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Scientific Reports May 2024The current monochromatic beam mode (i.e., uHDR irradiation mode) of the scanned carbon-ion beam lacks a dedicated dose monitor, making the beam control challenging. We...
The current monochromatic beam mode (i.e., uHDR irradiation mode) of the scanned carbon-ion beam lacks a dedicated dose monitor, making the beam control challenging. We developed and characterized a dedicated dose monitor for uHDR-scanned carbon-ion beams. Furthermore, a simple measurable dose rate (dose rate per spot (DR)) was suggested by using the developed dose monitor and experimentally validating quantities relevant to the uHDR scanned carbon-ion beam. A large plane-parallel ionization chamber (IC) with a smaller electrode spacing was used to reduce uHDR recombination effects, and a dedicated operational amplifier was manufactured for the uHDR-scanned carbon-ion beam. The dose linearity of the IC was within ± 1% in the range of 1.8-12.3 Gy. The spatial inhomogeneity of the dose response of the IC was ± 0.38% inside the ± 40-mm detector area, and a systematic deviation of approximately 2% was measured at the edge of the detector. uHDR irradiation with beam scanning was tested and verified for different doses at the corresponding dose rates (in terms of both the average dose rate and DR). We confirmed that the dose monitor can highlight the characteristics (i.e., dose, dose rate, and dose profile) of uHDR-scanned carbon-ion beams at several dose levels in the monochromatic beam mode.
PubMed: 38773165
DOI: 10.1038/s41598-024-62148-2 -
Reproductive Biology Dec 2023Low-dose radiation is generally considered less harmful than high-dose radiation. However, its impact on ovaries remains debated. Since previous reports predominantly...
Low-dose radiation is generally considered less harmful than high-dose radiation. However, its impact on ovaries remains debated. Since previous reports predominantly employed low-dose radiation delivered at a high dose rate on the ovary, the effect of low-dose radiation at a low dose rate on the ovary remains unknown. We investigated the effect of low-dose ionizing radiation delivered at a low dose rate on murine ovaries. Three- and ten-week-old mice were exposed to 0.1 and 0.5 Gy of radiation at a rate of 6 mGy/h and monitored after 3 and 30 days. While neither body weight nor ovarian area showed significant changes, ovarian cells were damaged, showing apoptosis and a decrease in cell proliferation after exposure to 0.1 and 0.5 Gy radiation. Follicle numbers decreased over time in both age groups proportionally to the radiation dose. Younger mice were more susceptible to radiation damage, as evidenced by decreased follicles in 3-week-old mice after 30 days of 0.1 Gy exposure, while 10-week-old mice showed reduced follicles only following 0.5 Gy exposure. Primordial or primary follicles were the most vulnerable to radiation. These findings suggest that even low-dose radiation, delivered at a low dose rate, can adversely affect ovarian function, particularly in the early follicles of younger mice.
Topics: Female; Mice; Animals; Ovarian Follicle; Ovary
PubMed: 37890397
DOI: 10.1016/j.repbio.2023.100817 -
Transplant Immunology Oct 2023The immunogenicity and efficacy of COVID-19 vaccination varied by demographic, including solid organ transplant recipients on immunosuppressive therapy. (Review)
Review
INTRODUCTION
The immunogenicity and efficacy of COVID-19 vaccination varied by demographic, including solid organ transplant recipients on immunosuppressive therapy.
AIM
This purpose of this study is to assess seropositivity and seroconversion in solid-organ transplant recipients before and after third-dose COVID-19 vaccination.
METHODS
This study is a systematic review and meta-analysis performed using PRISMA guidelines. To analyze clinical and cohort studies reporting immunologic response and seroconversion third-dose vaccination, a systematic search was performed using electronic databases (PubMed, Scopus, Cochrane, Directory of Open Access Journal (DOAJ), and Clinicaltrials.gov).
RESULT
There were 18 full-text papers that could be analyzed qualitatively and quantitatively. After the third vaccination, the pooled rate seropositivity was 67.00% (95% CI 59.511; 74.047, I2 = 93.82%), and the pooled rate seroconversion was 52.51% (95% CI 44.03; 60.91, I2 = 92.15%). The pooled rate of seroconversion after the mRNA-based booster was 52.380% (95% CI 40.988; 63.649, I2 = 94.35%), and after the viral-vector-based booster was 42.478% (95% CI 35.222; 49.900, I2 = 0.00%).
CONCLUSION
Based on the analysis of immunologic responses and seroconversion findings, the third-dose vaccination of solid organ transplant recipients is an effective method in establishing better immunity against COVID-19.
