of glomus cells, vascular spaces, and smooth muscle. Glomangiomas are often treated due to associated pain, particularly when located on pressure areas such as the back or extensor surfaces, which can cause difficulty with certain activities and occupational functions. Histologically glomangiomas consist of prominent dilated vascular spaces lined by glomus cells typically situated in the deep-dermis to subcutaneous fat which limits treatment to modalities capable of reaching the depth of the tumor including excision, sclerotherapy, and laser therapy. To our knowledge laser treatment of glomangiomas has been reported with Nd:YAG (neodymium-doped yttrium aluminum garnet), long-pulsed KTP (potassium-titanyl-phosphate), and PDL (pulsed-dye laser). The objective of our case is to compare the clinical and histologic treatment response of glomangiomas to the 595 nm PDL, 755 nm Alexandrite, and 1064 nm Nd:YAG lasers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>Two different laser sessions were performed consisting of PDL (Vbeam Prima Pulsed Dye Laser, Candela), Nd: YAG and Alexandrite (GentleMax Pro, Candela) laser pulses. The GentleMax Pro was utilized for both Nd:YAG and Alexandrite laser pulses as it is capable of functioning in both modalities to deliver 1064 nm and 755 nm wavelengths, respectively. Settings were selected to minimize any risk of potential scarring. Punch biopsies were performed following the second session to assess the histologic response to each laser modality.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Treatment response, as measured by clinical flattening, clearance of obvious blue-red vascular coloration, and resolution of pain, was noted to be most effective for the Alexandrite and Nd:YAG lasers. Procedural and post-procedural pain was noted to be the lowest with Alexandrite. Anatomically, greatest degree of clinical flattening, color normalization with surrounding skin, and sustained clearance was noted for glomangiomas located on acral sites and the trunk.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conlusions</h3>\u0000 \u0000 <p>Optimal treatment of glomulovenous malformation while minimizing patient discomfort may best be achieved with Alexandrite. The exception would be palmar glomangiomas which appeared to respond better to Nd:YAG.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17961,"journal":{"name":"Lasers in Surgery and Medicine","volume":"57 1","pages":"41-45"},"PeriodicalIF":2.2,"publicationDate":"2024-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142907368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Introduction 2025 Special Dermatology Plastic Surgery Issue","authors":"Macrene Alexiades","doi":"10.1002/lsm.23874","DOIUrl":"10.1002/lsm.23874","url":null,"abstract":"","PeriodicalId":17961,"journal":{"name":"Lasers in Surgery and Medicine","volume":"57 1","pages":"7"},"PeriodicalIF":2.2,"publicationDate":"2024-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jenna E. Montague, Gabrielle V. Hutchens, Caitlin C. Howard, Photini F. S. Rice, David G. Besselsen, Michael Slayton, Urs Utzinger, Jennifer K. Barton, Travis W. Sawyer
Objectives
To study the healing response of rat Achilles tendon when lacerated or treated with intense therapeutic ultrasound (ITU) via utilization of multiphoton microscopy (MPM) imaging and histology.
Materials and Methods
The right Achilles tendon of each Sprague Dawley rat within a cohort was partially lacerated. 1 to 2 days post-surgery, each rat received ITU treatment of the Achilles tendon on either the right or left leg. Rats were euthanized in groups at 1, 3, 7, 14, or 28 days posttreatment and their tendons were explanted, formalin fixed, paraffin embedded, sectioned, and placed on slides for imaging. Slides from each time point were imaged using a laboratory built MPM with a 780 nm Ti:Sapphire laser. The resulting second harmonic generation (SHG) and two-photon excited fluorescence (2PEF) signals were captured, assessed, and compared to brightfield microscopy images of the same section subsequently stained with hematoxylin and eosin.
Results
At early timepoints, 2PEF images show the presence of red blood cells, infiltration of inflammatory cells and formation of a fibrin clot at laceration sites, and attraction of fibroblasts to ITU coagula. SHG images indicate an absence of organized collagen in both types of lesions. At later timepoints, new organized collagen can be seen at the laceration sites, and the concentration of inflammatory cells has noticeably decreased. Automated detection of red blood cells and infiltrative cells, as well as analysis of SHG signal intensity and homogeneity was performed at laceration locations. Results show that all quantities except SHG signal intensity approach normal values by day 28. Thus, combined analysis of 2PEF and SHG images elucidates tendon healing processes that align with and complement histological findings.
