Search

Proton dose calculation in media other than water may be of interest for either research purposes or clinical practice. Current study aims to quantify the required parameters for analytical proton dosimetry in muscle, bone, and PMMA. Required analytical dosimetry parameters were extracted from ICRU-49 report and Janni study. Geant4 Toolkit was also used for Bragg curve simulation inside the investigated media at different proton energies. Calculated and simulated dosimetry data were compared using gamma analysis. Simulated and calculated Bragg curves are consistent, a fact that confirms the validity of reported parameters for analytical proton dosimetry inside considered media. Furthermore, derived analytical parameters for these media are different from those of water. Listed parameters can be reliably utilized for analytical proton dosimetry inside muscle, bone, and PMMA. Furthermore, accurate proton dosimetry inside each medium demands dedicated analytical parameters and one is not allowed to use the water coefficients for non-water media., (© 2024. The Author(s), under exclusive licence to Japanese Society of Radiological Technology and Japan Society of Medical Physics.)

In studies of electron and proton radiotherapy, ultrahigh dose rates of FLASH radiotherapy appear to produce fewer toxicities than standard dose rates while maintaining local tumor control. FLASH-proton radiotherapy (F-PRT) brings the spatial advantages of PRT to FLASH dose rates (>40 Gy/second), making it important to understand if and how F-PRT spares normal tissues while providing antitumor efficacy that is equivalent to standard-proton radiotherapy (S-PRT). Here we studied PRT damage to skin and mesenchymal tissues of muscle and bone and found that F-PRT of the C57BL/6 murine hind leg produced fewer severe toxicities leading to death or requiring euthanasia than S-PRT of the same dose. RNA-seq analyses of murine skin and bone revealed pathways upregulated by S-PRT yet unaltered by F-PRT, such as apoptosis signaling and keratinocyte differentiation in skin, as well as osteoclast differentiation and chondrocyte development in bone. Corroborating these findings, F-PRT reduced skin injury, stem cell depletion, and inflammation, mitigated late effects including lymphedema, and decreased histopathologically detected myofiber atrophy, bone resorption, hair follicle atrophy, and epidermal hyperplasia. F-PRT was equipotent to S-PRT in control of two murine sarcoma models, including at an orthotopic intramuscular site, thereby establishing its relevance to mesenchymal cancers. Finally, S-PRT produced greater increases in TGFβ1 in murine skin and the skin of canines enrolled in a phase I study of F-PRT versus S-PRT. Collectively, these data provide novel insights into F-PRT-mediated tissue sparing and support its ongoing investigation in applications that would benefit from this sparing of skin and mesenchymal tissues. SIGNIFICANCE: These findings will spur investigation of FLASH radiotherapy in sarcoma and additional cancers where mesenchymal tissues are at risk, including head and neck cancer, breast cancer, and pelvic malignancies., (©2021 The Authors; Published by the American Association for Cancer Research.)

Photobiomodulation therapy (PBMT) has been used to improve the physical performance of individuals with advanced age; however, there are no studies in the literature that support the application of light-emitting diode (LED) therapy for the muscular performance of individuals with diabetes mellitus who show a decline in functionality. The aim of the study was to analyze the acute effects of PBMT on strength and functional performance in type 2 diabetic individuals. Sixty-three volunteers were recruited and randomized into five groups: control (C), sham (S), red LED (R), infrared LED (IR), and red LED + infrared LED (R + IR). On the first day, the volunteers were evaluated using the time up and go (TUG), the 6-min walk test (6MWT), and isokinetic dynamometer of the ankle. In the following 3 days, groups R, IR, R + IR, and S returned for application of PBMT bilaterally, with 180 J of energy on each leg. On the fifth day, a reassessment was performed. There was no statistical difference between groups for the variables of the isokinetic dynamometer, TUG, and 6MWT. Analysis of the size of the clinical effect for the isokinetic variables showed that there was no pattern among the effects observed. There is a moderate effect in favor of R, IR, and R + IR in relation to C for the TUG and a moderate effect of R + IR in relation to C for the 6MWT. The PBMT applied for a short period does not bring important gains for the muscular performance and functionality of diabetic individuals.

Hereditary DNA repair defects affect tissues differently, suggesting that in vivo cells respond differently to DNA damage. Knowledge of the DNA damage response, however, is largely based on in vitro and cell culture studies, and it is currently unclear whether DNA repair changes depending on the cell type. Here, we use in vivo imaging of the nucleotide excision repair (NER) endonuclease ERCC-1/XPF-1 in C. elegans to demonstrate tissue-specific NER activity. In oocytes, XPF-1 functions as part of global genome NER (GG-NER) to ensure extremely rapid removal of DNA-helix-distorting lesions throughout the genome. In contrast, in post-mitotic neurons and muscles, XPF-1 participates in NER of transcribed genes only. Strikingly, muscle cells appear more resistant to the effects of DNA damage than neurons. These results suggest a tissue-specific organization of the DNA damage response and may help to better understand pleiotropic and tissue-specific consequences of accumulating DNA damage., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: To assess post-treatment subcutaneous edema, muscle edema, and seroma in MRI after soft-tissue sarcoma (STS) resection with regard to muscle involvement of STS and therapy., Methods: In all, 177 patients were included and received 1.5-T MRI follow-up examinations after treatment. Post-treatment changes were classified according to type of therapy (therapy 1-surgery; therapy 2-surgery with radiation therapy) and primary tumor localization in soft tissue (localization 1, subcutaneous tissue; localization 2, muscle involvement). Subcutaneous and muscle edema were divided into three grades: grade 0, absence of edema; grade 1, low-to-moderate edema; and grade 2, high-grade edema., Results: The mean age of the patients was 55.7 ± 18.2 years and the mean volume of the resected primary STS was 321.5 cm 3 . After therapy 1 of a sarcoma in localization 1, patients significantly more often showed low-grade subcutaneous tissue edema and an absence of muscle edema (p < 0.001) than high-grade edema. The risk for grade 2 subcutaneous tissue and muscle edema significantly increased with a tumor in localization 2 (RR = 2.58, p = 0.016 and RR = 15, p = 0.0065/RR = 2.05 , p = 0.021, respectively) and after therapy 2 (RR = 15, p = 0.0087 and RR = 2.05, p < 0.0001, respectively). Of the patients with sarcoma in localization 2, 88% developed grade 2 muscle edema after therapy 2; 40% of the patients developed post-treatment seroma. The risk for seroma is significantly higher after surgery and radiation therapy than after surgery alone (p < 0.001)., Conclusion: High-grade postoperative subcutaneous and muscle edema are significantly associated with muscle involvement of primary STS both in patients with and without radiation therapy. The risk for seroma is significantly higher after surgery with additional radiation therapy than after surgery alone., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Linac calibration is done in water, but patients are comprised primarily of soft tissue. Conceptually, and specified in NRG/RTOG trials, dose should be reported as dose-to-muscle to describe the dose to the patient. Historically, the dose-to-water of the linac calibration was often converted to dose-to-muscle for patient calculations through manual application of a 0.99 dose-to-water to dose-to-muscle correction factor, applied during the linac clinical reference calibration. However, many current treatment planning system (TPS) dose calculation algorithms approximately provide dose-to-muscle (tissue), making application of a manual scaling unnecessary. There is little guidance on when application of a scaling factor is appropriate, resulting in highly inconsistent application of this scaling by the community. In this report we provide guidance on the steps necessary to go from the linac absorbed dose-to-water calibration to dose-to-muscle in patient, for various commercial TPS algorithms. If the TPS does not account for the difference between dose-to-water and dose-to-muscle, then TPS reference dose scaling is warranted. We have tabulated the major vendors' TPS in terms of whether they approximate dose-to-muscle or calculate dose-to-water and recommend the correction factor required to report dose-to-muscle directly from the TPS algorithm. Physicists should use this report to determine the applicable correction required for specifying the reference dose in their TPS to achieve this goal and should remain attentive to possible changes to their dose calculation algorithm in the future., (© 2019 American Association of Physicists in Medicine.)