PubMed: 37494981
DOI: 10.1016/j.trim.2023.101902 -
Medical Physics Jun 2024Although the FLASH radiotherapy (FLASH) can improve the sparing of organs-at-risk (OAR) via the FLASH effect, it is generally a tradeoff between the physical dose...
BACKGROUND
Although the FLASH radiotherapy (FLASH) can improve the sparing of organs-at-risk (OAR) via the FLASH effect, it is generally a tradeoff between the physical dose coverage and the biological FLASH coverage, for which the concept of FLASH effective dose (FED) is needed to quantify the net improvement of FLASH, compared to the conventional radiotherapy (CONV).
PURPOSE
This work will develop the first-of-its-kind treatment planning method called simultaneous dose and dose rate optimization via dose modifying factor modeling (SDDRO-DMF) for proton FLASH that directly optimizes FED.
METHODS
SDDRO-DMF models and optimizes FED using FLASH dose modifying factor (DMF) models, which can be classified into two categories: (1) the phenomenological model of the FLASH effect, such as the FLASH effectiveness model (FEM); (2) the mechanistic model of the FLASH radiobiology, such as the radiolytic oxygen depletion (ROD) model. The general framework of SDDRO-DMF will be developed, with specific DMF models using FEM and ROD, as a demonstration of general applicability of SDDRO-DMF for proton FLASH via transmission beams (TB) or Bragg peaks (BP) with single-field or multi-field irradiation. The FLASH dose rate is modeled as pencil beam scanning dose rate. The solution algorithm for solving the inverse optimization problem of SDDRO-DMF is based on iterative convex relaxation method.
RESULTS
SDDRO-DMF is validated in comparison with IMPT and a state-of-the-art method called SDDRO, with demonstrated efficacy and improvement for reducing the high dose and the high-dose volume for OAR in terms of FED. For example, in a SBRT lung case of the dose-limiting factor that the max dose of brachial plexus should be no more than 26 Gy, only SDDRO-DMF met this max dose constraint; moreover, SDDRO-DMF completely eliminated the high-dose (V70%) volume to zero for CTV10mm (a high-dose region as a 10 mm ring expansion of CTV).
CONCLUSION
We have proposed a new proton FLASH optimization method called SDDRO-DMF that directly optimizes FED using phenomenological or mechanistic models of DMF, and have demonstrated the efficacy of SDDO-DMF in reducing the high-dose volume or/and the high-dose value for OAR, compared to IMPT and a state-of-the-art method SDDRO.
PubMed: 38873848
DOI: 10.1002/mp.17251 -
Physics in Medicine and Biology Sep 2023Laser plasma-based accelerators (LPAs) of protons can contribute to research of ultra-high dose rate radiobiology as they provide pulse dose rates unprecedented at...
Laser plasma-based accelerators (LPAs) of protons can contribute to research of ultra-high dose rate radiobiology as they provide pulse dose rates unprecedented at medical proton sources. Yet, LPAs pose challenges regarding precise and accurate dosimetry due to the high pulse dose rates, but also due to the sources' lower spectral stability and pulsed operation mode. Formodels, further challenges arise from the necessary small field dosimetry for volumetric dose distributions. For these novel source parameters and intended applications, a dosimetric standard needs to be established.In this work, we present a dosimetry and beam monitoring framework forirradiations of small target volumes with LPA protons, solving aforementioned challenges. The volumetric dose distribution in a sample (mean dose value and lateral/depth dose inhomogeneity) is provided by combining two independent dose measurements using radiochromic films (dose rate-independent) and ionization chambers (dose rate-dependent), respectively. The unique feature of the dosimetric setup is beam monitoring with a transmission time-of-flight spectrometer to quantify spectral fluctuations of the irradiating proton pulses. The resulting changes in the depth dose profile during irradiation of ansample are hence accessible and enable pulse-resolved depth dose correction for each dose measurement.A first successful small animal pilot study using an LPA proton source serves as a testcase for the presented dosimetry approach and proves its performance in a realistic setting.With several facilities worldwide either setting up or already using LPA infrastructure for radiobiological studies with protons, the importance of LPA-adapted dosimetric frameworks as presented in this work is clearly underlined.
Topics: Animals; Protons; Pilot Projects; Radiometry; Lasers; Radiobiology; Film Dosimetry
PubMed: 37579761
DOI: 10.1088/1361-6560/acf025 -
Alternative Therapies in Health and... Nov 2023To explore and analyze the efficacy of luteolin on the proliferation and apoptosis of cerebral glioma and its possible mechanism, providing a theoretical basis for...