Conclusion
These results indicate that multiphoton imaging can effectively visualize the healing response to mechanical (laceration) and thermal (ITU) injury, including the organization of new collagen which is more difficult to visualize with histology.
{"title":"Multiphoton Microscopy Assessment of Healing From Tendon Laceration and Microthermal Coagula in a Rat Model","authors":"Jenna E. Montague, Gabrielle V. Hutchens, Caitlin C. Howard, Photini F. S. Rice, David G. Besselsen, Michael Slayton, Urs Utzinger, Jennifer K. Barton, Travis W. Sawyer","doi":"10.1002/lsm.23871","DOIUrl":"10.1002/lsm.23871","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>To study the healing response of rat Achilles tendon when lacerated or treated with intense therapeutic ultrasound (ITU) via utilization of multiphoton microscopy (MPM) imaging and histology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>The right Achilles tendon of each Sprague Dawley rat within a cohort was partially lacerated. 1 to 2 days post-surgery, each rat received ITU treatment of the Achilles tendon on either the right or left leg. Rats were euthanized in groups at 1, 3, 7, 14, or 28 days posttreatment and their tendons were explanted, formalin fixed, paraffin embedded, sectioned, and placed on slides for imaging. Slides from each time point were imaged using a laboratory built MPM with a 780 nm Ti:Sapphire laser. The resulting second harmonic generation (SHG) and two-photon excited fluorescence (2PEF) signals were captured, assessed, and compared to brightfield microscopy images of the same section subsequently stained with hematoxylin and eosin.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>At early timepoints, 2PEF images show the presence of red blood cells, infiltration of inflammatory cells and formation of a fibrin clot at laceration sites, and attraction of fibroblasts to ITU coagula. SHG images indicate an absence of organized collagen in both types of lesions. At later timepoints, new organized collagen can be seen at the laceration sites, and the concentration of inflammatory cells has noticeably decreased. Automated detection of red blood cells and infiltrative cells, as well as analysis of SHG signal intensity and homogeneity was performed at laceration locations. Results show that all quantities except SHG signal intensity approach normal values by day 28. Thus, combined analysis of 2PEF and SHG images elucidates tendon healing processes that align with and complement histological findings.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These results indicate that multiphoton imaging can effectively visualize the healing response to mechanical (laceration) and thermal (ITU) injury, including the organization of new collagen which is more difficult to visualize with histology.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17961,"journal":{"name":"Lasers in Surgery and Medicine","volume":"57 2","pages":"204-218"},"PeriodicalIF":2.2,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rikke L. Christensen, Heehwa G. Son, Eray Yihui Zhou, Uffe H. Olesen, Lilit Garibyan, William A. Farinelli, Fernanda H. Sakamoto, R. Rox Anderson, Merete Haedersdal, Shadmehr Demehri
<div> <section> <h3> Objective</h3> <p>Physical treatment modalities, such as ablative fractional laser (AFL), electrocautery, and cryotherapy, are extensively used in the field of dermatology. This study aimed to characterize the short-term innate and adaptive immune responses induced by AFL compared with heat- and cold-based procedures.</p> </section> <section> <h3> Materials and Methods</h3> <p>Innate (CD11b<sup>+</sup>Ly6G<sup>+</sup> neutrophils) and adaptive (CD8<sup>+</sup>CD3<sup>+</sup> T cells) immune cell infiltration and histopathological changes were examined in murine skin on Days 1 and 7, following AFL, monopolar-electrocautery (RF), thermocautery, and cryotherapy. Interventions were standardized to reach the reticular dermis. Clinical skin reactions were photo-documented daily. As a comparator, the adaptive immune response was examined in murine basal cell carcinomas (BCC) on Day 7 after AFL exposure.