Showing papers in "International Journal of Hyperthermia in 2011"
TL;DR: The Health Council of the Netherlands (HCN) discusses the need for this, considering consistency, applicability, quantification, causality, comprehensibility and acceptability, and concludes that it seems unlikely that a change of dosimetric quantity will help us forward in the discussion on the scientific controversies regarding the existence or non-thermal effects in humans following long duration, low intensity exposure to electromagnetic fields as discussed by the authors.
Abstract: The Health Council of the Netherlands (HCN) and other organisations hold the basic assumption that induced electric current and the generation and absorption of heat in biological material caused by radiofrequency electromagnetic fields are the only causal effects with possible adverse consequences for human health that have been scientifically established to date. Hence, the exposure guidelines for the 10 MHz-10 GHz frequency range are based on avoiding adverse effects of increased temperatures that may occur of the entire human body at a specific absorption rate (SAR) level above 4 W/kg. During the workshop on Thermal Aspects of Radio Frequency Exposure on 11-12 January 2010 in Gaithersburg, Maryland, USA, the question was raised whether there would be a practical advantage in shifting from expressing the exposure limits in SAR to expressing them in terms of a maximum allowable temperature increase. This would mean defining adverse time-temperature thresholds. In this paper, the HCN discusses the need for this, considering six points: consistency, applicability, quantification, causality, comprehensibility and acceptability. The HCN concludes that it seems unlikely that a change of dosimetric quantity will help us forward in the discussion on the scientific controversies regarding the existence or non-existence of non-thermal effects in humans following long duration, low intensity exposure to electromagnetic fields. Therefore, the HCN favours maintaining the current approach of basic restrictions and reference levels being expressed as SAR and in V/m or µT, respectively. © 2011 Informa UK Ltd All rights reserved.
623 citations
TL;DR: This review covers published literature for the consecutive years from 2002–2009 on thermal thresholds for tissue damage with particular emphasis on brain and testis, and utilises thermal dosimetric principles to address sensitivity of a variety of tissues.
Abstract: The purpose of this review is to summarise a literature survey on thermal thresholds for tissue damage. This review covers published literature for the consecutive years from 2002-2009. The first review on this subject was published in 2003. It included an extensive discussion of how to use thermal dosimetric principles to normalise all time-temperature data histories to a common format. This review utilises those same principles to address sensitivity of a variety of tissues, but with particular emphasis on brain and testis. The review includes new data on tissues that were not included in the original review. Several important observations have come from this review. First, a large proportion of the papers examined for this review were discarded because time-temperature history at the site of thermal damage assessment was not recorded. It is strongly recommended that future research on this subject include such data. Second, very little data is available examining chronic consequences of thermal exposure. On a related point, the time of assessment of damage after exposure is critically important for assessing whether damage is transient or permanent. Additionally, virtually no data are available for repeated thermal exposures which may occur in certain recreational or occupational activities. For purposes of regulatory guidelines, both acute and lasting effects of thermal damage should be considered.
557 citations
TL;DR: The results show that impairments in cognitive function with passive hyperthermia and the beneficial effect of head cooling are task dependent and suggests that exposure to a hot environment is a competing variable to the cognitive processes.
Abstract: The objectives of this study were to (1) assess the effect of passive heating upon attention and memory task performance, and (2) evaluate the effectiveness of the application of cold packs to the head on preserving these functions. Using a counterbalance design 16 subjects underwent three trials: a control (CON, 20°C, 40% rH), hot (HOT, 50°C, 50% rH) and hot with the head kept cool (HHC). In each condition, three attention tests and two memory tests were performed. Mean core, forehead and tympanic temperatures were all significantly higher (p< 0.05) during HOT (38.6° ±0.1°, 39.6° ±0.2° and 38.8°±0.1°C, respectively) and HHC (38°±0.2, 37.7°±0.3° and 37.7°C, respectively) than in CON (37.1°±0.6°, 33.3° ±0.2° and 35.9°±0.3°C, respectively). Results indicate that there was impairment in working memory with heat exposure (p < 0.05) without alteration in attentional processes. The regular application of cold packs only prevented the detrimental effect of hyperthermia on short-term memory. Our results show that impairments in cognitive function with passive hyperthermia and the beneficial effect of head cooling are task dependent and suggests that exposure to a hot environment is a competing variable to the cognitive processes.
172 citations
TL;DR: Stability, imageability, and MR-HIFU monitoring and control of content release suggest that MR-Doxorubicin and Gd-HP-DO3A combined with iLTSL may enable real-time monitoring and spatial control ofcontent release.
