Evaluation of two-dimensional total bone uptake (2D-TBU) and bone scan index (BSI) extracted from active bone metastatic burden on the bone scintigraphy in patients with radium-223 treatment.

OBJECTIVE: Radium-223 is a first alpha-emitting radionuclide treatment for metastatic castration-resistant prostate cancer (mCRPC) patients with bone metastases. Although the spread-based bone scan index (BSI) and novel index of the intensity-based two-dimensional total bone uptake (2D-TBU) from bone scintigraphy may provide useful input in radium-223 treatment, they have not been evaluated in detail yet. This study aimed to fill this gap by evaluating BSI and 2D-TBU in patients treated with radium-223. METHODS: Twenty-seven Japanese patients with mCRPC treated with radium-223 were retrospectively analyzed. The patients were evaluated via blood tests and bone scans at baseline and 3 cycles intervals of treatment. BSI and 2D-TBU were analyzed via VSBONE BSI in terms of correlations, response to radium-223 treatment, association with treatment completion, and the Kaplan-Meier survival analysis was performed. RESULTS: Nineteen patients (70.4%) completed six cycles of radium-223 treatment, whereas eight patients (29.6%) did not complete the treatment regimen. A significant difference in baseline BSI and 2D-TBU was observed between these groups of patients. Both BSI and 2D-TBU were highly correlated (r = 0.96, p < 0.001). Univariate analysis showed an association between radium-223 completion in median BSI and 2D-TBU values (p = 0.015) and completion percentage differences (91.7% vs. 45.5%; p = 0.027). The Kaplan-Meier product limit estimator showed that the median overall survival was 25.2 months (95% CI 14.0-33.6 months) in the completion group and 7.5 months (95% CI 3.3-14.2 months) in the without completion group (p < 0.001). The overall survival based on median cutoff levels showed a significant difference in 2D-TBU (p = 0.007), but not in BSI (p = 0.15). CONCLUSIONS: The 2D-TBU may offer advantages over BSI in classifying patients towards radium-223 treatment based on the degree of progression of bone metastases. This study supports the importance of preliminary assessment of bone metastasis status using BSI and 2D-TBU extracted from VSBONE BSI for radium-223 treatment decisions.

Stochastic parametric skeletal dosimetry model for humans: General approach and application to active marrow exposure from bone-seeking beta-particle emitters.

The objective of this study is to develop a skeleton model for assessing active marrow dose from bone-seeking beta-emitting radionuclides. This article explains the modeling methodology which accounts for individual variability of the macro- and microstructure of bone tissue. Bone sites with active hematopoiesis are assessed by dividing them into small segments described by simple geometric shapes. Spongiosa, which fills the segments, is modeled as an isotropic three-dimensional grid (framework) of rod-like trabeculae that "run through" the bone marrow. Randomized multiple framework deformations are simulated by changing the positions of the grid nodes and the thickness of the rods. Model grid parameters are selected in accordance with the parameters of spongiosa microstructures taken from the published papers. Stochastic modeling of radiation transport in heterogeneous media simulating the distribution of bone tissue and marrow in each of the segments is performed by Monte Carlo methods. Model output for the human femur at different ages is provided as an example. The uncertainty of dosimetric characteristics associated with individual variability of bone structure was evaluated. An advantage of this methodology for the calculation of doses absorbed in the marrow from bone-seeking radionuclides is that it does not require additional studies of autopsy material. The biokinetic model results will be used in the future to calculate individual doses to members of a cohort exposed to 89,90Sr from liquid radioactive waste discharged to the Techa River by the Mayak Production Association in 1949-1956. Further study of these unique cohorts provides an opportunity to gain more in-depth knowledge about the effects of chronic radiation on the hematopoietic system. In addition, the proposed model can be used to assess the doses to active marrow under any other scenarios of 90Sr and 89Sr intake to humans.

Correlation between the γ passing rates of IMRT plans and the volumes of air cavities and bony structures in head and neck cancer.