Contamination of the environment after the Chernobyl and Fukushima Daiichi nuclear power plant (NPP) disasters led to the exposure of a large number of humans and wild animals to radioactive substances. However, the sub-lethal consequences induced by these absorbed radiological doses remain understudied and the long-term biological impacts largely unknown. We assessed the biological effects of chronic exposure to ionizing radiation (IR) on embryonic development by exposing zebrafish embryo from fertilization and up to 120 hours post-fertilization (hpf) at dose rates of 0.5 mGy/h, 5 mGy/h and 50 mGy/h, thereby encompassing the field of low dose rates defined at 6 mGy/h. Chronic exposure to IR altered larval behaviour in a light-dark locomotor test and affected cardiac activity at a dose rate as low as 0.5 mGy/h. The multi-omics analysis of transcriptome, proteome and transcription factor binding sites in the promoters of the deregulated genes, collectively points towards perturbations of neurogenesis, muscle development, and retinoic acid (RA) signaling after chronic exposure to IR. Whole-mount RNA in situ hybridization confirmed the impaired expression of the transcription factors her4.4 in the central nervous system and myogenin in the developing muscles of exposed embryos. At the organ level, the assessment of muscle histology by transmission electron microscopy (TEM) demonstrated myofibers disruption and altered neuromuscular junctions in exposed larvae at 5 mGy/h and 50 mGy/h. The integration of these multi-level data demonstrates that chronic exposure to low dose rates of IR has an impact on neuronal and muscle progenitor cells, that could lead to motility defects in free swimming larvae at 120 hpf. The mechanistic understanding of these effects allows us to propose a model where deregulation of RA signaling by chronic exposure to IR has pleiotropic effects on neurogenesis and muscle development.

A new methodology has been proposed to measure optical properties of homogeneous tissue where a laser beam is used to induce heat to a tissue. The induced heat increased the temperature inside the tissue, which is detected by a thermocouple. These readings are compared with that obtained from the solution of the finite element solution that used iterative values of optical properties in determining temperature distribution. The two temperature distributions are used to determine tissue optical properties using the Levenberg-Marquardt iteration. An accurate result is obtained in determining absorption coefficient and reduced scattering coefficient. The work is extended to obtain three parameters (i.e., absorption coefficient, scattering coefficient, and anisotropy). The only limitation is that the temperature readings have to be measured with a high-accuracy thermocouple (i.e., less than 0.4% of maximum-recorded temperature).

Preoperative radiation is associated with an increased risk of wound complications. However, the influences of radiation on musculofascial wound healing remains unclear. The purpose of the study was to investigate the short-term effects of preoperative local radiation on the musculofascial healing of laparotomy incisions in a rat model. Eighteen Fischer 344 rats received radiation doses of 0, 10, or 20 Gy to the abdominal wall and underwent laparotomy 4 weeks later. Two weeks after laparotomy, samples of irradiated muscle were harvested for mechanical tests, histological (Hematoxylin & Eosin, and Masson's Trichrome) and immunohistochemical analyses using KI67, CD31, TGF-β, and MYOD1 antibodies. The elastic modulus (EM), maximum strain (MS), and ultimate tensile strength (UTS) in the 20-Gy group were significantly weaker than those in the 0-Gy group. The EM and UTS in the 20-Gy group were significantly lower than those in the 10-Gy group. The UTS and MS in the 10-Gy group were significantly lower than those in the 0-Gy group. The mean number of inflammatory cells per mm 2 in the 20-Gy group was significantly larger than those in the 10- and 0-Gy groups. The mean numbers of CD31-, KI67-, and MYOD1-positive cells, the optical density of TGF-β, and the microvessel density in the 20-Gy group were significantly smaller than those in the 10- and 0-Gy groups. These results indicated that radiation delays musculofascial healing and decreases mechanical strength of the laparotomy incision by creating a chronic inflammatory environment, inhibiting cell proliferation, angiogenesis, granulation maturation, collagen deposition, and muscular regeneration in a dose-dependent manner. The impaired biomechanical, histological and molecular properties may be associated with the higher risk of wound complications in patients who undergo radiotherapy prior to laparotomy.

It is important to confirm the dose distribution and its biophysiological response in patients subjected to carbon-ion radiotherapy (CIRT) by using medical imaging methods. In this study, the correlation between the signal intensity changes of muscles observed in magnetic resonance imaging (MRI) after CIRT and planned dose distribution was evaluated. Seven patients were arbitrarily selected from among localized prostate cancer patients on whom CIRT was performed in our facilities in 2010. All subjects received the same dose of CIRT, namely, 57.6 Gy relative biological effectiveness (RBE) in 16 fractions. The following two types of images were acquired for each subject: planning computed tomography (CT) images overlaying the dose distribution of CIRT and MRI T2-weighted images (T2WI) taken 1 year after CIRT. The fusion image of the planning CT and MRI images was registered by using a treatment-planning system, and the CIRT dose distribution was compared with changes observed in the MRI of the obturator internus muscles located near the prostate. The signal changes in the axial image passing through the isocenter of the planning target volume were digitized, and a scatter diagram was created showing the relationship between the radiation dose and digitized signal changes. A strong correlation between the radiation dose and the MRI signal intensity changes was observed, and a quadratic function was found to have the best fit. However, estimating the dose distribution from the normalized MRI signal intensity is difficult at this point, owing to the wide variation. Therefore, further investigation is required., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

The aim of the present study was to synthesize mixture solutions which can accurately mimic the dielectric properties of biological tissues, specifically muscle and adipose tissues between 500 MHz and 50 GHz. Mixtures utilizing concentrations of bovine serum albumin (BSA) dissolved in phosphate buffered saline (PBS) and Ringer's solutions were synthesized to mimic in vivo and ex vivo muscle tissues. Solutions consisting of concentrations of peanut oil and Triton X-100 (TX) in PBS and Ringer's solutions were also synthesized to mimic in vivo and ex vivo adipose tissue. Results were then analysed and compared to measured dielectric properties of in vivo and ex vivo biological tissues from another previous study. Good agreement with said dielectric property measurements were obtained since the solutions from this study yielded low RMSE and RMSRE values. This implied that such solutions can be utilized in the construction of human body phantoms for narrowband and ultra-wideband microwave devices for near field breast cancer imaging.

The knowledge of frequency and temperature dependent dielectric properties of tissue is essential to develop ultra-wideband diagnostic technologies, such as a non-invasive temperature monitoring system during hyperthermia treatment. To this end, we characterized the dielectric properties of animal liver, muscle, fat and blood in the microwave frequency range from 0.5 GHz to 7 GHz and in the temperature range between 30 °C and 50 °C. The measured data were modeled to a two-pole Cole-Cole model and a second-order polynomial was introduced to fit the Cole-Cole parameters as a function of temperature. The parametric model provides access to the dielectric properties of tissue at any frequency and temperature in the specified range.

Ultrasound tissue characterization based on the coefficient of nonlinearity, β n  = 1 + B/2A, has been demonstrated to produce added diagnostic value due to its large variation and sensitivity to tissue structure. However, the parameter has been observed to be significantly correlated to the speed of sound and density. These relationships are analyzed empirically as well as theoretically by developing a pressure-density relation based on a thermodynamic model and the Mie intermolecular potential. The results indicate that for many soft tissues, the coefficient of nonlinearity is largely determined by the isentropic compressibility, κ s . Consequently, for tissue characterization, estimating the nonlinear response of the medium, given by β p  = β n κ s , appears to be beneficial due to correlated quantities.

Triple negative breast cancer (TNBC) is the most lethal one for all types of breast cancer. Though radiotherapy is an efficient treatment, long-term survival rate of TNBC patients is still suboptimal. Hyprofractionated radiotherapy, an improved radiotherapy, has made an inspiring result in clinic. However, the mechanism underlying TNBC treated with hyprofractionated radiotherapy is not clear. Decorin (DCN) is a small poteoglycan of matrix which has an inhibitory effect on the breast cancer and is secreted by muscle under certain conditions. In this study, we demonstrated that peritumoral muscles secrete more DCN at higher dose irradiation than that at conventional irradiation dose in TNBC tumor-bearing mice. Thus, it indicates that DCN secreted from peritumoral muscle may be one of the reasons why hyprofractionated radiotherapy could inhibit the growth of TNBC more effectively. Moreover, we also indicated that the up-regulated DCN attenuated lung metastasis of TNBC. In conclusion, we demonstrated that hypofractionated radiation promotes the secretion of DCN in peritumoral muscle, thus enhancing the inhibitory effect on TNBC, which might help to optimize the strategy of radiotherapy for TNBC patients in the future.