Abstract: Purpose: Objectives of this study were to: 1) develop iLTSL, a low temperature sensitive liposome co-loaded with an MRI contrast agent (ProHance® Gd-HP-DO3A) and doxorubicin, 2) characterise doxorubicin and Gd-HP-DO3A release from iLTSL and 3) investigate the ability of magnetic resonance-guided high intensity focused ultrasound (MR-HIFU) to induce and monitor iLTSL content release in phantoms and in vivo.Methods: iLTSL was passively loaded with Gd-HP-DO3A and actively loaded with doxorubicin. Doxorubicin and Gd-HP-DO3A release was quantified by fluorescence and spectroscopic techniques, respectively. Release with MR-HIFU was examined in tissue-mimicking phantoms containing iLTSL and in a VX2 rabbit tumour model.Results: iLTSL demonstrated consistent size and doxorubicin release kinetics after storage at 4°C for 7 days. Release of doxorubicin and Gd-HP-DO3A from iLTSL was minimal at 37°C but fast when heated to 41.3°C. The magnitude of release was not significantly different between doxorubicin and Gd-HP-...
166 citations
TL;DR: The results show the potential of MRI-controlled focused ultrasound hyperthermia for enhanced local drug delivery with temperature-sensitive drug carriers as well as thermally mediated localised drug delivery in vivo.
Abstract: Purpose: Thermosensitive liposomes provide a mechanism for triggering the local release of anticancer drugs, but this technology requires precise temperature control in targeted regions with minimal heating of surrounding tissue. The objective of this study was to evaluate the feasibility of using MRI-controlled focused ultrasound (FUS) and thermosensitive liposomes to achieve thermally mediated localised drug delivery in vivo.Materials and methods: Results are reported from ten rabbits, where a FUS beam was scanned in a circular trajectory to heat 10–15 mm diameter regions in normal thigh to 43°C for 20–30 min. MRI thermometry was used for closed-loop feedback control to achieve temporally and spatially uniform heating. Lyso-thermosensitive liposomal doxorubicin was infused intravenously during hyperthermia. Unabsorbed liposomes were flushed from the vasculature by saline perfusion 2 h later, and tissue samples were harvested from heated and unheated thigh regions. The fluorescence intensity of the homog...
153 citations
TL;DR: In vivo animal experiments on implanted prostatic tumours in mice to measure temperature distribution in the tumour during magnetic nanoparticle hyperthermia and the increase in the nanoparticle distribution volume after the heating suggests possible nanoparticle re-distribution in the malignant tumours during the heating.
Abstract: Among a variety of hyperthermia methods, magnetic nanoparticle hyperthermia is a highly promising approach for its confined heating within the tumour. In this study we perform in vivo animal experiments on implanted prostatic tumours in mice to measure temperature distribution in the tumour during magnetic nanoparticle hyperthermia. Temperature elevations are induced by a commercially available ferrofluid injected via a single injection to the centre of the tumour, when the tumour is subject to an alternating magnetic field. Temperature mapping in the tumours during magnetic nanoparticle hyperthermia has demonstrated the feasibility of elevating tumour temperatures higher than 50°C using only 0.1 cm3 ferrofluid injected in the tumour under a relatively low magnetic field (3 kA/m). Detailed 3-D nanoparticle concentration distribution is quantified using a high-resolution microCT imaging system. The calculated nanoparticle distribution volume based on the microCT scans is useful to analyse nanoparticle depo...
96 citations
TL;DR: Preliminary results demonstrate the safety of clinical application of HIFU for pancreatic cancer and reveal it to be a promising mode of treatment for palliation of pain associated with pancreatic cancers.
Abstract: Objective: To evaluate the pain-alleviating action, feasibility and efficacy of high intensity focused ultrasound (HIFU) for palliation of inoperable pancreatic cancer in humans.Methods: Forty patients with advanced pancreatic cancer were treated with HIFU. There were 13 patients with stage III, and 27 patients with stage IV disease. The locations of the tumours were as follows: head of pancreas in 9 patients, body and/or tail of pancreas in 31 patients. Pain relief, local tumour control rate, median survival and complications were monitored after HIFU treatment. The primary endpoint was to assess pain relief rate and pain relief time (PRT). Secondary endpoints included local progression-free survival time, overall survival (OS), and side effects.Results: There were no severe complications or adverse events related to HIFU therapy in any of the patients treated. Pain relief was achieved in 87.5% of patients, median PRT was 10 weeks. The median local progression-free survival time for all patients was 5 mo...
