A Public Health Research Agenda for Managing Infodemics: Methods and Results of the First WHO Infodemiology Conference.

BACKGROUND: An infodemic is an overflow of information of varying quality that surges across digital and physical environments during an acute public health event. It leads to confusion, risk-taking, and behaviors that can harm health and lead to erosion of trust in health authorities and public health responses. Owing to the global scale and high stakes of the health emergency, responding to the infodemic related to the pandemic is particularly urgent. Building on diverse research disciplines and expanding the discipline of infodemiology, more evidence-based interventions are needed to design infodemic management interventions and tools and implement them by health emergency responders. OBJECTIVE: The World Health Organization organized the first global infodemiology conference, entirely online, during June and July 2020, with a follow-up process from August to October 2020, to review current multidisciplinary evidence, interventions, and practices that can be applied to the COVID-19 infodemic response. This resulted in the creation of a public health research agenda for managing infodemics. METHODS: As part of the conference, a structured expert judgment synthesis method was used to formulate a public health research agenda. A total of 110 participants represented diverse scientific disciplines from over 35 countries and global public health implementing partners. The conference used a laddered discussion sprint methodology by rotating participant teams, and a managed follow-up process was used to assemble a research agenda based on the discussion and structured expert feedback. This resulted in a five-workstream frame of the research agenda for infodemic management and 166 suggested research questions. The participants then ranked the questions for feasibility and expected public health impact. The expert consensus was summarized in a public health research agenda that included a list of priority research questions. RESULTS: The public health research agenda for infodemic management has five workstreams: (1) measuring and continuously monitoring the impact of infodemics during health emergencies; (2) detecting signals and understanding the spread and risk of infodemics; (3) responding and deploying interventions that mitigate and protect against infodemics and their harmful effects; (4) evaluating infodemic interventions and strengthening the resilience of individuals and communities to infodemics; and (5) promoting the development, adaptation, and application of interventions and toolkits for infodemic management. Each workstream identifies research questions and highlights 49 high priority research questions. CONCLUSIONS: Public health authorities need to develop, validate, implement, and adapt tools and interventions for managing infodemics in acute public health events in ways that are appropriate for their countries and contexts. Infodemiology provides a scientific foundation to make this possible. This research agenda proposes a structured framework for targeted investment for the scientific community, policy makers, implementing organizations, and other stakeholders to consider.

Electrochemical Therapy of In Vivo Rabbit Cutaneous Tissue.

OBJECTIVES: To examine the acid-base and histological changes in in vivo rabbit cutaneous tissue after electrochemical therapy. STUDY DESIGN: In vivo rabbit tissue study. METHODS: The shaved skin on the backs of female Oryctolagus cuniculi were assigned to treatments with or without tumescence with normal saline. Two platinum-needle electrodes were inserted into each treatment area and connected to a direct current (DC) power supply. Voltage (3-5 V) was varied and applied for 5 minutes. The wound-healing process was monitored via digital photography and ultrasonography until euthanasia at day 29. Treatment areas were biopsied, and specimens were sectioned through a sagittal midline across both electrode insertion sites. Samples were then evaluated utilizing light microscopy (hematoxylin and eosin, Masson's Trichrome, and Picrosirius red). RESULTS: Treatment sites developed mild inflammation that dissipated at lower voltages or became scabs at higher voltages. Ultrasonography demonstrated acoustic shadowing with spatial spread that increased with increasing voltage application. The 4- and 5-V sites treated with saline had localized areas of increased tissue density at day 29. Although specimens treated with 3 V did not look significantly different from control tissue, 4- and 5-V samples with and without saline tumescence had finer, less-organized collagen fibers and increased presence of fibrocytes and inflammatory infiltrates. CONCLUSIONS: Electrochemical therapy caused localized injury to in vivo rabbit cutaneous tissue, prompting regenerative wound repair. With future development, this technology may offer precise, low-cost rejuvenation to restore the functionality and appearance of dermal scars and keloids. LEVEL OF EVIDENCE: NA Laryngoscope, 131:E2196-E2203, 2021.

Electrochemical degradation and saponification of porcine adipose tissue.

