Beckman Laser Institute & Medical Clinic

OBJECTIVES: Cryogen spray cooling (CSC) is critical for protecting the epidermis during laser dermatologic procedures. The widely used cryogen, R134a, has a high global warming potential (GWP), motivating interest in environmentally favorable alternatives such as HFO-1234ze. This study evaluated whether HFO-1234ze provides epidermal protection comparable to R134a during laser exposure and investigated the mechanistic basis underlying any differences in cooling performance. METHODS: Laser-induced epidermal injury in conjunction with two cryogens was assessed in K14-SCF Mc1r^e/e mice with pharmacologically controllable interfollicular epidermal pigmentation. Laser treatment sites were assigned fluences relative to baseline skin lightness (L*) to span subthreshold to suprathreshold injury conditions, with cryogen assignment randomized. Hypopigmentation at Day 7 served as the primary injury endpoint and was scored independently by three blinded raters. Surface cooling induced by each cryogen was measured separately using thin-film thermocouples on a skin phantom, and subsurface temperature distributions were estimated using one-dimensional transient heat-transfer modeling. RESULTS: Mean hypopigmentation scores did not differ significantly between R134a- and HFO-1234ze-cooled sites across the full range of pigmentation and fluence studied (p = 0.46). Heat-map analysis and regression modeling confirmed that hypopigmentation increased with fluence and darker pigmentation but was independent of cryogen type. Surface temperature measurements using skin phantom revealed that R134a produced more aggressive transient cooling than HFO-1234ze, reaching approximately 10°C lower minimum temperatures. However, numerical modeling of skin cooling using heat flux inferred from phantom measurement showed that this surface advantage decayed rapidly with depth, resulting in ≤ 2°C-3°C differences within the viable epidermis. CONCLUSIONS: Despite differences in surface cooling magnitude, R134a and HFO-1234ze provided equivalent epidermal protection under clinically relevant conditions. These findings support HFO-1234ze as an effective, lower-GWP alternative to R134a for CSC in laser dermatologic applications.

Objectives: Stroke in sickle cell disease (SCD) is often attributed to large vessel involvement in the disorder, whereas the contribution of cerebral microvascular disease has been less explored. In this study, we investigated the formation of cerebral microvascular lesions and the involvement of mast cells in a humanized SCD mouse model. Methods: We studied hemorrhagic microvascular disease in a well-characterized mouse model of humanized transgenic sickle (HbSS-BERK) expressing >99% human sickle hemoglobin (HbS) and a control (HbAA-BERK) mouse model expressing normal human hemoglobin A (HbA). Mouse brains were analyzed by Prussian blue staining to detect cerebral microhemorrhage (CMH) formation. Mast cell identification was performed by toluidine blue staining. Results: SCD brain sections exhibited approximately 86% more CMH than controls (mean ± SE of 1.17 ± 0.22 vs. 0.63 ± 0.13 number/cm², P = .02). Mast cells were positively correlated with CMH number in SCD mice (Spearman r = 0.42, P < .05), but not in control mice. Conclusion: SCD mice demonstrated significantly increased CMH load compared with control mice, and SCD microhemorrhages were associated with the number of mast cells. These findings highlight the significance of cerebral microvascular disease in SCD and imply that cerebral mast cells may be a novel therapeutic target in SCD.

Background/Objectives: Effective screening for oral cancer (OC) remains challenging. Inaccuracies contribute to delayed diagnosis and poor outcomes. Tobacco-related changes in oral mucosa may compromise the accuracy of oral screening approaches, and, in emerging "smart" screening modalities, they may overshadow the influence of other predictive variables. The objective of this study was to evaluate the screening accuracy of an imaging- and risk factor-based OC screening platform in individuals practicing different types of tobacco usage. Methods: 318 subjects who had previously screened positive for increased OC risk were recruited and sorted into "tobacco smoker", "tobacco vaper", "tobacco chewer", "hookah user", "multiple tobacco usage", or "tobacco non-user" groups. Next, demographic information, risk factors, outcome of clinical examination, as well as AFI and pWLI were recorded using a prototype OC screening platform. The OC risk assessment outcome from the OC screening platform was compared to that from an oral medicine specialist. Results: The screening platform demonstrated high sensitivity in tobacco chewers and hookah users, and it also exceeded 90% in smokers, vapers, and multi-product users. In tobacco non-users, 80% screening sensitivity was recorded. Screening specificity was considerably better in tobacco non-users than in the tobacco-user groups, and low in tobacco chewers (33.3%), vapers (55.6%), and smokers (62.5%). Across all groups, agreement between the screening platform outcome and specialist evaluation exceeded 80%. Significant differences in probe accuracy were noted between tobacco non-users and users (p < 0.05), except for tobacco vapers. Conclusions: These findings highlight the need to consider the effects of type of tobacco use on the OC screening approach, and to integrate these variables into imaging-and risk-factor-based algorithms for OC screening.

