-
Scientific Reports Dec 2022The Radiological Research Accelerator Facility has modified a decommissioned Varian Clinac to deliver ultra-high dose rates: operating in 9 MeV electron mode (FLASH...
The Radiological Research Accelerator Facility has modified a decommissioned Varian Clinac to deliver ultra-high dose rates: operating in 9 MeV electron mode (FLASH mode), samples can be irradiated at a Source-Surface Distance (SSD) of 20 cm at average dose rates of up to 600 Gy/s (3.3 Gy per 0.13 µs pulse, 180 pulses per second). In this mode multiple pulses are required for most irradiations. By modulating pulse repetition rate and irradiating at SSD = 171 cm, dose rates below 1 Gy/min can be achieved, allowing comparison of FLASH and conventional irradiations with the same beam. Operating in 6 MV photon mode, with the conversion target removed (SuperFLASH mode), samples are irradiated at higher dose rates (0.2-150 Gy per 5 µs pulse, 360 pulses per second) and most irradiations can be performed with a single very high dose rate pulse. In both modes we have seen the expected inverse relation between dose rate and irradiated area, with the highest dose rates obtained for beams with a FWHM of about 2 cm and ± 10% uniformity over 1 cm diameter. As an example of operation of the ultra-high dose rate FLASH irradiator, we present dose rate dependence of dicentric chromosome yields.
Topics: Particle Accelerators; Photons; Electrons; Radiotherapy Dosage; Radiometry
PubMed: 36550150
DOI: 10.1038/s41598-022-19211-7 -
The British Journal of Radiology Jul 2014Inoperable endometrial cancer may be treated with curative aim using radical radiotherapy alone. The radiation techniques are external beam radiotherapy (EBRT) alone,... (Review)
Review
Inoperable endometrial cancer may be treated with curative aim using radical radiotherapy alone. The radiation techniques are external beam radiotherapy (EBRT) alone, EBRT plus brachytherapy and brachytherapy alone. Recently, high-dose-rate brachytherapy has been used instead of low-dose-rate brachytherapy. Image-guided brachytherapy enables sufficient coverage of tumour and reduction of dose to the organs at risk, thus increasing the therapeutic ratio of treatment. Local control rates with three-dimensional brachytherapy appear better than with conventional techniques (about 90-100% and 70-90%, respectively).
Topics: Brachytherapy; Endometrial Neoplasms; Female; Humans; Magnetic Resonance Imaging; Radiotherapy Dosage; Radiotherapy, Image-Guided
PubMed: 24807067
DOI: 10.1259/bjr.20140018 -
International Journal of Molecular... Oct 2022FLASH radiotherapy, or the delivery of a dose at an ultra-high dose rate (>40 Gy/s), has recently emerged as a promising tool to enhance the therapeutic index in cancer... (Review)
Review
FLASH radiotherapy, or the delivery of a dose at an ultra-high dose rate (>40 Gy/s), has recently emerged as a promising tool to enhance the therapeutic index in cancer treatment. The remarkable sparing of normal tissues and equivalent tumor control by FLASH irradiation compared to conventional dose rate irradiation—the FLASH effect—has already been demonstrated in several preclinical models and even in a first patient with T-cell cutaneous lymphoma. However, the biological mechanisms responsible for the differential effect produced by FLASH irradiation in normal and cancer cells remain to be elucidated. This is of great importance because a good understanding of the underlying radiobiological mechanisms and characterization of the specific beam parameters is required for a successful clinical translation of FLASH radiotherapy. In this review, we summarize the FLASH investigations performed so far and critically evaluate the current hypotheses explaining the FLASH effect, including oxygen depletion, the production of reactive oxygen species, and an altered immune response. We also propose a new theory that assumes an important role of mitochondria in mediating the normal tissue and tumor response to FLASH dose rates.