BACKGROUND: Both patient-specific dose recalculation and γ passing rate analysis are important for the quality assurance (QA) of intensity modulated radiotherapy (IMRT) plans. The aim of this study was to analyse the correlation between the γ passing rates and the volumes of air cavities (Vair) and bony structures (Vbone) in target volume of head and neck cancer. METHODS: Twenty nasopharyngeal carcinoma and twenty nasal natural killer T-cell lymphoma patients were enrolled in this study. Nine-field sliding window IMRT plans were produced and the dose distributions were calculated by anisotropic analytical algorithm (AAA), Acuros XB algorithm (AXB) and SciMoCa based on the Monte Carlo (MC) technique. The dose distributions and γ passing rates of the targets, organs at risk, air cavities and bony structures were compared among the different algorithms. RESULTS: The γ values obtained with AAA and AXB were 95.6 ± 1.9% and 96.2 ± 1.7%, respectively, with 3%/2 mm criteria (p > 0.05). There were significant differences (p < 0.05) in the γ values between AAA and AXB in the air cavities (86.6 ± 9.4% vs. 98.0 ± 1.7%) and bony structures (82.7 ± 13.5% vs. 99.0 ± 1.7%). Using AAA, the γ values were proportional to the natural logarithm of Vair (R2 = 0.674) and inversely proportional to the natural logarithm of Vbone (R2 = 0.816). When the Vair in the targets was smaller than approximately 80 cc or the Vbone in the targets was larger than approximately 6 cc, the γ values of AAA were below 95%. Using AXB, no significant relationship was found between the γ values and Vair or Vbone. CONCLUSION: In clinical head and neck IMRT QA, greater attention should be paid to the effect of Vair and Vbone in the targets on the γ passing rates when using different dose calculation algorithms.

FLASH Proton Radiotherapy Spares Normal Epithelial and Mesenchymal Tissues While Preserving Sarcoma Response.

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 TGFß1 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.

Amelioration of bone fragility by pulsed electromagnetic fields in type 2 diabetic KK-Ay mice involving Wnt/ß-catenin signaling.

Type 2 diabetes mellitus (T2DM) results in compromised bone microstructure and quality, and subsequently increased risks of fractures. However, it still lacks safe and effective approaches resisting T2DM bone fragility. Pulsed electromagnetic fields (PEMFs) exposure has proven to be effective in accelerating fracture healing and attenuating osteopenia/osteoporosis induced by estrogen deficiency. Nevertheless, whether and how PEMFs resist T2DM-associated bone deterioration remain not fully identified. The KK-Ay mouse was used as the T2DM model. We found that PEMF stimulation with 2 h/day for 8 wk remarkably improved trabecular bone microarchitecture, decreased cortical bone porosity, and promoted trabecular and cortical bone material properties in KK-Ay mice. PEMF stimulated bone formation in KK-Ay mice, as evidenced by increased serum levels of bone formation (osteocalcin and P1NP), enhanced bone formation rate, and increased osteoblast number. PEMF significantly suppressed osteocytic apoptosis and sclerostin expression in KK-Ay mice. PEMF exerted beneficial effects on osteoblast- and osteocyte-related gene expression in the skeleton of KK-Ay mice. Nevertheless, PEMF exerted no effect on serum biomarkers of bone resorption (TRAcP5b and CTX-1), osteoclast number, or osteoclast-specific gene expression (TRAP and cathepsin K). PEMF upregulated gene expression of canonical Wnt ligands (including Wnt1, Wnt3a, and Wnt10b), but not noncanonical Wnt5a. PEMF also upregulated skeletal protein expression of downstream p-GSK-3ß and ß-catenin in KK-Ay mice. Moreover, PEMF-induced improvement in bone microstructure, mechanical strength, and bone formation in KK-Ay mice was abolished after intragastric administration with the Wnt antagonist ETC-159. Together, our results suggest that PEMF can improve bone microarchitecture and quality by enhancing the biological activities of osteoblasts and osteocytes, which are associated with the activation of the Wnt/ß-catenin signaling pathway. PEMF might become an effective countermeasure against T2DM-induced bone deterioration.NEW & NOTEWORTHY PEMF improved trabecular bone microarchitecture and suppressed cortical bone porosity in T2DM KK-Ay mice. It attenuated T2DM-induced detrimental consequence on trabecular and cortical bone material properties. PEMF resisted bone deterioration in KK-Ay mice by enhancing osteoblast-mediated bone formation. PEMF also significantly suppressed osteocytic apoptosis and sclerostin expression in KK-Ay mice. The therapeutic potential of PEMF on T2DM-induced bone deterioration was associated with the activation of Wnt/ß-catenin signaling.