76 citations
TL;DR: The addition of hyperthermia improved the local tumour control, and the results indicated a positive impact on PFS of NPC patients.
Abstract: Purpose: To compare the local tumour control, survival, and acute mucous toxicity of nasopharyngeal cancer (NPC) patients treated with conventional radiotherapy (RT) combined with intracavity hyperthermia versus conventional RT alone.Methods and materials: Previously untreated NPC patients were assigned randomly into the conventional RT group and the hyperthermia group. In addition to curative RT, hyperthermia group patients received intracavity hyperthermia before or after RT; T90 was 42.5°–43°C for 50 min twice a week for 7 weeks.Results: From August 2001 to July 2006, 180 eligible patients with NPC were enrolled in this study. The complete response (CR) rate in the two arms (RT plus hyperthermia versus conventional RT) was 95.6% and 81.1%, respectively (p = 0.003, χ2 test). CR rates for T2 and T3 patients in the hyperthermia group were 97.1% and 96.9%, respectively, while in the conventional RT group they were 79.5% and 76.7%, respectively. The difference between the two groups was statistically signif...
74 citations
TL;DR: The human embryo and foetus may be especially vulnerable to chemical and physical insults during defined stages of development, and significant absorption by the mother as well as heat dissipation due to conductive and convective exchange would offer significant protection.
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. Corre...
65 citations
TL;DR: The strategy of heat treatment of DCs offers a promising means to improve DC functions during immune activation which, as a physical method, facilitates straight-forward applications in clinical DC vaccination protocols.
Abstract: Dendritic cell (DC)-based immunotherapy has been shown to be a promising strategy for anti-cancer therapy. Nevertheless, only a low overall clinical response rate has been observed in vaccinated patients with advanced cancer and therefore methods to improve DC immuno-stimulatory functions are currently under intense investigation. In this respect, we exposed human monocyte-derived DCs to a physiological temperature stress of 40°C for up to 24 h followed by analysis for (i) expression of different heat shock proteins, (ii) survival, (iii) cell surface maturation markers, (iv) cytokine secretion, and (v) migratory capacity. Furthermore, we examined the ability of heat-shocked DCs to prime naive CD8(+) T cells after loading with MelanA peptide, by transfection with MelanA RNA, or by transduction with MelanA by an adenovirus vector. The results clearly indicate that in comparison to control DCs, which remained at 37°C, heat-treated cells revealed no differences concerning the survival rate or their migratory capacity. However, DCs exposed to thermal stress showed a time-dependent enhanced expression of the immune-chaperone heat shock protein 70A and both an up-regulation of co-stimulatory molecules such as CD80, CD83, and CD86 and of the inflammatory cytokine TNF-α. Moreover, these cells had a markedly improved capacity to prime autologous naive CD8(+) T cells in vitro in an antigen-specific manner, independent of the method of antigen-loading. Thus, our strategy of heat treatment of DCs offers a promising means to improve DC functions during immune activation which, as a physical method, facilitates straight-forward applications in clinical DC vaccination protocols.
64 citations
TL;DR: Directed macroautophagy, with its key role in protein quality control, seems an attractive target for a therapy such as hyperthermia that functions principally through denaturing the proteome.
Abstract: Purpose: We aim to explore the role of macroautophagy in cellular responses to hyperthermia. Protein damage incurred during hyperthermia can either lead to cell death or may be repaired by polypeptide quality control pathways including: (1) the deterrence of protein unfolding by molecular chaperones and (2) proteolysis of the denatured proteins within the proteasome. A third pathway of protein quality control is triggered by formation of protein aggregates in the heat shocked cell. This is the macroautophagy pathway in which protein aggregates are transported to specialised organelles called autolysosomes capable of degrading the aggregates. The consequences for cell viability of triggering this pathway are complex and may involve cell death, although under many circumstances, including exposure of cells to hyperthermia, autophagy leads to enhanced cell survival. We have discussed mechanisms by which cells detect protein aggregates and recruit them into the macroautophagy pathway as well as the potential ...
TL;DR: A TRPV1 compound is developed that blocks responses to capsaicin and acid while leaving temperature sensitivity intact and may help to identify previously unexplored mechanisms in different tissues that are responsive to thermal stress.