Coaxial sensors are effective for measurement of dielectric properties of biological tissues. Several measurement methods used to derive dielectric properties have been investigated for the measurement with a coaxial sensor at microwave frequencies. While the measurement accuracy depends on the method used, there has been insufficient intercomparison of these methods and their model approximation errors. On the other hand, we have developed a coaxial sensor for the measurement of complex permittivity at millimeter-wave (MMW) frequencies of up to 100 GHz. However, the scarcity of reference data at MMW frequencies makes the validation of the measurement system difficult. Thus, it is essential to clarify the model approximation error of the method used in the measurement system, particularly at MMW frequencies. This study aims to clarify the model approximation errors of methods for dielectric property measurement using a coaxial sensor at MMW frequencies. The model approximation errors were assessed by comparing results obtained by the methods with those based on the theoretical formula of the full-wave modal expression of Maxwell's equations. The measurement uncertainty for the theoretical formula was estimated for a standard liquid sample to clarify the contribution of the model approximation errors to the uncertainty. Furthermore, the methods were applied to the measurement of porcine tissues at body temperature, and the measurement accuracy and usability for measurement at MMW frequencies are discussed.

Tendons are mechanosensitive tissues that connect and transmit the forces generated by muscles to bones by allowing the conversion of mechanical input into biochemical signals. These physical forces perform the fundamental work of preserving tendon homeostasis assuring body movements. However, overloading causes tissue injuries, which leads us to the field of tendon regeneration. Recently published reviews have broadly shown the use of biomaterials and different strategies to attain tendon regeneration. In this review, our focus is the use of magnetic fields as an alternative therapy, which has demonstrated clinical relevance in tendon medicine because of their ability to modulate cell fate. Yet the underlying cellular and molecular mechanisms still need to be elucidated. While providing a brief outlook about specific signalling pathways and intracellular messengers as framework in play by tendon cells, application of magnetic fields as a subcategory of physical forces is explored, opening up a compelling avenue to enhance tendon regeneration. We outline here useful insights on the effects of magnetic fields both at in vitro and in vivo levels, particularly on the expression of tendon genes and inflammatory cytokines, ultimately involved in tendon regeneration. Subsequently, the potential of using magnetically responsive biomaterials in tendon tissue engineering is highlighted and future directions in magnetotherapy are discussed., (© 2018 Wiley Periodicals, Inc.)

Macrophages play a very important role in the conduction of several regenerative processes mainly due to their plasticity and multiple functions. In the muscle repair process, while M1 macrophages regulate the inflammatory and proliferative phases, M2 (anti-inflammatory) macrophages direct the differentiation and remodelling phases, leading to tissue regeneration. The aim of this study was to evaluate the effect of red and near infrared (NIR) photobiomodulation (PBM) on macrophage phenotypes and correlate these findings with the repair process following acute muscle injury. Wistar rats were divided into 4 groups: control; muscle injury; muscle injury + red PBM; and muscle injury + NIR PBM. After 2, 4 and 7 days, the tibialis anterior muscle was processed for analysis. Macrophages phenotypic profile was evaluated by immunohistochemistry and correlated with the different stages of the skeletal muscle repair by the qualitative and quantitative morphological analysis as well as by the evaluation of IL-6, TNF-α and TGF-β mRNA expression. Photobiomodulation at both wavelengths was able to decrease the number of CD68 + (M1) macrophages 2 days after muscle injury and increase the number of CD163 + (M2) macrophages 7 days after injury. However, only NIR treatment was able to increase the number of CD206 + M2 macrophages (Day 2) and TGF-β mRNA expression (Day 2, 4 and 7), favouring the repair process more expressivelly. Treatment with PBM was able to modulate the inflammation phase, optimize the transition from the inflammatory to the regeneration phase (mainly with NIR light) and improve the final step of regeneration, enhancing tissue repair., (© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Background: Muscle abnormalities such as low muscle mass and low muscle radiodensity are well known risk factors for unfavourable cancer prognosis. However, little is known in regard to the degree and impact of longitudinal changes in muscle mass and radiodensity within the context of cancer. Here, we explore the relationship between muscle wasting and mortality in a large population-based study of patients with non-metastatic colorectal cancer (CRC)., Methods: A total of 1924 patients with stage I-III CRC who underwent surgical resection in the Kaiser Permanente Northern California Health System were included. Muscle mass and radiodensity were quantified using computed tomography images obtained at diagnosis and after approximately 14 months. Cox proportional-hazards models were used to estimate hazard ratios for all-cause mortality., Results: The hazard ratio for all-cause mortality among patients with the largest deterioration in muscle mass (≥2 SD; ≥11.4% loss from baseline), as compared with those who remained stable (±1 SD; 0.0 ± 5.7%) was 2.15 [95% confidence interval (CI): 1.59-2.92; P < 0.001]. The hazard ratio for all-cause mortality among patients who experienced the largest deterioration in muscle radiodensity (≥2 SD; ≥20.2% loss from baseline), as compared with those who remained stable (±1 SD; 0.0 ± 10.1%) was 1.61 (95% CI: 1.20-2.15; P = 0.002)., Conclusions: In patients with stage I-III CRC, muscle wasting is a risk factor for mortality, independent of change in body mass and other body composition parameters., (© 2018 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.)

High-intensity focused ultrasound (HIFU) under magnetic resonance imaging (MRI) guidance can achieve a noninvasive and precise ablation of the solid tumor. In the study, an MRI-compatible 1-MHz 16-channel ring-shaped transducer was developed to minimize the burn risk of breast skin and perform volumetric ablation for short treatment time. The measured electroacoustic conversion efficiency of the transducer was 50.90% ± 5. The transducer could produce a point and a quasi-hollow-cylinder lesion in a thermal-sensitive phantom or an ex vivo pork by tuning the phase of each element. It may achieve volumetric ablation of 1.5 cm 3 when the point lesion is located inside the hollow lesion. Ex vivo ablation experiments showed that the transducer could cause a coagulative necrosis in the pork from the surrounded subcutaneous fat by 5 mm without fat damage. The temperature and region of the pork ablation were quantified by MRI technique. There was no MRI interference from HIFU and vice versa while both systems operated concurrently.

Purpose: To investigate the potential of texture analysis applied on T2-w and postcontrast T1-w images acquired before radiotherapy for prostate cancer (PCa) and 12 months after its completion in quantitatively characterizing local radiation effect on the muscular component of internal obturators, as organs potentially involved in urinary toxicity., Methods: T2-w and postcontrast T1-w MR images were acquired at 1.5 T before treatment (MRI1) and at 12 months of follow-up (MRI2) in 13 patients treated with radiotherapy for PCa. Right and left internal obturator muscle contours were manually delineated upon MRI1 and then automatically propagated on MRI2 by an elastic registration method. Planning CT images were coregistered to both MRIs and dose maps were deformed accordingly. A high-dose region receiving >55 Gy and a low-dose region receiving <55 Gy were identified in each muscle volume. Eighteen textural features were extracted from each region of interest and differences between MRI1 and MRI2 were evaluated., Results: A signal increase was highlighted in both T2-w and T1-w images in the portion of the obturators near the prostate, i.e., in the region receiving medium-high doses. A change in the spatial organization was identified, as an increase in homogeneity and a decrease in contrast and complexity, compatible with an inflammatory status. In particular, the region receiving medium-high doses presented more significant or, at least, stronger differences., Conclusions: Texture analysis applied on T1-w and T2-w MR images has demonstrated its ability in quantitative evaluating radiation-induced changes in obturator muscles after PCa radiotherapy., (© 2018 American Association of Physicists in Medicine.)

The aim of this study was to determine whether oxidative stress markers are influenced by low-intensity laser therapy (LLLT) in rats subjected to a high-intensity resistive exercise session (RE). Female Wistar rats divided into three experimental groups (Ctr: control, 4J: LLLT, and RE) and subdivided based on the sampling times (instantly or 24 h postexercise) underwent irradiation with LLLT using three-point transcutaneous method on the hind legs, which was applied to the gastrocnemius muscle at the distal, medial, and proximal points. Laser (4J) or placebo (device off) were carried out 60 sec prior to RE that consisted of four climbs bearing the maximum load with a 2 min time interval between each climb. Lipoperoxidation levels and antioxidant capacity were obtained in muscle. Lipoperoxidation levels were increased (4-HNE and CL markers) instantly post-RE. LLLT prior to RE avoided the increase of the lipid peroxidation levels. Similar results were also notified for oxidation protein assays. The GPx and FRAP activities did not reduce instantly or 24 h after RE. SOD increased 24 h after RE, while CAT activity did not change with RE or LLLT. In conclusion, LLLT prior to RE reduced the oxidative stress markers, as well as, avoided reduction, and still increased the antioxidant capacity.