Evaluation of high-linearity bone radiation detectors exposed to gamma-rays via FTIR measurements.

In radiation physics, the study of new alternative dosimeters is of interest to the growing branch of dosimetric characterization for radiotherapy applications. The goal of this work was to expose bone samples to high doses and evaluate their linearity response to gamma rays. The Fourier Transform Infrared (FTIR) spectrophotometry technique was employed as the evaluation technique, and based on the spectrophotometry absorbance profiles the linearity was assessed based on the following methods: Area Under the Curve (AUC), Wavenumber Method (WM), Partial Component Regression (PCR) and Partial Least-Square Regression (PLSR) methods. The bone samples were irradiated with absorbed doses of 10 Gy up to 500 Gy using a 60Co Gamma Cell-220 system. The results showed, for the calibration curves of the system, adequate linearity on all methods. In conclusion, the results indicate a good linear response and therefore an interesting potential radiation detector.

Impact of High-Dose-Rate and Low-Dose-Rate Brachytherapy Boost on Toxicity, Functional and Cancer Outcomes in Patients Receiving External Beam Radiation Therapy for Prostate Cancer: A National Population-Based Study.

PURPOSE: External beam radiation therapy (EBRT) with brachytherapy boost reduces cancer recurrence in patients with prostate cancer compared with EBRT monotherapy. However, randomized controlled trials or large-scale observational studies have not compared brachytherapy boost types directly. METHODS AND MATERIALS: This observational cohort study used linked national cancer registry data, radiation therapy data, administrative hospital data, and mortality records of 54,642 patients with intermediate-risk, high-risk, and locally advanced prostate cancer in England. The records of 11,676 patients were also linked to results from a national patient survey collected at least 18 months after diagnosis. Competing risk regression analyses were used to compare gastrointestinal (GI) toxicity, genitourinary (GU) toxicity, skeletal-related events (SRE), and prostate cancer-specific mortality (PCSM) at 5 years with adjustment for patient and tumor characteristics. Linear regression was used to compare Expanded Prostate Cancer Index Composite 26-item version domain scores (scale, 0-100, with higher scores indicating better function). RESULTS: Five-year GI toxicity was significantly increased after low-dose-rate brachytherapy boost (LDR-BB) (32.3%) compared with high-dose-rate brachytherapy boost (HDR-BB) (16.7%) or EBRT monotherapy (18.7%). Five-year GU toxicity was significantly increased after both LDR-BB (15.8%) and HDR-BB (16.6%), compared with EBRT monotherapy (10.4%). These toxicity patterns were matched by the mean patient-reported bowel function scores (LDR-BB, 77.3; HDR-BB, 85.8; EBRT monotherapy, 84.4) and the mean patient-reported urinary obstruction/irritation function scores (LDR-BB, 72.2; HDR-BB, 78.9; EBRT monotherapy, 83.8). Five-year incidences of SREs and PCSM were significantly lower after HDR-BB (2.4% and 2.7%, respectively) compared with EBRT monotherapy (2.8% and 3.5%, respectively). CONCLUSIONS: Compared with EBRT monotherapy, LDR-BB has worse GI and GU toxicity and HDR-BB has worse GU toxicity. HDR-BB has a lower incidence of SREs and PCSM than EBRT monotherapy.

