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      New experimental model for single liver lobe hyperthermia in small animals using non-directional microwaves

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          Abstract

          Purpose

          Our aim was to develop a new experimental model for in vivo hyperthermia using non-directional microwaves, applicable to small experimental animals. We present an affordable approach for targeted microwave heat delivery to an isolated liver lobe in rat, which allows rapid, precise and stable tissue temperature control.

          Materials and methods

          A new experimental model is proposed. We used a commercial available magnetron generating 2450 MHz, with 4.4V and 14A in the filament and 4500V anodic voltage. Modifications were required in order to adjust tissue heating such as to prevent overheating and to allow for fine adjustments according to real-time target temperature. The heating is controlled using a virtual instrument application implemented in LabView® and responds to 0.1° C variations in the target. Ten healthy adult male Wistar rats, weighing 250–270 g were used in this study. The middle liver lobe was the target for controlled heating, while the rest of the living animal was protected.

          Results

          In vivo microwave delivery using our experimental setting is safe for the animals. Target tissue temperature rises from 30°C to 40°C with 3.375°C / second (R 2 = 0.9551), while the increment is lower it the next two intervals (40–42°C and 42–44°C) with 0.291°C/ s (R 2 = 0.9337) and 0.136°C/ s (R 2 = 0.7894) respectively, when testing in sequences. After reaching the desired temperature, controlled microwave delivery insures a very stable temperature during the experiments.

          Conclusions

          We have developed an inexpensive and easy to manufacture system for targeted hyperthermia using non-directional microwave radiation. This system allows for fine and stable temperature adjustments within the target tissue and is ideal for experimental models testing below or above threshold hyperthermia

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          Most cited references43

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          Thermal ablation of tumours: biological mechanisms and advances in therapy.

          Minimally invasive thermal ablation of tumours has become common since the advent of modern imaging. From the ablation of small, unresectable tumours to experimental therapies, percutaneous radiofrequency ablation, microwave ablation, cryoablation and irreversible electroporation have an increasing role in the treatment of solid neoplasms. This Opinion article examines the mechanisms of tumour cell death that are induced by the most common thermoablative techniques and discusses the rapidly developing areas of research in the field, including combinatorial ablation and immunotherapy, synergy with conventional chemotherapy and radiation, and the development of a new ablation modality in irreversible electroporation.
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            Basic principles of thermal dosimetry and thermal thresholds for tissue damage from hyperthermia.

            This paper is one of several in this Special Issue of the International Journal of Hyperthermia that discusses the current state of knowledge about the human health risks of hyperthermia. This special issue emanated from a workshop sponsored by the World Health Organization in the Spring of 2002 on this topic. It is anticipated that these papers will help to establish guidelines for human exposure to conditions leading to hyperthermia. This comprehensive review of the literature makes it clear that much more work needs to be done to clarify what the thresholds for thermal damage are in humans. This review summarizes the basic principles that govern the relationships between thermal exposure (temperature and time of exposure) and thermal damage, with an emphasis on normal tissue effects. Methods for converting one time-temperature combination to a time at a standardized temperature are provided as well as a detailed discussion about the underlying assumptions that go into these calculations. There are few in vivo papers examining the type and extent of damage that occurs in the lower temperature range for hyperthermic exposures (e.g. 39-42 degrees C). Therefore, it is clear that estimation of thermal dose to effect at these thermal exposures is less precise in that temperature range. In addition, there are virtually no data that directly relate to the thermal sensitivity of human tissues. Thus, establishment of guidelines for human exposure based on the data provided must be done with significant caution. There is detailed review and presentation of thermal thresholds for tissue damage (based on what is detectable in vivo). The data are normalized using thermal dosimetric concepts. Tables are included in an Appendix Database which compile published data for thresholds of thermal damage in a variety of tissues and species. This database is available by request (contact MWD or PJH), but not included in this manuscript for brevity. All of the studies reported are for single acute thermal exposures. Except for brain function and physiology (as detailed in this issue by Sharma et al) one notes the critical lack of publications examining effects of chronic thermal exposures as might be encountered in occupational hazards. This review also does not include information on the embryo, which is covered in detail elsewhere in this volume (see article by Edwards et al.) as well as in a recent review on this subject, which focuses on thermal dose.
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              Thresholds for thermal damage to normal tissues: an update.

              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.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: InvestigationRole: Writing – original draft
                Role: Data curationRole: InvestigationRole: MethodologyRole: Writing – original draft
                Role: InvestigationRole: MethodologyRole: SoftwareRole: Writing – original draft
                Role: ConceptualizationRole: MethodologyRole: Resources
                Role: ConceptualizationRole: Data curationRole: Writing – original draft
                Role: ConceptualizationRole: InvestigationRole: MethodologyRole: SupervisionRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: Project administrationRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                21 September 2017
                2017
                : 12
                : 9
                : e0184810
                Affiliations
                [1 ] Department of Physiology, Grigore T. Popa University of Medicine and Pharmacy, Iasi, Romania
                [2 ] Department of Surgery, Grigore T. Popa University of Medicine and Pharmacy, Iasi, Romania
                [3 ] Department of Surgery, Regional Institute of Oncology, Iasi, Romania
                [4 ] Faculty of Electrical Engineering, Gheorghe Asachi Technical University, Iaşi, Romania
                [5 ] Department of Engineering, Regional Institute of Oncology, Iasi, Romania
                [6 ] Department of Pharmacology, Grigore T. Popa University of Medicine and Pharmacy, Iasi, Romania
                University of Florida, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                ‡ These authors are joint senior authors on this work.

                Article
                PONE-D-16-16331
                10.1371/journal.pone.0184810
                5608293
                28934251
                7a2f879d-8e93-4b2b-a1b7-bedcb0a879f5
                © 2017 Tudorancea et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 22 April 2016
                : 31 August 2017
                Page count
                Figures: 8, Tables: 0, Pages: 16
                Funding
                Funded by: Euronanomed, ERA Net
                Award ID: CheTherDel
                Award Recipient :
                This work was developed within the research grant CheTherDel (Chemo-hyperthermal Delivery—Combined chemo-hyperthermal control of hepatic tumors, based on microwave-activated subendothelial-targeted nano-assemblies), funded by ERA-Net EuroNanoMed JTC 2011 program.
                Categories
                Research Article
                Physical Sciences
                Physics
                Electromagnetic Radiation
                Microwave Radiation
                Medicine and Health Sciences
                Diagnostic Medicine
                Signs and Symptoms
                Hyperthermia
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Signs and Symptoms
                Hyperthermia
                Biology and Life Sciences
                Physiology
                Physiological Parameters
                Body Temperature
                Medicine and Health Sciences
                Physiology
                Physiological Parameters
                Body Temperature
                Physical Sciences
                Chemistry
                Chemical Elements
                Aluminum
                Engineering and Technology
                Equipment
                Measurement Equipment
                Thermocouples
                Medicine and Health Sciences
                Oncology
                Cancer Treatment
                Medicine and Health Sciences
                Anesthesiology
                Anesthesia
                Medicine and Health Sciences
                Pharmaceutics
                Drug Therapy
                Anesthesia
                Biology and Life Sciences
                Biochemistry
                Tissue Distribution
                Medicine and Health Sciences
                Pharmacology
                Pharmacokinetics
                Tissue Distribution
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

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