Selective photothermolysis in acne treatment: The impact of laser power.

BACKGROUND: Selective photothermolysis (SPT) using a 1726 nm laser has emerged as a safe and effective treatment option for acne vulgaris by targeting sebaceous glands (SG). Power output plays a crucial role in determining treatment selectivity and efficacy. AIMS: This work highlights the advantages of a higher-power laser source and outlines the limitations of lower-power laser sources and the subsequent impact on treatment. METHODS: Light transport and bioheat transfer simulations were performed to demonstrate photothermal impact on the SG and the surrounding dermis when irradiated by a high- or lower-power laser source. RESULTS: The simulations showed that a single higher-power-shorter-pulse (HPSP) selectively increases SG temperature well beyond bulk temperatures, which is desirable for SPT. Selectivity decreases linearly with power for the single lower-power-longer-pulses (LPLP) exposure. A multiple-LPLP approach elevates bulk temperatures significantly more than a single-pulse strategy, compromising selectivity. CONCLUSION: The goal of SPT is to damage SG safely and effectively by creating an intense temperature rise localized to the SG while moderately increasing the dermis temperature. This goal is mostly achieved with higher-power lasers that deliver a single HPSP. Lower-power lasers, longer pulse widths, and multi-pulse strategies result in higher bulk temperatures and lower SG selectivity, making such treatment challenging to execute while adding a higher risk of discomfort and downtime.

Optimized virtual optical waveguides enhance light throughput in scattering media.

Ultrasonically-sculpted gradient-index optical waveguides enable non-invasive light confinement inside scattering media. The confinement level strongly depends on ultrasound parameters (e.g., amplitude, frequency), and medium optical properties (e.g., extinction coefficient). We develop a physically-accurate simulator, and use it to quantify these dependencies for a radially-symmetric virtual optical waveguide. Our analysis provides insights for optimizing virtual optical waveguides for given applications. We leverage these insights to configure virtual optical waveguides that improve light confinement fourfold compared to previous configurations at five mean free paths. We show that virtual optical waveguides enhance light throughput by 50% compared to an ideal external lens, in a medium with bladder-like optical properties at one transport mean free path. We corroborate these simulation findings with real experiments: we demonstrate, for the first time, that virtual optical waveguides recycle scattered light, and enhance light throughput by 15% compared to an external lens at five transport mean free paths.

A novel 1726-nm laser system for safe and effective treatment of acne vulgaris.

Selective photothermolysis of the sebaceous glands has the potential to be an effective alternative for treating acne vulgaris. However, the translation of this technique to clinical settings has been hindered by a lack of appropriate energy sources to target sebaceous glands, concerns surrounding safety, and treatment-related discomfort and downtime. In this work, we introduce the first FDA-approved system that combines a 1726-nm laser and efficient contact cooling to treat mild, moderate, and severe acne effectively while ensuring safety and minimal patient discomfort without adjunct pain mitigation techniques. Light transport and bioheat transfer simulations were performed to demonstrate the system's efficacy and selectivity. The resulting thermal damage to the skin and sebaceous glands was modeled using the Arrhenius kinetic model. Numerical simulations demonstrated that combining laser energy and optimal contact cooling could induce a significant temperature increase spatially limited to the sebaceous gland; this results in highly selective targeting and maximum damage to the sebaceous gland while preserving other skin structures. In vivo human facial skin histology results corroborated the simulation results. The studies reported here demonstrate that the presented 1726-nm laser system induces selective photothermolysis of the sebaceous gland, providing a safe and effective method for the treatment of acne vulgaris.

Overcoming the tradeoff between confinement and focal distance using virtual ultrasonic optical waveguides.

A conventional optical lens can be used to focus light into the target medium from outside, without disturbing the medium. The focused spot size is proportional to the focal distance in a conventional lens, resulting in a tradeoff between penetration depth in the target medium and spatial resolution. We have shown that virtual ultrasonically sculpted gradient-index (GRIN) optical waveguides can be formed in the target medium to steer light without disturbing the medium. Here, we demonstrate that such virtual waveguides can relay an externally focused Gaussian beam of light through the medium beyond the focal distance of a single external physical lens, to extend the penetration depth without compromising the spot size. Moreover, the spot size can be tuned by reconfiguring the virtual waveguide. We show that these virtual GRIN waveguides can be formed in transparent and turbid media, to enhance the confinement and contrast ratio of the focused beam of light at the target location. This method can be extended to realize complex optical systems of external physical lenses and in situ virtual waveguides, to extend the reach and flexibility of optical methods.

Remote nongenetic optical modulation of neuronal activity using fuzzy graphene.

