Terahertz Imaging Takes Aim at Dermatology and Dentistry

MARIE FREEBODY, CONTRIBUTING EDITOR, marie.freebody@photonics.com

The first terahertz image was taken at the AT&T Bell Laboratories more than 20 years ago in 1995. The astonishingly clear image of the inside of a packaged semiconductor integrated circuit brought immense attention to terahertz imaging for applications ranging from security, astronomy, remote sensing and chemical sensing to biomedical imaging.

Just five years later, in 2000, initial investigations of melanoma skin cancers using terahertz imaging and spectroscopy began at TeraView, in Cambridge, England, by pioneering terahertz scientist Emma MacPherson as part of her Ph.D. Around the same time, researchers also examined tooth decay using terahertz imaging.

As skin is occluded, water accumulates in the stratum corneum (outermost layer of skin). During this process, the reflected terahertz signal decreases and can be monitored in real time. The signal before occlusion (red, time zero) and after 20 minutes of occlusion (blue) is highlighted. The system is so sensitive that even occluding for five seconds affects the terahertz response. Courtesy of Emma MacPherson, CUHK.

Studies have been scarce in dentistry and dermatology since then, though, because of one big showstopper: the difficulty of terahertz radiation to penetrate in depth any substance with a high water content. Recently, however, great strides have been made in improving terahertz sources and detectors that address some of these difficulties head on.

Research groups have successfully detected skin cancer using terahertz light. However, because of the low resolution of current imaging approaches, the cancer can often only be seen after it has grown quite large.

Earlier this year, in a bid to boost image resolution, Rayko Stantchev, Ph.D., published a setup to measure near-field interactions between terahertz waves and the object being imaged in the OSA journal Optica. In the setup, Stantchev and his team used a digital micromirror device (DMD) to project a pattern of 800-nm light onto a silicon wafer. If exposed to a very intense laser, the wafer becomes opaque to terahertz waves. When the terahertz wave passes through the wafer, it creates a patterned beam on the other side that interacts with the object being imaged.

Because the pattern created by the DMD is known, a computer can reconstruct an image of an object placed on the exit interface of the wafer. The technique can be used for improving signal-to-noise in other near-field and low-signal imaging techniques, including early detection of skin cancers without the need for a skin biopsy.

A graduate student at the University of Exeter at the time he built the setup, Stantchev currently works in the group led by MacPherson, who is a professor at the Chinese University of Hong Kong (CUHK) in Shatin, Hong Kong.

Since being part of the team that first applied terahertz imaging to detect skin cancer, MacPherson has built a reputation of being at the forefront of terahertz imaging and spectroscopy for biomedical applications. While still running her team in Hong Kong, she recently moved to Warwick, England, and joined the Warwick University Physics Department.

MacPherson currently is addressing the penetration problem of terahertz radiation using occlusion, which helps to determine conditions in deeper layers of the skin by identifying properties in the uppermost layers. She is addressing the penetration problem by exploiting the sensitivity of terahertz radiation to water. Skin cancer tissues have different water content than healthy skin, which means that examining properties in the uppermost layer can help determine conditions in deeper layers. Changes in the upper layers can indicate anything from skin cancer to hydration levels. Besides identifying cosmetic factors related to aging and hydration, this opens the way for early detection of subclinical skin cancer.

“We have done some interesting work on scar imaging as well as recently showing how terahertz is very sensitive to skin hydration,” MacPherson said. “We show how when imaging human skin in vivo, the terahertz properties change as the skin becomes occluded during the measurement. I have some ideas as to how to use this to improve the status quo of skin imaging and in turn the treatment and diagnosis of skin conditions.”

To push this research forward, MacPherson plans to collaborate with medics at the University Hospitals Coventry and Warwickshire Trust.

In the meantime, researchers in MacPherson’s CUHK group are probing how terahertz reflection imaging can be used to study how water flows in and out of the top-most layers of the skin. Terahertz allows values to be obtained even when the skin is occluded by an imaging window. Placing samples on the window helps alignment and image registration, but for living subjects, it blocks a surface that skin would normally breathe through.

The terahertz reflection imaging system for the measurement of skin. The emitter and detector pair are scanned in 2D dimensions to see if the skin placed on the imaging window has abnormalities. Current imaging speeds are too slow, and the patient would have to remain completely still for about 10 minutes before being able to change the area being imaged. Courtesy of Rayko Stantchev, CUHK.

Stantchev, now a postdoctoral research assistant, highlights the specificity of the approach. “The technique has great sensitivity and can obtain the water diffusivity values in occluded skin, whereas other methods require the skin to breathe,” he said.

Elsewhere, there has been promising work using terahertz for diabetic foot imaging. The feet of diabetic people present, in many cases, a combination of microvascular and neurological deterioration that leads to poor irrigation and loss of sensitivity. This combination of conditions causes dehydration of the skin. Enrique Castro-Camus’ Applied Terahertz Science Group in Guanajuato, Mexico, found that this tell-tale dehydration could be detected using terahertz imaging.

In dentistry, as in dermatology, what can be seen at the surface can tell us a lot about what is going on inside. Terahertz reflected from a tooth is being used to detect if there is any chemical change in the enamel. This could be indicative of the development of dental caries. But there remains limitations to the use of this technique. Because terahertz is highly sensitive to water, Stanchev pointed out, you will get different results if there are different amounts of saliva on teeth.