Body contouring achieved via subcutaneous adipose tissue reduction has notably advanced over the past century, from suction assisted lipectomy to techniques with reduced degrees of invasiveness including laser, radiofrequency, high frequency focused ultrasound, cryolipolysis, and drug-based injection approaches. These costly techniques have focused on damaging adipocyte cell membranes, hydrolyzing triglycerides (TGs), or inducing apoptosis. Here, we present a simple, low-cost technique, termed electrochemical lipolysis (ECLL). During ECLL, saline is injected into the subcutaneous adipose tissue, followed by insertion of needle electrodes and application of an electrical potential. Electrolysis of saline creates localized pH gradients that drive adipocyte death and saponification of TGs. Using pH mapping, various optical imaging techniques, and biochemical assays, we demonstrate the ability of ECLL to induce acid and base injury, cell death, and the saponification of triglycerides in ex vivo porcine adipose tissue. We define ECLL's potential role as a minimally-invasive, ultra-low-cost technology for reducing and contouring adipose tissue, and present ECLL as a potential new application of an emerging electrochemical redox based treatment modality.

The biophysical effects of localized electrochemical therapy on porcine skin.

BACKGROUND: Minimally-invasive methods to treat scars address a common pathway of altering collagen structure, leading to collagen remodeling. OBJECTIVE: In this study, we employed in situ redox chemistry to create focal pH gradients in skin, altering dermal collagen, in a process we refer to as electrochemical therapy (ECT). The effects of ECT to induce biochemical and structural changes in ex vivo porcine skin were examined. METHODS: During ECT, two platinum electrodes were inserted into fresh porcine skin, and following saline injection, an electrical potential was applied. pH mapping, high frequency ultrasonography, and two photon excitation microscopy and second harmonic generation (SHG) microscopy were used to evaluate treatment effects. Findings were correlated with histology. RESULTS: Following ECT, pH mapping depicted acid and base production at anode and cathode sites respectively, with increasing voltage and application time. Gas formation during ECT was observed with ultrasonography. Anode sites showed significant loss of SHG signal, while cathode sites showed disorganized collagen structure with fewer fibrils emitting an attainable signal. Histologically, collagen denaturation at both sites was confirmed. CONCLUSION: We demonstrated the production of in situ acid and base in skin occurring via ECT. The effects chemically and precisely alter collagen structure through denaturation, giving insight on the potential of ECT as a simple, low-cost, and minimally-invasive means to remodel skin and treat scars.

Multiphoton Microscopy of Collagen Structure in Ex Vivo Human Skin Following Electrochemical Therapy.

OBJECTIVES: Injury to healthy dermis and the dermoepidermal junction initiates a robust healing process consisting of fibrous tissue overgrowth, collagen deposition, and scar formation. The conventional management of scars and other skin injuries has largely relied upon surgical soft tissue transfer to resurface and/or replace damaged and dysmorphic tissue with new skin. However, these strategies are invasive, expensive, and may further exacerbate integumentary injury. In this study, we examine the creation of in situ redox generated pH changes in fresh human skin. We believe this process of "electrochemical therapy" (ECT) leads to changes in collagen matrix structure. Our objective is to map local tissue pH landscapes and image changes in collagen structure of non-injured skin following ECT. STUDY DESIGN: Ex vivo human study involving ECT of human skin. METHODS: Remnant fresh ex vivo human facial skin from facelift operations was enveloped in saline-soaked gauze for a maximum of 2 hours prior to ECT and imaging. ECT was performed by inserting platinum-plated needle electrodes connected to a DC power supply. Voltage (4, 5, or 6 V) and time (3, 4, or 5 minutes) were varied systematically. High frequency ultrasound (25 MHz) was performed immediately after ECT on each sample. Treated samples were also imaged using multiphoton microscopy (MPM) with second harmonic generation (SHG) to specifically visualize collagen fibers in the dermis. The pH landscapes were mapped using indicator dyes in bisected specimens and the MPM images were compared with histologic findings. RESULTS: Above 4 V and 3 minutes, a profound reduction in dermal collagen SHG signal was observed at the anode. Although there was less blunting of SHG signal seen at the cathode, a decrease in the fluorescence of the dermoepidermal junction was observed. The pH application suggests ECT spatial selectivity and a direct relationship between voltage and application time. Ultrasound demonstrated gas formation between the anode and cathode, which is consistent with ECT's mechanism of action. Importantly, these electrochemical changes occurred without disrupting dermal and epidermal histologic architecture. CONCLUSION: ECT alters tissue pH leading to dermal collagen structural change. These results offer additional insight into the translational potential of ECT to locally remodel the soft-tissue matrix. Future directions aim to expand into a skin injury model to determine if similar collagen effects are observed in vivo. ECT is incredibly inexpensive (~$5) and may be a means to treat soft tissue injuries using simple needle-based devices and DC battery power supplies. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Quantitative Analysis and Classification of the Nasal Base Using a Parametric Model.

