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Abstract— Terahertz (THz) radiation lies between the infrared and microwave regions of the electromagnetic spectrum. The THz technology has important opened up many opportunities in the area of medical. Advances in THz medical imaging field are immature. In this paper presents a review of the status of the THz imaging system and application in area of biomedical such as breast and colon cancer tissue. We give the main focus of this study of mapping margins of tumors in earlier stage based on terahertz imaging system such as terahertz pulse imaging, terahertz time domain spectroscopy, continuous wave terahertz, and THz generation with schottky diode and without beam stop.

Index Term

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I. INTRODUCTION

Over the past quarter century terahertz (THz) imaging technology has become increasingly important for biological applications such as breast tumors, skin cancer, cervical cancer and colon cancer. The THz frequency range is particularly interesting for biosensing applications because numerous characteristics vibrational modes of macro-molecules, like proteins or DNA [1-6]. Recently cancer is a leading cause of death worldwide. According to World Health Organization (WHO), an estimated data of people worldwide were diagnosed with cancer in 2008 is given in Table I.

About 70% of all cancer deaths occurred in low- and middle-income groups. Deaths from cancer worldwide are projected to continue to rise to over 13.1 million in 2030 [7]. Breast Cancer is the second leading cause of death in US and India. Breast Cancer patients diagnosed are characterized into three cases, first case 90% patients diagnosed will undergo surgery to treat the disease, in second case, 60% will undergo breast conserving surgery, according to breast conserving surgery the primary tumor is removed with a margin of normal tissue around it and remaining mastectomy.

A. K. Panwar is with the Department of Applied Science, Delhi T echnological University, Shahbad Daulatpur, Main Bawana Road,

Delhi-42, India ([email protected]).

A. Singh is with the Department of Electronics Engineering, Radha Govind Engineering College, Meerut, UP, India

([email protected]).

A. Kumar and Hiesik Kim are with the Department of Electrical, Electronics, and Computers Engineering, University of Seoul, South Korea

(Corresponding Author: [email protected] and

[email protected])

Around 10 – 15% of patients will require a second operation, as the margins are not free of cancer on histopathology [8].

TABLE I

DEATH DATA VS CANCER (WHOSTANDARDS 2008)

C ance r Name C ase s

Lung Cancer 1.37 Million

Stomach Cancer 0.736 Million

Liver Cancer 0.695 Million

Colorectal Cancer 0.0608 Million

Breast Cancer 0.458 Million

Cervical Cancer 0.275 Million

Most women with breast cancer will have some type of surgery. Surgery is often combined with other treatments such as radiation therapy, chemotherapy, hormone therapy, and/or targeted therapy. Surgery and radiation therapy are associated with each other. Radiation is used to destroy cancer cells remaining in the breast, chest wall, or underarm area after breast -conserving surgery. Radiation may also be needed after mastectomy in patients with either a cancer that is larger than 5 cm in size or when cancer is found in the lymph nodes. There are two types of radiation therapy. External beam radiation is the usual type of radiation for women with breast cancer. Radiation is focused from a machine outside the body on the area affected by cancer. This usually includes the whole breast and, depending on the size and extent of the cancer, may include the chest wall and underarm area as well. External beam radiation therapy is typically administered over a period of 5 to 6 weeks; however, in recent studies, shortening the treatment to 3 weeks appears to be just as effective. Internal radiation therapy, known as brachy-therapy, uses a radioactive substance sealed in needles , seeds, wires, or catheters that are placed directly into or near the cancer. Some patients are treated with both internal and external radiation therapies in combination. The way the radiation therapy is given depends on the type, stage, and location of the tumor being treated [9,10]. The third common cancer in both woman and man is a colon (gastrointestinal) cancer. As with most cancers, early detection is essential for improved survival rates. The other method is endoscopy, endoscopy is the accepted go ld standard for screening and surveillance of these cancers, but the technique is far from perfect. Because during routine endoscopy, multiple random biopsies are often required, during this procedure increases the risk of bleeding. These biopsies are processed, cut into thin slices, and observed under a microscope (histopathology). A large proportion may turn out normal and thus were not required. There is a need for better endoscopic visualization in specific circumstances such as the detection of dysplastic lesions (precancerous tissue), with the ultimate goal of improving sensitivity and specificity compared with

A.

