Thermal thresholds for teratogenicity, reproduction, and development.
ABSTRACT 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.
- [show abstract] [hide abstract]
ABSTRACT: Prospective use of the CEM43 degrees CT90 thermal dose parameter has been proposed for hyperthermia treatments. This study evaluates the CEM43 degrees CT90 parameter by means of a retrospective analysis of recurrent breast cancer patients receiving reirradiation plus hyperthermia. CEM43 degrees CT90 was calculated for 72 patients who received 8 x 4 Gy reirradiation plus 8 x 1 h hyperthermia for adenocarcinoma recurrences at the chest wall. Associations of prognostic factors CEM43 degrees CT90 and tumor maximum diameter with endpoints complete response (CR), duration of local control (DLC), and overall survival (OS) were determined. A highly significant inverse association between CEM43 degrees CT90 and tumor maximum diameter (rho = -0.7, p < 1e-6) was found. The association between CR and CEM43 degrees CT90 was not significant (p > or = 0.7). CEM43 degrees CT90 was associated with DLC. Both CEM43 degrees CT90 and tumor maximum diameter had a significant association with survival (p < or = 0.01). The association with thermal dose, when adjusted for tumor maximum diameter, was not significant for either CR, DLC, or OS (p > 0.2). In this retrospective study, no clear CEM43 degrees CT90 thermal dose targets or associations with clinical endpoints could be established.Strahlentherapie und Onkologie 08/2010; 186(8):436-43. · 4.16 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: OBJECTIVE: To define thresholds of safe local temperature increases for MR equipment that exposes patients to radiofrequency fields of high intensities for long duration. These MR systems induce heterogeneous energy absorption patterns inside the body and can create localised hotspots with a risk of overheating. METHODS: The MRI + EUREKA research consortium organised a "Thermal Workshop on RF Hotspots". The available literature on thresholds for thermal damage and the validity of the thermal dose (TD) model were discussed. RESULTS/CONCLUSIONS: The following global TD threshold guidelines for safe use of MR are proposed: 1. All persons: maximum local temperature of any tissue limited to 39 °C 2. Persons with compromised thermoregulation AND (a) Uncontrolled conditions: maximum local temperature limited to 39 °C (b) Controlled conditions: TD < 2 CEM43°C 3. Persons with uncompromised thermoregulation AND (a) Uncontrolled conditions: TD < 2 CEM43°C (b) Controlled conditions: TD < 9 CEM43°C The following definitions are applied: Controlled conditions A medical doctor or a dedicated trained person can respond instantly to heat-induced physiological stress Compromised thermoregulation All persons with impaired systemic or reduced local thermoregulation KEY POINTS : • Standard MRI can cause local heating by radiofrequency absorption. • Monitoring thermal dose (in units of CEM43°C) can control risk during MRI. • 9 CEM43°C seems an acceptable thermal dose threshold for most patients. • For skin, muscle, fat and bone,16 CEM43°C is likely acceptable.European Radiology 04/2013; · 3.55 Impact Factor