Halftone spatial frequency domain imaging enables kilohertz high-speed label-free non-contact quantitative mapping of optical properties for strongly turbid media

The ability to quantify optical properties (i.e., absorption and scattering) of strongly turbid media has major implications on the characterization of biological tissues, fluid fields, and many others. However, there are few methods that can provide wide-field quantification of optical properties, and none is able to perform quantitative optical property imaging with high-speed (e.g., kilohertz) capabilities. Here we develop a new imaging modality termed halftone spatial frequency domain imaging (halftone-SFDI), which is approximately two orders of magnitude faster than the state-of-the-art, and provides kilohertz high-speed, label-free, non-contact, wide-field quantification for the optical properties of strongly turbid media. This method utilizes halftone binary patterned illumination to target the spatial frequency response of turbid media, which is then mapped to optical properties using model-based analysis. We validate the halftone-SFDI on an array of phantoms with a wide range of optical properties as well as in vivo human tissue. We demonstrate with an in vivo rat brain cortex imaging study, and show that halftone-SFDI can longitudinally monitor the absolute concentration as well as spatial distribution of functional chromophores in tissue. We also show that halftone-SFDI can spatially map dual-wavelength optical properties of a highly dynamic flow field at kilohertz speed. Together, these results highlight the potential of halftone-SFDI to enable new capabilities in fundamental research and translational studies including brain science and fluid dynamics.

Diffuse Terahertz Spectroscopy in Turbid Media Using a Wavelet-Based Bimodality Spectral Analysis

Current terahertz (THz) spectroscopy techniques only use the coherent light beam for spectral imaging. In the presence of electromagnetic scattering, however, the scattering-mitigated incoherent beams allow for flexible emitter-detector geometries, which enable applications such as seeing through turbid media. Despite this potential, THz spectroscopy using diffuse waves has not been demonstrated. The main obstacles are the very poor signal to noise ratios of the diffused fields and the resonance-like spectral artifacts due to multiple Mie scattering events that obscure the material absorption signatures. In this work, we demonstrate diffuse THz spectroscopy of a heterogeneous sample through turbid media using a novel technique based on the wavelet multiresolution analysis and the bimodality coefficient spectrum, which we define here for the first time using the skewness and kurtosis of the spectral images. The proposed method yields broadband and simultaneous material characterization at detection angles as high as 90o with respect to the incident beam. We determined the accuracy of the wavelet-based diffuse spectroscopy at oblique detection angles, by evaluating the area under the Receiver Operating Characteristic (ROC) curves, to be higher than 95%. This technique is agnostic to any a priori information on the spectral signatures of the sample materials or the characteristics of the scattering medium, and can be expanded for other broadband spectroscopic modalities.

Diffuse terahertz spectroscopy in turbid media using a wavelet-based bimodality spectral analysis

Current terahertz (THz) spectroscopy techniques only use the coherent light beam for spectral imaging. In the presence of electromagnetic scattering, however, the scattering-mitigated incoherent beams allow for flexible emitter-detector geometries, which enable applications such as seeing through turbid media. Despite this potential, THz spectroscopy using diffuse waves has not been demonstrated. The main obstacles are the very poor signal to noise ratios of the diffused fields and the resonance-like spectral artifacts due to multiple Mie scattering events that obscure the material absorption signatures. In this work, we demonstrate diffuse THz spectroscopy of a heterogeneous sample through turbid media using a novel technique based on the wavelet multiresolution analysis and the bimodality coefficient spectrum, which we define here for the first time using the skewness and kurtosis of the spectral images. The proposed method yields broadband and simultaneous material characterization at detection angles as high as 90° with respect to the incident beam. We determined the accuracy of the wavelet-based diffuse spectroscopy at oblique detection angles, by evaluating the area under the receiver operating characteristic curves, to be higher than 95%. This technique is agnostic to any a priori information on the spectral signatures of the sample materials or the characteristics of the scattering medium, and can be expanded for other broadband spectroscopic modalities.

Diattenuation and retardance signature of plasmonic gold nanorods in turbid media revealed by Mueller matrix polarimetry

Plasmonic gold nanorods (GNRs) are finding increasing use in biomedicine due to their unique electromagnetic properties, optical contrast enhancement and biocompatibility; they also show promise as polarization contrast agents. However, quantification of their polarization-enhancing properties within heterogeneous turbid media remains challenging. We report on polarization response in controlled tissue phantoms consisting of dielectric microsphere scatterers with varying admixtures of GRNs. Experimental Mueller matrix measurements and polarization sensitive Monte-Carlo simulations show excellent agreement. Despite the GNRs’ 3D random orientation and distribution in the strong multiply scattering background, significant linear diattenuation and retardance were observed. These exclusive measurable characteristics of GNRs suggest their potential uses as contrast enhancers for polarimetric assessment of turbid biological tissue.