DTPA-Coated Liposomes as a New Delivery Vehicle for Plutonium Decorporation.

Administration of diethylenetriaminepentaacetic acid (DTPA) is the treatment approach used to promote the decorporation of internalized plutonium. Here we evaluated the efficacy of PEGylated liposomes coated with DTPA, primarily designed to prevent enhanced plutonium accumulation in bones, compared to marketed nonliposomal DTPA and liposomes encapsulating DTPA. The comparative effects were examined in terms of reduction of activity in tissues of plutonium-injected rats. The prompt treatment with DTPA-coated liposomes elicited an even greater efficacy than that with liposome-encapsulated DTPA in limiting skeletal plutonium. This advantage, undoubtedly due to the anchorage of DTPA to the outer layer of liposomes, is discussed, as well as the reason for the loss of this superiority at delayed times after contamination. Plutonium complexed with DTPA-coated liposomes in extracellular compartments was partly diverted into the liver and the spleen. These complexes and those directly formed inside hepatic and splenic cells appeared to be degraded, then released from cells at extremely slow rates. This transitory accumulation of activity, which could not be counteracted by combining both liposomal forms, entailed an underestimation of the efficacy of DTPA-coated liposomes on soft tissue plutonium until total elimination probably more than one month after treatment. DTPA-coated liposomes may provide the best delivery vehicle of DTPA for preventing plutonium deposition in tissues, especially in bone where nuclides become nearly impossible to remove once fixed. Additional development efforts are needed to limit the diversion or to accelerate cell release of plutonium bound to DTPA-coated liposomes, using a labile bond for DTPA attachment.

Gamma-ray buildup factor and radiation absorbed dose enhancement at tissue-bone interfaces.

During superficial radiotherapy, and for cases where bony structures lie relatively close to the surface behind the tissue region being treated, perturbations to delivered dose are expected due to the change in tissue scattering conditions and the value of buildup factor near the tissue/bone interface. The absorbed dose distribution within bone, muscle, and muscle-bone-muscle interfaces was estimated for photons within the energy range 0.05 to 1.333 MeV. The energy absorption buildup factor is computed using the (GP) fitting method for a geometry of adjacent layers within a multilayer tissue matrix where a thick slab of solid bone is located in-between slabs of muscles of the same thickness. It was observed that dose enhancement was limited only to a few millimeters close to the interface. Also, variations in dose at the interface were found significant only for low photon energies and relatively insignificant at photon energies higher than 0.06 MeV.

The effects of chronic diseases on plutonium urinary excretion in former workers of the Mayak Production Association.

The radiochemical analysis of plutonium activity in urine is the main method for indirect estimation of doses of internal exposure from plutonium incorporation in professional workers. It was previously shown that late-in-life acute diseases, particularly those that affect the liver, can promote accelerated rates of release of plutonium from the liver with enhanced excretion rates. This initial study examines the relationships of some chronic diseases on plutonium excretion as well as the terminal relative distribution of plutonium between the liver and skeleton. Fourteen cases from former workers at the Mayak Production Association (Mayak PA) who provided from 4-9 urine plutonium bioassays for plutonium, had an autopsy conducted after death, and had sufficient clinical records to document their health status were used in this study. Enhanced plutonium excretion was associated with more serious chronic diseases, including cardiovascular diseases and other diseases that involved the liver. These chronic diseases were also associated with relatively less plutonium found in the liver relative to the skeleton determined by analyses conducted after autopsy. These data further document health conditions that affect plutonium biokinetics and organ deposition and retention patterns and suggest that health status should be considered when conducting plutonium bioassays as these may alter subsequent dosimetry and risk models.

Overall survival in mCPRC patients treated with Radium-223 in association with bone health agents: a national multicenter study.