K. Panwar, Abhisek Singh, Anuj Kumar, and Hiesik Kim

131502-5757-IJET-IJENS © April 2013 IJENS histopathology [8]. There is a clinical need to be able to

accurate defines the margins of tumor and accuracy during surgery, conserve normal tissue and minimize the number of second surgical procedures /unnecessary biopsies [11,12]. Researchers and Scientist presented many imaging technique for mapping margins of tumors [13] but currently this field is immature. In view of ever increasing the cas es of breast cancer, skin cancer, cervical cancer and colon cancer these system should have the facilities to detect and quantify the cancer tissue in primary stage. Hence, there is a growing demand for automatic, low cost, and easy to operate THz imaging System. In this paper, introduce a terahertz imaging with breast cancer and provides a short review of recent advances in terahertz imaging system and system for biomedical applications .

II. TERAHERTZ RADIATION

Terahertz (THz) radiation (frequency: 0.1-10THz, wavelength: 3mm - 30µm, wave-number: 3.3 – 333cm-1, energy: 0.41 – 41MeV, color temperature: 1 – 100K) lies between infrared light and microwave in the electromagnetic spectrum, and it shares some properties with each of these [14]. Like infrared and microwave radiation, terahertz radiation travels in a line of sight and is non-ionizing. Like microwave radiation, terahertz radiation can penetrate a wide variety of non-conducting materials. Terahertz radiation can pass through clothing, paper, cardboard, wood, masonry, plastic and ceramics. The penetration depth is typically less than that of microwave radiation. Terahertz radiation has limited penetration through fog and clouds and cannot penetrate liquid water or metal [15].

Terahertz radiation is emitted as part of the black body radiation from anything with temperatures greater than about 10K. While this thermal emission is very weak, observations at these frequencies are important for characterizing the cold 10-20K dust in the interstellar medium in the Milky Way galaxy, and in distant starburst galaxies. Telescopes operating in this band include the James Clerk Maxwell Telescope, the Caltech Sub -millimeter Observatory and the Sub--millimeter array at the Mauna Kea Observatory in Hawaii, the BLAST balloon borne telescope, the Herschel Space Observatory, and the Heinrich Hertz Sub-millimeter Telescope at the Mount Graham International Observatory in Arizona. The Atacama Large Millimeter Array, under construction, will operate in the sub-millimeter range. The opacity of the Earth's atmosphere to sub-millimeter radiation restricts these observatories to very high altitude sites, or to space [16-19].

Contrary to X-rays, terahertz radiation has relatively low photon energy for damaging tissues and DNA. Some frequencies of terahertz radiation can penetrate several millimeters of tissue with low water content (e.g., fatty tissue) and reflect back. Terahertz radiation can also detect differences in water content and density of a tissue. Such methods could allow effective detection of epithelial cancer with a safer and less invasive or painful system using imaging. Some frequencies of terahertz radiation can be

used for 3D imaging of teeth and may be more accurate than conventional X-ray imaging in dentistry [20-22].

Experiments with THz radiation date back to measurements of black body radiation using a bolometer by Heinrich Reubens and Ernest Fox Nichols in the 1890s [23,24]. In 1975, David Auston at AT&T Bell Laboratories developed a photoconductive emitter gated with an optical pulse that accelerated progress towards bridging the THz gap [25-27].

III. TERAHERTZ IM AGING SYSTEM

Medical imaging is the technique and process used to create images of the human body for clinical purposes (seeking to reveal, diagnose or examine disease) or medical science. Although imaging of removed organs and tissues can b e performed for medical reasons. Measurement and recording techniques which are not primarily designed to produce images, such as electroencephalography (EEG), magneto-encephalography (MEG), electrocardiography (EKG) and others, but which produce data susceptible to be represented as maps (i.e. containing positional information), now a days can be seen as forms of medical imaging. Currently medical imaging dependents on terahertz imaging, Terahertz imaging is still a very immature field, with the majority of research focused on Instrumentation and hardware. The THz imaging system are classified into two categories active (imaging or spectroscopy) and passive (incoherent), active further classified into two categories such as pulsed and continuous wave (CW). Many research groups have explained the THz imaging technique and system [28-44].