</p> </section> <section> <h3> Results</h3> <p>Baseline histopathology confirmed immediate deep dermal tissue impact by all procedures. Immune cell dynamics varied across treatments throughout the progression of clinical and histopathological responses. On Day 1, AFL and heat-based procedures triggered an innate immune response, characterized by CD11b<sup>+</sup>Ly6G<sup>+</sup> neutrophil cell infiltration that correlated with histopathological findings and immediate onset of clinical skin reactions. In addition, heat-based procedures led to an increase in overall dermal CD45<sup>+</sup> cells (Day 1), which continued to rise for AFL and RF-electrocautery at Day 7 posttreatment. On the contrary, cryotherapy did not induce immediate (Day 1) innate immune responses, but instead a delayed increase in neutrophil and CD45<sup>+</sup> cell infiltration (Day 7), which coincided with the late onset of clinical reaction. CD3<sup>+</sup> T cells and CD8<sup>+</sup>CD3<sup>+</sup> T cells demonstrated a similar pattern, with an increase observed for heat-based procedures on Day 1 and a delayed increase for cryotherapy on Day 7. Distinctive for AFL-treated skin, the level of dermal CD3<sup>+</sup> T cells increased over time, significant by Day 7, and AFL-treated mouse BCCs responded with increased CD8<sup>+</sup> T cell infiltration at Day 7 posttreatment.</p> </section> <section> <h3> Conclusion</h3> <p>Heat- and cold-based procedures developed distinct cutaneous immune responses, with cryotherapy resulting in a delayed response compared to immediate immune responses from heat-based procedures. The substantial T cell response induced by AFL in the skin and BCC tumors indicates a potential for AFL as an adjuvant in immunotherape
{"title":"Cutaneous Immune Responses to Ablative Fractional Laser, Heat- and Cold-Based Dermatological Procedures","authors":"Rikke L. Christensen, Heehwa G. Son, Eray Yihui Zhou, Uffe H. Olesen, Lilit Garibyan, William A. Farinelli, Fernanda H. Sakamoto, R. Rox Anderson, Merete Haedersdal, Shadmehr Demehri","doi":"10.1002/lsm.23868","DOIUrl":"10.1002/lsm.23868","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Physical treatment modalities, such as ablative fractional laser (AFL), electrocautery, and cryotherapy, are extensively used in the field of dermatology. This study aimed to characterize the short-term innate and adaptive immune responses induced by AFL compared with heat- and cold-based procedures.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>Innate (CD11b<sup>+</sup>Ly6G<sup>+</sup> neutrophils) and adaptive (CD8<sup>+</sup>CD3<sup>+</sup> T cells) immune cell infiltration and histopathological changes were examined in murine skin on Days 1 and 7, following AFL, monopolar-electrocautery (RF), thermocautery, and cryotherapy. Interventions were standardized to reach the reticular dermis. Clinical skin reactions were photo-documented daily. As a comparator, the adaptive immune response was examined in murine basal cell carcinomas (BCC) on Day 7 after AFL exposure.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Baseline histopathology confirmed immediate deep dermal tissue impact by all procedures. Immune cell dynamics varied across treatments throughout the progression of clinical and histopathological responses. On Day 1, AFL and heat-based procedures triggered an innate immune response, characterized by CD11b<sup>+</sup>Ly6G<sup>+</sup> neutrophil cell infiltration that correlated with histopathological findings and immediate onset of clinical skin reactions. In addition, heat-based procedures led to an increase in overall dermal CD45<sup>+</sup> cells (Day 1), which continued