PURPOSE: Radium-223 has demonstrated efficacy in improving overall survival (OS) and in delaying symptomatic skeletal-related events (SREs). Bone Health Agents (BHA), i.e. RANK ligand inhibitor (Denosumab) and bisphosphonate such as zoledronic acid, are indicated to prevent SREs without a clear survival benefit. SREs on patient health have a high impact and it is, therefore, important to consider the role of new therapies with BHA to better understand the involvement of combination therapy. The primary aim of this multicentric study is to assess OS in mCRPC patients treated with Radium-223 in combination with BHA. MATERIALS AND METHODS: 430 consecutive patients treated with Radium-223 alone or in combination with BHA, affected by mCRPC, from January 2015 to July 2019 in six Italian Nuclear Medicine Units, were included. Furthermore, data were collected at baseline, after every Radium-223 administration, and during follow-up, at 3 and 6 months and 1 year after the 6th cycle. Clinical data have been evaluated before starting treatment with Radium-223 and at the end of treatment and/or at progression. Patients who received target bone therapy with BHA before Radium-223 treatment together with patients who did not receive this therapy at all (NO BHA GROUP), were compared to patients treated with concomitant Radium-223 and BHA (BHA GROUP). RESULTS: In univariate models (p < .05) several clinical aspects have an impact on OS: concomitant BHA (p = .018), BMI (p .001), ECOG PS (p = .000), Baseline Hb (p = .000), Baseline PSA (p = .000), Baseline tALP (p = .000), Baseline LDH (p = .000), and Baseline neutrophils (p = .009). Baseline Hb, Baseline tALP, and Baseline LDH have been confirmed as statistically significant parameters in multivariate models. Indeed, concomitant BHA has not a significant impact on OS (p = .244) in multivariate models. CONCLUSIONS: At univariate analysis, our data showed that NO BHA GROUP and BHA GROUP differ in OS by 7 months (95%CI: (1-16.4), p = .02). This is not confirmed at multivariate analysis where after adjusting for other baseline factors, BHA is not significant anymore. This is clearly explained as bias by indication: patients with the same levels of tALP, Hb, and LDH receiving or not receiving BHA are expected to have a similar survival. Our results support and confirm the role of Radium-223 therapy on OS and, furthermore, appear to confirm that BHA treatment has not a survival benefit.

NIR light-assisted phototherapies for bone-related diseases and bone tissue regeneration: A systematic review.

Recently, the rapid development of biomaterials has induced great interest in the precisely targeted treatment of bone-related diseases, including bone cancers, infections, and inflammation. Realizing noninvasive therapeutic effects, as well as improving bone tissue regeneration, is essential for the success of bone­related disease therapies. In recent years, researchers have focused on the development of stimuli-responsive strategies to treat bone-related diseases and to realize bone regeneration. Among the various external stimuli for targeted therapy, near infrared (NIR) light has attracted considerable interests due to its high tissue penetration capacity, minimal damage toward normal tissues, and easy remote control properties. The main objective of this systematic review was to reveal the current applications of NIR light-assisted phototherapy for bone-related disease treatment and bone tissue regeneration. Database collection was completed by June 1, 2020, and a total of 81 relevant studies were finally included. We outlined the various therapeutic applications of photothermal, photodynamic and photobiomodulation effects under NIR light irradiation for bone­related disease treatment and bone regeneration, based on the retrieved literatures. In addition, the advantages and promising applications of NIR light-responsive drug delivery systems for spatiotemporal-controlled therapy were summarized. These findings have revealed that NIR light-assisted phototherapy plays an important role in bone-related disease treatment and bone tissue regeneration, with significant promise for further biomedical and clinical applications.

Attempts to Target Staphylococcus aureus Induced Osteomyelitis Bone Lesions in a Juvenile Pig Model by Using Radiotracers.