IMPORTANCE: The nasal base view is often overlooked in rhinoplasty analysis and, unlike lateral and frontal views, lacks detailed quantitative analysis and descriptors. While shape-category analysis of the nasal base is well established, these descriptive methods remain subjective and do not facilitate quantitative analysis. OBJECTIVE: To establish a simple and quantitative classification scheme using a multiple-parameter numerical model for analyzing and describing the shape of the nasal base. DESIGN, SETTING, AND PARTICIPANTS: Deidentified photographs of the nasal base view were analyzed without knowledge of patients' pathology or medical history. Each nose was classified into 1 of 6 categories derived from literature (equilateral, narrow, flat, cloverleaf, boxy, and round). Finite parametric modeling was performed on each nose, and the correlations between the resulting parameters and the 6 categories were analyzed. Photographs for this study were acquired from the practice of a single facial plastic surgeon (B.J.F.W.) at a tertiary care academic medical center. One hundred twenty-one consecutive patients who had nasal base view photographs taken were included in the study. MAIN OUTCOMES AND MEASURES: All of the 121 images were classified into 1 of the 6 categories by 1 reviewer (C.H.B.). The contour of each nasal base was curve fit to a 5-parameter numerical model. The 5 parameters controlled base size, deviation from the midline, projection-to-width ratio, degree of nasal alar recurvature, and anterior-posterior positioning of nasal base bulk. A numerical value for each nasal base shape type was predicted by the parametric model. RESULTS: In 121 patient photographs, the parametric model generated shapes that accurately matched the tracing of the actual nasal base contours with an average correlation coefficient of greater than 0.98. This finding indicates close approximation of the nasal base shape with the curve fit constructed by the PM. Parameters b (projection-to-width ratio) and e (roundedness) were shown to have significant differences among the groups (F statistic, 8.88; P < .001 and F statistic, 13.05; P < .001, respectively). These two curve-fit parameters alone could be used to classify nasal shape into 1 of the 6 clinically determined base geometries. CONCLUSIONS AND RELEVANCE: A numerical approach to classify nasal base shape was developed using a 5-parameter model and tested against subjective analysis. This model may aid in the advancement of algorithm-driven objective nasal analysis techniques, preoperative modeling, intraoperative guidance, and surgical outcome measures beyond using Likert scales. LEVEL OF EVIDENCE: NA.

Association of Electrochemical Therapy With Optical, Mechanical, and Acoustic Impedance Properties of Porcine Skin.

IMPORTANCE: The classic management of burn scars and other injuries to the skin has largely relied on soft-tissue transfer to resurface damaged tissue with local tissue transfer or skin graft placement. In situ generation of electrochemical reactions using needle electrodes and an application of current may be a new approach to treat scars and skin. OBJECTIVE: To examine the changes in optical, mechanical, and acoustic impedance properties in porcine skin after electrochemical therapy. DESIGN, SETTING, AND PARTICIPANTS: This preclinical pilot study, performed from August 1, 2015, to November 1, 2016, investigated the effects of localized pH-driven electrochemical therapy of ex vivo porcine skin using 24 skin samples. Platinum-plated needle electrodes were inserted into fresh porcine skin samples. A DC power supply provided a voltage of 4 to 5 V with a 3-minute application time. Specimens were analyzed using optical coherence tomography, optical coherence elastography, and ultrasonography. Ultrasonography was performed under 3 conditions (n = 2 per condition), optical coherence tomography was performed under 2 conditions (n = 2 per condition), and optical coherence elastography was performed under 2 conditions (n = 2 per condition). The remaining samples were used for the positive and negative control groups (n = 10). EXPOSURES: Platinum-plated needle electrodes were inserted into fresh porcine skin samples. A DC power supply provided a voltage of 4 to 5 V with a 3-minute application. MAIN OUTCOMES AND MEASURES: Tissue softening was observed at the anode and cathode sites as a result of electrochemical modification. Volumetric changes were noted using each optical and acoustic technique. RESULTS: A total of 24 ex vivo porcine skin samples were used for this pilot study. Optical coherence tomography measured spatial distribution of superficial tissue changes around each electrode site. At 4 V for 3 minutes, a total volumetric effect of 0.47 mm3 was found at the anode site and 0.51 mm3 at the cathode site. For 5 V for 3 minutes, a total volumetric effect of 0.85 mm3 was found at the anode site and 1.05 mm3 at the cathode site. CONCLUSIONS AND RELEVANCE: Electrochemical therapy is a low-cost technique that is on par with the costs of suture and scalpel. The use of electrochemical therapy to create mechanical and physiologic changes in tissue has the potential to locally remodel the soft-tissue matrix, which ultimately may lead to an inexpensive scar treatment or skin rejuvenation therapy. LEVEL OF EVIDENCE: NA.