Fig. 1. First schematic of the T Hz imaging system proposed by Hu and Nuss [27].

Wallace et al developed a pulses generates instrument of broadband terahertz radiation in the range 0.05 to 4 THz with a spectral resolution of 0.03 THz. The broadband signal-to-noise ratio is typically around 4000:1. The optics is raster scanned in the x-y plane to collect a grid of pulses. The dataset is three-dimensional with time as the third axis. The sample is placed on the quartz imaging plate and a 2 cm2 area can be scanned in a few minutes [40]. Dobroiu et al present an imaging system designed for use in the terahertz range. As the radiation source a backward -wave oscillator was chosen for its special features such as high output power, good wave-front quality, good stability, and wavelength tune-ability from 520 to 710 GHz. Detection is achieved with a pyro-electric sensor operated at room temperature. The alignment procedure for the optical elements is described, and several methods to reduce the etalon effect that are inherent in monochromatic sources are discussed. The terahertz spot size in the sample plane is 550 µm (nearly the diffraction limit), and the signal-to-noise ratio is 10,000:1; and are also measured other characteristics. A number of preliminary applications are also shown that cover various areas : nondestructive real-time testing for plastic tubes and packaging seals; biological terahertz imaging of fresh, frozen, or freeze-dried samples; paraffin-embedded specimens of cancer tissue; and measurement of the absorption coefficient of water by use of a wedge-shaped cell [45]. K. Kawase et al developed a novel basic technology for terahertz imaging, which allows detection and identification of drugs concealed in envelopes, by introducing the component spatial pattern analysis. The spatial distributions of the targets are obtained from terahertz multispectral trans -illumination images, using absorption spectra measured with a tunable terahertz-wave source. As a reference, methamphetamine and MDMA samples are used because these samples are illegal drugs in Japan, and aspirin [46]. Wu et al presented a novel electro-optic sampling system for real-time terahertz (THz) imaging applications. By illuminating a 6×8 mm2 ZnTe crystal with a 300 μW optical sampling beam and detecting the beam with a digital CCD camera, we achieved time-resolved images of pulsed far-infrared radiation emitted from an unbiased GaAs wafer. At the focal point of the peak far-infrared field, the THz beam diameter is approximately 0.75 mm (full width at half-maximum). The

131502-5757-IJET-IJENS © April 2013 IJENS Fig. 2. Schematic of T Hz-T DS System [50,51].

Lee et al. presented a real-time, continuous -wave terahertz imaging with a 10 mW, 2.52 THz (118.8 µm) far-infrared gas laser and a 160×120 element micro-bolometer camera. The micro-bolometer camera is designed for wavelengths of 7.5-14 µm but retains sensitivity at terahertz (THz) frequencies. The setup has no moving parts, and transmission-mode THz images can be obtained at the video rate of 60 frames/s. The peak signal-to-noise ratio is estimated to be 13 dB for a single frame of video, acquired in 16 ms. With this setup, THz imaging through a FedEx envelope is demonstrated, showing the feasibility of real-time mail screening [54-56]. Knobloch et al. presents a THz investigation of histo-pathological samples including the larynx of a pig and a human liver with metastasis. Knobloch measurements show that different types of tissue can be clearly distinguished in THz transmission images, either within a single image or by a comparison of images obtained for different frequency windows. This leads to the problem that images obtained for different frequencies inherently have a different spatial resolution. An image obtained from two such images by a simple mathematical operation may contain arte facts and discussed measures to deal with this problem. Finally, presents The possibility of improving the spatial resolution of THz images and the CW THz imaging system based on a photomixer and an external cavity semiconductor laser that allows for simult aneous two-mode operation [57]. Gregory et al. presented a continuous-wave all-optoelectronic terahertz imaging system based on diode lasers. The coherent detection scheme is phase sensitive and operates at room temperature. Continuous-wave terahertz (CW-THz) radiation can be produced by photo-mixing two CW lasers in a photoconductor. The difference in frequency of the two lasers is tuned to the THz region, and monochromatic CW -THz is emitted at the beat frequency. This can be achieved using diode lasers, addressing the issue of cost. The schematic diagram of CW-THz system as shown in Fig 3 and shows a combining beam-splitter, optical delay line and imaging optics. A typical CW system that mixing of two wavelength using two CW lasers in a photoconductor produces beating, which can modulate the conductance of a photoconductive switch at the THz difference frequency, since the source spectrum of the CW system is narrow and