Electroporation-based treatments typically consist of the application of high-voltage dc pulses. As an undesired side effect, these dc pulses cause electrical stimulation of excitable tissues such as motor nerves. The present in vivo study explores the use of bursts of sinusoidal voltage in a frequency range from 50 kHz to 2 MHz, to induce irreversible electroporation (IRE) whilst avoiding neuromuscular stimulation. A series of 100 dc pulses or sinusoidal bursts, both with an individual duration of 100 µs, were delivered to rabbit liver through thin needles in a monopolar electrode configuration, and thoracic movements were recorded with an accelerometer. Tissue samples were harvested three hours after treatment and later post-processed to determine the dimensions of the IRE lesions. Thermal damage due to Joule heating was ruled out via computer simulations. Sinusoidal bursts with a frequency equal to or above 100 kHz did not cause thoracic movements and induced lesions equivalent to those obtained with conventional dc pulses when the applied voltage amplitude was sufficiently high. IRE efficacy dropped with increasing frequency. For 100 kHz bursts, it was estimated that the electric field threshold for IRE is about 1.4 kV cm -1 whereas that of dc pulses is about 0.5 kV cm -1 .

Researches have been performed to investigate the effects of phototherapy on improving performance and reduction of muscular fatigue. However, a great variability in the light parameters and protocols of the trials are a concern to establish the efficacy of this therapy to be used in sports or clinic. The aim of this study is to investigate the effectiveness, moment of application of phototherapy within an exercise protocol, and which are the parameters optimally effective for the improvement of muscular performance and the reduction of muscular fatigue in healthy people. Systematic searches of PubMed, PEDro, Cochrane Library, EMBASE, and Web of Science databases were conducted for randomized clinical trials to March 2017. Analyses of risk of bias and quality of evidence of the included trials were performed, and authors were contacted to obtain any missing or unclear information. We included 39 trials (861 participants). Data were reported descriptively through tables, and 28 trials were included in meta-analysis comparing outcomes to placebo. Meta-analysis was performed for the variables: time until reach exhaustion, number of repetitions, isometric peak torque, and blood lactate levels showing a very low to moderate quality of evidence and some effect in favor to phototherapy. Further investigation is required due the lack of methodological quality, small sample size, great variability of exercise protocols, and phototherapy parameters. In general, positive results were found using both low-level laser therapy and light-emitting diode therapy or combination of both in a wavelength range from 655 to 950 nm. Most of positive results were observed with an energy dose range from 20 to 60 J for small muscular groups and 60 to 300 J for large muscular groups and maximal power output of 200 mW per diode.

Methods: After injecting 25.6 ± 8.8 MBq (0.7 ± 0.2 mCi) of 18F-Fluoro-L-DOPA intravenously, three static PET scans were acquired at 20, 30, and 40 min post injection in 3-D mode on 10 patients (6 male, 4 female) with congenital hyperinsulinism. Regions of interest (ROIs) were drawn over several organs visible in the reconstructed PET/CT images and time activity curves (TACs) were generated. Residence times were calculated using the TAC data. The radiation absorbed dose for the whole body was calculated by entering the residence times in the OLINDA/EXM 1.0 software., Results: The mean residence times for the 18F-Fluoro-L-DOPA in the liver, lungs, kidneys, muscles, and pancreas were 11.54 ± 2.84, 1.25 ± 0.38, 4.65 ± 0.97, 17.13 ± 2.62, and 0.89 ± 0.34 min, respectively. The mean effective dose equivalent for 18F-Fluoro-L-DOPA was 0.40 ± 0.04 mSv/MBq. The CT scan used for attenuation correction delivered an additional radiation dose of 5.7 mSv. The organs receiving the highest radiation absorbed dose from 18F-Fluoro-L-DOPA were the urinary bladder wall (2.76 ± 0.95 mGy/MBq), pancreas (0.87 ± 0.30 mGy/MBq), liver (0.34 ± 0.07 mGy/MBq), and kidneys (0.61 ± 0.11 mGy/MBq). The renal system was the primary route for the radioactivity clearance and excretion., Conclusions: The estimated radiation dose burden from 18F-Fluoro-L-DOPA is relatively modest to newborns.

Electroporation based treatments consist in applying one or multiple high voltage pulses to the tissues to be treated. As an undesired side effect, these pulses cause electrical stimulation of excitable tissues such as nerves and muscles. This increases the complexity of the treatments and may pose a risk to the patient. To minimize electrical stimulation during electroporation based treatments, it has been proposed to replace the commonly used monopolar pulses by bursts of short bipolar pulses. In the present study, we have numerically analyzed the rationale for such approach. We have compared different pulsing protocols in terms of their electroporation efficacy and their capability of triggering action potentials in nerves. For that, we have developed a modeling framework that combines numerical models of nerve fibers and experimental data on irreversible electroporation. Our results indicate that, by replacing the conventional relatively long monopolar pulses by bursts of short bipolar pulses, it is possible to ablate a large tissue region without triggering action potentials in a nearby nerve. Our models indicate that this is possible because, as the pulse length of these bipolar pulses is reduced, the stimulation thresholds raise faster than the irreversible electroporation thresholds. We propose that this different dependence on the pulse length is due to the fact that transmembrane charging for nerve fibers is much slower than that of cells treated by electroporation because of their geometrical differences.

The effect of radiation on the aquatic environment is of major concern in recent years. Limited data is available on the genotoxicity of gamma radiation on different tissues of aquatic organisms. Hence, the present investigation was carried out to study the DNA damage induced by gamma radiation in the gill and muscle tissues and their relative sensitivity using the comet assay in the freshwater teleost fish, common carp (Cyprinus carpio). The comet assay was optimized and validated in common carp using cyclophosphamide (CP), a reference genotoxic agent. The fish were exposed (acute) to various doses of gamma radiation (2, 4, 6, 8 and 10Gy) and samplings (gill and muscle tissue) were done at regular intervals (24, 48 and 72h) to assess the DNA damage. A significant increase in DNA damage was observed as indicated by an increase in % tail DNA for all doses of gamma radiation in both tissues. We also observed a dose-related increase and a time-dependent decrease of DNA damage. In comparison, DNA damage showed different sensitivity among the tissues at different doses. This shows that a particular dose may have different effects on different tissues which could be due to physiological factors of the particular tissue. Our study also suggests that the gills and muscle of fish are sensitive and reliable tissues for evaluating the genotoxic effects of reference and environmental agents, using the comet assay., (Copyright © 2017. Published by Elsevier Inc.)

Exposure to high-dose ionizing radiation during medical treatment exerts well-documented deleterious effects on bone health, reducing bone density and contributing to bone growth retardation in young patients and spontaneous fracture in postmenopausal women. However, the majority of human radiation exposures occur in a much lower dose range than that used in the radiation oncology clinic. Furthermore, very few studies have examined the effects of low-dose ionizing radiation on bone integrity and results have been inconsistent. In this study, mice were irradiated with a total-body dose of 0.17, 0.5 or 1 Gy to quantify the early (day 3 postirradiation) and delayed (day 21 postirradiation) effects of radiation on bone microarchitecture and bone marrow stromal cells (BMSCs). Female BALBc mice (4 months old) were divided into four groups: irradiated (0.17, 0.5 and 1 Gy) and sham-irradiated controls (0 Gy). Micro-computed tomography analysis of distal femur trabecular bone from animals at day 21 after exposure to 1 Gy of X-ray radiation revealed a 21% smaller bone volume (BV/TV), 22% decrease in trabecular numbers (Tb.N) and 9% greater trabecular separation (Tb.Sp) compared to sham-irradiated controls (P < 0.05). We evaluated the differentiation capacity of bone marrow stromal cells harvested at days 3 and 21 postirradiation into osteoblast and adipocyte cells. Osteoblast and adipocyte differentiation was decreased when cells were harvested at day 3 postirradiation but enhanced in cells isolated at day 21 postirradiation, suggesting a compensatory recovery process. Osteoclast differentiation was increased in 1 Gy irradiated BMSCs harvested at day 3 postirradiation, but not in those harvested at day 21 postirradiation, compared to controls. This study provides evidence of an early, radiation-induced decrease in osteoblast activity and numbers, as well as a later recovery effect after exposure to 1 Gy of X-rays, whereas osteoclastogenesis was enhanced. A better understanding of the effects of radiation on osteoprogenitor cell populations could lead to more effective therapeutic interventions that protect bone integrity for individuals exposed to low-dose ionizing radiation.