Background [18F]FDG Positron Emission Tomography cannot differentiate between sterile inflammation and infection. Therefore, we, aimed to develop more specific radiotracers fitted for differentiation between sterile and septic infection to improve the diagnostic accuracy. Consequently, the clinicians can refine the treatment of, for example, prosthesis-related infection. METHODS: We examined different target points; Staphylococcus aureus biofilm (68Ga-labeled DOTA-K-A9 and DOTA-GSGK-A11), bone remodeling ([18F]NaF), bacterial cell membranes ([68Ga]Ga-Ubiquicidin), and leukocyte trafficking ([68Ga]Ga-DOTA-Siglec-9). We compared them to the well-known glucose metabolism marker [18F]FDG, in a well-established juvenile S. aureus induced osteomyelitis (OM) pig model. RESULTS: [18F]FDG accumulated in the OM lesions seven days after bacterial inoculation, but disappointingly we were not able to identify any tracer accumulation in OM with any of the supposedly more specific tracers. CONCLUSION: These negative results are, however, relevant to report as they may save other research groups from conducting the same animal experiments and provide a platform for developing and evaluating other new potential tracers or protocol instead.

Wound Healing and Cell Dynamics Including Mesenchymal and Dental Pulp Stem Cells Induced by Photobiomodulation Therapy: An Example of Socket-Preserving Effects after Tooth Extraction in Rats and a Literature Review.

High-intensity laser therapy (HILT) and photobiomodulation therapy (PBMT) are two types of laser treatment. According to recent clinical reports, PBMT promotes wound healing after trauma or surgery. In addition, basic research has revealed that cell differentiation, proliferation, and activity and subsequent tissue activation and wound healing can be promoted. However, many points remain unclear regarding the mechanisms for wound healing induced by PBMT. Therefore, in this review, we present an example from our study of HILT and PBMT irradiation of tooth extraction wounds using two types of lasers with different characteristics (diode laser and carbon dioxide laser). Then, the effects of PBMT on the wound healing of bone tissues are reviewed from histological, biochemical, and cytological perspectives on the basis of our own study of the extraction socket as well as studies by other researchers. Furthermore, we consider the feasibility of treatment in which PBMT irradiation is applied to stem cells including dental pulp stem cells, the theme of this Special Issue, and we discuss research that has been reported on its effect.

Biomechanical and morphological changes produced by ionizing radiation on bone tissue surrounding dental implant.

OBJECTIVE: This study analyzed the effect of ionizing radiation on bone microarchitecture and biomechanical properties in the bone tissue surrounding a dental implant. METHODOLOGY: Twenty rabbits received three dental morse taper junction implants: one in the left tibia and two in the right tibia. The animals were randomized into two groups: the nonirradiated group (control group) and the irradiated group, which received 30 Gy in a single dose 2 weeks after the implant procedure. Four weeks after the implant procedure, the animals were sacrificed, and the implant/bone specimens were used for each experiment. The specimens (n=10) of the right tibia were examined by microcomputed tomography to measure the cortical volume (CtV, mm3), cortical thickness (CtTh, mm) and porosity (CtPo, %). The other specimens (n=10) were examined by dynamic indentation to measure the elastic modulus (E, GPa) and Vickers hardness (VHN, N/mm2) in the bone. The specimens of the left tibia (n=10) were subjected to pull-out tests to calculate the failure load (N), displacement (mm) up to the failure point and interface stiffness (N/mm). In the irradiated group, two measurements were performed: close, at 1 mm surrounding the implant surface, and distant, at 2.5 mm from the external limit of the first measurement. Data were analyzed using one-way ANOVA, Tukey's test and Student's t-test (α=0.05). RESULTS: The irradiated bone closer to the implant surface had lower elastic modulus (E), Vickers hardness (VHN), Ct.Th, and Ct.V values and a higher Ct.Po value than the bone distant to the implant (P<0.04). The irradiated bone that was distant from the implant surface had lower E, VHN, and Ct.Th values and a higher Ct.Po value than the nonirradiated bone (P<0.04). The nonirradiated bone had higher failure loads, displacements and stiffness values than the irradiated bone (P<0.02). CONCLUSION: Ionizing radiation in dental implants resulted in negative effects on the microarchitecture and biomechanical properties of bone tissue, mainly near the surface of the implant.