Histologic changes associated with talaporfin sodium-mediated photodynamic therapy in rat skin.

BACKGROUND AND OBJECTIVE: Alternative treatments are needed to achieve consistent and more complete port wine stain (PWS) removal, especially in darker skin types; photodynamic therapy (PDT) is a promising alternative treatment. To this end, we previously reported on Talaporfin Sodium (TS)-mediated PDT. It is essential to understand treatment tissue effects to design a protocol that will achieve selective vascular injury without ulceration and scarring. The objective of this work is to assess skin changes associated with TS-mediated PDT with clinically relevant treatment parameters. STUDY DESIGN/MATERIALS AND METHODS: We performed TS (0.75 mg/kg)-mediated PDT (664 nm) on Sprague Dawley rats. Radiant exposures were varied between 15 and 100 J/cm2 . We took skin biopsies from subjects at 9 hours following PDT. We assessed the degree and depth of vascular and surrounding tissue injury using histology and immunohistochemical staining. RESULTS: TS-mediated PDT at 0.75 mg/kg combined with 15 and 25 J/cm2 light doses resulted in vascular injury with minimal epidermal damage. At light dose of 50 J/cm2 , epidermal damage was noted with vascular injury. At light doses >50 J/cm2 , both vascular and surrounding tissue injury were observed in the forms of vasculitis, extravasated red blood cells, and coagulative necrosis. Extensive coagulative necrosis involving deeper adnexal structures was observed for 75 and 100 J/cm2 light doses. Observed depth of injury increased with increasing radiant exposure, although this relationship was not linear. CONCLUSION: TS-mediated PDT can cause selective vascular injury; however, at higher light doses, significant extra-vascular injury was observed. This information can be used to contribute to design of safe protocols to be used for treatment of cutaneous vascular lesions. Lasers Surg. Med. 49:767-772, 2017. © 2017 Wiley Periodicals, Inc.

Photobiomodulation by laser therapy rescued auditory neuropathy induced by ouabain.

Auditory neuropathy is a hearing disorder caused by impaired auditory nerve function. The lack of information about the pathophysiology of this disease limits early diagnosis and further treatment. Laser therapy is a novel approach to enhance nerve growth or induce axonal regeneration. We induced auditory neural degeneration sparing the sensory epithelium with local ouabain application in an animal model and observed the rescue effect of photobiomodulation (PBM), showing recovered auditory function and favorable histologic outcome. Hearing was evaluated using the auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE). Seven days after ouabain application, the animals were sacrificed to evaluate the morphological changes. DPOAE change was not observed in all groups after ouabain application indicating no changes of outer hair cell function. Ouabain application increased the ABR thresholds increase, while the use of ouabain plus laser produced lower threshold compared to the ouabain group. Hematoxylin and Eosin staining of cochlea mid-modiolar sections in animals treated with ouabain showed damaged spiral ganglion cells, neurofilaments, and post synaptic puncta. Ouabain plus laser group showed higher number of spiral ganglion cells, higher density of neurofilaments, and higher number post synaptic puncta counts compared with ouabain application group. Short-term application of ouabain caused spiral ganglion cell damage while sparing the inner and outer hair cells in gerbils. Photobiomodulation alleviated the hearing loss caused by ouabain induced auditory neuropathy. The results indicate the possible role of photobiomodulation therapy for inner ear diseases accompanied by spiral ganglion degeneration.

Simultaneous bilateral laser therapy accelerates recovery after noise-induced hearing loss in a rat model.