Abstract: The past decade has witnessed the cloning of a new family of ion channels that are responsive to temperature. Six of these transient receptor potential (TRP) channels are proposed to be involved in thermosensation and are located in sensory nerves and skin. The TRPV1, TRPV2, TRPV3, and TRPV4 channels have incompletely overlapping functions over a broad thermal range from warm to hot. Deletion of the individual TRPV1, TRPV3, and TRPV4 channels in mice has established their physiological role in thermosensation. In all cases thermosensation is not completely abolished - suggesting some functional redundancy among the channels. Notably, the TRPV2 channel is responsive to hot temperatures in heterologous systems, but its physiological relevance in vivo has not been established. Cool and cold temperatures are sensed by TRPM8 and TRPA1 family members. Currently, the pharmaceutical industry is developing agonists and antagonists for the various TRP channels. For instance, TRPV1 receptor agonists produce hypothermia, while antagonists induce hyperthermia. Recent investigations have found that different regions of the TRPV1 receptor are responsive to temperature, nociceptive stimuli, and various chemical agents. With this information, it has been possible to develop a TRPV1 compound that blocks responses to capsaicin and acid while leaving temperature sensitivity intact. These channels have important implications for hyperthermia research and may help to identify previously unexplored mechanisms in different tissues that are responsive to thermal stress.
TL;DR: MWA combined with transcatheter arterial chemoembolization appears to be an effective and promising approach for the treatment of large-sized unresectable hepotocellular carcinoma, however, large-scale randomized clinical trials are needed to determine the future role of this treatment.
Abstract: Purpose: To evaluate the efficacy and safety of microwave ablation combined with transcatheter arterial chemoembolization for unresectable large-sized hepotocellular carcinoma.Materials and methods: Institutional review board approval and informed consent were obtained. Between May 2004 and December 2006, 34 consecutive patients with large unresectable hepatocellular carcinoma (>5 cm) were alternately enrolled in one of two treatment groups: group 1 (n = 18), in which TACE was performed alone, and group 2 (n = 16), in which percutaneous ablation of HCC with microwave ablation was performed 2–4 weeks after TACE. All patients were followed up for 2–28 months to observe long-term therapeutic effects and complications in both groups. Tumor reduction rates, median survival time, and cumulative survival rates in both groups were calculated by using the unpaired Student t test and Kaplan-Meier method.Results: Follow-up images showed reduction in tumor size was seen in 21 patients (61.7%; 7/18 in group 1, 14/16 i...
TL;DR: US-guided HIFU ablation could be used as an effective minimally invasive therapy for local control of extra-abdominal desmoid tumours.
Abstract: Purpose: The aim of this study was to evaluate the feasibility, safety and therapeutic effects of ultrasound (US)-guided high intensity focused US (HIFU) ablation in the treatment of extra-abdominal desmoid tumours.Materials and methods: From May 2006 to May 2010, ten consecutive patients with pathologically proven extra-abdominal desmoid tumours were treated by US-guided HIFU ablation. Eight patients with multiple recurrent tumours were treated with a palliative aim, two patients with new solitary tumours were treated with a curative aim. The mean size of the largest tumour was 9.2 cm (range 5.9–12.8 cm). An acoustic power of 300–500 W was used according to the echogenic changes after energy exposure, intermittent HIFU exposure of 2–3 s was applied until the planned target area became hyperechoic on US. Outcome of HIFU ablation was observed by serial contrast-enhanced imaging examinations during follow up.Results: HIFU ablation was successfully performed without major complications. Large volume coagulat...
TL;DR: Suppression of HSP production using adjuvant liposomal quercetin can increase apoptosis and improve RF ablation-induced tumour destruction and further increases in tumour coagulation can be seen.
Abstract: Purpose: To investigate the effect of heat shock protein (HSP) modulation on tumour coagulation by combining radiofrequency (RF) ablation with adjuvant liposomal quercetin and/or doxorubicin in a rat tumour model.Methods: Sixty R3230 breast adenocarcinoma tumours/animals were used in this IACUC-approved study. Initially, 60 tumours (n = 6, each subgroup) were randomised into five groups: (1) RF alone, (2) intravenous (IV) liposomal quercetin alone (1 mg/kg), (3) IV liposomal quercetin followed 24 h later with RF, (4) RF followed 15 min later by IV liposomal doxorubicin (8 mg/kg), (5) IV liposomal quercetin 24 h before RF followed by IV liposomal doxorubicin 15 min post-ablation. Animals were sacrificed 4 or 24 h post-treatment and gross coagulation diameters were compared. Next, immunohistochemistry staining was performed for Hsp70 and cleaved caspase-3 expression. Comparisons were performed by using Student t-tests or ANOVA.Results: Combination RF-quercetin significantly increased coagulation size compar...