Examination of the effect of combined use of Er:YAG laser irradiation and mechanical force loading on bone metabolism using primary human gingival fibroblasts.

Prolonged treatment and painful tooth movement are major problems for patients undergoing orthodontic treatment. Accelerating the movement of teeth leads to shortening of the treatment period, so various studies on the movement of teeth have been conducted in the field of orthodontics. In previous studies, we performed a fiber incision-like fiberotomy using an Er:YAG laser in rats and confirmed acceleration of tooth movement. Therefore, in this study, the effect of Er:YAG laser irradiation on human gingival fibroblasts was investigated in vitro. Human gingival fibroblasts (2.0 × 105 cells) were seeded in a 6-well plate and reached 80% confluence 24 h later. A control group not undergoing any irradiation and 3 groups undergoing laser irradiation at 0.6 W, 1.0 W, and 1.2 W were investigated. Laser irradiation was performed 24 h after cell seeding. The cells were then recovered 24 h later, and the cyclooxygenase-2 (COX-2), interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), bone morphogenetic protein-2 (BMP-2), and BMP-4 genes were confirmed by PCR. In addition, a control group not undergoing any procedures, a group undergoing only Er:YAG laser irradiation, a group undergoing only centrifugal loading, and a group undergoing both Er:YAG laser irradiation and centrifugal force loading were investigated. After 24 h, cells were collected and PCR was performed. Twenty-four hours after laser irradiation, gene expressions were examined by quantitative RT-PCR, which showed that the gene expressions of COX-2, IL-1ß, TNF-α, BMP-2, and BMP-4 increased depending on the amount of irradiation energy, with the largest value at 1.2 W. Gene expressions of COX-2, IL-1ß, TNF-α, BMP-2, and BMP-4 were significantly higher in the laser with centrifugal load group than in the load group. These results suggest that genes related to bone metabolism are activated in human gingival fibroblasts when mechanical stimulation and laser irradiation are combined. This helps to elucidate the effects of Er:YAG laser irradiation during tooth movement.

Effectiveness of Pulsed Electromagnetic Fields on Bone Healing: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

The effect of pulsed electromagnetic field (PEMF) on bone healing is still uncertain and it has not been established as a standardized treatment. The aim of this systematic review and meta-analysis is to evaluate the effect of PEMF on bone healing in patients with fracture. We searched CNKI, Wan Fang, VIP, EMbase, PubMed, CENTRAL, Web of Science, Physiotherapy Evidence Database, and Open Grey websites for randomized controlled trials (published before July 2019 in English or Chinese) comparing any form of PEMF to sham. Reference lists were also searched. Related data were extracted by two investigators independently. The bias risk of the articles and the evidence strength of the outcomes were evaluated. Twenty-two studies were eligible and included in our analysis (n = 1,468 participants). The pooled results of 14 studies (n = 1,131 participants) demonstrated that healing rate in PEMF group was 79.7% (443/556), and that in the control group was 64.3% (370/575). PEMF increased healing rate (RR = 1.22; 95% confidence interval [CI] = 1.10-1.35; I2 = 48%) by the Mantel-Haenszel analysis, relieved pain (standardized mean difference (SMD) = -0.49; 95% CI = -0.88 to -0.10; I2 = 60%) by the inverse variance analysis, and accelerated healing time (SMD = -1.01; 95% CI = -2.01 to -0.00; I2 = 90%) by the inverse variance analysis. Moderate quality evidence suggested that PEMF increased healing rate and relieved pain of fracture, and very low-quality evidence showed that PEMF accelerated healing time. Larger and higher quality randomized controlled trials and pre-clinical studies of optimal frequency, amplitude, and duration parameters are needed. © 2020 Bioelectromagnetics Society.