Background: Hypoxia imaged by positron emission tomography (PET) is a potential target for optimization in radiotherapy. However, the implementation of this approach with respect to the conversion of intensities in the images into oxygenation and radiosensitivity maps is not straightforward. This study investigated the feasibility of applying two conversion approaches previously derived for 18 F-labeled fluoromisonidazole ( 18 F-FMISO)-PET images for the hypoxia tracer 18 F-flortanidazole ( 18 F-HX4)., Material and Methods: Ten non-small-cell lung cancer patients imaged with 18 F-HX4 before the start of radiotherapy were considered in this study. PET image uptake was normalized to a well-oxygenated reference region and subsequently linear and non-linear conversions were used to determine tissue oxygenations maps. These were subsequently used to delineate hypoxic volumes based partial oxygen pressure (pO 2 ) thresholds. The results were compared to hypoxic volumes segmented using a tissue-to-background ratio of 1.4 for 18 F-HX4 uptake., Results: While the linear conversion function was not found to result in realistic oxygenation maps, the non-linear function resulted in reasonably sized sub-volumes in good agreement with uptake-based segmented volumes for a limited range of pO 2 thresholds. However, the pO 2 values corresponding to this range were significantly higher than what is normally considered as hypoxia. The similarity in size, shape, and relative location between uptake-based sub-volumes and volumes based on the conversion to pO 2 suggests that the relationship between uptake and pO 2 is similar for 18 F-FMISO and 18 F-HX4, but that the model parameters need to be adjusted for the latter., Conclusions: A non-linear conversion function between uptake and oxygen partial pressure for 18 F-FMISO-PET could be applied to 18 F-HX4 images to delineate hypoxic sub-volumes of similar size, shape, and relative location as based directly on the uptake. In order to apply the model for e.g., dose-painting, new parameters need to be derived for the accurate calculation of dose-modifying factors for this tracer.

The visible (VIS) and near-infrared (NIR) lasers are now widely used in therapeutic and other medical applications. Some of these applications require to deliver the laser energy deep toward the desired tissue target or organ. The aim of this in vitro study is to investigate practically whether the modulation of laser energy by employing the therapeutic ultrasound or electrical energies can increase the penetration depth of the laser light inside the tissue. Such modulation was implemented in this study by coupling the (c.w.) diode and Nd:YAG laser energies with the ultrasound or AC current simultaneously as they pass through preprepared ex vivo bovine muscular tissue strips. Two wavelengths of diode lasers were used, 637 and 808 nm beside the 1064-nm Nd:YAG laser. The results showed a noticeable decrease of these laser attenuation factors as they pass through the tissue strips in the presence of the ultrasound or AC energies. By using this coupling modulation, the capability of increasing the laser penetration depths inside the tissue was confirmed without having to increase their applied power.

Dropped head syndrome (DHS) is a famous but unusual late complication of multimodality treatment for head and neck carcinoma. We reported this early-onset complication and analyzed the dose to the neck extensor muscles. We examined the records of three patients with DHS after radiotherapy. The doses to the neck extensor muscles were compared between three patients with DHS and nine patients without DHS. The mean dose to the neck extensor muscles of the three patients with DHS were 58.5 Gy, 42.3 Gy and 60.9 Gy, while the dose was <50 Gy in all nine patients in the control group. The onset of this syndrome was 5 months, 6 months and 15 months. The early-onset DHS may have something to do with dose to the neck extensor muscles. The proposed dose to the neck extensor muscles might be <46 Gy (or at least <50 Gy)., (© The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

The purpose of this study was to investigate the effect of subacute exposure to static magnetic fields (SMF) on hematological and muscle biochemical parameters in rats. Male Wistar rats, daily exposed to SMF, were exposed to SMF (128 mT, 1 h/day) during 15 consecutive days. SMF-exposed rats showed a significant decrease in red blood cell (RBC) count, hemoglobin (Hb), and hematocrit (Ht) values compared to sham-exposed rats (p < 0.05). Concomitant decreases of plasma iron level against increase in transferrin amount were also observed after SMF exposure (p < 0.0.05). In postprandial condition, SMF-exposed rats presented higher plasma lactate (p < 0.01). Additionally, SMF exposure increased monocarboxylate transporters (MCT4) and glucose transporter 4 (Glut4)'s contents only in glycolytic muscle (p < 0.05). SMF exposure induced alteration of hematological parameters; importantly, we noticed a pseudoanemia status, which seems to affect tissue oxygen delivery. Additionally, SMF exposure seems to favor the extrusion of lactate from the cell to the blood compartment. Given that, these arguments advocate for an adaptive response to a hypoxia status following SMF exposure.

Light-emitting diode therapy (LEDT) applied over the leg, gluteus and lower-back muscles of mice using a LED cluster (630 nm and 850 nm, 80 mW/cm(2) , 7.2 J/cm(2) ) increased muscle performance (repetitive climbing of a ladder carrying a water-filled tube attached to the tail), ATP and mitochondrial metabolism; oxidative stress and proliferative myocyte markers in mice subjected to acute and progressive strength training. Six bi-daily training sessions LEDT-After and LEDT-Before-After regimens more than doubled muscle performance and increased ATP more than tenfold. The effectiveness of LEDT on improving muscle performance and recovery suggest applicability for high performance sports and in training programs. Positioning of the mice and light-emitting diode therapy (LEDT) applied on mouse legs, gluteus and lower-back muscles without contact., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: Nowadays, the efficacies of (68)Ga-based tracers are comparable to that of (18)F-based agents and have stimulated researchers to investigate the potential of (68)Ga-based positron emission tomography (PET) imaging agents. In this study, the human absorbed dose of (68)Ga labeled with ethylenecysteamine cysteine (68)Ga-ECC and (67)Ga-ECC was estimated based on biodistribution data in mice by the medical internal radiation dose (MIRD) method., Methods: For biodistribution of (67)Ga/(68)Ga-ECC, three mice were killed by CO2 asphyxiation at each selected times after injection (15, 30, 45, 60, 120 min for (68)Ga-ECC and 0.5, 2 and 48 h for (67)Ga-ECC), and then the tissue (heart, lung, brain, intestine, skin, stomach, kidneys, liver, muscle and bone) was removed., Results: (68)Ga-ECC as a new PET renal imaging agent was prepared with radiochemical purity of >97 % in less than 30 min. The biodistribution data for (68)Ga-ECC showed that the most of the activity extracted from the urinary tract very fast. Comparison between human absorbed dose estimation for these two agents indicated that the absorbed dose of the most organs after injection of (67)Ga-ECC is approximately tenfold higher than the amount after (68)Ga-ECC injection., Conclusion: The results showed that (68)Ga-ECC is a more appropriate agent rather than (67)Ga-ECC and generally can be a good candidate for PET renal imaging applications.

Purpose: The imaging of positron emitting isotopes produced during patient irradiation is the only in vivo method used for hadrontherapy dose monitoring in clinics nowadays. However, the accuracy of this method is limited by the loss of signal due to the metabolic decay processes (biological washout). In this work, a generic modeling of washout was incorporated into the GATE simulation platform. Additionally, the influence of the washout on the β(+) activity distributions in terms of absolute quantification and spatial distribution was studied., Methods: First, the irradiation of a human head phantom with a (12)C beam, so that a homogeneous dose distribution was achieved in the tumor, was simulated. The generated (11)C and (15)O distribution maps were used as β(+) sources in a second simulation, where the PET scanner was modeled following a detailed Monte Carlo approach. The activity distributions obtained in the presence and absence of washout processes for several clinical situations were compared., Results: Results show that activity values are highly reduced (by a factor of 2) in the presence of washout. These processes have a significant influence on the shape of the PET distributions. Differences in the distal activity falloff position of 4 mm are observed for a tumor dose deposition of 1 Gy (Tini = 0 min). However, in the case of high doses (3 Gy), the washout processes do not have a large effect on the position of the distal activity falloff (differences lower than 1 mm). The important role of the tumor washout parameters on the activity quantification was also evaluated., Conclusions: With this implementation, GATE/GEANT4 is the only open-source code able to simulate the full chain from the hadrontherapy irradiation to the PET dose monitoring including biological effects. Results show the strong impact of the washout processes, indicating that the development of better models and measurement of biological washout data are essential.