TL;DR: Exposure to heat stress can improve the immunogenicity of exosomes obtained from malignant ascites of gastric cancer patients, and in vitro studies suggest thatExosomes derived from heat-treated malignant Ascites are able to promote dendritic cell maturation and induce a tumour-specific cytotoxic T lymphocyte (CTL) response.
Abstract: Purpose: Tumour cell-derived exosomes may represent a novel type of cancer vaccine. However, the immunogenicity of exosomes derived from tumour cells has been shown to be poor. Therefore, in this study, exosome immunogenicity following heat treatment of exosomes from malignant ascites obtained from gastric cancer patients was evaluated.Materials and methods: Tumour-derived exosomes were isolated from heat-treated and untreated malignant ascites of gastric cancer patients using serial centrifugation and sucrose gradient ultracentrifugation. Next, in vitro experiments were performed to investigate the influence of heat treatment on exosome immunogenicity.Results: Exosomes from heat-treated malignant ascites of gastric cancer patients (HS exosomes) were found to contain higher concentrations of heat shock proteins, Hsp70 and Hsp60, than exosomes derived from untreated malignant ascites obtained from gastric cancer patients. Additional in vitro studies suggest that exosomes derived from heat-treated malignant...
TL;DR: The usual mathematical model in hyperthermia studies, the thermal isoeffect dose is not an effective description of the higher temperature effects because multiple processes occur in parallel, so the Arrhenius formulation based on the theory of absolute reaction rates is much more useful and descriptive in laser heating.
Abstract: Laser sources are under increasing study for in vivo tumour ablation. Photo-thermal ablation in tissues varies tremendously in governing physical phenomena, depending on wavelength, owing to wide variation in the optical properties of tissues, specifically the dominant chromophore and degree and type of scattering. Once converted into local tissue heating, however, the governing thermodynamic principles remain the same. Observed irreversible thermal alterations range from substantial structural disruption due to steam evolution in high temperature short-term activations to low temperature rise, longer-term initiation of the complex protein cascades that result in apoptosis and/or necroptosis. The usual mathematical model in hyperthermia studies, the thermal isoeffect dose, arising from the relative reaction rate formulation, is not an effective description of the higher temperature effects because multiple processes occur in parallel. The Arrhenius formulation based on the theory of absolute reaction rates is much more useful and descriptive in laser heating since the multiple thermodynamically independent processes may be studied separately.
TL;DR: PMTA for fibroid is feasible and safe, and it is an easy and fast procedure that is minimally invasive.
Abstract: Objective: The aim of this study was to assess the feasibility, safety and therapeutic effects of ultrasound (US)-guided percutaneous microwave thermal ablation (PMTA) in situ for the treatment of symptomatic uterine fibroid.Materials and methods: The microwave (MW) antenna was percutaneously inserted into the fibroid under US guidance to perform the ablation. The ultrasound images, any complications and side effects were assessed during and after ablation. The shrinkage rate of the fibroid was calculated after the treatment.Results: Forty patients underwent the treatment. The baseline fibroid volume was 14.6 to 341.1 cm3 (mean 140.1 ± 87.4 cm3). When the MW therapy started, a heightened echo around the MW emission aperture of the antenna was observed and gradually propagated throughout the fibroid while the ablation continued. The mean ablation time was 490 s. Contrast enhanced MRI showed no enhancement in the fibroid post-ablation. The shrinkage rate of the fibroid was 61.8%, 78.7%, 73.2% and 93.1% at 3...
TL;DR: CEUS-guided MW ablation is an efficient and feasible treatment method for patients with hepatocellular carcinoma inconspicuous on conventional US.