sometimes only the intensity information is of interest, the data structure and post-processing are quite simple [58]. Verghese et al. also demonstrated that coherent detection is possible in the reverse scheme [59]. Menikh discussed a primary goal of current research in this field is to improve the THz sensor dynamic ranges, achieve faster data acquisition, and reduce water vapor absorption, THz bio-sensing capabilities, progress and limitations. THz-Generation System without beam-stop is shown in Fig 4. THz generation system used a pair of photodiodes measures the difference in current intens ities. A photodiode is a type of photo-detector capable of converting light into either current or voltage, depending upon the mode of operation. Photodiodes are similar to regular semiconductor diodes and advantageous of photodiodes are fast response time, Excellent linearity of output current as a function of incident light, low noise, low cost, and long life time [60]. Yu et al. discussed a recent advances in terahertz imaging, spectroscopy techniques for cancer diagnosis. In Fig 5, the source is frequency tunable THz oscillator module and the detector is a schottky diode. In this case, the schottky diodes work as a receiver to detect the power of the transmitted through the sample. A schottky diode is a type of semiconductor which has a metal-semiconductor barrier; it is fast switching action, very low forward voltage drop, low junction capacitance, less temperature dependence, and highly sensitive at the low frequency region for power detection . The main advantage of schottky diode is the switching speed controlled by thermalization of hot injected electrons across the barrier picoseconds. [61]. Tonouchi presents an overview of the status of the technology, its uses and its future prospects are presented [62]. Tewari et al developed a reflective THz imaging system sensitive to small variations in water concentrations. Biological tissues such as skin, eyes and teeth are imaged to ascertain the systems response to tissue hydration. Difference in water concentrations translated to contrast in the THz images. Contrast is also seen in THz images of skin cancer and burns suggesting the potential diagnostic capability of THz imaging system in clinical settings. All specimens analyzed were freshly excised ex-vivo tissues. These encouraging preliminary results have motivated us to explore the in vivo potential of our imaging system [63]. Joseph et al presents a continuous wave terahertz imaging system of non-invasive medical imaging modality for detecting different types of human cancers [64].

Fig. 5. T Hz system with schottky diode (proposed by Calvin Yu) [61]. Fig. 4. T Hz-Generation system without beam stop (A. Menikh) [60].

TABLE II

AVAILABLE T HZ SYSTEM DEVELOP ED BY WELL KNOWN GROUP [65]

Popovic and Grossman presented an overview of measurement techniques used in the THz region of the electromagnetic spectrum, from about 100 GHz to several THz and also described components of measurements for THz metrology, such as sources, detectors and available instru mentation for THz metrology. Table II represents the available THz imaging system developed by well known group [65]. Friederich et al investigated of five active THz imaging modalities during the last few years for real-time imaging [66]. Taylor et al presented a THz imaging based two medical applications such as skin burns and cornea. For burns, images of second degree, partial thickness burns are obtained in rat models in vivo over

an 8 hour period. These images clearly show the formation and progression of edema in and around the burn wound area. For cornea, experimental data measuring the hydration of ex

vivo porcine cornea under drying is presented demonstrating

utility in ophthalmologic applications [67]. Ajito and Ueno present a THz-TDS spectroscopy beneficial for analytical chemistry and improved the sensitivity of THz time-domain (TDS). THz chemical imagings are very powerful tool in biology, pharmacology, and life sciences hydrogen bond distributions. THz-TDS is also promising for the quantitative chemical analysis and detection of molecules and clusters in nano-space and ice [68-70]. Special-purpose instruments have been demonstrated for imaging [71,72], spectroscopy [73,74], radio-astronomy [75], sensing [76], biology, etc. Calibration techniques of the instrument are presents in [77].