Topics: Humans; Radiotherapy Dosage; Reactive Oxygen Species; Neoplasms; Oxygen
PubMed: 36292961
DOI: 10.3390/ijms232012109 -
Frontiers in Oncology 2019For patients with unfavorable or high-risk prostate cancer, dose escalated radiation therapy leads to improved progression free survival but attempts to deliver... (Review)
Review
For patients with unfavorable or high-risk prostate cancer, dose escalated radiation therapy leads to improved progression free survival but attempts to deliver increased dose by external beam radiation therapy (EBRT) alone can be limited by late toxicities to nearby genitourinary and gastrointestinal organs at risk. Brachytherapy is a method to deliver dose escalation in conjunction with EBRT with a potentially improved late toxicity profile and improved prostate cancer related outcomes. At least three randomized controlled trials have demonstrated improved biochemical control with the addition of either low-dose rate (LDR) or high-dose rate (HDR) brachytherapy to EBRT, although only ASCENDE-RT compared brachytherapy to dose-escalated EBRT but did report an over 50% improvement in biochemical failure with a LDR boost. Multiple single institution and comparative research series also support the use of a brachytherapy boost in the DE-EBRT era and demonstrate excellent prostate cancer specific outcomes. Despite improved oncologic outcomes with a brachytherapy boost in the high-risk setting, the utilization of both LDR, and HDR brachytherapy use is declining. The acute genitourinary toxicities when brachytherapy boost is combined with EBRT, particularly a LDR boost, are of concern in comparison to EBRT alone. HDR brachytherapy boost has many physical properties inherent to its rapid delivery of a large dose which may reduce acute toxicities and also appeal to the radiobiology of prostate cancer. We herein review the evidence for use of either LDR or HDR brachytherapy boost for high-risk prostate cancer and summarize comparisons between the two treatment modalities.
PubMed: 31921640
DOI: 10.3389/fonc.2019.01378 -
Current Issues in Molecular Biology Aug 2023The output constancy of the accelerator used for boron neutron capture therapy (BNCT) is essential to ensuring anti-tumor efficacy and safety. BNCT as currently...
The output constancy of the accelerator used for boron neutron capture therapy (BNCT) is essential to ensuring anti-tumor efficacy and safety. BNCT as currently practiced requires a wide variety of beam quality assessments to ensure that RBE dose errors are maintained within 5%. However, the necessity of maintaining a constant beam dose rate has not been fully discussed. We therefore clarified the effect of different physical dose rates of the accelerator BNCT on biological effects. SAS and A172 cells exposed to B-boronophenylalanine were irradiated using a neutron beam (normal operating current, 100 μA) at the Aomori Quantum Science Center. Thermal neutron flux was attenuated to 50.0 ± 0.96% under 50 μA irradiation compared to that under 100 μA irradiation. Cells were given physical doses of 1.67 and 3.36 Gy at 30 and 60 mC, respectively, and survival was significantly increased after 50 μA irradiation for both cell types ( = 0.0052 for SAS; = 0.046 for A172, for 60 mC). Differences in accelerator BNCT beam dose rates have non-negligible effects on biological effects. Dose rate fluctuations and differences should not be easily permitted to obtain consistent biological effects.
PubMed: 37754225
DOI: 10.3390/cimb45090441 -
Cells Nov 2021Anti-inflammatory low-dose therapy is well established, whereas the immunomodulatory impact of doses below 0.1 Gy is much less clear. In this study, we investigated...
Anti-inflammatory low-dose therapy is well established, whereas the immunomodulatory impact of doses below 0.1 Gy is much less clear. In this study, we investigated dose, dose rate and time-dependent effects in a dose range of 0.005 to 2 Gy on immune parameters after whole body irradiation (IR) using a pro-inflammatory (ApoE-/-) and a wild type mouse model. Long-term effects on spleen function (proliferation, monocyte expression) were analyzed 3 months, and short-term effects on immune plasma parameters (IL6, IL10, IL12p70, KC, MCP1, INFγ, TGFβ, fibrinogen, sICAM, sVCAM, sE-selectin/CD62) were analyzed 1, 7 and 28 days after Co60 γ-irradiation (IR) at low dose rate (LDR, 0.001 Gy/day) and at high dose rate (HDR). In vitro measurements of murine monocyte (WEHI-274.1) adhesion and cytokine release (KC, MCP1, IL6, TGFβ) after low-dose IR (150 kV X-ray unit) of murine endothelial cell (EC) lines (H5V, mlEND1, bEND3) supplement the data. RT-PCR revealed significant reduction of Ki67 and CD68 expression in the spleen of ApoE-/- mice after 0.025 to 2 Gy exposure at HDR, but only after 2 Gy at LDR. Plasma levels in wild type mice, showed non-linear time-dependent induction of proinflammatory cytokines and reduction of TGFβ at doses as low as 0.005 Gy at both dose rates, whereas sICAM and fibrinogen levels changed in a dose rate-specific manner. In ApoE-/- mice, levels of sICAM increased and fibrinogen decreased at both dose rates, whereas TGFβ increased mainly at HDR. Non-irradiated plasma samples revealed significant age-related enhancement of cytokines and adhesion molecules except for sICAM. In vitro data indicate that endothelial cells may contribute to systemic IR effects and confirm changes of adhesion properties suggested by altered sICAM plasma levels. The differential immunomodulatory effects shown here provide insights in inflammatory changes occurring at doses far below standard anti-inflammatory therapy and are of particular importance after diagnostic and chronic environmental exposures.
