Melanin is known to provide strong third-harmonic generation (THG) contrast in human skin. With a high concentration in basal cell cytoplasm, THG contrast provided by melanin overshadows other THG sources in human skin studies. For better understanding of the THG signals in keratinocytes without the influence of melanin, an in vivo THG microscopy (THGM) study was first conducted on vitiliginous skin. As a result, the THG-brightness ratio between the melanin-lacking cytoplasm of basal cells and collagen fibers is about 1.106 at the dermal-epidermal junctions of vitiliginous skin, indicating high sensitivity of THGM for the presence of melanin. We further applied the in vivo THGM to assist evaluating the therapeutic outcome from the histopathological point of view for those showed no improvement under narrowband ultraviolet B therapy based on the seven-point Physician Global Assessment score. Our clinical study indicates the high potential of THGM to assist the histopathological assessment of the therapeutic efficacy of vitiligo treatments. © The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.

A THz near-field transmission imaging system was successfully demonstrated to image the vessels inside the ears of nude mice in vivo. Wave-guided illumination and near-field scanning detection with a sub-wavelength aperture were applied. An operating frequency of 340 GHz was chosen to achieve a higher penetration depth in tissues with a reasonable signal-to-noise ratio. The near-field pattern of the power transmittance through the vessel was also numerically simulated and showed good correspondence to the measured results. The capability of the system for long-term monitoring in vivo was also demonstrated.

Melasma, which is thought to be associated with hyperactivation of melanocytes, is a common hyperpigmentary skin disorder. To treat this skin disorder, dermatologists can benefit from in vivo information of cellular morphometrics to evaluate pathologies of melasma and effectiveness of treatments. To acquire this useful information, we applied the in vivo slidefree label-free harmonic generation microscopy (HGM) to retrieve real-time HGM images and subsequent critical histopathological parameters. These in vivo quantitative parameters included melanin mass density (MMD), melanocyte dendricity score (MDS), melanophage density (MPD), and thickness of dermal papilla zone (DPZ). The statistical results from 33 recruited Asian female melasma patients showed that MMD, MDS, and MPD in melasma lesions were significantly higher than those in the surrounding normal skin; by contrast, the DPZ was lower. After treatment, the MMD, MPD, and DPZ restored toward the normal level; however, we observed no significant change of MDS. Our study indicates that these parameters are able to serve as clinical indices to evaluate the histopathological characteristics of melasma patients and the effectiveness of treatments.

Atopic dermatitis (AD) is a cutaneous disease resulting from a defective barrier and dysregulated immune response. The severity scoring of atopic dermatitis (SCORAD) is used to classify AD. Noninvasive imaging approaches supplementary to SCORAD were investigated. Cr:forsterite laser‐based microscopy was employed to analyze endogenous third‐harmonic generation (THG) and second‐harmonic generation (SHG) signals from skin. Imaging parameters were compared between different AD severities. Three‐dimensional reconstruction of imaged skin layers was performed. Finally, statistic models from quantitative imaging parameters were developed for predicting disease severity. Our data demonstrate that THG signal intensity of lesional skin in AD were significantly increased and was positively correlated with AD severity. Characteristic gray level co‐occurrence matrix (GLCM) values were observed in more severe AD. In the 3D reconstruction video, individual dermal papilla and obvious fibrosis in the upper papillary dermis were easily identified. Our estimation models could predict the disease severity of AD patients with an accuracy of nearly 85%. The THG signal intensity and characteristic GLCM patterns are associated with AD severity and can serve as quantitative predictive parameters. Our imaging approach can be used to identify the histopathological changes of AD objectively, and to complement the SCORAD index, thus improving the accuracy of classifying AD severity.

Background: Wearable and unobtrusive sensing devices are rapidly evolving for long-term cardiovascular monitoring. However, most of the cardiovascular device requires multi-channel physiological signals acquisition, especially in continuous blood pressure (BP) measurement using pulse transition time (PTT) based methods. The multi-devices implementation could impede wearable applications. Objective: This study developed a wearable neck patch device using single-channel impedance plethysmography (IPG) sensing for cardiovascular monitoring, including continuous BP and heart rate (HR) measurement. Methods: IPG-based BP model was derived based on the Bramwell-Hill equation. A patch IPG device was designed and installed above the carotid artery of the subject neck. To validate the BP and HR functions of our device, the Bland-Altman plots were performed to evaluate the estimation error between the reference and the proposed devices within 20 healthy subjects. Results: The BP performance indicates that systolic BP (SBP) estimation error was-0.16 ± 2.97 mmHg and 2.43 ± 1.71 mmHg in terms of mean error (ME) and mean absolute error (MAE), and 0.09 ± 3.30 mmHg and 2.83 ± 1.68 mmHg for diastolic BP (DBP) estimation. Moreover, the HR accuracy has the ME and MAE of 0.02 ± 0.17 bpm and 0.14 ± 0.08 bpm; mean percentage error (MPE) and mean absolute percentage error (MAPE) obtained 0.04 ± 0.23 % and 0.19 ± 0.12 %. Based on statistical results, the BP and HR function of our device satisfied with AAMI/ANSI criteria below 5 ± 8 mmHg and ± 5 bpm or ± 10%. Conclusion: This study implemented a wearable neck patch device with singlechannel IPG acquisition that provided two significant cardiovascular parameters of continuous BP and HR, and its performance agreed with standard criteria based on validation with reference sensors. Significance: The proposed proof-of-concept IPG neck patch device has a high potential for wearable applications and lowcost manufacturing in cardiovascular monitoring.