IV. CANCER STUDY

THz imaging system should then be able to detect the early cancer before it is visible or sensitive to any other means. The terahertz imaging system means terahertz radiation is non-ionizing and not highly scattered in tissues (unlike optical emission), thus making it elegant for use in biomedical applications [8, 13]. Researchers were studied to the terahertz properties such as absorption coefficient and refractive index of the images of the cases of breast and colon cancer. The absorption coefficient and refractive index of breast tumor/colon cancer tissue are higher in comparison to the normal tissue. These changes are dependable of higher water content and structural changes, like increased cell and protein density. The absorption spectrum of water exhibits a very strong, broad peak centered at 5.6 THz attributed to resonant stretching of the hydrogen bond between water molecules. The effect of this absorption peak, which extends down to the frequency range used in terahertz pulse imaging, makes this technique highly sensitive to water concentration. Thus, water absorption is evident in the terahertz properties measured for soft tissues, which explains the contrast seen between, for example, muscle and adipose tissue [40].

V. CONCLUSIONS

THz imaging is an initial stage of development for breast cancer and colon detection technique. However, THz imaging has great potential to be a valuable imaging technique in the future, particularly for cancer diagnosis. Mostly

THz-Mode l Name

Fre que ncy or Spectral Range and Re solution

Me asu-re me nt

Groups

T PS Spectra 3000

0.06THz – 4 THz (2cm-1 – 120cm-1),

resolution 7.5GHz, SNR 70dB

T DS

Anteral

T eraview OSCAT

T ERA Image

≥3 T Hz

(resolution upto 250MHz, dynamic range 60 dB

ASOPS-THz (T win -250)

Reception rate-250MHz, time measurement window – 4ns, wavelength – 1560nm, scan duration – 1s to 0.1ms

ASOPS Dual Color 1560/780nm

Reception rate – 100MHz, time measurement window – 10ns, scan duration 1s to 0.1ms, two color – 1560nm, 780nm

T ERA – K15

≥3 T Hz, scane range – 300ps, wavelength 1560nm

Menlo-system

T ERA – K8 ≥3 T Hz, wavelength 780nm

T -Spec Upto 3.5THz (116cm-1_{), excellent}

spectral resolution better than 5GHz

(0.17cm-1), non-dest. measurement

PB-7100 0.1 – 1.9T Hz, 0.1GHz resolution,

SNR 80dB @200GHz, SNR 60dB@1T Hz

FDS

Emcorep-hotonic system

T Hz-CW 0.05 – 1.8THz, Accuracy – 0.1GHz, resolution 1MHz, SNR –

70dB@500GHz

T optica

CW-400 0.05 – 1.5THz, resolution – 0.1GHz,

SNR- 50dB@500GHz

T eraview

T ray – 400 0.02 – 2THz, scan range 2.8ns, SNR –

70dB

T DS Picometrix

Mini-Z 0.1 – 4 T Hz, resolution < 50GHz,

SNR – [email protected]

131502-5757-IJET-IJENS © April 2013 IJENS generation systems are classified into two parts such as

sources and detectors. Sources are further classified into two categories: pulsed broadband and continuous narrowband. The most common approaches for generating broadband THz pulses are photoconductive antenna and optical rectification, while voltage controlled oscillators or dielectric resonators are the two widely used sources for generating low power narrowband continuous THz waves. A THz-Generation System without beam stop is a highly sensitive detection system. Some THz generation system used the broadband detectors. The broadband detectors based on thermal absorption are commonly used to detect low THz signal. In this reason, they require cooling units, to reduce thermal background. For pulsed THz detection, in THz time domain systems, coherent detectors are required. The whole CW system dependent of laser diodes and thus it can be made compact and inexpensive and CW systems are provides some limited information and give the information of particular frequencies. The Continuous -wave terahertz (CW-THz) system is less expensive and more compact than conventional time-domain imaging systems. The THz-TDS compared to other techniques are that it has a smaller spectral range than fourier transform spectroscopy (FTS) and provides lower resolution than narrowband THz spectroscopy. The THz beams which can be produced are still very low power.

More work is required to the improvement and development of THz-imaging system for will be added advantages such as prototype; low cost; fully functionalized and easy to operate; energy efficient, and contrast between diseased and healthy tissue.

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