by Dr. Huma Rasheed, Fawad Maqbool and Mick Syed, AmpliTech Inc.

Radio Frequency Microwaves (RFM) exert various effects on the biological system and possess a great impact in medical applications, for instance by heating, altering chemical reactions, or inducing electrical current in tissues and cells. The knowledge of temperature-dependent electrical properties of biological tissues is important to calculate the deposition of electromagnetic energy in a variety of diagnostic procedures and treatments. Every single the molecule of biological system is continuously generating electromagnetic field due to thermal agitation of charged particles that is directly proportional to its frequency, so the higher frequency indicates higher energy as indicated by the photon energy formula:

E = hf

Where,

E = Energy per photon

h = Planck’s constant = 6.63 x 10-34 J x s

f = frequency of radiation

Figure 1: Malignant tissues can be modeled as a two-port network with a S-parameter matrix

The human tissues can be electrically treated by being modeled as a two-port network with its own scattering matrix or S-parameters (Figure 1). These S-parameters will change as a function of the type of the tissues (normal or malignant). The analysis of the scattering matrix can determine the type of malignant tissues such as melanoma, carcinoma, sarcoma etc., by observing the different amounts of MW radiation absorbed or reflected by the tumor model. Using this method, we can catalog and characterize the different radar returns until enough data can be collected and analyzed and used as a lookup table and data base. The current advancement in the research technology, especially telecommunication, has raised great concerns regarding possible effects of excessive RF/MW exposure. The biological system when exposed to RF radiations they can be reflected, transmitted, refracted or absorbed (1). Based on the amount of absorbed energy within the biosystem, effects can be divided into thermal and non-thermal and the mechanism of RF interaction with the body is the increased tissue or body temperature which is responsible for cellular and intracellular changes. The amount of heat depends on the intensity of radiation, electrical properties of exposed tissue and body’s thermoregulatory mechanism (2).

According to Dodge and Glaser, 1977 (3), the exposure level established in the United States adheres to a level of 10 mW/cm2 averaged over 0.1 h. It is reported that minimum energy required for these processes should exceed 26 meV, the average energy of thermal noise measured at body temperature. These effects could only be observed if certain biological structures had the same vibration frequencies as the applied electromagnetic field (EM). For example, microtubule reassembly was related to the peak of cellular EM field emission during replication, suggesting the crucial role in their generation. Interestingly, microtubules can vibrate in kHz to GHz frequency region (4). Adey reported that RF/MW radiation seems to induce electric oscillations that disturb cell membrane proteins, activating enzyme cascades that may transfer cell surface signals to the intracellular system (5). Foster et. al. in 2016 (6) performed a study on RF-induced increase in skin temperature in the frequency range from 3 GHz through the millimeter frequency range (30-300 GHz). They developed a model based on Pennes’ Bioheat equation (BHTE) and the parameter analysis showed small irradiated areas (less than about 0.5-1 cm in radius); the temperature increase at the skin surface is chiefly limited by conduction of heat into deeper tissue layers, while for larger irradiated areas, the steady-state temperature increase is limited by convective cooling by blood perfusion. The study supported the use and limitations for using MW radiation in the biological system.

Table 1: Temperature-dependent electrical properties of normal and malignant human tissues studied by the researchers. The presented conductivity and diffusivity were calculated for 37°C; original values were presented temperatures different from 37°C. Data taken from Rossmann et .al., 2014 (7). +c calculated via k/alpha/rho *The values and the coefficient were calculated for the temperature range 20 to 70°C

Based on these findings, scientists investigated the involvement of MW in the diagnosis and treatment of cancer and other related diseases. Researchers have proposed the biophysical mechanism of novel diagnostic methods based on MW radiation technology for cancer detection. These methods are related to the frequency-based absorption of electromagnetic waves emitted by the malignant tumors.

This review presents the literature survey of recent progress in MW technology for early detection and treatment of cancer based on scientific research. These MW techniques will bring new paradigms for cancer imaging and therapy may emerge soon that challenges conventional methods for diagnosing, staging and treating cancer and metastatic diseases.

Dielectric Properties of Normal and Malignant Human Tissues

Every cell and tissue of the human body possesses different electric environment and behave differently when exposed to MWs. At MW frequencies, dielectric properties are determined by water content and thus less affected by tissue removal than at RF frequencies. The application of temperatures greater than 50-60°C likely causes irreversible changes in the electrical properties as result of dehydration, shutdown of perfusion, and other cellular and molecular changes and can be responsible for malignant tissue or cells (7).