Monte-Carlo-computed dose, kerma and fluence distributions in heterogeneous slab geometries irradiated by small megavoltage photon fields.

Small-field dosimetry is central to the planning and delivery of radiotherapy to patients with cancer. Small-field dosimetry is beset by complex issues, such as loss of charged-particle equilibrium (CPE), source occlusion and electron-scattering effects in low-density tissues. The purpose of the present research is the elucidation of the fundamental physics of small fields through the computation of absorbed dose, kerma and fluence distributions in heterogeneous media using the Monte-Carlo (MC) method. Absorbed dose and kerma were computed using the DOSRZnrc MC user-code for beams with square field sizes ranging from 0.25 × 0.25 to 7 × 7 cm2 (for 6 MV 'full linac' geometry) and 0.25 × 0.25 to 16 × 16 cm2 (for 15 MV 'full linac' geometry). In the bone inhomogeneity the dose increases (vs. homogeneous water) for field sizes <1 × 1 cm2 at 6 MV and ⩽3 × 3 cm2 at 15 MV and decreases (vs. homogeneous water) for field sizes ⩾3 × 3 cm2 at 6 MV and ⩾5 × 5 cm2 at 15 MV. In the lung inhomogeneity there is negligible decrease in dose compared to in uniform water for field sizes >5 × 5 cm2 at 6 MV and ⩾16 × 16 cm2 at 15 MV, consistent with the Fano theorem. The near-unity value of the absorbed-dose to collision-kerma ratio, D/K col, at the centre of the bone and lung slabs in the heterogeneous phantom demonstrates that CPE is achieved in bone for field sizes >1 × 1 cm2 at 6 MV and ⩾5 × 5 cm2 at 15 MV; CPE is achieved in lung at field sizes >5 × 5 cm2 at 6 MV and ⩾16 × 16 cm2 at 15 MV. Electron-fluence perturbation factors for the 0.25 × 0.25 cm2 field were 1.231 and 1.403 for bone-to-water and 0.454 and 0.333 for lung-to-water at 6 and 15 MV, respectively. For field sizes large enough for quasi-CPE, the MC-derived dose-perturbation factors, lung-to-water, [Formula: see text] were close to unity; electron-fluence perturbation factors, lung-to-water, [Formula: see text] were ∼1.0, consistent with the Fano theorem. At 15 MV in the lung inhomogeneity the magnitude and also the 'shape' of the primary electron-fluence spectrum differ significantly from that in water. Beam penumbrae relative to water are narrower in the bone inhomogeneity and broader in the lung inhomogeneity for all field sizes.

A new registration algorithm of electronic portal imaging devices images based on the automatic detection of bone edges during radiotherapy.

The precision and efficiency of the registration of megavolt-level electronic portal imaging devices (EPID) images with the naked eye in the orthogonal window are reduced. This study aims to develop a new registration algorithm with enhanced accuracy and efficiency. Ten setup errors with different translation and rotation were simulated with the phantom. For each error, one set of simulated computer tomography images and EPID images were acquired and registered with the traditional and the new method. The traditional method was performed by two senior physicists with the Varian Offline Review software. The new method is basing on the comparison of the precise contours of the same bone structure in the digital reconstruction radiography images and the EPID images, and the contours were fitted with an automatic edge detection algorithm based on gradient images. The average error of the new method was decreased by 44.44%, 28.33%, 49.09% in the translation of X, Y, and Z axes (The traditional vs. the new: X axes, 0.45 mm vs. 0.25 mm; Y axes, 0.75 mm vs. 0.35 mm; Z axes, 0.55 mm vs. 0.28 mm), 42.86% and 40.48% in the rotation of X and Z axes (The traditional vs. the new: X axes, 0.49° vs. 0.28°; Z axes, 0.42° vs. 0.25°), respectively. The average elapsed time in the new method was reduced by 11.14% (The traditional vs. the new: 44 s vs. 39.1 s). The new registration method has significant advantages of accuracy and efficiency compared with the traditional method.