OBJECTIVE
To explore and analyze the efficacy of luteolin on the proliferation and apoptosis of cerebral glioma and its possible mechanism, providing a theoretical basis for luteolin in glioma treatment.
METHODS
The cell line of Human cerebral glioma U87 was utilized for our current research. The study group were added with 0, 20, 40, and 80 μmol/L luteolin, respectively. Luteolin's Inhibitory function in the proliferation of U87 cells was detected by CCK-8, the Transwell chamber test was used to measure cell migration and invasion, while flow cytometry was used to assess apoptosis and Western Blot to gauge the expression of JNK/STAT3 pathway proteins.
RESULTS
In comparison with the control group, the intervention of various doses of luteolin could effectively inhibit glioma cell proliferation, the inhibitory rate uplifted remarkably with an increase of dose as well as intervention time (95% CI. 92.160-107.494, P < .05), which presented a significant time and dose dependence. The apoptosis rate of the low-dose, medium-dose, and high-dose categories was higher than that of the comparison group after 2 days of luteolin intervention (P < .05), and the apoptosis rate appeared to increase with the increase in intervention dose (P < .05). After 2 days of luteolin intervention, there were significantly more migratory and invasive cells in 3 categories than that in the control group (P < .05), and the number increased as the luteolin intervention dose was raised (P < .05). Bax and Cyt-c expressions dropped after 2 days of luteolin treatment when compared with the control set (P < .05), and the expression of Bax and Cyt-c fell considerably with increasing luteolin dose. Bcl-2, Caspase-3 and PARP expressions were significantly elevated in comparison to the control group (P < .05), and the increase was more obvious with the rise of the luteolin dose.
CONCLUSION
Luteolin has a good inhibiting function on the proliferation of glioma cells, inhibiting cellular invasion and migration and promoting the apoptosis of glioma cells and the expression of apoptosis-related proteins, which has laid a good foundation for the application of luteolin to treat glioma cells.
PubMed: 37971457
DOI: No ID Found -
Cancers Mar 2024What treatment options are there for patients having uveal melanoma? A randomized, prospective, multi-institutional clinical trial (COMS) showed no difference in... (Review)
Review
What treatment options are there for patients having uveal melanoma? A randomized, prospective, multi-institutional clinical trial (COMS) showed no difference in survival between brachytherapy and enucleation for medium-sized lesions. With the obvious benefit of retaining the eye, brachytherapy has flourished and many different approaches have been developed such as low-dose-rate sources using alternate low-energy photon-emitting radionuclides, different plaque designs and seed-loading techniques, high-dose-rate brachytherapy sources and applicators, and low- and high-dose-rate beta-emitting sources and applicators. There also have been developments of other radiation modalities like external-beam radiotherapy using linear accelerators with high-energy photons, particle accelerators for protons, and gamma stereotactic radiosurgery. This article examines the dosimetric properties, targeting capabilities, and outcomes of these approaches. The several modalities examined herein have differing attributes and it may be that no single approach would be considered optimal for all patients and all lesion characteristics.
PubMed: 38473430
DOI: 10.3390/cancers16051074 -
Applied Radiation and Isotopes :... Aug 2023Multi-facility nuclear sites with research reactors have several environmental area gamma monitors in a network as a part of their surveillance capability. However, the...
Multi-facility nuclear sites with research reactors have several environmental area gamma monitors in a network as a part of their surveillance capability. However, the routine release of low levels of Ar gas from the reactor is prone to interfere with the recorded gamma dose rate and mask the genuine processes being monitored at the network's central control room. As a potential solution, machine learning techniques have been used in this study to autonomously identify and discriminate the genuine processes, viz., the radioactive consignment loading and its movement, at an interim radiopharmaceutical facility located close to a research reactor. To increase the richness of the recorded univariate dose rate time series, several additional features were created. A labelled dataset of process and non-process dose rate sub-sequences or segments was generated by subject matter experts, based on practical knowledge of the facility, and aided by k-means clustering algorithm. The labelled dataset was used to train several supervised classification models and the random forest class of models gave superior performance. The optimised random forest model was able to identify process sub-sequences with a precision of 82.35% and a specificity of 97.11%. The overall balanced accuracy of the model was 91% with a f1 score of 82%. This machine learning approach proved useful to autonomously identify genuine process driven sub-sequences in the univariate dose rate time series. It has an application in reducing the false alarms at exit portal monitors, especially at those sites where there is a potential for external interference in the monitored dose rate.