Topics: Aging; Animals; Apolipoproteins E; Cell Adhesion; Cell Line; Cytokines; Dose-Response Relationship, Radiation; Endothelial Cells; Female; Inflammation; Interleukin-6; Mice, Inbred C57BL; Monocytes; Radiation, Ionizing; Spleen; Time Factors; Mice
PubMed: 34831473
DOI: 10.3390/cells10113251 -
Journal of Radiation Research Apr 2018We previously found that high-dose-rate radiation induced a replenishment of the colonic Lgr5+ stem cell pool, whereas low-dose-rate radiation did not. To identify key... (Review)
Review
We previously found that high-dose-rate radiation induced a replenishment of the colonic Lgr5+ stem cell pool, whereas low-dose-rate radiation did not. To identify key molecules that determine the dose-rate effects on this stem cell pool, we harvested colonic Lgr5+ stem cells by cell sorting at 2 weeks after exposure to 1 Gy of high-dose-rate (30 Gy/h) or low-dose-rate (0.003 Gy/h) radiation and analyzed their gene expression profiles using RNA-Seq. We found that pathways related to DNA damage response, cell growth, cell differentiation and cell death were upregulated in Lgr5+ stem cells irradiated with high dose rates, whereas pathways related to apical junctions and extracellular signaling were upregulated in low-dose-rate-irradiated colonic Lgr5+ stem cells. Interestingly, biological events involving apical junctions are known to play an important role in the exclusion of transformed cells that are surrounded by normal epithelial cells through 'cell competition'. We speculated that cell competition, through apical junctions and extracellular ligands, might contribute to the dose-rate effect on Lgr5+ cell replenishment. To understand this mechanism, we focused on 69 genes that were significantly upregulated in low-dose-rate-irradiated cells, which we named DREDGE (Dose-Rate Effect Determining GEnes). Based on these findings, we propose a possible mechanism underlying the dose-rate effect observed in the colonic stem cell pool.
Topics: Animals; Carcinogenesis; Colon; Dose-Response Relationship, Radiation; Gene Expression Profiling; Humans; Radiation Exposure; Receptors, G-Protein-Coupled; Stem Cells
PubMed: 29281035
DOI: 10.1093/jrr/rrx078 -
Zeitschrift Fur Medizinische Physik May 2022Robotic systems to assist needle placements for low-dose rate brachytherapy enable conformal dose planning only restricted to path planning around risk structures. We...
PURPOSE
Robotic systems to assist needle placements for low-dose rate brachytherapy enable conformal dose planning only restricted to path planning around risk structures. We report a treatment planning system (TPS) combining multiple direction needle-path planning with inverse dose optimization algorithms.
METHODS
We investigated in a path planning algorithm to efficiently locate needle injection points reaching the target volume without puncturing risk structures. A candidate needle domain with all combinations of trajectories is used for the optimization process. We report a modular algorithm for inverse radiation plan optimization. The initial plan with V100>99% is generated by the "greedy optimizer". The "remove-seed algorithm" reduces the number of seeds in the high dose regions. The "depth-optimizer" varies the insertion depth of the needles. The "coverage-optimizer" locates under-dosed areas in the target volume and supports them with an additional amount of seeds. The dose calculation algorithm is benchmarked on an image set of a phantom with a liver metastasis (prescription dose D=100Gy) and is re-planned in a commercial CE-marked TPS to compare the calculated dose grids using a global gamma analysis. The inverse optimizer is benchmarked by calculating 10 plans on the same phantom to investigate the stability and statistical variability of the dose parameters.
