Three Quarters of a Century of Research on RF Exposure Assessment and Dosimetry-What Have We Learned?

This commentary, by three authors with an aggregate experience of more than a century in technology and health and safety studies concerning radiofrequency (RF) energy, asks what has been learned over the past 75 years of research on radiofrequency and health, focusing on technologies for exposure assessment and dosimetry. Research programs on health and safety of RF exposure began in the 1950s, initially motivated by occupational health concerns for military personnel, and later to address public concerns about exposures to RF energy from environmental sources and near-field exposures from RF transmitting devices such as mobile phones that are used near the body. While this research largely focused on the biological effects of RF energy, it also led to important improvements in exposure assessment and dosimetry. This work in the aggregate has made RF energy one of the best studied potential technological hazards and represents a productive response by large numbers of scientists and engineers, working in many countries and supported by diverse funding agencies, to the ever rapidly evolving uses of the electromagnetic spectrum. This review comments on present needs of the field, which include raising the quality of dosimetry in many RF bioeffects studies and developing improved exposure/dosimetric techniques for the higher microwave frequencies to be used by forthcoming communications technologies. At present, however, the major uncertainties in dosimetric modeling/exposure assessment are likely to be related to the inherent variability in real-world exposures, rather than imprecision in measurement technologies.

Time-temperature Thresholds and Safety Factors for Thermal Hazards from Radiofrequency Energy above 6 GHz.

ABSTRACT: Two major sets of exposure limits for radiofrequency (RF) radiation, those of the International Commission on Nonionizing Radiation Protection (ICNIRP 2020) and the Institute of Electrical and Electronics Engineers (IEEE C95.1-2019), have recently been revised and updated with significant changes in limits above 6 GHz through the millimeter wave (mm-wave) band (30-300 GHz). This review compares available data on thermal damage and pain from exposure to RF energy above 6 GHz with corresponding data from infrared energy and other heat sources and estimates safety factors that are incorporated in the IEEE and ICNIRP RF exposure limits. The benchmarks for damage are the same as used in ICNIRP IR limits: minimal epithelial damage to cornea and first-degree burn (erythema in skin observable within 48 h after exposure). The data suggest that limiting thermal hazard to skin is cutaneous pain for exposure durations less than ≈20 min and thermal damage for longer exposures. Limitations on available data and thermal models are noted. However, data on RF and IR thermal damage and pain thresholds show that exposures far above current ICNIRP and IEEE limits would be required to produce thermally hazardous effects. This review focuses exclusively on thermal hazards from RF exposures above 6 GHz to skin and the cornea, which are the most exposed tissues in the considered frequency range.

Modeling Tissue Heating From Exposure to Radiofrequency Energy and Relevance of Tissue Heating to Exposure Limits: Heating Factor.

This review/commentary addresses recent thermal and electromagnetic modeling studies that use image-based anthropomorphic human models to establish the local absorption of radiofrequency energy and the resulting increase in temperature in the body. The frequency range of present interest is from 100 MHz through the transition frequency (where the basic restrictions in exposure guidelines change from specific absorption rate to incident power density, which occurs at 3-10 GHz depending on the guideline). Several detailed thermal modeling studies are reviewed to compare a recently introduced dosimetric quantity, the heating factor, across different exposure conditions as related to the peak temperature rise in tissue that would be permitted by limits for local body exposure. The present review suggests that the heating factor is a robust quantity that is useful for normalizing exposures across different simulation models. Limitations include lack of information about the location in the body where peak absorption and peak temperature increases occur in each exposure scenario, which are needed for careful assessment of potential hazards. To the limited extent that comparisons are possible, the thermal model (which is based on Pennes' bioheat equation) agrees reasonably well with experimental data, notwithstanding the lack of theoretical rigor of the model and uncertainties in the model parameters. In particular, the blood flow parameter is both variable with physiological condition and largely determines the steady state temperature rise. We suggest an approach to define exposure limits above and below the transition frequency (the frequency at which the basic restriction changes from specific absorption rate to incident power density) to provide consistent levels of protection against thermal hazards. More research is needed to better validate the model and to improve thermal dosimetry in general. While modeling studies have considered the effects of variation in thickness of tissue layers, the effects of normal physiological variation in tissue blood flow have been relatively unexplored.

Tissue models for RF exposure evaluation at frequencies above 6 GHz.