Topics: Radiopharmaceuticals; Time Factors; Machine Learning; Algorithms; Random Forest
PubMed: 37247508
DOI: 10.1016/j.apradiso.2023.110878 -
Medical Physics Mar 2024Radiotherapy with charged particles at high dose and ultra-high dose rate (uHDR) is a promising technique to further increase the therapeutic index of patient...
BACKGROUND
Radiotherapy with charged particles at high dose and ultra-high dose rate (uHDR) is a promising technique to further increase the therapeutic index of patient treatments. Dose rate is a key quantity to predict the so-called FLASH effect at uHDR settings. However, recent works introduced varying calculation models to report dose rate, which is susceptible to the delivery method, scanning path (in active beam delivery) and beam intensity.
PURPOSE
This work introduces an analytical dose rate calculation engine for raster scanned charged particle beams that is able to predict dose rate from the irradiation plan and recorded beam intensity. The importance of standardized dose rate calculation methods is explored here.
METHODS
Dose is obtained with an analytical pencil beam algorithm, using pre-calculated databases for integrated depth dose distributions and lateral penumbra. Dose rate is then calculated by combining dose information with the respective particle fluence (i.e., time information) using three dose-rate-calculation models (mean, instantaneous, and threshold-based). Dose rate predictions for all three models are compared to uHDR helium ion beam (145.7 MeV/u, range in water of approximatively 14.6 cm) measurements performed at the Heidelberg Ion Beam Therapy Center (HIT) with a diamond-detector prototype. Three scanning patterns (scanned or snake-like) and four field sizes are used to investigate the dose rate differences.
RESULTS
Dose rate measurements were in good agreement with in-silico generated distributions using the here introduced engine. Relative differences in dose rate were below 10% for varying depths in water, from 2.3 to 14.8 cm, as well as laterally in a near Bragg peak area. In the entrance channel of the helium ion beam, dose rates were predicted within 7% on average for varying irradiated field sizes and scanning patterns. Large differences in absolute dose rate values were observed for varying calculation methods. For raster-scanned irradiations, the deviation between mean and threshold-based dose rate at the investigated point was found to increase with the field size up to 63% for a 10 mm × 10 mm field, while no significant differences were observed for snake-like scanning paths.
CONCLUSIONS
This work introduces the first dose rate calculation engine benchmarked to instantaneous dose rate, enabling dose rate predictions for physical and biophysical experiments. Dose rate is greatly affected by varying particle fluence, scanning path, and calculation method, highlighting the need for a consensus among the FLASH community on how to calculate and report dose rate in the future. The here introduced engine could help provide the necessary details for the analysis of the sparing effect and uHDR conditions.
Topics: Humans; Helium; Radiotherapy Planning, Computer-Assisted; Benchmarking; Monte Carlo Method; Proton Therapy; Radiotherapy Dosage; Ions; Water
PubMed: 37847027
DOI: 10.1002/mp.16793 -
Cureus Oct 2023In traditional treatment modalities and standard clinical practices, FLASH radiotherapy (FL-RT) administers radiation therapy at an exceptionally high dosage rate. When... (Review)
Review
In traditional treatment modalities and standard clinical practices, FLASH radiotherapy (FL-RT) administers radiation therapy at an exceptionally high dosage rate. When compared to standard dose rate radiation therapy, numerous preclinical investigations have demonstrated that FL-RT provides similar benefits in conserving normal tissue while maintaining equal antitumor efficacy, a phenomenon possible due to the 'FLASH effect' (FE) of FL-RT. The methodologies involve proton radiotherapy, intensity-modulated radiation treatment, and managing high-throughput damage by radiation to solid tissues. Recent results from animal studies indicate that FL-RT can reduce radiation-induced tissue damage, significantly enhancing anticancer potency. Focusing on the potential benefits of FL proton beam treatment in the years to come, this review details the FL-RT research that has been done so far and the existing theories illuminating the FL effects. This subject remains of interest, with many issues still needing to be answered. We offer a brief review to emphasize a few of the key efforts and difficulties in moving FL radiation research forward. The existing research state of FL-RT, its affecting variables, and its different specific impacts are presented in this current review. Key topics discussed include the biochemical mechanism during FL therapy, beam sources for FL therapy, the FL effect on immunity, clinical and preclinical studies on the protective effect of FL therapy, and parameters for effective FL therapy.
PubMed: 38021805
DOI: 10.7759/cureus.46928