RESULTS
The path planning algorithm efficiently removes 72.5% of all considered injection points. The candidate needle domain consists of combinations of 1971 tip points and 827 injection points. The global gamma analysis with gamma 1%=2.9Gy, 1mm showed a pass rate of 98.5%. The dose parameters were V100=99.1±0.3%, V150=76.4±2.5%, V200=44.5±5.5% and D90=125.9±3.6Gy and 10.7±1.3 needles with 34.0±0.8 seeds were used. The median of the TPS total running time was 4.4minutes.
CONCLUSIONS
The TPS generates treatment plans with acceptable dose coverage in a reasonable amount of time. The gamma analysis shows good accordance to the commercial TPS. The TPS allows taking full advantage of robotic navigation tools to enable a new precise and safe method of minimally invasive low-dose-rate brachytherapy.
Topics: Algorithms; Brachytherapy; Needles; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Robotic Surgical Procedures
PubMed: 34373188
DOI: 10.1016/j.zemedi.2021.06.003 -
Sensors (Basel, Switzerland) Jun 2023Estimating the gamma dose rate at one meter above ground level and determining the distribution of radioactive pollution from aerial radiation monitoring data are the...
Estimating the gamma dose rate at one meter above ground level and determining the distribution of radioactive pollution from aerial radiation monitoring data are the core technical issues of unmanned aerial vehicle nuclear radiation monitoring. In this paper, a reconstruction algorithm of the ground radioactivity distribution based on spectral deconvolution was proposed for the problem of regional surface source radioactivity distribution reconstruction and dose rate estimation. The algorithm estimates unknown radioactive nuclide types and their distributions using spectrum deconvolution and introduces energy windows to improve the accuracy of the deconvolution results, achieving accurate reconstruction of multiple continuous distribution radioactive nuclides and their distributions, as well as dose rate estimation of one meter above ground level. The feasibility and effectiveness of the method were verified through cases of single-nuclide (Cs) and multi-nuclide (Cs and Co) surface sources by modeling and solving them. The results showed that the cosine similarities between the estimated ground radioactivity distribution and dose rate distribution with the true value were 0.9950 and 0.9965, respectively, which could prove that the proposed reconstruction algorithm would effectively distinguish multiple radioactive nuclides and accurately restore their radioactivity distribution. Finally, the influences of statistical fluctuation levels and the number of energy windows on the deconvolution results were analyzed, showing that the lower the statistical fluctuation level and the more energy window divisions, the better the deconvolution results.
Topics: Radioactivity; Cesium Radioisotopes; Radiation Monitoring; Gamma Rays
PubMed: 37420794
DOI: 10.3390/s23125628 -
Journal of Applied Clinical Medical... Oct 2022Interventional cardiology involves catheter-based treatment of heart disease, generally through fluoroscopically guided interventional procedures. Patients can be...
Interventional cardiology involves catheter-based treatment of heart disease, generally through fluoroscopically guided interventional procedures. Patients can be subject to considerable radiation dose due to prolonged fluoroscopy time and radiographic exposure, and therefore efforts to minimize patient dose should always be undertaken. Developing standardized, effective quality control programs for these systems is a difficult task owing to cross-vendor differences and automated control of imaging protocols. Furthermore, analyses of radiation dose should be performed in the context of its associated effects on image quality. The aim of the study is to investigate radiation dose and image quality in two fluoroscopic systems used for interventional cardiology procedures. Image quality was assessed in terms of spatial resolution and modulation transfer function, signal-to-noise and contrast-to-noise ratios, and spatial-temporal resolution of fluoroscopy and cineradiography images with phantoms simulating various patient thicknesses under routine cardiology protocols. The entrance air kerma (or air kerma rate) was measured and used to estimate entrance surface dose (or dose rate) in the phantoms.
Topics: Humans; Radiation Dosage; Fluoroscopy; Phantoms, Imaging
PubMed: 35950644
DOI: 10.1002/acm2.13741