Exposures to radiofrequency (RF) energy above 6 GHz are characterized by shallow energy penetration, typically limited to the skin, but the subsequent increase in skin temperature is largely determined by heat transport in subcutaneous layers. A detailed analysis of the energy reflection, absorption, and power density distribution requires a knowledge of the properties of the skin layers and their variations. We consider an anatomically detailed model consisting of 3 or 4 layers (stratum corneum, viable epidermis plus dermis, subcutaneous fat, and muscle). The distribution of absorbed power in the different tissue layers is estimated based on electrical properties of the tissue layers inferred from measurements of reflected millimeter wavelength energy from skin, and literature data for the electrical properties of fat and muscle. In addition, the thermal response of the model is obtained using Pennes bioheat equation as well as a modified version incorporating blood flow rate-dependent thermal conductivity that provides a good fit to experimentally-found temperature elevations. A greatly simplified 3-layer model (Dermis, Fat, and Muscle) that assumes surface heating in only the skin layer clarifies the contribution of different tissue layers to the increase in surface skin temperature. The model shows that the increase in surface temperature is, under many circumstances, determined by the thermal resistance of subcutaneous tissues even though the RF energy may be deposited almost entirely in the skin layer. The limits of validity of the models and their relevance to setting safety standards are briefly discussed. Bioelectromagnetics. 39:173-189, 2018. © 2018 Wiley Periodicals, Inc.

Thermal Modeling for the Next Generation of Radiofrequency Exposure Limits: Commentary.

This commentary evaluates two sets of guidelines for human exposure to radiofrequency (RF) energy, focusing on the frequency range above the "transition" frequency at 3-10 GHz where the guidelines change their basic restrictions from specific absorption rate to incident power density, through the end of the RF band at 300 GHz. The analysis is based on a simple thermal model based on Pennes' bioheat equation (BHTE) (Pennes 1948) assuming purely surface heating; an Appendix provides more details about the model and its range of applicability. This analysis suggests that present limits are highly conservative relative to their stated goals of limiting temperature increase in tissue. As applied to transmitting devices used against the body, they are much more conservative than product safety standards for touch temperature for personal electronics equipment that are used in contact with the body. Provisions in the current guidelines for "averaging time" and "averaging area" are not consistent with scaling characteristics of the bioheat equation and should be refined. The authors suggest the need for additional limits on fluence for protection against brief, high intensity pulses at millimeter wave frequencies. This commentary considers only thermal hazards, which form the basis of the current guidelines, and excludes considerations of reported "non-thermal" effects of exposure that would have to be evaluated in the process of updating the guidelines.

Time constants for temperature elevation in human models exposed to dipole antennas and beams in the frequency range from 1 to 30 GHz.

This study computes the time constants of the temperature elevations in human head and body models exposed to simulated radiation from dipole antennas, electromagnetic beams, and plane waves. The frequency range considered is from 1 to 30 GHz. The specific absorption rate distributions in the human models are first computed using the finite-difference time-domain method for the electromagnetics. The temperature elevation is then calculated by solving the bioheat transfer equation. The computational results show that the thermal time constants (defined as the time required to reach 63% of the steady state temperature elevation) decrease with the elevation in radiation frequency. For frequencies higher than 4 GHz, the computed thermal time constants are smaller than the averaging time prescribed in the ICNIRP guidelines, but larger than the averaging time in the IEEE standard. Significant differences between the different head models are observed at frequencies higher than 10 GHz, which is attributable to the heat diffusion from the power absorbed in the pinna. The time constants for beam exposures become large with the increase in beam diameter. The thermal time constant in the brain is larger than that in the superficial tissues at high frequencies, because the brain temperature elevation is caused by the heat conduction of energy absorbed in the superficial tissue. The thermal time constant is minimized with an ideal beam with a minimum investigated diameter of 10 mm; this minimal time constant is approximately 30 s and is almost independent of the radiation frequency, which is supported by analytic methods. In addition, the relation between the time constant, as defined in this paper, and 'averaging time' as it appears in the exposure limits is discussed, especially for short intense pulses. Similar to the laser guidelines, provisions should be included in the limits to limit the fluence for such pulses.

Thermal Response of Human Skin to Microwave Energy: A Critical Review.

This is a review/modeling study of heating of tissue by microwave energy in the frequency range from 3 GHz through the millimeter frequency range (30-300 GHz). The literature was reviewed to identify studies that reported RF-induced increases in skin temperature. A simple thermal model, based on a simplified form of Pennes' bioheat equation (BHTE), was developed, using parameter values taken from the literature with no further adjustment. The predictions of the model were in excellent agreement with available data. A parametric analysis of the model shows that there are two heating regimes with different dominant mechanisms of heat transfer. For 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 results support the use of this simple thermal model to aid in the development and evaluation of RF safety limits at frequencies above 3 GHz and for millimeter waves, particularly when the irradiated area of skin is small. However, very limited thermal response data are available, particularly for exposures lasting more than a few minutes to areas of skin larger than 1-2 cm in diameter. The paper concludes with comments about possible uses and limitations of thermal modeling for setting exposure limits in the considered frequency range.

