A comparison of terahertz pulsed imaging with transmission microradiography for depth measurement of enamel demineralisation in vitro.

Terahertz pulsed imaging (TPI) is a relatively new, non-ionising and non-destructive imaging technique for studying hard tissues which does not require tooth section preparation, unlike transmission microradiography (TMR). If TPI can measure the depths of caries/demineralisation lesions accurately the same tooth samples could be reused and remeasured during in vitro and in situ studies on de- and/or re-mineralisation. The aim of this study was to compare TPI and TMR for measuring the depths of a range of artificially induced bovine enamel demineralised lesions in vitro. Bovine slabs with artificial caries, induced to different levels of demineralisation by two different but standard demineralisation techniques ('acid gel' and 'carbopol') were measured by TPI and TMR and the readings compared. The set of TPI/TMR measurements obtained on the gel-demineralised slabs showed an extremely high coefficient of determination (r(2) = 0.995). Detailed analysis of the results and theoretical considerations (involving the relationship between refractive index profiling and mineral loss profile) are used to explain the findings and show that for acid gel lesions TPI is measuring demineralisation in the range of 47% of that of TMR depth plus an intercept of 16 microm, with further calculations allowing the TMR depths to be determined to within 5% using TPI.

Nondestructive analysis of tablet coating thicknesses using terahertz pulsed imaging.

An understanding of the finished structure of complex pharmaceutical coating is becoming desirable, because tablet coatings are now one of the preferred routes to control the release of active pharmaceutical ingredients. There are few nondestructive techniques capable of examining the coatings of compressed tablets; for example laser induced breakdown spectroscopy has been used but this is a destructive method. Terahertz pulsed imaging offers a potential technique to examine coatings quickly and nondestructively. In the study reported herein, it was possible to distinguish between two brands of across-the-counter ibuprofen tablets. The terahertz maps obtained were compared with obtained photographs of cut-through sections; there was good agreement. The technique is fast: a waveform can be obtained in <20 ms allowing the technique to be considered as a candidate for on-line or at-line analysis in a process analytical environment. The lateral resolution of the technique is limited by diffraction of the terahertz focus to about 150 microm at 3 THz, whereas the axial resolution is limited by the terahertz pulse duration, which is <200 fs, to about 30 microm.

Simulating the response of terahertz radiation to basal cell carcinoma using ex vivo spectroscopy measurements.

Studies of basal cell carcinoma using terahertz pulsed imaging have revealed a significant difference between regions of tumor and healthy tissue. These differences are manifested in the reflected pulse due to what is thought to be changes in refractive index and absorption. We present measurements of the refractive index and absorption coefficient of excised normal tissue and basal cell carcinoma using terahertz (THz) transmission spectroscopy. We extract Debye parameters from these data and enter them into a finite difference time domain simulation to predict the shape of the waveforms reflected off the normal tissue and basal cell carcinoma and compare them with published in vivo data. Simulating the interaction of terahertz radiation with normal and cancerous tissue is a key step toward understanding the origin of contrast in terahertz images of skin cancer.

Terahertz pulse imaging: a pilot study of potential applications in dentistry.

The improvement in the detection of caries offers the possibility for dramatic improvement in dental healthcare. Current caries detection rates suggest that there may be scope for improvement. This paper describes a preliminary study to examine applications of terahertz pulse imaging (TPI) to caries detection. We present results for the detection of early stage caries in the occlusal enamel layer of a range of human tooth cross sections using TPI. Higher attenuation of terahertz radiation was observed in carious enamel as compared with healthy enamel. Hypomineralised enamel had different absorption spectra and contrast compared to carious enamel in TPI images. These results have important implications for extending TPI to other medical imaging applications where both early diagnosis and safety issues are important.

Terahertz pulse imaging of ex vivo basal cell carcinoma.

Terahertz pulse imaging has been used for the first time to study basal cell carcinoma ex vivo, the most common form of skin cancer. This noninvasive technique uses part of the electromagnetic spectrum in the frequency range 0.1-2.7 THz. A total of 21 samples were imaged; the study was performed blind and results were compared to histology. Each image consisted of possible diseased tissue and normal tissue from the same patient. The diseased tissue showed an increase in absorption compared to normal tissue, which is attributed to either an increase in the interstitial water within the diseased tissue or a change in the vibrational modes of water molecules with other functional groups. Seventeen of the images showed a significant difference between the normal and the diseased tissue. These were confirmed by histology to be basal cell carcinomas. Of the remaining four cases, three showed no contrast and were confirmed as blind controls of normal tissue; the fourth case was a suspected basal cell carcinoma but showed no contrast, and histology showed no tumor. Cross-sections of the terahertz images, showing the terahertz absorption, were compared to histology. Regions of increased terahertz absorption agreed well with the location of the tumor sites. Resolutions at 1 THz of 350 microm laterally and 40 microm axially in skin were attainable with our system. These results demonstrate the ability of terahertz pulse imaging to distinguish basal cell carcinoma from normal tissue, and this macroscopic technique may, in the future, help plan surgery.

Terahertz pulse imaging in reflection geometry of human skin cancer and skin tissue.

We demonstrate the application of terahertz pulse imaging (TPI) in reflection geometry for the study of skin tissue and related cancers both in vitro and in vivo. The sensitivity of terahertz radiation to polar molecules, such as water, makes TPI suitable for studying the hydration levels in the skin and the determination of the lateral spread of skin cancer pre-operatively. By studying the terahertz pulse shape in the time domain we have been able to differentiate between diseased and normal tissue for the study of basal cell carcinoma (BCC). Basal cell carcinoma has shown a positive terahertz contrast, and inflammation and scar tissue a negative terahertz contrast compared to normal tissue. In vivo measurements on the stratum corneum have enabled visualization of the stratum corneum-epidermis interface and the study of skin hydration levels. These results demonstrate the potential of terahertz pulse imaging for the study of skin tissue and its related disorders, both in vitro and in vivo.