While the academic research pushes forward, terahertz manufacturers continue to tackle four key challenges: measurement speed, signal quality, spatial resolution and system price. But there’s no apparent easy solution. “Optimize the setup in one direction and you will likely need to compromise on the other three,” said Anselm Deninger, Toptica’s product manager/director for terahertz technologies.

Fast terahertz imaging techniques are able to monitor water absorption dynamics in real time. In a proof-of-principle experiment, researchers from Toptica wetted the edges of three different samples — lump sugar (red), a sponge (blue) and a sheet of tissue paper (green) — with a droplet of water each. Within a few hundred milliseconds, the water spread out across the sample, reducing the transmitted terahertz intensity. Toptica’s researchers believe that the technique may be applicable to monitor biological processes on timescales of milliseconds or even microseconds. Courtesy of Toptica.

Current terahertz components, especially sources and detectors, are simply not cost-effective compared to the components adjacent in the spectrum such as infrared and microwave.

Even photoconductive antenna (PCA)-based technology (see sidebar below) is costly, as the required laser must emit very short pulses of light of around 100 fs. In addition, current terahertz technologies are bulky and difficult to use.

Terahertz pulses reflected from human skin that has been in contact with the imaging window for a certain amount of time (a). The reflected pulses decrease in amplitude as time increases. Researchers believe this is caused by the water not being able to flow out of the skin and thus building up in the top skin layer. On the vertical axis is the value of the top terahertz peak minus the bottom terahertz peak value, and on the horizontal axis is occlusion time (or time in contact with the imaging window) (b). Inset shows the same thing for a different test subject. Courtesy of Rayko Stantchev, CUHK.

“This results in lukewarm demand [and] a smaller community of trained engineers and workforce, which in turn further limits technology development,” said professor Seongsin Margaret Kim, a terahertz photonics and metamaterials specialist at the University of Alabama. “Therefore, economically, terahertz imaging still suffers from a technology-push versus application-pull issue that is prevalent to many emerging technologies.”

A small number of companies — such as Toptica and TeraView — have released sources, detectors and other terahertz optics components that can be easily integrated within a system. Probes such as Toptica’s TeraScan and TeraView’s TeraPulse can be used by nonspecialist nurses or doctors without the need for tricky alignment or special knowledge about the device.

On the laser side, the old Ti:Sapphire lasers, which were intricate in construction and sensitive to use, have been replaced by compact and highly robust femtosecond fiber lasers. Terahertz antennas have seen much improvement as well.

“When we started our terahertz activities a decade ago, we were dealing with power levels of a few hundred nanowatts,” Toptica’s Deninger said. “Today, we use emitters that generate a terahertz power of 50 µW or 100 µW. This is a power gain of two to three orders of magnitude.”

Academic researchers, too, are working to surmount some of the barriers to commercial entry. One of Kim’s recent projects developed a source that demonstrates terahertz generation from top-down fabricated semiconductor nanowires without any bias voltage.

“It demonstrates a great potential of better terahertz sources since it doesn’t require high bias voltage, which can save energy and [is] more cost-effective and highly efficient,” Kim said.

Mastering the Challenges in the Terahertz Window

The term “terahertz window” refers to frequencies between infrared light on the high-frequency side and microwaves on the lower-frequency end. The infrared region has been conquered by lasers. Microwaves can be generated using electronic devices, but there are severe challenges when it comes to frequencies around 2 THz.

Technologically, it is difficult to build practical intense terahertz sources and sensitive-enough terahertz detectors. As a result, terahertz imaging remains uncomfortably slow at attaining meaningful high signal-to-noise ratio and/or avoiding false positives even with the implementation of modern imaging signal processing.

Terahertz imaging also is intrinsically limited by water vapor in certain bands. This means that atmospheric attenuation is a showstopper for long-range measurements (anything above 1 meter or so), and the signal is tempered in in vivo biological materials.

Liquid water, by contrast, does not show any absorption bands. Rather, it exhibits a broadband damping effect. Not even window frequencies survive, and this is exactly the challenge for biological materials.

There is a need for stronger sources or more sensitive detectors to help alleviate these fundamental challenges.

“Existing lasers — so-called quantum-cascade systems — require cryogenic operation, which makes these instruments rather costly,” explained Anselm Deninger, product manager/director of terahertz technologies at Toptica.

One approach is to use resonant frequency doublers and triplers. But these must be machined with staggering precision and so become increasingly costly and less efficient when dealing with frequencies greater than a few hundred gigahertz. “We have been pursuing a third, indirect approach: We use near-infrared lasers and convert their output to terahertz light,” Deninger said. “This works both for pulsed lasers as well as for continuous-wave lasers, thanks to specially designed semiconductor elements: so-called photoconductive antennas (PCAs).”

This indirect approach may show promise, according to Seongsin Margaret Kim, a terahertz photonics and metamaterials specialist at the University of Alabama. Kim attributes many of the discoveries relating to terahertz imaging over the last two decades to advances in PCA technology and broadband terahertz sources. PCA-based sources can generate broadband terahertz radiation, she said, which is useful for many applications, particularly in scientific research.