Abstract: Objective: To evaluate the efficiency and feasibility of contrast-enhanced ultrasound (CEUS)-guided microwave ablation for hepatocellular carcinoma inconspicuous on conventional US. Materials and methods: From March 2006 to February 2010, 107 patients (93 male, 14 female; mean age 58.9 � 11.0 years) with 107 hepatocellular carcinoma (HCC) nodules (mean maximum diameter 19.5 � 8.5 mm) inconspicuous on conventional US underwent microwave (MW) ablation under CEUS guidance in this study. US contrast agent was SonoVue (Bracco, Milan, Italy), a second-generation contrast agent. CEUS was performed first, and then MW ablation was carried out by means of CEUS guidance under unconscious intravenous anaesthesia if the tumours were displayed on CEUS. Results: 105 tumours were successfully visualised on CEUS by using 1–2 times contrast agent injection and MW ablation was performed under CEUS guidance. The technical success rate was 98.13% (105/107). The number of antenna insertions for each tumour was 1.89 � 0.92, and the mean session of MW ablation for each tumour was 1.08 � 0.28. The mean duration of energy application for each tumour was 7.05 � 4.03 min. The follow-up time was 12–54 months (median 18 months). The technique effectiveness rate was 99.05% (104/105). The local tumour progression rate was 1.9% (2/105). There were no severe complications in any patients. Conclusion: CEUS-guided MW ablation is an efficient and feasible treatment method for patients with hepatocellular carcinoma inconspicuous on conventional US.
TL;DR: MWA by the simultaneous application of double antennae may be more advantageous for treating larger liver tumour than multipolar RFA in ex vivo porcine livers.
Abstract: Purpose: To compare the effectiveness of microwave ablation (MWA) and multipolar radiofrequency ablation (RFA) in ex vivo porcine livers, in both cases using a pair of internally cooled interstitial applicators.Materials and methods: MWA was performed on ex vivo porcine livers (n = 60) using a pair of simultaneously powered, internally cooled shaft interstitial antennae. Four power settings were used: 50 W, 60 W, 70 W and 80 W (n = 15 per setting). Multipolar RFA was also performed on ex vivo porcine livers (n = 30), also using a pair of simultaneously powered, internally cooled shaft interstitial bipolar applicators. This was performed for two applicator types T30 (3 cm length) and T40 (4 cm length) at a manufacturer prescribed power of 60 W and 80 W, respectively (n = 15 per applicator). Spacing between the two probes was 2 cm in all cases. Each power setting was applied for 15 ablations for 10 min each. The long-axis diameter (Dl), short-axis diameter (Ds) and the ratio Ds/Dl for each ablation were mea...
TL;DR: Temperature distribution within tissue has been investigated and it was showed that for the studied cases, unlike homogeneous distribution, Gaussian distribution of SAR is able to raise the temperature of tumour cells above the treatment temperature.
Abstract: In clinical applications of magnetic fluid hyperthermia (MFH) for cancer treatment it is very important to ensure maximum damage to the tumour while protecting the normal tissue. The resultant heating pattern by magnetic nanoparticles (MNPs) in the tumour is closely related to the dispersion of MNPs. In this study the effect of MNPs dispersion on temperature distribution in a tumour and surrounding healthy tissue, during MFH, has been investigated. Accordingly, the Pennes bio-heat equation (BHE) in a spherical tissue with Neumann curved boundary condition has been resolved. The effects of blood perfusion, metabolism heat generation as well as MNPs heat dissipation in an alternating magnetic field as source term, have been considered. To solve the Pennes BHE, the three dimensional lattice Boltzmann method (LBM) has been used. To show the accuracy of the model, simulations have been compared with analytical, experimental and numerical results, reported in the literature. Then, temperature distribution withi...
TL;DR: There is considerable need for more quantitative time temperature assessments using relevant animal models, more complete kinetic analyses to determine how long immunological effects persist, and for analysis of whether frequency of exposure has impact on immune function.
Abstract: There is interest in understanding the health impact of thermal effects as a result of exposure of humans to radiofrequency/microwave (RF/MW) fields. Immune cells and responses are affected by modest changes in temperature and it is important to quantify these effects and establish safety thresholds similar to what has been done with other tissue targets. Since previous summaries of thresholds for thermal damage to normal tissues have not focused much attention to cells of the immune system, this summary highlights recent studies which demonstrate positive and some negative effects of temperature shifts on human immune cells. We emphasise literature reporting adverse immunological endpoints (such as cell damage, death and altered function) and provide the temperature at which these effects were noted. Whereas there have been many in vitro studies of adverse temperature effects on immune cells, there has been limited validation of these temperature effects in vivo. However, data from heat stress/stroke pat...
TL;DR: With the above-mentioned low and medium parameter settings, ablative fractional photothermolysis is safe and effective in non-facial skin, however, dermal remodelling continues for up to 4 weeks, which should be the minimum space between treatment sessions.