Comparison of Thermal Safety Practice Guidelines for Diagnostic Ultrasound Exposures.

This article examines the historical evolution of various practice guidelines designed to minimize the possibility of thermal injury during a diagnostic ultrasound examination, including those published by the American Institute of Ultrasound in Medicine, British Medical Ultrasound Society and Health Canada. The guidelines for prenatal/neonatal examinations are in general agreement, but significant differences were found for postnatal exposures. We propose sets of thermal index versus exposure time for these examination categories below which there is reasonable assurance that an examination can be conducted without risk of producing an adverse thermal effect under any scanning conditions. If it is necessary to exceed these guidelines, the occurrence of an adverse thermal event is still unlikely in most situations because of mitigating factors such as transducer movement and perfusion, but the general principle of "as low as reasonably achievable" should be followed. Some limitations of the biological effects studies underpinning the guidelines also are discussed briefly.

Conditionally Increased Acoustic Pressures in Nonfetal Diagnostic Ultrasound Examinations Without Contrast Agents: A Preliminary Assessment.

The mechanical index (MI) has been used by the US Food and Drug Administration (FDA) since 1992 for regulatory decisions regarding the acoustic output of diagnostic ultrasound equipment. Its formula is based on predictions of acoustic cavitation under specific conditions. Since its implementation over 2 decades ago, new imaging modes have been developed that employ unique beam sequences exploiting higher-order acoustic phenomena, and, concurrently, studies of the bioeffects of ultrasound under a range of imaging scenarios have been conducted. In 2012, the American Institute of Ultrasound in Medicine Technical Standards Committee convened a working group of its Output Standards Subcommittee to examine and report on the potential risks and benefits of the use of conditionally increased acoustic pressures (CIP) under specific diagnostic imaging scenarios. The term "conditionally" is included to indicate that CIP would be considered on a per-patient basis for the duration required to obtain the necessary diagnostic information. This document is a result of that effort. In summary, a fundamental assumption in the MI calculation is the presence of a preexisting gas body. For tissues not known to contain preexisting gas bodies, based on theoretical predications and experimentally reported cavitation thresholds, we find this assumption to be invalid. We thus conclude that exceeding the recommended maximum MI level given in the FDA guidance could be warranted without concern for increased risk of cavitation in these tissues. However, there is limited literature assessing the potential clinical benefit of exceeding the MI guidelines in these tissues. The report proposes a 3-tiered approach for CIP that follows the model for employing elevated output in magnetic resonance imaging and concludes with summary recommendations to facilitate Institutional Review Board (IRB)-monitored clinical studies investigating CIP in specific tissues.

Millimeter waves: acoustic and electromagnetic.

This article is the presentation I gave at the D'Arsonval Award Ceremony on June 14, 2011 at the Bioelectromagnetics Society Annual Meeting in Halifax, Nova Scotia. It summarizes my research activities in acoustic and electromagnetic millimeter waves over the past 47 years. My earliest research involved acoustic millimeter waves, with a special interest in diagnostic ultrasound imaging and its safety. For the last 21 years my research expanded to include electromagnetic millimeter waves, with a special interest in the mechanisms underlying millimeter wave therapy. Millimeter wave therapy has been widely used in the former Soviet Union with great reported success for many diseases, but is virtually unknown to Western physicians. I and the very capable members of my laboratory were able to demonstrate that the local exposure of skin to low intensity millimeter waves caused the release of endogenous opioids, and the transport of these agents by blood flow to all parts of the body resulted in pain relief and other beneficial effects.

Effect of millimeter waves and cyclophosphamide on cytokine regulation.

We have reported previously that millimeter waves (MMWs) protect T-cell functions from the toxic side effects of cyclophosphamide (CPA), an anticancer drug. Since the effect of MMWs has been reported to be mediated by endogenous opioids, the present study was undertaken to investigate the role of endogenous opioids in protection of T-cell functions by MMWs. The effect of MMWs (42.2 GHz, incident power density = 38 mW/cm²) was studied on CPA-induced suppression of cytokine release by T cells in the presence of selective opioid receptor antagonists (ORA). Production of cytokines was measured in CD4 T cells isolated from splenocytes. Treatment of mice with CPA suppressed the formation of Th1 cytokines (TNF-α, IFN-γ, and IL-2), shifting the overall balance toward Th2 (IL-4 and IL-5). MMW irradiation of CPA-treated groups up-regulated the production of Th1 cytokines suppressed by CPA. Treatment of the CPA+MMW group with selective kappa (κ) ORA further potentiated this effect of MMWs on Th1 cytokine production, whereas treatment with µ or δ ORA increased the imbalance of cytokine production in the Th2 direction. These results provide further evidence that endogenous opioids are involved in immunomodulation by MMWs.