Significance: Short-wave infrared (SWIR) light has recently gained popularity in tissue spectroscopy and imaging applications for a wide range of biomedical applications, primarily due to advancements in hardware (e.g., cameras). Aim: We aim to provide a detailed review of SWIR-based biomedical optics studies from the past decade, during which there has been a proliferation of SWIR-based tissue-optics studies. Approach: We report literature occurring after the publication of our previous (2015) review of this space, describing next-generation SWIR-based techniques that hold significant promise for enhanced in vivo tissue characterization and clinical translation. Results: Interest from the biophotonics field in SWIR technology is typically attributable to (1) the capability of SWIR light to provide greater sensitivity to chromophores such as water and lipids, with absorption peaks not as prominent in the visible-to-near-infrared (VIS-NIR) spectral region, and (2) the potential for SWIR photons to penetrate through superficial tissue layers due to lower scattering in the SWIR than in the VIS-NIR, as well as substantially reduced attenuation from hemoglobin and melanin. Conclusion: This review of emerging SWIR biophotonic technologies illustrates the rapid growth in the use of SWIR light for in vivo tissue spectroscopy and imaging.

Significance: Prompt care is essential for burn wound recovery. Spatial frequency domain imaging (SFDI) has previously shown promise in predicting healing outcomes across burn severity grades. This study builds on that by demonstrating calibrated reflectance images ( ) from SFDI can estimate thermally induced collagen denaturation depth (CDD), a histology-based metric of burn severity linked to healing outcomes. These findings may simplify future hardware design by clarifying contrast sources in SFDI. Aim: To develop predictive models for: 1) Day-1 postburn CDD using SFDI and 2) Day-28 healing outcomes using day-1 CDD. Approach: Using a previously reported graded-severity porcine burn model ( ) with eight contact durations (5 to 40 s), we collected SFDI and color images on days 0, 1, 3, 7, 14, 21, and 28. Histological analysis using Picrosirius red staining and polarization microscopy was performed on days 1, 7, 14, 21, and 28 to assess CDD. Healing outcomes were clinically evaluated on day 28. For analysis, a two-step regression framework was applied:Step 1: Multiple linear regression, where day-1 SFDI R_d is used to predict same-day CDD.Step 2: Logistic regression, where day-1 CDD is used to predict day-28 healing outcome.Together, these steps established a regression framework to predict day-1 CDD and day-28 healing outcomes using day-1 SFDI R_d. Results: The linear model using across eight wavelengths (471-851 nm) and five spatial frequencies (0 to ) predicted CDD with a root mean square error of and adjusted of 0.71. The logistic model predicted healing outcomes with an ROC-AUC of 0.88, supporting CDD as an early indicator for burn severity assessed by healing potential. Conclusions: This two-step framework enables early prediction (as early as day 1) of burn severity and healing using SFDI .

Erythrocyte-derived microparticles containing near-infrared (NIR) dyes such as indocyanine green present a promising cell-based platform for optical imaging and phototherapeutics. Using real-time intravital NIR fluorescence imaging of mice vasculature, we investigated the effects of blood type, specifically O⁺ and B⁺, used in fabricating these particles, the number concentration (N_v) of the particles, and the relocalization of phosphatidylserine (PS) to the outer leaflet of the particles' membrane on the resulting circulation dynamics following a single retro-orbital injection. Additionally, we quantified the biodistribution of particles in various organs. We found that the fluorescence emission half-life for particles engineered from O⁺ blood type extended from 11.4 ± 3.0 to 43.1 ± 9.6 min with increased N_v from a low range of 0.4-0.6 to high range of 1.4-1.6 million particles/per μL, when only 30-55% of the particles demonstrated externalized PS. For these particles, the liver and gallbladder, lungs, and spleen showed similar levels of accumulation at 60 min post administration. When >90% of O⁺-particles showed PS externalization, or when the particles were fabricated from B⁺ blood type despite PS externalization in 30-55% of the particles, the emission half-life was reduced to 15.8 ± 5.9 and 18.1 ± 4.6 min, respectively. There was lower accumulation of these particles in the spleen as compared to the liver and gallbladder and the lungs. In vitro experiments demonstrated increased PS externalization correlated to a more efficient uptake of the particles by macrophages. These findings emphasize the importance of blood type, N_v, and PS in engineering erythrocyte-derived particles for future clinical applications.

Purpose of ReviewTo provide the most up-to-date clinical evidence of intracoronary optical coherence tomography (OCT), and clinical implications to guide future imaging research in cardiology.Recent FindingsIntracoronary OCT has demonstrated advanced system performance and high reproducibility in analyzing atherosclerotic lesions. It is an attractive tool due to its capability for functional classification and superior imaging resolution, enabling precise and reliable tissue assessments. Compared to traditional angiography, OCT has been associated with improved long-term clinical outcomes and serves as an effective tool for optimizing stent selection and post-intervention evaluation. The development of OCT variations and the combination of various intravascular imaging modalities further enhance its diagnostic capabilities, allowing a comprehensive assessment of complex vulnerable lesions and improving risk stratification for patients. SummaryCurrent and evolving system development presents a hopeful path for treating coronary artery disease by addressing the challenges of the intracoronary OCT technique. Future studies focusing on utilizing OCT system extensions, integrated multimodality imaging systems, and Artificial Intelligence (AI) derived image analysis will improve clinical endpoints and streamline the process.