to rise for AFL and RF-electrocautery at Day 7 posttreatment. On the contrary, cryotherapy did not induce immediate (Day 1) innate immune responses, but instead a delayed increase in neutrophil and CD45<sup>+</sup> cell infiltration (Day 7), which coincided with the late onset of clinical reaction. CD3<sup>+</sup> T cells and CD8<sup>+</sup>CD3<sup>+</sup> T cells demonstrated a similar pattern, with an increase observed for heat-based procedures on Day 1 and a delayed increase for cryotherapy on Day 7. Distinctive for AFL-treated skin, the level of dermal CD3<sup>+</sup> T cells increased over time, significant by Day 7, and AFL-treated mouse BCCs responded with increased CD8<sup>+</sup> T cell infiltration at Day 7 posttreatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Heat- and cold-based procedures developed distinct cutaneous immune responses, with cryotherapy resulting in a delayed response compared to immediate immune responses from heat-based procedures. The substantial T cell response induced by AFL in the skin and BCC tumors indicates a potential for AFL as an adjuvant in immunotherape","PeriodicalId":17961,"journal":{"name":"Lasers in Surgery and Medicine","volume":"57 1","pages":"101-111"},"PeriodicalIF":2.2,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dennis Eggert, David Gaertner, Adrian Rühm, Ronald Sroka, Christoph Arens, Nikolaos Davaris, Konrad Birkmeier, Andreas Brodschelm, Patrick Leisching, Hauke Studier, Wolfgang Becker, Karsten König, Christan S. Betz
Objectives
With over 184,000 new cases and more than 99,000 deaths per year, malignancies of the larynx are a global health problem. Currently, a dedicated screening method enabling a direct onsite diagnosis is missing. This can lead to delayed diagnosis and worse outcomes of the patients. An endoscopic optical method enabling a direct distinction between healthy tissue, dysplastic tissue and cancerous tissue would be an ideal tool for the detection of tumors of the upper aerodigestive tract (UADT). Healthy and tumor cells differ significantly in their metabolic state due to the different metabolic pathways they use (more oxidative phosphorylation in healthy cells, more glycolysis in tumor cells). Optical metabolic imaging (OMI) measuring relative intracellular concentration of NAD(P)H and FAD redox pairs could be a promising approach for early tumor detection and differentiation of suspicious mucosal lesions.
Methods
In this study, a specially designed endoscopic two-beam two-photon fluorescence lifetime imaging (FLIM) system was used to perform two-photon two-beam FLIM of NAD(P)H and FAD to image the metabolic state in different tissue samples of the UADT. FLIM data sets of 27 tissue samples from 16 patients were recorded directly after surgery ex vivo in a special tissue culture medium at 37°C on a dedicated microscope using multiphoton excitation.
Results
Based on the FLIM measurements of NAD(P)H and FAD, six of the most common indices for the characterization of the cells' metabolism were calculated. Three of them, the ratio of the exponential coefficients (amplitudes) of the short and long lifetime components both for NAD(P)H and FAD (NAD(P)H a1/a2 ratio and FAD a1/a2 ratio) and the fluorescence lifetime redox ratio (FLIRR) enabled differentiation between healthy tissue, benign lesions, dysplastic tissue, and cancer tissue with statistical significance.
Conclusions
We showed by measurements on freshly collected tissue samples that mucosal lesions of the UADT can be differentiated using our newly designed endoscopic FLIM device. In vivo measurements in healthy volunteers were also possible. By means of this technology, differentiation of cancerous, pre-cancerous, and healthy tissue in the UADT by OMI could be possible. Of six indices used to characterize cell metabolism we calculated, the FLIRR showed the most significant differences between tissue types.