Thermal thresholds for teratogenicity, reproduction, and development.

The human embryo and foetus may be especially vulnerable to chemical and physical insults during defined stages of development. In particular, the scheduled processes of cell proliferation, cell migration, cell differentiation, and apoptosis that occur at different times for different organ structures can be susceptible to elevated temperatures. With limited ability to regulate temperature on its own, the developing embryo and foetus is entirely dependent upon the mother's thermoregulatory capacity. As a general rule, maternal core body temperature increases of ∼2°C above normal for extended periods of time, 2-2.5°C above normal for 0.5-1 h, or ≥4°C above normal for 15 min have resulted in developmental abnormalities in animal models. Significant differences in thermoregulation and thermoneutral ambient temperatures make direct extrapolation of animal data to humans challenging, and the above temperatures may or may not be reasonable threshold predictions for adverse developmental effects in humans. Corresponding specific absorption rate (SAR) values that would be necessary to cause such temperature elevations in a healthy adult female would be in the range of ≥15 W/kg (whole body average or WBA), with ∼4 W/kg required to increase core temperature 1°C. However, smaller levels of thermal stress in the mother that are asymptomatic might theoretically result in increased shunting of blood volume to the periphery as a heat dissipation mechanism. This could conceivably result in altered placental and umbilical blood perfusion and reduce heat exchange with the foetus. It is difficult to predict the magnitude and threshold for such an effect, as many factors are involved in the thermoregulatory response. However, a very conservative estimate of 1.5 W/kg WBA (1/10th the threshold to protect against measurable temperature increases) would seem sufficient to protect against any significant reduction in blood flow to the embryo or foetus in the pregnant mother. This is more than three times above the current WBA limit for occupational exposure (0.4 W/kg) as outlined in both IEEE C95.1-2005 and ICNIRP-1998 international safety standards for radiofrequency (RF) exposures. With regard to local RF exposure directly to the embryo or foetus, significant absorption by the mother as well as heat dissipation due to conductive and convective exchange would offer significant protection. However, a theoretical 1-W/kg exposure averaged over the entire 28-day embryo, or averaged over a 1-g volume in the foetus, should not elevate temperature more than 0.2°C. Because of safety standards, exposures to the foetus this great would not be attainable with the usual RF sources. Foetal exposures to ultrasound are limited by the US Food and Drug Administration (FDA) to a maximum spatial peak temporal average intensity of 720 mW/cm(2). Routine ultrasound scanning typically occurs at lower values and temperature elevations are negligible. However, some higher power Doppler ultrasound devices under some conditions are capable of raising foetal temperature several degrees and their use in examinations of the foetus should be minimised.

The thermal index: its strengths, weaknesses, and proposed improvements.

The thermal index (TI) has been used as a relative indicator of thermal risk during diagnostic ultrasound examinations for many years. It is useful in providing feedback to the clinician or sonographer, allowing assessment of relative, potential risks to the patient of an adverse effect due to a thermal mechanism. Recently, several shortcomings of the TI formulations in quantifying the risk to the patient have been identified by members of the basic scientific community, and possible improvements to address these shortcomings have been proposed. For this reason, the Output Standards Subcommittee of the American Institute of Ultrasound in Medicine convened a subcommittee to review the strengths of the TI formulations as well as their weaknesses and proposed improvements. This article summarizes the findings of this subcommittee. After a careful review of the literature and an assessment of the cost of updating the TI formulations while maximizing the quality of patient care, the Output Standards Subcommittee makes the following recommendations: (1) some inconsistencies in the current TI formulations should be resolved, and the break point distance should be redefined to take focusing into consideration; (2) an entirely new indicator of thermal risk that incorporates the time dependence not be implemented at this time but be included in continuing efforts toward standards or consensus documents; (3) the exponential dependence of risk on temperature not be incorporated into a new definition of the TI formulations at this time but be included in continuing efforts toward standards or consensus documents; (4) the TI formulations not be altered to include nonlinear propagation at this time but be included in continuing efforts toward standards or consensus documents; and (5) a new indicator for risk from thermal mechanisms should be developed, distinct from the traditional TI formulations, for new imaging modalities such as acoustic radiation force impulse imaging, which have more complicated pulsing sequences than traditional imaging.