Noise-induced hearing loss is a common type of hearing loss. The effects of laser therapy have been investigated from various perspectives, including in wound healing, inflammation reduction, and nerve regeneration, as well as in hearing research. A promising feature of the laser is its capability to penetrate soft tissue; depending on the wavelength, laser energy can penetrate into the deepest part of the body without damaging non-target soft tissues. Based on this idea, we developed bilateral transtympanic laser therapy, which uses simultaneous laser irradiation in both ears, and evaluated the effects of bilateral laser therapy on cochlear damage caused by noise overexposure. Thus, the purpose of this research was to assess the benefits of simultaneous bilateral laser therapy compared with unilateral laser therapy and a control. Eighteen Sprague-Dawley rats were exposed to narrow-band noise at 115 dB SPL for 6 h. Multiple auditory brainstem responses were measured after each laser irradiation, and cochlear hair cells were counted after the 15th such irradiation. The penetration depth of the 808 nm laser was also measured after sacrifice. Approximately 5% of the laser energy reached the contralateral cochlea. Both bilateral and unilateral laser therapy decreased the hearing threshold after noise overstimulation in the rat model. The bilateral laser therapy group showed faster functional recovery at all tested frequencies compared with the unilateral laser therapy group. However, there was no difference in the endpoint ABR results or final hair cell survival, which was analyzed histologically.

The Role of Laser Speckle Imaging in Port-Wine Stain Research: Recent Advances and Opportunities.

Here, we review our current knowledge on the etiology and treatment of port-wine stain (PWS) birthmarks. Current treatment options have significant limitations in terms of efficacy. With the combination of 1) a suitable preclinical microvascular model, 2) laser speckle imaging (LSI) to evaluate blood-flow dynamics, and 3) a longitudinal experimental design, rapid preclinical assessment of new phototherapies can be translated from the lab to the clinic. The combination of photodynamic therapy (PDT) and pulsed-dye laser (PDL) irradiation achieves a synergistic effect that reduces the required radiant exposures of the individual phototherapies to achieve persistent vascular shutdown. PDL combined with anti-angiogenic agents is a promising strategy to achieve persistent vascular shutdown by preventing reformation and reperfusion of photocoagulated blood vessels. Integration of LSI into the clinical workflow may lead to surgical image guidance that maximizes acute photocoagulation, is expected to improve PWS therapeutic outcome. Continued integration of noninvasive optical imaging technologies and biochemical analysis collectively are expected to lead to more robust treatment strategies.

Hemoporfin-mediated photodynamic therapy on normal vasculature: implications for phototherapy of port-wine stain birthmarks.

BACKGROUND: Port-wine stain (PWS) birthmarks currently are treated using a pulsed dye laser (PDL) combined with transient cooling of the epidermis. PDL treatment protocols utilize short pulses of light (585 or 595 nm wavelength) to heat selectively the microvasculature due to absorption by intravascular hemoglobin. Although most patients respond to PDL therapy, few experience complete removal of the PWS. An alternate treatment option to PDL therapy of PWS is photodynamic therapy (PDT). Research groups have reported on various photosensitizers for PDT of PWS, including Hemoporfin, Benzoporphyrin Derivative monoacid ring A, and talaporfin sodium. AIM: Our aim was to evaluate, with an established preclinical in-vivo model, the efficacy of photodynamic therapy (PDT) with Hemoporfin to achieve persistent vascular shutdown. METHODS: To monitor the microvasculature, a dorsal window chamber was surgically installed on 24 adult mice. The PDT excitation source emitted 150mW of 532nm light, with an irradiance of 100mW/cm2. A retroorbital injection of Hemoporfin (2 mg/kg) was performed to deliver the drug into the bloodstream. Laser irradiation was initiated immediately after injection. To monitor blood-flow dynamics in response to PDT, we used laser speckle imaging. We employed a dose-response experimental design to study the efficacy of Hemoporfin-mediated PDT to achieve persistent vascular shutdown observed on Day 7 after PDT. RESULTS: We observed four general hemodynamic responses to PDT: (1) At low radiant exposures, we did not observe any persistent vascular shutdown; (2) at intermediate radiant exposures, we observed delayed vascular shutdown effect with significant change to the vascular structure; (3) at intermediate radiant exposures, we observed an acute vascular shutdown effect with gradual restoration of blood flow and no significant changes to the vascular structure; and (4) at high radiant exposures, we observed acute vascular shutdown that persisted during the entire 7-day monitoring period, with no change in vascular structure. With light dose-response analysis, we estimated a characteristic radiant exposure of 359 J/cm2 that was required to achieve persistent vascular shutdown observed on Day 7 after PDT. CONCLUSIONS: The experimental data collectively suggest that Hemoporfin-mediated PDT can achieve persistent vascular shutdown of normal microvasculature. However, compared with our previous data using Talaporfin Sodium as photosensitizer, Hemoporfin-mediated PDT is less efficient and requires a considerably longer (~four times) irradiation time. RELEVANCE FOR PATIENTS: Patients with PWS lesions may benefit from the advantages that PDT potentially offers over conventional PDL therapy. PDT potentially is safer for patients of all skin types and more effective at treatment of recalcitrant lesions. Although clinical data suggest that Hemoporfin-mediated PDT is a promising alternative to PDL therapy, our results suggest that additional study of other photosensitizers is warranted.