{"title":"Differentiation of Tumors of the Upper Respiratory Tract Using Optical Metabolic Imaging","authors":"Dennis Eggert, David Gaertner, Adrian Rühm, Ronald Sroka, Christoph Arens, Nikolaos Davaris, Konrad Birkmeier, Andreas Brodschelm, Patrick Leisching, Hauke Studier, Wolfgang Becker, Karsten König, Christan S. Betz","doi":"10.1002/lsm.23870","DOIUrl":"10.1002/lsm.23870","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>With over 184,000 new cases and more than 99,000 deaths per year, malignancies of the larynx are a global health problem. Currently, a dedicated screening method enabling a direct onsite diagnosis is missing. This can lead to delayed diagnosis and worse outcomes of the patients. An endoscopic optical method enabling a direct distinction between healthy tissue, dysplastic tissue and cancerous tissue would be an ideal tool for the detection of tumors of the upper aerodigestive tract (UADT). Healthy and tumor cells differ significantly in their metabolic state due to the different metabolic pathways they use (more oxidative phosphorylation in healthy cells, more glycolysis in tumor cells). Optical metabolic imaging (OMI) measuring relative intracellular concentration of NAD(P)H and FAD redox pairs could be a promising approach for early tumor detection and differentiation of suspicious mucosal lesions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this study, a specially designed endoscopic two-beam two-photon fluorescence lifetime imaging (FLIM) system was used to perform two-photon two-beam FLIM of NAD(P)H and FAD to image the metabolic state in different tissue samples of the UADT. FLIM data sets of 27 tissue samples from 16 patients were recorded directly after surgery ex vivo in a special tissue culture medium at 37°C on a dedicated microscope using multiphoton excitation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Based on the FLIM measurements of NAD(P)H and FAD, six of the most common indices for the characterization of the cells' metabolism were calculated. Three of them, the ratio of the exponential coefficients (amplitudes) of the short and long lifetime components both for NAD(P)H and FAD (NAD(P)H a1/a2 ratio and FAD a1/a2 ratio) and the fluorescence lifetime redox ratio (FLIRR) enabled differentiation between healthy tissue, benign lesions, dysplastic tissue, and cancer tissue with statistical significance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We showed by measurements on freshly collected tissue samples that mucosal lesions of the UADT can be differentiated using our newly designed endoscopic FLIM device. In vivo measurements in healthy volunteers were also possible. By means of this technology, differentiation of cancerous, pre-cancerous, and healthy tissue in the UADT by OMI could be possible. Of six indices used to characterize cell metabolism we calculated, the FLIRR showed the most significant differences between tissue types.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17961,"journal":{"name":"Lasers in Surgery and Medicine","volume":"57 2","pages":"147-153"},"PeriodicalIF":2.2,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/lsm.23870","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142837331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
David A. Hashemi, Joy Tao, Jordan V. Wang, Roy G. Geronemus
Introduction
The 595-nm wavelength pulsed dye laser (PDL) is well-established in the treatment of vascular lesions. In June 2023, it received FDA clearance for the treatment of port-wine birthmarks (PWB) and infantile hemangiomas (IH) in the pediatric population.
Objective
Review the evidence regarding the efficacy, safety, and implications of using PDL for management of pediatric PWB and IH.
Methods
A systematic literature search was performed to identify peer-reviewed articles and clinical trials published between July 2002 and December 2022 in which PDL was used to treat pediatric PWB and IH.
Results
After application of criteria, 33 journal articles with 7725 total patients were included. Only 16 (0.8%) of the 2,033 patients with PWB and 11 (0.2%) of the 5692 patients with hemangioma reported permanent adverse effects including scarring, keloids, or permanent pigmentation change, and none reported blindness or other serious injury. Good, excellent, or complete clearance after PDL–on average or in greater than 50% of patients–was reported in 17 of 19 studies (89%) that reported these measures for PWB, and seven of the seven studies (100%) for IH.
Conclusion
The 595-nm PDL is an excellent treatment option for early intervention in pediatric patients with PWB or IH.
