Emma Pickwell-MacPherson

Terahertz pulsed spectroscopy of freshly excised human breast cancer

The complex refractive indices of freshly excised healthy breast tissue and breast cancers collected from 20 patients were measured in the range of 0.15 - 2.0 THz using a portable terahertz pulsed transmission spectrometer. Histology was performed to classify the tissue samples as healthy adipose tissue, healthy fibrous breast tissue, or breast cancers. The average complex refractive index was determined for each group and it was found that samples containing cancer had a higher refractive index and absorption coefficient. The terahertz properties of the tissues were also used to simulate the impulse response functions expected when imaging breast tissue in a reflection geometry as in terahertz pulsed imaging (TPI). Our results indicate that both TPS and TPI can be used to distinguish between healthy adipose breast tissue, healthy fibrous breast tissue and breast cancer due to the differences in the fundamental optical properties.

The potential of terahertz imaging for cancer diagnosis: A review of investigations to date.

The terahertz region lies between the microwave and infrared regions of the electromagnetic spectrum such that it is strongly attenuated by water and very sensitive to water content. Terahertz radiation has very low photon energy and thus it does not pose any ionization hazard for biological tissues. Because of these characteristic properties, there has been an increasing interest in terahertz imaging and spectroscopy for biological applications within the last few years and more and more terahertz spectra are being reported, including spectroscopic studies of cancer. The presence of cancer often causes increased blood supply to affected tissues and a local increase in tissue water content may be observed: this acts as a natural contrast mechanism for terahertz imaging of cancer. Furthermore the structural changes that occur in affected tissues have also been shown to contribute to terahertz image contrast. This paper introduces terahertz technology and provides a short review of recent advances in terahertz imaging and spectroscopy techniques. In particular investigations relating to the potential of terahertz imaging and spectroscopy for cancer diagnosis will be highlighted.

Tissue characterization using terahertz pulsed imaging in reflection geometry

Terahertz pulsed imaging (TPI) is a non-ionizing and non-destructive imaging technique that has been recently used to study a wide range of biological materials. The severe attenuation of terahertz radiation in samples with high water content means that biological samples need to be very thin if they are to be measured in transmission geometry. To overcome this limitation, samples could be measured in reflection geometry and this is the most feasible way in which TPI could be performed in a clinical setting. In this study, we therefore used TPI in reflection geometry to characterize the terahertz properties of several organ samples freshly harvested from laboratory rats. We observed differences in the measured time domain responses and determined the frequency-dependent optical properties to characterize the samples further. We found statistically significant differences between the tissue types. These results show that TPI has the potential to accurately differentiate between tissue types non-invasively.

Terahertz pulsed imaging of freshly excised human colonic tissues

We present the results from a feasibility study which measures properties in the terahertz frequency range of excised cancerous, dysplastic and healthy colonic tissues from 30 patients. We compare their absorption and refractive index spectra to identify trends which may enable different tissue types to be distinguished. In addition, we present statistical models based on variations between up to 17 parameters calculated from the reflected time and frequency domain signals of all the measured tissues. These models produce a sensitivity of 82% and a specificity of 77% in distinguishing between healthy and all diseased tissues and a sensitivity of 89% and a specificity of 71% in distinguishing between dysplastic and healthy tissues. The contrast between the tissue types was supported by histological staining studies which showed an increased vascularity in regions of increased terahertz absorption.

Direct evidence to support the restriction of intramolecular rotation hypothesis for the mechanism of aggregation-induced emission: temperature resolved terahertz spectra of tetraphenylethene

In contrast to the traditional fluorescent dyes that exhibit a decrease in fluorescence upon aggregation, Aggregation-Induced Emission (AIE) molecules are a family of fluorophors which exhibit increased fluorescence upon aggregation. Consequently, AIE molecules represent an interesting new material with potential applications in fluorescent chemo/biosensors, light emitting devices and medical diagnostics. Numerous mechanisms have been proposed to explain this phenomenon, including E–Z isomerization, and restriction of intramolecular rotations (RIR). However, there has not been any direct experimental evidence to support either one of these hypotheses. Here we use terahertz time-domain-spectroscopy (THz-TDS) and solid-state computational simulations of an AIE molecule to link the increase in intensity of intramolecular rotation and rocking modes to the measured fluorescence and reveal direct evidence supporting the RIR hypothesis. This is the first time that terahertz spectroscopy has been used to directly probe such molecular motions in AIE materials and in doing so we have found conclusive evidence to fully explain the AIE mechanism.