Targeted narrowband intense pulsed light on cutaneous vasculature.

BACKGROUND AND OBJECTIVES: Laser based therapies are the standard treatment protocol for port wine stain in the United States, but complete removal is infrequently achieved. Intense pulsed light (IPL) offers a broadband light spectrum approach as a viable treatment alternative. Previous studies suggest that IPL can be more effective in treatment of port wine stain by utilizing multiple wavelengths to selectively target different peaks in oxy- and deoxy-hemoglobin. Our study objectives were to (i) determine a characteristic radiant exposure able to achieve persistent vascular shutdown with narrowband IPL irradiation, (ii) determine the degree to which narrowband IPL irradiation can achieve persistent vascular shutdown, and (iii) compare the effectiveness of narrowband IPL radiation to single wavelength pulsed dye laser (PDL) irradiation in achieving persistent vascular shutdown. STUDY DESIGN/MATERIALS AND METHODS: We utlized either single pulse or double, stacked pulses in narrowband IPL experiments, with the IPL operating over a 500-600 nm wavelength range on the rodent dorsal window chamber model. We compared the results from our narrowband IPL experiments to acquired PDL data from a previous study and determined that narrowband IPL treatments can also produce persistent vascular shutdown. We ran Monte Carlo simulations to investigate the relationship between absorbed energy, wavelength, and penetration depth. RESULTS: For single and double pulse narrowband IPL irradiation we observed (i) little to no change in blood flow, resulting in no persistent vascular shutdown, (ii) marked acute disruption in blood flow and vascular structure, followed by partial to full recovery of blood flow, also resulting in no persistent vascular shutdown, and (iii) immediate changes in blood flow and vascular structure, resulting in prolonged and complete vascular shutdown. Monte Carlo modeling resulted in a 53.2% and 69.0% higher absorbed energy distribution in the top half and the total simulated vessel when comparing the composite narrowband IPL to the 595 nm (PDL), respectively. CONCLUSIONS: Our data collectively demonstrate the potential to achieve removal of vascular lesions using a 500-600 nm range. Additionally, the narrowband IPL was tuned to optimize a specific wavelength range that can be used to treat PWS, whereas the PDL can only operate at one discrete wavelength.

Preclinical in vivo evaluation of NPe6-mediated photodynamic therapy on normal vasculature.

BACKGROUND AND OBJECTIVE: Current treatments of port-wine stain birthmarks typically involve use of a pulsed dye laser (PDL) combined with cooling of the skin. Currently, PDL therapy protocols result in varied success, as some patients experience complete blanching, while others do not. Over the past decade, we have studied the use of photodynamic therapy (PDT) as either a replacement or adjuvant treatment option to photocoagulate both small and large vasculature. The objective of the current study was to evaluate a PDT protocol that involves use of an alternate intravascular photosensitizer mono-L-aspartylchlorin-e6 (NPe6) activated by an array of low-cost light emitting diodes. STUDY DESIGN/MATERIALS AND METHODS: To monitor the microvasculature, a dorsal window chamber model was installed on 22 adult male mice. The light source consisted of a custom-built LED array that emitted 10 W at a center wavelength of 664 nm (FWHM = 20 nm). The light source was positioned at a fixed distance from the window chamber to achieve a fixed irradiance of 127 mW/cm(2). A retroorbital injection of NPe6 (5 mg/kg) was performed to deliver the drug into the bloodstream. Laser irradiation was initiated immediately after injection. To monitor blood-flow dynamics in response to PDT, we used laser speckle imaging. We employed a dose-response experimental design to evaluate the efficacy of NPe6-mediated PDT. RESULTS: We observed three general hemodynamic responses to PDT: (1) At low radiant exposures, we did not observe any persistent vascular shutdown; (2) at intermediate radiant exposures, we observed an acute decrease in blood flow followed by gradual restoration of blood flow over the 7-day monitoring period; and (3) at high radiant exposures, we observed acute vascular shutdown that persisted during the entire 7-day monitoring period. Dose-response analysis enabled identification of 85 J/cm(2) as a characteristic radiant exposure required to achieve persistent vascular shutdown at Day 7 following PDT. CONCLUSION: The experimental data suggest that NPe6-mediated PDT can achieve persistent vascular shutdown of normal microvasculature.