Abstract: Purpose: Ablative fractional photothermolysis is a new concept for treatment of aged skin. Despite the low frequency of side effects there are now several reports about scarring, especially in non-facial regions like the neck. Our study aimed to investigate the in vivo wound healing process and remodelling in an area prone to scarring using a fractional ablative CO2 laser with three different energy protocols.Materials and methods: Six patients with photo-damaged skin received a single fractional ablative treatment using a 250-µm scanning CO2 laser. Three areas on the neck were treated with 50, 100 and 300 mJ/microbeam at densities of 200, 150 and 100/cm2, respectively. Biopsies were taken from untreated skin (control) and 10 minutes, 3 days, 14 days, 21 days and 28 days post-intervention.Results: Fractional ablation with higher energies resulted in increased total thermal damage. Overall, 50 mJ was effective up to the superficial dermis, 100 mJ up to the mid-dermis, and 300 mJ resulted in deep dermal abl...
TL;DR: The model-based dynamic closed-loop predictive control algorithms in the framework, facilitated by the coupling of mathematical modelling and computer simulation with real-time imaging feedback, has great potential to enable a novel methodology in thermal medicine.
Abstract: In this article, the major idea and mathematical aspects of model-based planning and real-time predictive control for laser-induced thermal therapy (LITT) are presented. In particular, a computational framework and its major components developed by authors in recent years are reviewed. The framework provides the backbone for not only treatment planning but also real-time surgical monitoring and control with a focus on MR thermometry enabled predictive control and applications to image-guided LITT, or MRgLITT. Although this computational framework is designed for LITT in treating prostate cancer, it is further applicable to other thermal therapies in focal lesions induced by radio-frequency (RF), microwave and high-intensity-focused ultrasound (HIFU). Moreover, the model-based dynamic closed-loop predictive control algorithms in the framework, facilitated by the coupling of mathematical modelling and computer simulation with real-time imaging feedback, has great potential to enable a novel methodology in t...
TL;DR: In HOT, the increase in Tcore limited force production capacity possibly via alterations occurring upstream the motor cortex but also via a decrement in motor cortical excitability failed to explain the cognitive alterations that can originate from an additional cognitive load imposed by temperature variations.
Abstract: To investigate what triggers cognitive and neuromuscular alterations during passive heat exposure, eight volunteers performed simple (One Touch Stockings of Cambridge, OTS-4) and complex (OTS-6) cognitive tasks as well as neuromuscular testing (maximal isometric voluntary contractions of the thumb with electrical stimulation of the motor nerve and magnetic stimulation of the motor cortex). These tests were performed at the start (T1), after 1 h 30 min (T2), 3 h (T3) and 4 h 30 min (T4) of exposure in both hot (HOT) (Wet Bulb Globe Temperature [WBGT] = 38° ± 1.4°C) and neutral control (CON) (WBGT = 19° ± 0.3°C) environments. Environmental temperatures were adjusted during the HOT session to induce target core temperatures (T(core)) (T1 ∼ 37.3°; T2 ∼ 37.8°; T3 ∼ 38.3°; T4 ∼ 38.8°C). At T1 and T4 the OTS-6 was lower in HOT than in CON in response to the rapid increase in skin temperature and to hyperthermia, respectively. In HOT, the increase in T(core) limited force production capacity possibly via alterations occurring upstream the motor cortex (from T(core) ∼ 37.8°C) but also via a decrement in motor cortical excitability (from T(core) ∼ 38.3°C). These alterations in cortex excitability failed to explain the cognitive alterations that can originate from an additional cognitive load imposed by temperature variations.
TL;DR: These studies demonstrate Herceptin-directed nanoparticles can selectively kill HER-2+ cancer cells via hyperthermia after AMF activation.
Abstract: Purpose: HER-2 is in the EGF tyrosine kinase receptor family, overexpressed by many human cancers and minimally expressed by normal adult tissues. HER-2 expression in human cancers is correlated with reduced survival, increased metastasis, reduced apoptosis and increased proliferation. Herceptin is a humanised mouse antibody that targets and inactivates HER-2. In the present study, Herceptin was used to deliver ferric oxide-enriched nanoparticles to HER-2+ cancer cells. If exposed to alternating magnetic field (AMF), the nanoparticles heat. We tested the ability of AMF-activated Herceptin-directed nanoparticles to selectively kill HER-2+ human cancer cells.Methods: Herceptin-conjugated nanoparticles were incubated with normal human mammary epithelial cells (HMEC)(HER-2-) or malignant human mammary epithelial cells (SK-BR-3)(HER-2+). Cells were stained to detect Herceptin or iron and the kinetics of binding quantified. Once conditions were optimised for binding, cells were exposed to either antibody-direct...