A promising diagnostic method: Terahertz pulsed imaging and spectroscopy

The terahertz band lies between the microwave and infrared regions of the electromagnetic spectrum. This radiation has very low photon energy and thus it does not pose any ionization hazard for biological tissues. It is strongly attenuated by water and very sensitive to water content. Unique absorption spectra due to intermolecular vibrations in this region have been found in different biological materials. These unique features make terahertz imaging very attractive for medical applications in order to provide complimentary information to existing imaging techniques. There has been an increasing interest in terahertz imaging and spectroscopy of biologically related applications within the last few years and more and more terahertz spectra are being reported. This paper introduces terahertz technology and provides a short review of recent advances in terahertz imaging and spectroscopy techniques, and a number of applications such as molecular spectroscopy, tissue characterization and skin imaging are discussed.

Frequency-wavelet domain deconvolution for terahertz reflection imaging and spectroscopy

In terahertz reflection imaging, a deconvolution process is often employed to extract the impulse function of the sample of interest. A band-pass filter such as a double Gaussian filter is typically incorporated into the inverse filtering to suppress the noise, but this can result in over-smoothing due to the loss of useful information. In this paper, with a view to improving the calculation of terahertz impulse response functions for systems with a low signal to noise ratio, we propose a hybrid Frequency-Wavelet Domain Deconvolution (FWDD) for terahertz reflection imaging. Our approach works well; it retrieves more accurate impulse response functions than existing approaches and these impulse functions can then also be used to better extract the terahertz spectroscopic properties of the sample.

Improved sample characterization in terahertz reflection imaging and spectroscopy

For imaging applications involving biological subjects, the strong attenuation of terahertz radiation by water means that terahertz pulsed imaging is most likely to be successfully implemented in a reflection geometry. Many terahertz reflection geometry systems have a window onto which the sample is placed - this window may introduce unwanted reflections which interfere with the reflection of interest from the sample. In this paper we derive a new approach to account for the effects of these reflections and illustrate its success with improved calculations of sample optical properties.

Evaluating liquid crystal properties for use in terahertz devices

Despite the wide application of liquid crystals (LCs) in the visible frequency range, their properties in the terahertz range have not yet been extensively investigated. In this paper we have investigated the terahertz properties of LCs E7, BL037, RDP-94990 and RDP-97304 using terahertz time-domain-spectroscopy. We find that RDP-94990 has the largest birefringence and smallest absorption in the terahertz range compared to E7 and BL037. We highlight the importance of investigating all parameters, not just the birefringence, when designing fast, efficient and transmissive terahertz LC devices.

Accuracy and resolution of THz reflection spectroscopy for medical imaging

The use of THz radiation as a potential tool for medical imaging is of increasing interest. In this paper three methods of analysis of THz spectroscopic information for diagnosis of tissue pathologies at THz frequencies are presented. The frequency-dependent absorption coefficients, refractive indices and Debye relaxation times of pure water and pure lipids were measured and used as prior knowledge in the different theoretical methods for the determination of concentration. Three concentration analysis methods were investigated: (a) linear spectral decomposition, (b) spectrally averaged dielectric coefficient method and (c) the Debye relaxation coefficient method. These methods were validated on water and lipid emulsions by determining the concentrations of phantom chromophores and comparing to the known composition. The accuracy and resolution of each method were determined to assess the potential of each method as a tool for medical diagnosis at THz frequencies.