Dielectric properties of human skin at an acupuncture point in the 50-75 GHz frequency range: a pilot study.

The reason for using acupuncture points as exposure sites in some applications of millimeter wave therapy has been unclear. Acupuncture points have been suspected to exhibit particular direct current (DC), low-frequency electrical and optical properties compared to surrounding skin. To assess if such a biophysical correlation could exist at millimeter wave frequencies used in the therapy, we investigated the dielectric properties of an acupuncture point on the forearm skin within the 50-75 GHz range. These properties were compared with those of a neighboring ipsilateral control area and a corresponding contralateral control area. The complex reflection coefficient at the end of an open-ended rectangular waveguide loaded with a Teflon plug was measured with a vector network analyzer. A suitable model of the aperture admittance was used to calculate the dielectric properties of the skin at the measured spots. Statistical analyses were conducted with an ANOVA to compare the three sites. From these analyses, the dielectric properties of the acupuncture site were found to be somewhat different from those of surrounding non-acupuncture sites from 50 to about 61 GHz, in the case of the real part of the complex permittivity.

Enhanced absorption of millimeter wave energy in murine subcutaneous blood vessels.

The aim of the present study was to determine millimeter wave (MMW) absorption by blood vessels traversing the subcutaneous fat layer of murine skin. Most calculations were performed using the finite-difference time-domain (FDTD) technique. We used two types of models: (1) a rectangular block of multilayer tissue with blood vessels traversing the fat layer and (2) cylindrical models with circular and elliptical cross-sections simulating the real geometry of murine limbs. We found that the specific absorption rate (SAR) in blood vessels normally traversing the fat layer achieved its maximal value at the parallel orientation of the E-field to the vessel axis. At 42 GHz exposure, the maximal SAR in small blood vessels could be more than 30 times greater than that in the skin. The SAR increased with decreasing the blood vessel diameter and increasing the fat thickness. The SAR decreased with increasing the exposure frequency. When the cylindrical or elliptical models of murine limbs were exposed to plane MMW, the greatest absorption of MMW energy occurred in blood vessels located on the lateral areas of the limb model. At these areas the maximal SAR values were comparable with or were greater than the maximal SAR on the front surface of the skin. Enhanced absorption of MMW energy by blood vessels traversing the fat layer may play a primary role in initiating MMW effects on blood cells and vasodilatation of cutaneous blood vessels.

The potential of multiple synovial-fluid protein-concentration analyses in the assessment of knee osteoarthritis.

CONTEXT: Joint trauma is a risk factor for osteoarthritis (OA), which is becoming an increasingly important orthopedic concern for athletes and nonathletes alike. For advances in OA prevention, diagnosis, and treatment to occur, a greater understanding of the biochemical environment of the affected joint is needed. OBJECTIVE: To demonstrate the potential of a biochemical technique to enhance our understanding of and diagnostic capabilities for osteoarthritis. DESIGN: Cross-sectional. SETTING: Outpatient orthopedic practice. PARTICIPANTS: 8 subjects: 4 OA-knee participants (65 ± 6 y of age) and 4 normal-knee participants (54 ± 10 y) with no history of knee OA based on bilateral standing radiographs. INTERVENTION: The independent variable was group (OA knee, normal knee). MAIN OUTCOME MEASURES: 16 knee synovial-protein concentrations categorized as follows: 4 as pro-inflammatory, or catabolic, cytokines; 5 as anti-inflammatory, or protective, cytokines; 3 as catabolic enzymes; 2 as tissue inhibitors of metalloproteinases [TIMPs]; and 2 as adipokines. RESULTS: Two anti-inflammatory cytokines (interleukin [IL]-13 and osteoprotegerin) and a pro-inflammatory cytokine (IL-1ß) were significantly lower in the OA knees. Two catabolic enzymes (matrix metalloproteinase [MMP]-2 and MMP-3) were significantly elevated in OA knees. TIMP-2, an inhibitor of MMPs, was significantly elevated in OA knees. CONCLUSIONS: Six of the 16 synovial-fluid proteins were significantly different between OA knees and normal knees in this study. Future research using a similar multiplex ELISA approach or other proteomic techniques may enable researchers and clinicians to develop more accurate biochemical profiles of synovial fluid to help diagnose OA, identify subsets of OA or individual characteristics, guide clinical decisions, and identify patients at risk for OA after knee injury.