TL;DR: Although no cytotoxicity was observed from GNP incubation alone, their presence along with MW led to a decrease in survival rate, such that the lethal effects of MW hyperthermia with GNPs were comparable with that of doxorubicin.
Abstract: Objective: Hyperthermia, generated using microwave (MW), infrared, ultrasound and other methods, is often utilised as an adjuvant technique to sensitise cancer lesions to radiation therapy and chemotherapy. In the current research, MW hyperthermia efficacy in synergism with chemotherapy was investigated in the presence and absence of gold nanoparticles (GNPs).Materials and methods: Saos-2 cell line derived from human osteogenic sarcoma was used in the study. Various experiments were performed on the cells in the presence of doxorubicin and GNPs with MW hyperthermia. All required control groups were also considered. The in vitro experiments were conducted for GNPs of 20 and 40 nm, each at two concentrations of 13.2 and 26.4 µg/mL. After 48 hours, MTT assay was performed in order to evaluate the effectiveness of therapeutic parameters on cell survival.Results: In groups with GNP-incubated cells, the cell survival was more than 95%. After chemotherapy, survival was determined as 37.1% and 62.8% with and with...
TL;DR: This present contribution summarises some of the major conclusions of the speakers, and offers comments by one of the present authors on proposed research priorities and the implications of the material presented at the workshop for setting improved thermally based limits for human exposure to RF energy.
Abstract: This special issue contains papers presented at an international workshop entitled ‘Thermal Aspects of Radio Frequency Exposure’ convened in Gaithersburg, Maryland, USA on 11–12 January 2010, and co-sponsored by the Mobile Manufacturers Forum, the GSM Association, and the US Food and Drug Administration. The goals of the workshop were to (1) identify appropriate health endpoints associated with thermal hazards and their time-dependence thresholds, and (2) outline future directions for research that might lead to an improved understanding of health and safety implications of human exposure to radiofrequency energy and design of improved exposure limits for this energy. This present contribution summarises some of the major conclusions of the speakers, and offers comments by one of the present authors on proposed research priorities and the implications of the material presented at the workshop for setting improved thermally based limits for human exposure to RF energy.
TL;DR: Results demonstrate the computational model of the bioheat transfer may provide a reasonable approximation of the laser–tissue interaction, which could be useful for treatment planning, but cannot readily replace MR temperature imaging in a complex environment such as the brain.
Abstract: Purpose: Magnetic resonance‐guided laser‐induced thermal therapy (MRgLITT) is currently undergoing initial safety and feasibility clinical studies for the treatment of intracranial lesions in humans. As studies progress towards evaluation of treatment efficacy, predictive computational models may play an important role for prospective 3D treatment planning. The current work critically evaluates a computational model of laser induced bioheat transfer against retrospective multiplanar MR thermal imaging (MRTI) in a canine model of the MRgLITT procedure in the brain.Methods: A 3D finite element model of the bioheat transfer that couples Pennes equation to a diffusion theory approximation of light transport in tissue is used. The laser source is modelled conformal with the applicator geometry. Dirichlet boundary conditions are used to model the temperature of the actively cooled catheter. The MRgLITT procedure was performed on n = 4 canines using a 1‐cm diffusing tip 15‐W diode laser (980 nm). A weighted norm...
TL;DR: Better quality hyperthermia treatments should be possible when simplified hybrid model simulations are performed routinely as part of the clinical pretreatment plan, according to the feasibility of using coupled electromagnetic and thermodynamic simulations.
Abstract: Purpose: This article explores the feasibility of using coupled electromagnetic and thermodynamic simulations to improve planning and control of hyperthermia treatments for cancer. The study investigates the usefulness of preplanning to improve heat localisation in tumour targets in treatments monitored with PRFS-based magnetic resonance thermal imaging (MRTI).Methods: Heating capabilities of a cylindrical radiofrequency (RF) mini-annular phased array (MAPA) applicator were investigated with electromagnetic and thermal simulations of SAR in homogeneous phantom models and two human leg sarcomas. High frequency structure simulator (HFSS) (Ansoft) was used for electromagnetic simulations and SAR patterns were coupled into EPhysics (Ansoft) for thermal modelling with temperature-dependent variable perfusion. Simulations were accelerated by integrating tumour-specific anatomy into a pre-gridded whole body tissue model. To validate this treatment planning approach, simulations were compared with MR thermal imag...