Rapid and label-free histological imaging of unprocessed surgical tissues via dark-field reflectance ultraviolet microscopy.

Routine examination for intraoperative histopathologic assessment is lengthy and laborious. Here, we present the dark-field reflectance ultraviolet microscopy (DRUM) that enables label-free imaging of unprocessed and thick tissues with subcellular resolution and a high signal-to-background ratio. To the best of our knowledge, DRUM provides image results for pathological assessment with the shortest turnaround time (2-3 min in total from sample preparation to tissue imaging). We also proposed a virtual staining process to convert DRUM images into pseudo-colorized images and enhance the image familiarity of pathologists. By imaging various tissues, we found DRUM can resolve cell nuclei and some extranuclear features, which are comparable to standard H&E images. Furthermore, the essential diagnostic features of intraoperatively excised tumor tissues also can be revealed by DRUM, demonstrating its potential as an additional aid for intraoperative histopathology.

In vivo THz imaging of human skin: Accounting for occlusion effects.

In vivo terahertz (THz) imaging of human skin needs to be done in reflection geometry due to the high attenuation of THz light by water in the skin. To aid the measurement procedure, there is typically an imaging window onto which the patient places the area of interest. The window enables better pulse alignment and helps keep the patient correctly positioned during the measurement. In this paper, we demonstrate how the occlusion caused by the skin contact with the imaging window during the measurement affects the THz response. By studying both rapid point measurements and imaging over an area of a human volar forearm, we find that even 5 seconds of occlusion affects the THz response. As the occlusion time increases, the skin surface water content increases, resulting in the reduction of the amplitude of the reflected THz pulse, especially in the first 3 minutes. Furthermore, it was found that the refractive index of the volar forearm increased by 10% to 15% after 20 minutes of occlusion. In this work, we examine and propose a model for the occlusion effects due to the quartz window with a view to compensating for its influence.

Composite multiscale entropy analysis of reflective terahertz signals for biological tissues.

We demonstrate a composite multiscale entropy (CMSE) method of terahertz (THz) signal complexity analysis to distinguish different biological tissues. The THz signals reflected from fresh porcine skin and muscle tissues were measured and analyzed. The statistically significant difference and separation of the two tissues based on several parameters were analyzed and compared for THz spectroscopy and imaging, which verified the better performance of the CMSE method and further enhancement of the contrast among THz signals that interact with different tissues. This process provides a better analysis and discrimination method for THz spectroscopy and imaging in biomedical applications.

Determination of terahertz permittivity of dehydrated biological samples.

A key step in transforming terahertz imaging to a practical medical imaging modality lies in understanding the interactions between terahertz (THz) waves and biological tissues. Most of the models in the literature use the permittivity of liquid water to simulate the THz-tissue interactions, but they often neglect contributions from the biological background such as proteins and lipids because dehydrated biological samples are experimentally difficult to prepare. In this work, we present a method to prepare thin and flat dehydrated samples which can be easily handled and measured in a transmission setup. Our results will provide fundamental parameters for modelling THz-tissue interactions.

Recent advances in terahertz technology for biomedical applications.

Terahertz instrumentation has improved significantly in recent years such that THz imaging systems have become more affordable and easier to use. THz systems can now be operated by non-THz experts greatly facilitating research into many potential applications. Due to the non-ionising nature of THz light and its high sensitivity to soft tissues, there is an increasing interest in biomedical applications including both in vivo and ex vivo studies. Additionally, research continues into understanding the origin of contrast and how to interpret terahertz biomedical images. This short review highlights some of the recent work in these areas and suggests some future research directions.

Freeze-thaw hysteresis effects in terahertz imaging of biomedical tissues.

There have recently been several studies published involving terahertz (THz) imaging of frozen biomedical samples. In this paper, we investigate the effects of the freeze-thaw cycle on THz properties of porcine muscle and fat samples. For ordinary freezing, there was a significant change in the THz properties after thawing for muscle tissue but not for fat tissue. However, if snap-freezing was combined with fast-thawing instead of ordinary freezing and ordinary thawing, then the freeze-thaw hysteresis was removed.