Ultra-wide Band (UWB) Antenna Sensor Base MW Imaging:

MW imaging was defined by Fear et al. in 2003 (8) as “seeing the internal structure of an object by means of electromagnetic fields at MW frequencies of 300 MHz to 30 GHz.” MW imaging techniques have been intensely studied as a promising diagnostic tool for rapid and cost-effective early-stage cancer detection. Ultra-wideband (UWB) antenna imaging technology began since the last decade and is used mainly for the detection of breast cancer. The antenna acts as a transmitting and receiving sensor. The breast tissues are exposed to MW signals from transmitting sensor and the back-scattered signals from the breast tissues are collected from receiving sensors. The changes in the back-scattered signal are analyzed and used to identify tumor cells inside the breast, which exhibit higher dielectric constants than normal cells (9). Recent studies show that the antenna sensor should have high gain, the ability to transmit a wide range of frequencies with higher efﬁciency, directive radiation of power, small size and model simplicity, compatible penetration of human tissue and the ability to operate at both low and high frequencies. (10, 11) Ultra-wideband (UWB) antenna technology has some useful features, like high-speed data rates, very small interference, simple low-cost designs and low power spectrum density and it is reported that high gain and wideband of approximately 8 GHz has shown quite good results. Since 2002, the Federal Communications Commission (FCC) has allowed UWB bands of 7.5 GHz (from 3.1 to 10.6 GHz) for commercial usage (12). Recently MW tomography and ultra-wideband (UWB) radar imaging for breast cancer detection is also gaining importance and UWB radar imaging is important for histological procedures.

MW-induced Thermoacoustic Imaging (TAI):

TAI uses the same physical principal as PAI, except that short electromagnetic pulses between 0.3 and 3 GHz are used as the source for excitation and images are proportional to the absorbed MW energy. Because tumors with higher water content differentially absorb MWs compared to surrounding tissue (e.g., adipose), TAI has been proposed as a novel approach for diagnostic breast imaging, and a pilot study at 434 MHz revealed 3D in vivo images of the human breast with excellent sensitivity for detecting tumors. However, limitations in MW and ultrasound hardware in these early studies prevented high resolution characterization and accurate classification of suspicious lesions (14). Because resolution in TAI depends on the duration of the excitation pulse, the long MW pulse of 1 μs contributed to poor spatial resolution (> 1 mm) (14). To overcome this drawback, two research teams recently tested a novel broadband transmitter for TAI with ultrashort impulse excitation. Instead of a traditional tube-based amplifier, the low-cost excitation source exploited a high-voltage triggered spark gap for generating short electromagnetic impulses (10 ns duration) with high peak power (up to 40 MW).

MW Ablation (MWA):

Radio frequency ablation (RFA) and MW ablation (MWA) are the two percutaneous thermal ablative techniques for the treatment of unresectable tumors and for MW ablation, the important properties are relative permittivity and effective conductivity. In comparison with surgical resection, percutaneous image-guided ablation delivers a minimally invasive treatment source, ideal for nonoperative candidates but the rate of blood perfusion in each tissue is important for both RF and MW ablation. RF MWs in low frequencies are also reported to kill cancer cells thereby reported as cytotoxic and can be a promising tool for the treatment of cancer of various origins. In addition, percutaneous radio-frequency ablation has been widely accepted as the first-line treatment of early-stage hepatocellular carcinoma (HHC) and many randomized controlled trials have shown significant differences between these local ablation techniques. MW technology is a new thermal ablation technique for different types of tumors, providing all the benefits of radio frequency and substantial advantages. MW ablation has been applied to liver, lung, kidney and more rarely to bone, pancreas and adrenal glands (15). One study shows that MWA is a preferable treatment modality for benign thyroid nodules with less complications. Hyperthermia has been found very effective in the treatment of cancer patients in addition to chemotherapy, hormone therapy surgical resection and radiation therapy with minimal toxicity. MWA offers potentially better local control in larger and perivascular tumors.

Mechanism of MW-induced Hyperthermia in Cancer Cell Death

The mechanism of MW induced cell death is still unclear and under investigation. However, some of the recent studies show that MWs’ induced anti-cancer effect is due to various cellular changes such as increased cellular permeability, disassembly of cytoskeleton, enlarged tumor pores, protein denaturation, DNA fragmentation or strand breakage that contribute to apoptosis (17). Researchers have studied MW-induced apoptosis in bladder cancer, lung cancer and prostatic adenomas.

Figure 2: Schematic block diagram of MW imaging using UWB antenna sensor (13)

Figure 3: Schematic representation of MW-induced thermoacoustic imaging system (14)

Figure 4: Triaxial MW ablation antenna. The antenna has to be designed with the specific pattern which targets the affected areas without damaging the surrounding normal tissues (16). Multiple antenna arrays can accomplish more precise alignment and pin-point the tumors for MW ablation.