The ability to modulate cellular electrophysiology is fundamental to the investigation of development, function, and disease. Currently, there is a need for remote, nongenetic, light-induced control of cellular activity in two-dimensional (2D) and three-dimensional (3D) platforms. Here, we report a breakthrough hybrid nanomaterial for remote, nongenetic, photothermal stimulation of 2D and 3D neural cellular systems. We combine one-dimensional (1D) nanowires (NWs) and 2D graphene flakes grown out-of-plane for highly controlled photothermal stimulation at subcellular precision without the need for genetic modification, with laser energies lower than a hundred nanojoules, one to two orders of magnitude lower than Au-, C-, and Si-based nanomaterials. Photothermal stimulation using NW-templated 3D fuzzy graphene (NT-3DFG) is flexible due to its broadband absorption and does not generate cellular stress. Therefore, it serves as a powerful toolset for studies of cell signaling within and between tissues and can enable therapeutic interventions.

Ultrasonically sculpted virtual relay lens for in situ microimaging.

We demonstrate in situ non-invasive relay imaging through a medium without inserting physical optical components. We show that a virtual optical graded-index (GRIN) lens can be sculpted in the medium using in situ reconfigurable ultrasonic interference patterns to relay images through the medium. Ultrasonic wave patterns change the local density of the medium to sculpt a graded refractive index pattern normal to the direction of light propagation, which modulates the phase front of light, causing it to focus within the medium and effectively creating a virtual relay lens. We demonstrate the in situ relay imaging and resolving of small features (22 µm) through a turbid medium (optical thickness = 5.7 times the scattering mean free path), which is normally opaque. The focal distance and the numerical aperture of the sculpted optical GRIN lens can be tuned by changing the ultrasonic wave parameters. As an example, we experimentally demonstrate that the axial focal distance can be continuously scanned over a depth of 5.4 mm in the modulated medium and that the numerical aperture can be tuned up to 21.5%. The interaction of ultrasonic waves and light can be mediated through different physical media, including turbid media, such as biological tissue, in which the ultrasonically sculpted GRIN lens can be used for relaying images of the underlying structures through the turbid medium, thus providing a potential alternative to implanting invasive endoscopes.

In situ 3D reconfigurable ultrasonically sculpted optical beam paths.

We demonstrate that optical beams can be spatially and temporally shaped in situ by forming 3D reconfigurable interference patterns of ultrasound waves in the medium. In this technique, ultrasonic pressure waves induce a modulated refractive index pattern that shapes the optical beam as it propagates through the medium. Using custom-designed cylindrical ultrasonic arrays, we demonstrate that complex patterns of light can be sculpted in the medium, including dipole and quadrupole shapes. Additionally, through a combination of theory and experiment, we demonstrate that these optical patterns can be scanned in radial and azimuthal directions. Moreover, we show that light can be selectively confined to different extrema of the spatial ultrasound pressure profile by temporally synchronizing lightwave and ultrasound. Finally, we demonstrate that this technique can also be used to define spatial patterns of light in turbid media. The notion of in situ 3D sculpting of optical beam paths using ultrasound interference patterns can find intriguing applications in biological imaging and manipulation, holography, and microscopy.

Ultrasonic sculpting of virtual optical waveguides in tissue.

Optical imaging and stimulation are widely used to study biological events. However, scattering processes limit the depth to which externally focused light can penetrate tissue. Optical fibers and waveguides are commonly inserted into tissue when delivering light deeper than a few millimeters. This approach, however, introduces complications arising from tissue damage. In addition, it makes it difficult to steer light. Here, we demonstrate that ultrasound can be used to define and steer the trajectory of light within scattering media by exploiting local pressure differences created by acoustic waves that result in refractive index contrasts. We show that virtual light pipes can be created deep into the tissue (>18 scattering mean free paths). We demonstrate the application of this technology in confining light through mouse brain tissue. This technology is likely extendable to form arbitrary light patterns within tissue, extending both the reach and the flexibility of light-based methods.

Ultrasonically Steerable Graded-Index Optical Waveguides for Deep Tissue Light Delivery: Theory and Applications.

Graded-index (GRIN) fibers have been used as implantable optical waveguides to guide light and relay images through the depth of the tissue. We have recently shown that non-invasive ultrasound can generate refractive index gradients within the tissue that form virtual GRIN lenses for imaging and photostimulation deep into the tissue. Here we present the theory behind this idea by analyzing the coupled acoustic-photonic system that models the interaction of light with the ultrasonically modulated medium. We will discuss how changing the parameters of ultrasound will change the confinement and guiding of light within the modulated medium. We will also demonstrate that using a custom-designed cylindrical ultrasonic array, the pressure interference can be controlled to sculpt complex patterns of light in the medium, such as dipole and quadrupole shapes, suitable for multisite imaging. Finally, we will discuss experimental results corroborating the theoretical predictions to generate single and multisite in situ virtual lenses that can be used for fluorescent imaging of mouse brain tissue that expresses green fluorescent protein (GFP).