This study aimed to examine the safety profile of microwave therapy on limbs with metal implants. New Zealand white rabbits were implanted with titanium alloy internal fixation plates. Femurs were exposed to 20, 40, 60, or 80 W of microwave radiation for 30 min (microwave applicator at 2450 MHz), and temperatures of the implants and muscles adjacent to implants were recorded. To evaluate thermal damage, nerves were electrodiagnostically assessed immediately after radiation, and histologic studies performed on nerve and muscle sections. As expected, implant temperature was highest in the exposure field. Temperatures of limbs with titanium alloy implants increased significantly at 60 and 80 W, with a significant decline in the nerve conduction velocity and acute thermal injuries in nerves and muscles adjacent to implants. However, temperature remained unchanged and no adverse effects were observed in nerves and muscles at 20 and 40 W. These findings are inconsistent with the current notion that surgical metal implants in the treatment field are contraindications for microwave therapy. Hence, we believe that a lower dose of continuous wave microwave irradiation is safe for limbs with titanium alloy implants., (© 2015 Wiley Periodicals, Inc.)

Background and Objective: Radiofrequency currents are commonly used in dermatology to treat cutaneous and subcutaneous tissues by heating. The subcutaneous morphology of tissue consists of a fine, collagenous and fibrous septa network enveloping clusters of adipocyte cells. The architecture of this network, namely density and orientation of septa, varies among patients and, furthermore, it correlates with cellulite grading. In this work we study the effect of two clinically relevant fibrous septa architectures on the thermal and elastic response of subcutaneous tissue to the same RF treatment; in particular, we evaluate the thermal damage and thermal stress induced to an intermediate- and a high-density fibrous septa network architecture that correspond to clinical morphologies of 2.5 and 0 cellulite grading, respectively., Study Design/materials and Methods: We used the finite element method to assess the electric, thermal and elastic response of a two-dimensional model of skin, subcutaneous tissue and muscle subjected to a relatively long, constant, low-power RF treatment. The subcutaneous tissue is constituted by an interconnected architecture of fibrous septa and fat lobules obtained by processing micro-MRI sagittal images of hypodermis. As comparison criteria for the RF treatment of the two septa architectures, we calculated the accumulated thermal damage that corresponds to 63% loss in cell viability., Results: Electric currents preferentially circulated through the fibrous septa in the subcutaneous tissue. However, the intensity of the electric field was higher within the fat because it is a poor electric conductor. The power absorption in the fibrous septa relative to that in the fat varied with septum orientation: it was higher in septa with vertical orientation and lower in septa with horizontal orientation. Overall, maximum values of electric field intensity, power absorption and temperature were similar for both fibrous septa architectures. However, the high-density septa architecture (cellulite grade 0) had a more uniform and broader spatial distribution of power absorption, resulting in a larger cross-sectional area of thermal damage (≈1.5 times more). Volumetric strains (expansion and contraction) were small and similar for both network architectures. During the first seconds of RF exposure, the fibrous septa were subjected to thermal expansion regardless of orientation. In the long term, the fibrous septa contracted due to the thermal expansion of fat. Skin and muscle were subjected to significantly higher Von Mises stresses (measure of yield) or distortion energy than the subcutaneous tissue., Conclusion: The distribution of electric currents within subcutaneous tissues depends on tissue morphology. The electric field is more intense in septum oriented along the skin to muscle (top to bottom) direction, creating lines or planes of preferential heating. It follows that the more septum available for preferential heating, the larger the extent of volumetric RF-heating and thermal damage to the subcutaneous tissue. Thermal load alone, imposed by long-exposure to heating up to 50 °C, results in small volumetric expansion and contraction in the subcutaneous tissue. The subcutaneous tissue is significantly less prone to non-reversible deformation by a thermal load than the skin and muscle., (© 2015 Wiley Periodicals, Inc.)

Objective: The purpose of the preliminary study was to investigate the value of (18)F-FLT micro-PET/CT in predicting radiosensitivity of human nasopharyngeal carcinoma (NPC) xenografts in nude mice models., Methods: Twelve BALB/c-nu nude mice were randomly divided into two groups. They were subcutaneously injected with either CNE1 or CNE2 cell suspension. Xenograft volumes were measured after tumor formation. When the tumors reached nearly 10 mm in diameter, they received 15-Gy irradiation. Before and 24 h after irradiation, mice were performed with (18)F-FLT micro-PET/CT. The region of interest (ROI) was manually drawn, and the percent of injected dose per gram of the tumor and muscle in the ROIs was recorded. Tumor-to-muscle ratio (T/M) was calculated and compared with volume changes. Additionally, we also used ten untreated mice as control group., Results: After irradiation, CNE2 tumors decreased significantly while CNE1 tumors continuously grew and became stable after 1 week. However, in control group, CNE1 and CNE2 tumors continuously enlarged in the observed time. Therefore, we could regard CNE2 group as irradiation responder while CNE1 group as non-responder. In irradiation group, the value of T/M before irradiation (T/M 0) of CNE1 mice was statistically lower than CNE2 mice (1.62 ± 0.38 versus 5.57 ± 1.30; P = 0.004). Besides, T/M decreased significantly in CNE2 group after irradiation (5.57 ± 1.30 versus 3.59 ± 1.06; P < 0.001). By means of a receiver operating characteristic curve, the optimal cut value of T/M 0 and ∆T/M to predict responder was 2.38 and -0.15, respectively (both sensitivity and specificity = 100.0 %)., Conclusions: (18)F-FLT PET/CT has the potential to predict radiosensitivity in NPC xenografts nude mice models.

Phototherapy is an electrophysical intervention being considered for the retardation of peripheral muscular fatigue usually observed in chronic obstructive pulmonary disease (COPD). The objective of this study was to evaluate the acute effects of combination of super-pulsed laser and light-emitting diodes phototherapy on isokinetic performance in patients with COPD. Thirteen patients performed muscular endurance tests in an isokinetic dynamometer. The maximum voluntary isometric contraction (MVIC), peak torque (PT), and total work (TW) of the non-dominant lower limb were measured in two visits. The application of phototherapy or placebo (PL) was conducted randomly in six locations of femoral quadriceps muscle by using a cluster of 12 diodes (4 of 905 nm super-pulsed lasers, 0.3125 mW each; 4 of 875 nm LEDs, 17.5 mW each; and 4 of 640 nm LEDs, 15 mW each, manufactured by Multi Radiance Medical™). We found statistically significant increases for PT (174.7 ± 35.7 N · m vs. 155.8 ± 23.3 N · m, p = 0.003) and TW after application of phototherapy when compared to placebo (778.0 ± 221.1 J vs. 696.3 ± 146.8 J, p = 0.005). Significant differences were also found for MVIC (104.8 ± 26.0 N · m vs. 87.2 ± 24.0 N · m, p = 0.000), sensation of dyspnea (1 [0-4] vs. 3 [0-6], p = 0.003), and fatigue in the lower limbs (2 [0-5] vs. 5 [0.5-9], p = 0.002) in favor of phototherapy. We conclude that the combination of super-pulsed lasers and LEDs administered to the femoral quadriceps muscle of patients with COPD increased the PT by 20.2% and the TW by 12%. Phototherapy with a combination of super-pulsed lasers and LEDs prior to exercise also led to decreased sensation of dyspnea and fatigue in the lower limbs in patients with COPD.

