太赫兹时域光谱技术已经用于皮肤癌、 皮肤烧伤以及皮肤疤痕治疗效果的诊断和过程监测, 通常采用太赫兹时域和频域光谱参数作为区分皮肤组织不同状态的诊断参量。 目前最常用的皮肤活体反射式太赫兹测量装置需将皮肤放置于介质窗上来提高测量的准确性, 这使得皮肤表层水分含量因为阻塞而发生变化, 从而影响太赫兹诊断皮肤的精确性。 随着太赫兹生物应用从离体检测到活体测量方向发展, 需要分析阻塞情况下皮肤太赫兹光谱参数的变化规律。 采用太赫兹反射系统对手臂皮肤在石英介质窗上的阻塞过程进行了连续测量, 然后对不同时刻时域波形的峰峰值、 半波脉宽等13个特征量进行了分析。 结果表明: 时域信号和传递函数的峰峰值、 最大值与最小值之间的拟合斜率等参量随阻塞时间而呈指数衰减; 传递函数的最大值与最小值时间差、 最大值与最小值的斜率等随阻塞时间呈指数增加; 时域波形的半峰全宽、 对数频谱等保持不变。 然后用双德拜模型来模拟皮肤组织在0.2～1 THz频段的介电常数, 采用遗传算法和Levenberg-Marquardt相结合的优化算法得到了皮肤阻塞情况下不同时刻的双德拜参数, 结果表明: ε∞和εs均随着时间呈指数上升, 5 min内增幅分别达到了27.8%和12.5%; ε2、 弛豫时间常数τ1和τ2基本保持不变。 将皮肤组织视为多层媒质结构, 基于Bruggeman有效介质模型, 将计算得到的太赫兹反射率和测量得到的反射率作为目标函数, 再采用上述混合优化算法得出了皮肤含水量随时间的变化规律。 结果表明: 随着阻塞时间的增加, 皮肤角质层中的水分以指数函数的形式增加, 5 min的阻塞时间即可增加23.8%。 因此, 在进行临床应用和研究时, 必须谨慎考虑皮肤与介质窗接触阻塞而导致的参数变化。 该研究有利于提高太赫兹活体检测的准确性和推动太赫兹时域光谱技术的临床应用。

Terahertz time-domain spectroscopy (THz-TDS) has been applied in the detection of skin cancer, skin burn, scar treatment, and the THz spectral parameters in the time domain and frequency domain are used to discriminate the different tissues. In the general reflection THz in vivo measurement, the skin should be placed on the top surface of a medium window, resulting in water content change in skin surface because of occlusion, and finally, interfere the accuracy of the measurement. THz biomedical application is transferring from ex vivo to in vivo, the THz spectral parameters changing should be analyzed when measuring the occluded skin. In this paper, the occlusion process is measured using THz reflection system, and 13 feature parameters of measured THz signals such as peak to a peak value and Full width at half maximum (FWHM) are proposed and analyzed. Results show that the peak to the peak value of time-domain signals and transfer function and fitting slope of maximum and minimum value decay exponentially over occluding time while fitting slope and time distance of maximum and minimum value of transfer function increase exponentially over occluding time. The FWHM and log spectrum remain stable along with the occluding time. Afterwards, the double Debye model is used to describe the dielectric constant of skin in 0.2~1 THz frequency, and the combined genetic algorithm and Levenberg-Marquardt optimization method are used to extract the Debye parameters at a different occluding time. Results show that ε∞ and εs both increase exponentially with an increase of 27.8% and 12.5% respectively in 5 minutes, while the ε2, τ1 and τ2 remain stable over the occluding time. Next, the skin is taken regard as a stratified medium, based on the Bruggeman effective medium theory, the previous optimization algorithm which takes the measured reflectivity and calculated reflectivity as the objective function is also used to extract the skin water content along with occluding time. Results show that water content in stratum corneum grows exponentially with occluding time and increases by 23.8% in 5 minutes. Consequently, the THz spectral change results from occlusion of the skin due to the contact of the medium window should be carefully considered when applying the THz-TDs in clinical application. Our research could improve the accuracy of THz in vivo detection and promote its clinical application.