Conclusion

Based on the published literature on implementation of MW radiation in the clinical and medical industry gained a great importance for the scientists and investigators. Further investigations need to be carried out to study the effect of MW on in-vitro and in-vivo experiments for the treatment and detection of cancer.

References:

1. Vecchia P, Matthes R, Ziegelberger G, Lin J, Saunders R, Swerdlow A, editors. Exposure to High Frequency Electromagnetic Fields, Biological Effects and Health Consequences (100 kHz-300 GHz). Oberschleißheim: ICNIRP; 2009.

2. Adey WR. Cell and molecular biology associated with radiation fi elds of mobile telephones. In: Stone WR, Ueno S, editors. Review of radio science 1996-1999. Oxford: Oxford University Press; 1999. p. 845-72

3. Dodge CH, Glaser ZR.Trends in nonionizing electomagnetic radiation bioeffects research and related occupational health aspects. J. Microw Power. 1977 Dec;12(4):319-4.

4. Cifra M, Fields JZ, Farhadi A. Electromagnetic cellular interactions. Prog Biophys Mol Biol 2011; 105:223-46.

5. Adey WR. Cell and molecular biology associated with radiation fi elds of mobile telephones. In: Stone WR, Ueno S, editors. Review of radio science 1996-1999. Oxford: Oxford University Press; 1999. p. 845-72

6. Foster KR1, Ziskin MC, Balzano Q. Thermal Response of Human Skin to MW Energy: A Critical Review. Health Phys. 2016 Dec;111(6):528-541.

7. Rossmann C, Garrett-Mayer E, Rattay F, Haemmerich D. Dynamics of tissue shrinkage during ablative temperature exposures. Physiol Meas. 2014 Jan;35(1):55-67.

8. Fear, E.C.; Meaney, P.M.; Stuchly, M.A. MWs for breast cancer detection? IEEE Potentials 2003, 22, 12–18. [CrossRef]

9. Zhang, Y.; Hong, W.; Yu, C.; Kuai, Z.-Q.; Don, Y.-D.; Zhou, J.-Y. Planar ultrawideband antennas with multiple notched bands based on etched slots on the patch and/or split ring resonators on the feed line. IEEE Trans. Antennas Propag. 2008, 56, 3063–3068. [CrossRef]

10. Jalilvand, M.; Li, X.; Zwirello, L.; Zwick, T. Ultra-wideband compact near-field imaging system for breast cancer detection. IET Microw. Antennas Propag. 2015, 9, 1009–1014. [CrossRef] 7.

11. Aguilar, S.M.; Al-Joumayly, M.A.; Burfeindt, M.J.; Behdad, N.; Hagness, S.C. Multiband miniaturized patch antennas for a compact, shielded MW breast imaging array. IEEE Trans. Antennas Propag. 2014, 62, 1221–1231. [CrossRef] [PubMed]

12. Revision of Part 15 of the Commission’s Rules Regarding Ultra-Wideband Transmission Systems. Available online: https://www.fcc.gov/document/revision-part-15-commissions-rules-regarding-ultra-widebandtransmission-systems-4 (accessed on 11 April 2018)

13. Zhurbenko, V.; Rubæk, T.; Krozer, V.; Meincke, P. Design and realisation of a MW three-dimensional imaging system with application to breast-cancer detection. IET Microw. Antennas Propag. 2010, 4, 2200–2211

14. Soltani M, Rahpeima R, Kashkooli FM. Breast cancer diagnosis with MW thermoacoustic imaging technique-a numerical approach. Med Biol Eng Comput. 2019 Mar 27. doi: 10.1007/s11517-019-01961-8

15. Carrafiello G1, Laganà D, Mangini M, Fontana F, Dionigi G, Boni L, Rovera F, Cuffari S, Fugazzola C. MW tumors ablation: principles, clinical applications and review of preliminary experiences. Int J Surg. 2008;6 Suppl 1:S65-9.

16. Brace CL1. Radiofrequency and MW ablation of the liver, lung, kidney, and bone: what are the differences? Curr Probl Diagn Radiol. 2009 May-Jun;38(3):135-43. doi: 10.1067/j.cpradiol.2007.10.001.

17. Zhao YY, Wu Q, Wu ZB, Zhang JJ, Zhu LC, Yang Y, Ma SL, Zhang SR. Int J Oncol. 2018 Aug;53(2):539-550. doi: 10.3892/ijo.2018.4439. Epub 2018 Jun 13.





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