Purpose: The aim of this study was to characterise changes in tissue volume during image-guided microwave ablation in order to arrive at a more precise determination of the true ablation zone., Materials and Methods: The effect of power (20-80 W) and time (1-10 min) on microwave-induced tissue contraction was experimentally evaluated in various-sized cubes of ex vivo liver (10-40 mm ± 2 mm) and muscle (20 and 40 mm ± 2 mm) embedded in agar phantoms (N = 119). Post-ablation linear and volumetric dimensions of the tissue cubes were measured and compared with pre-ablation dimensions. Subsequently, the process of tissue contraction was investigated dynamically during the ablation procedure through real-time X-ray CT scanning., Results: Overall, substantial shrinkage of 52-74% of initial tissue volume was noted. The shrinkage was non-uniform over time and space, with observed asymmetry favouring the radial (23-43 % range) over the longitudinal (21-29%) direction. Algorithmic relationships for the shrinkage as a function of time were demonstrated. Furthermore, the smallest cubes showed more substantial and faster contraction (28-40% after 1 min), with more considerable volumetric shrinkage (>10%) in muscle than in liver tissue. Additionally, CT imaging demonstrated initial expansion of the tissue volume, lasting in some cases up to 3 min during the microwave ablation procedure, prior to the contraction phenomenon., Conclusions: In addition to an asymmetric substantial shrinkage of the ablated tissue volume, an initial expansion phenomenon occurs during MW ablation. Thus, complex modifications of the tissue close to a radiating antenna will likely need to be taken into account for future methods of real-time ablation monitoring.

There has been an increased interest in 165Dy radiossynovectomy, which emits relatively high-energy (> 1 MeV) beta rays. The production of in vivo bremsstrachlung radiation hazards warrants evaluation. The bremsstrahlung component of the decay scheme of 165Dy has been traditionally ignored in internal dosimetry calculations. We have estimated the bremsstrahlung dose of 165Dy distributed in muscle and bone to body by various internal organs (adrenals, brain, breasts, gallbladder wall, LLI wall, small intestine, stomach, ULI wall, heart wall, kidneys, liver, lungs, muscle, ovaries, pancreas, red marrow, bone surfaces, skin, spleen, testes, thymus, thyroid, urine bladder wall, uterus, fetus, placenta, and total body) during radiosynovictomy. In the present study, muscle and bone are considered to be source organs. These estimated values show that the bremsstrahlung radiation absorbed dose contribution from an organ to itself is very small compared to that originating from the beta source. However, contribution to other organs is not always negligible, especially when large amounts of 165Dy may be involved, such as in therapy applications. Hence the component of the total dose due to bremsstrahlung dose should be considered in radiosynovictomy or other therapy applications.

We demonstrated the application of relative radiance-based continuous wave (cw) measurements for recovering absorption and scattering properties (the effective attenuation coefficient, the diffusion coefficient, the absorption coefficient and the reduced scattering coefficient) of bulk porcine muscle phantoms in the 650-900 nm spectral range. Both the side-firing fiber (the detector) and the fiber with a spherical diffuser at the end (the source) were inserted interstitially at predetermined locations in the phantom. The porcine phantoms were prostate-shaped with ∼4 cm in diameter and ∼3 cm thickness and made from porcine loin or tenderloin muscles. The described method was previously validated using the diffusion approximation on simulated and experimental radiance data obtained for homogenous Intralipid-1% liquid phantom. The approach required performing measurements in two locations in the tissue with different distances to the source. Measurements were performed on 21 porcine phantoms. Spectral dependences of the effective attenuation and absorption coefficients for the loin phantom deviated from corresponding dependences for the tenderloin phantom for wavelengths <750 nm. The diffusion constant and the reduced scattering coefficient were very close for both phantom types. To quantify chromophore presence, the plot for the absorption coefficient was matched with a synthetic absorption spectrum constructed from deoxyhemoglobin, oxyhemoglobin and water. The closest match for the porcine loin spectrum was obtained with the following concentrations: 15.5 µM (±30% s.d.) Hb, 21 µM (±30% s.d.) HbO2 and 0.3 (±30% s.d.) fractional volume of water. The tenderloin absorption spectrum was best described by 30 µM Hb (±30% s.d), 19 µM (±30% s.d.) HbO2 and 0.3 (±30% s.d.) fractional volume of water. The higher concentration of Hb in tenderloin was consistent with a dark-red appearance of the tenderloin phantom. The method can be applied to a number of biological tissues and organs for interstitial optical interrogation.

Objectives: While radiation dose to the larynx and pharyngeal constrictors has been the focus of swallowing complications, the suprahyoid muscles, or floor of mouth (FoM) muscles, are critical for hyoid and laryngeal elevation and effective bolus diversion, preventing penetration and aspiration. We hypothesize that radiation dose to these muscles may be important in the development of dysphagia., Materials and Methods: We studied 46 patients with OPSCC treated with CRT and who underwent baseline swallowing evaluations and post-treatment videofluoroscopic swallowing studies (VFSS) from 2007 to 2010. Patients with abnormal penetration aspiration scores (PAS>2) served as the study population and patients with normal PAS scores (≤ 2) served as the control cohort. Three suprahyoid muscles and two extrinsic tongue muscles were individually delineated and collectively referred to as the FoM muscles. Radiation dose-volume relationships for these muscles were calculated. Univariate logistic regression analysis was used to determine parameters of significance between patients with normal or abnormal PAS scores. A multivariate regression analysis was subsequently performed to isolate the most statistically critical structures associated with abnormal PAS., Results: Univariate analysis resulted in significance/borderline significance of multiple structures associated with abnormal PAS following irradiation. However, when a multivariate model was applied, only the mean dose to the floor of mouth and minimum dose to the geniohyoid were associated with post-radiation abnormal PAS., Conclusions: The dose and volume delivered to the collective FoM muscles may be associated with an increased risk of laryngeal penetration/aspiration to a greater degree than previously recognized organs at risk., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

High-intensity focused ultrasound induces focalized tissue coagulation by increasing the tissue temperature in a tight focal region. Several methods have been proposed to monitor high-intensity focused ultrasound-induced thermal lesions. Currently, ultrasound imaging techniques that are clinically used for monitoring high-intensity focused ultrasound treatment are standard pulse-echo B-mode ultrasound imaging, ultrasound temperature estimation, and elastography-based methods. On the contrary, the efficacy of two-dimensional Nakagami parametric imaging based on the distribution of the ultrasound backscattered signals to quantify properties of soft tissue has recently been evaluated. In this study, ultrasound radio frequency echo signals from ex vivo tissue samples were acquired before and after high-intensity focused ultrasound exposures and then their Nakagami parameter and scaling parameter of Nakagami distribution were estimated. These parameters were used to detect high-intensity focused ultrasound-induced thermal lesions. Also, the effects of changing the acoustic power of the high-intensity focused ultrasound transducer on the Nakagami parameters were studied. The results obtained suggest that the Nakagami distribution's scaling and Nakagami parameters can effectively be used to detect high-intensity focused ultrasound-induced thermal lesions in tissue ex vivo. These parameters can also be used to understand the degree of change in tissue caused by high-intensity focused ultrasound exposures, which could be interpreted as a measure of degree of variability in scatterer concentration in various parts of the high-intensity focused ultrasound lesion.

Lymphatic node chains of the human body are particularly difficult to realistically model in computational human phantoms. In the absence of a lymphatic node model, researchers have used the following surrogate tissues to calculate the radiation dose to the lymphatic nodes: blood vessels, muscle and the combination of the muscle and adipose tissues. In the present work, the authors investigated whether and in which extent the use of different surrogate tissues is appropriate to assess the lymph node dose, using a realistic model of lymphatic nodes that the authors recently reported. Using a Monte Carlo radiation transport method coupled with the adult male hybrid phantom that included the lymph node model, the air kerma-to-absorbed dose conversion coefficients (Gy Gy(-1)) to the lymph nodes and other tissues used as surrogates for external photon beams of 15 discrete energies (0.015-10 MeV) were computed using the following six idealised geometries: anterior-posterior (AP), posterior-anterior (PA), right lateral, left lateral, rotational and isotropic. To validate the results of this study, the lymph node dose calculated here was compared with the dose published by the International Commission on Radiological Protection for the adult male reference phantom. The lymph node dose conversion coefficients with the values calculated for the blood vessels, muscle, adipose tissue and the combination of muscle and adipose tissues were then compared. It was found that muscle was the best estimator for the lymph nodes, with a dose difference averaged across energies >0.08 MeV of <8 % in all irradiation geometries excluding the AP and PA geometries for which the blood vessels were found to be the best estimator. In conclusion, muscle and blood vessels may preferably be used as surrogate tissues in the absence of lymphatic nodes in a given voxel phantom. For energies <0.08 MeV, for which the authors observed a difference of up to 30-fold, an explicit lymph node model may be required to prevent increasing differences with the lymph node dose as the photon energy decreases, though the absolute values of the dose conversion coefficients are smaller than at higher energy.