{"title":"The 595-nm Wavelength Pulsed Dye Laser for Pediatric Port-Wine Birthmarks and Infantile Hemangiomas: A Systematic Review","authors":"David A. Hashemi, Joy Tao, Jordan V. Wang, Roy G. Geronemus","doi":"10.1002/lsm.23864","DOIUrl":"10.1002/lsm.23864","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The 595-nm wavelength pulsed dye laser (PDL) is well-established in the treatment of vascular lesions. In June 2023, it received FDA clearance for the treatment of port-wine birthmarks (PWB) and infantile hemangiomas (IH) in the pediatric population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Review the evidence regarding the efficacy, safety, and implications of using PDL for management of pediatric PWB and IH.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A systematic literature search was performed to identify peer-reviewed articles and clinical trials published between July 2002 and December 2022 in which PDL was used to treat pediatric PWB and IH.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>After application of criteria, 33 journal articles with 7725 total patients were included. Only 16 (0.8%) of the 2,033 patients with PWB and 11 (0.2%) of the 5692 patients with hemangioma reported permanent adverse effects including scarring, keloids, or permanent pigmentation change, and none reported blindness or other serious injury. Good, excellent, or complete clearance after PDL–on average or in greater than 50% of patients–was reported in 17 of 19 studies (89%) that reported these measures for PWB, and seven of the seven studies (100%) for IH.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The 595-nm PDL is an excellent treatment option for early intervention in pediatric patients with PWB or IH.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17961,"journal":{"name":"Lasers in Surgery and Medicine","volume":"57 1","pages":"27-36"},"PeriodicalIF":2.2,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11776443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142837340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Joshua Zev Glahn, Michael Wang-Evers, Abigail R. Carlson, Haley Marks, Daniel Karasik, Felix Hilge, Jeremy Goverman, Dieter Manstein
Background
Ablative fractional CO2 laser (10,600 nm) treatment creates an array of microscopic treatment zones composed of an ablation zone (AZ) surrounded by a denatured coagulation zone (CZ). The CZ is believed to play a functional role in skin tightening, posttreatment inflammation, and laser-assisted drug delivery. This study investigates the viability of enzymatic post-processing to remove the CZ without affecting the surrounding tissue.
Methods
Ex vivo skin samples were treated with either control, papain, urea, or papain–urea solutions before being covered with occlusive dressing and incubated at 37°C for 1 h. Tissue viability as well as AZ and CZ geometries were assessed histologically.
Results
Treatment with all three experimental solutions resulted in a decrease in CZ. The largest average reduction in CZ area was observed in the papain–urea group (44%, p < 0.001), followed by the papain (14%, p < 0.001) and urea (11%, p < 0.001) only groups. Only the papain–urea group showed a significant increase in AZ (14%) and changes in lesion geometry.
Conclusion
This exploratory study of enzymatic post-processing with papain–urea highlighted the potential of selectively removing the CZ after treatment with ablative fractional laser therapy. If results can be translated to in vivo studies, these findings could expand the use of high-fluence CO2 laser therapy with functional implications for lowering posttreatment recovery time, providing clinicians more control over skin tightening, and enabling a broader range of laser-assisted drug delivery.
{"title":"Evaluation of Papain–Urea for Enzymatic Debridement of Coagulation Zones Following Ablative Fractional Laser Treatment","authors":"Joshua Zev Glahn, Michael Wang-Evers, Abigail R. Carlson, Haley Marks, Daniel Karasik, Felix Hilge, Jeremy Goverman, Dieter Manstein","doi":"10.1002/lsm.23865","DOIUrl":"10.1002/lsm.23865","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Ablative fractional CO<sub>2</sub> laser (10,600 nm) treatment creates an array of microscopic treatment zones composed of an ablation zone (AZ) surrounded by a denatured coagulation zone (CZ). The CZ is believed to play a functional role in skin tightening, posttreatment inflammation, and laser-assisted drug delivery. This study investigates the viability of enzymatic post-processing to remove the CZ without affecting the surrounding tissue.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Ex vivo skin samples were treated with either control, papain, urea, or papain–urea solutions before being covered with occlusive dressing and incubated at 37°C for 1 h. Tissue viability as well as AZ and CZ geometries were assessed histologically.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Treatment with all three experimental solutions resulted in a decrease in CZ. The largest average reduction in CZ area was observed in the papain–urea group (44%, <i>p</i> < 0.001), followed by the papain (14%, <i>p</i> < 0.001) and urea (11%, <i>p</i> < 0.001) only groups. Only the papain–urea group showed a significant increase in AZ (14%) and changes in lesion geometry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This exploratory study of enzymatic post-processing with papain–urea highlighted the potential of selectively removing the CZ after treatment with ablative fractional laser therapy. If results can be translated to in vivo studies, these findings could expand the use of high-fluence CO<sub>2</sub> laser therapy with functional implications for lowering posttreatment recovery time, providing clinicians more control over skin tightening, and enabling a broader range of laser-assisted drug delivery.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17961,"journal":{"name":"Lasers in Surgery and Medicine","volume":"57 1","pages":"112-120"},"PeriodicalIF":2.2,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11776449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142837338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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