This study was framed to investigate the (60)Co gamma radiation induced morphological and histological variations in freshwater prawn Macrobrachium rosenbergii. The LD50 value of (60)Co gamma irradiated M. rosenbergii observed (by probit analysis) at 30 Gy. Prawns were irradiated to four different dose levels (3 mGy, 30 mGy, 300 mGy and 3,000 mGy) using Theratron Phoenix TeleCobalt Unit [P-33] and one control group (without irradiation) maintained separately. Irradiated groups exhibited several morphological variations such as discoloration; damaged rostrum; opaque coloration in cephalothorax; black bands and dot formation in abdomen; deformed uropods and telson in tail regions when compared with control group. The Hepato Somatic Index reflected the severity of radiation on hepatopancreas. Histological variations in gills, hepatopancreas and muscles of irradiated groups were observed. In gills, structural changes such as swollen and fused lamellae, abnormal gill tips, hyperplasic, necrotic and clavate-globate lamellae were observed in gamma irradiated prawns. Accumulation of hemocytes in hemocoelic space, interstitial sinuses filled with abnormal infiltrated hemocytes, the tubular epithelium with ruptured basal laminae, abnormal and coagulated lumen, necrotic tubules, thickened basal laminae, tissue debris, necrotic hepatocytes were observed in irradiated prawn hepatopancreas. In muscle, shrinkage of muscular fiber and necrotic musculature were observed in irradiated prawns. These structural alterations of the organs it is felt could affect the vital physiological functions such as respiration, osmotic and ionic regulation in gills and muscles; absorption, storage and secretion of the hepatopancreas which in turn could adversely affect the growth and survival of freshwater prawn M. rosenbergii., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Purpose: Describing the implementation of nuclear reactions in the extension of the Monte Carlo code (MC) PENELOPE to protons (PENH) and benchmarking with Geant4., Methods: PENH is based on mixed-simulation mechanics for both elastic and inelastic electromagnetic collisions (EM). The adopted differential cross sections for EM elastic collisions are calculated using the eikonal approximation with the Dirac-Hartree-Fock-Slater atomic potential. Cross sections for EM inelastic collisions are computed within the relativistic Born approximation, using the Sternheimer-Liljequist model of the generalized oscillator strength. Nuclear elastic and inelastic collisions were simulated using explicitly the scattering analysis interactive dialin database for (1)H and ICRU 63 data for (12)C, (14)N, (16)O, (31)P, and (40)Ca. Secondary protons, alphas, and deuterons were all simulated as protons, with the energy adapted to ensure consistent range. Prompt gamma emission can also be simulated upon user request. Simulations were performed in a water phantom with nuclear interactions switched off or on and integral depth-dose distributions were compared. Binary-cascade and precompound models were used for Geant4. Initial energies of 100 and 250 MeV were considered. For cases with no nuclear interactions simulated, additional simulations in a water phantom with tight resolution (1 mm in all directions) were performed with FLUKA. Finally, integral depth-dose distributions for a 250 MeV energy were computed with Geant4 and PENH in a homogeneous phantom with, first, ICRU striated muscle and, second, ICRU compact bone., Results: For simulations with EM collisions only, integral depth-dose distributions were within 1%/1 mm for doses higher than 10% of the Bragg-peak dose. For central-axis depth-dose and lateral profiles in a phantom with tight resolution, there are significant deviations between Geant4 and PENH (up to 60%/1 cm for depth-dose distributions). The agreement is much better with FLUKA, with deviations within 3%/3 mm. When nuclear interactions were turned on, agreement (within 6% before the Bragg-peak) between PENH and Geant4 was consistent with uncertainties on nuclear models and cross sections, whatever the material simulated (water, muscle, or bone)., Conclusions: A detailed and flexible description of nuclear reactions has been implemented in the PENH extension of PENELOPE to protons, which utilizes a mixed-simulation scheme for both elastic and inelastic EM collisions, analogous to the well-established algorithm for electrons/positrons. PENH is compatible with all current main programs that use PENELOPE as the MC engine. The nuclear model of PENH is realistic enough to give dose distributions in fair agreement with those computed by Geant4.

The effect of transgenerational exposure to low dose rate (2.4 and 21 mGy/day) gamma irradiation on the yield of DNA double-strand breaks and oxidized guanine (8-hydroxyguanine) has been studied in the muscle and liver tissue of a model organism, the Japanese medaka fish. We found the level of unrepaired 8-hydroxyguanine in muscle tissue increased nonlinearly over four generations and the pattern of this change depended on the radiation dose rate, suggesting that our treatment protocols initiated genomic instability and an adaptive response as the generations progressed. The yield of unrepaired double-strand breaks did not vary significantly among successive generations in muscle tissue in contrast to liver tissue in which it varied in a nonlinear manner. The 8-hydroxyguanine and DSB radiation yields were significantly higher at 2.4 mGy/day than at 21 mGy/day in both muscle and liver tissue in all generations. These data are consistent with the hypothesis of a threshold for radiation-induced activation of DNA repair systems below which tissue levels of DNA repair enzymes remain unchanged, leading to the accumulation of unrepaired damage at very low doses and dose rates.

Background and Objectives: Radiofrequency (RF) energy exposure is a popular non-invasive method for generating heat within cutaneous and subcutaneous tissues. Subcutaneous fat consists of fine collagen fibrous septa meshed with clusters of adipocytes having distinct structural, electrical and thermal properties that affect the distribution and deposition of RF energy. The objectives of this work are to (i) determine the electric and thermal effects of the fibrous septa in the RF heating; (ii) investigate the RF heating of individual fat lobules enclosed by fibrous septa; and, (iii) discuss the clinical implications., Methods and Results: We used the finite element method to model the two-dimensional, time-dependent, electro-thermal response of a three-layer tissue (skin, subcutaneous fat, and muscle). We considered two different configurations of subcutaneous fat tissue: a homogenous layer of fat only and a honeycomb-like layer of fat with septa. Architecture of the fibrous septa was anatomically accurate, constructed from sagittal images from human micro-MRI. For a large electrode applied to the skin surface, results show that the absorbed electric power density is greater in some septa than in the surrounding fat lobules, favoring the flux of electric current density. Fibers aligned parallel to the electric field have higher electric flux and, consequently, absorb more power. Heat transfer from the septa occurs over time during and after RF energy delivery. There is a greater temperature rise in fat with fibrous septa., Conclusions: The presence of septa affects the local distribution of the static electric field, facilitates the flux of electric current and enhances the bulk electric power absorption of the subcutaneous fat layer. Fibrous septa aligned with the local electric field have higher absorbed power density than septa oriented perpendicular to the electric field. Individual fat lobules gain heat instantly by local power absorption and, eventually, by diffusion from the surrounding septa., (Copyright © 2013 Wiley Periodicals, Inc.)

Special properties of laser light have led to its usefulness in many applications in therapy. Excitation of endogenous chromophores in biotissues and generation of free radicals could be involved in its biological effects. DNA lesions induced by free radicals are repaired by base excision repair pathway. In this work, we evaluated the expression of APE1 and OGG1 genes related to repair of DNA lesions induced by free radicals. Skin and muscle tissues of Wistar rats were exposed to low-intensity infrared laser at different fluences and frequencies. After laser exposition of 1 and 24 h, tissue samples were withdrawn for total RNA extraction, cDNA synthesis, and evaluation of APE1 and OGG1 gene expression by quantitative polymerase chain reaction. Data obtained show that laser radiation alters the expression of APE1 and OGG1 mRNA differently in skin and muscle tissues of Wistar rats depending of the fluence, frequency, and time after exposure. Our study suggests that low-intensity infrared laser affects expression of genes involved in repair of DNA lesions by base excision repair pathway.

Dielectric properties are the most important parameters determining energy deposition when biological tissues are exposed to radio frequency and microwave fields. Energy absorption is determined by the specific absorption rate (SAR). SAR distributions can be computed accurately only if the complex relative permittivity of the target tissue is known to a sufficiently high accuracy, and currently there is a lack of data on the dielectric properties of biological tissues at high frequencies. In this study, tissue dielectric properties are measured using an open-ended coaxial probe technique from 500 MHz up to 40 GHz. We present dielectric data for ex vivo bovine and porcine muscle and liver tissues at 37 °C. One-pole Cole-Cole model is used to fit the measured data as a function of frequency and the dispersion parameters are presented. This data is supported by an accurate study on reference liquids such as methanol and ethanediol.