Carbon Ion Beams Research Articles

Extraction simulation of a carbon ion beam with particle distribution in a three-electrode system

In this study, the conventional simulations on particle beam extraction was performed using a plasma-based or particle-in-cell method. Subsequently, its validity was verified through comparisons with the conventional simulation results using the finite element method. A three-dimensional finite element method was employed as a tool to simulate the motion of charged particles that are constrained by a specific geometric structure and subjected to various specified forces. This study investigated the features of carbon-ion beam extraction and the effects of the particle beam conditions on the three-electrode extraction system of a gaseous ion source by simulating the ion beam properties using the COMSOL Multiphysics software package. The AC/DC module in this software package was used to simulate the electrostatic field, whereas the Particle Tracing Module in the package was used to extract the ion beam. This package was used to analyze the beam trajectories and their dependence on particle properties under electrostatic boundary conditions, using bidirectionally coupled particle tracing. Consequently, Twiss parameters and root mean square (rms) beam emittance of the particle beam were calculated for the particle positions and divergence in their phase space. The feasibility of the particle beam extraction performed using this approach was confirmed through comparisons with the simulation results obtained using other ion source extraction programs. Furthermore, the effectiveness of a more user-friendly multiphysics based simulation was evaluated based on the rms beam emittance.

Evaluation of the effect of a 2D ripple filter on the averaged LET and RBE for proton and carbon ion beams: a Monte Carlo simulation study

Evaluation of the effect of a 2D ripple filter on the averaged LET and RBE for proton and carbon ion beams: a Monte Carlo simulation study

Using convergent half width half Maximum(c-HWHM) tilting method to determine the virtual source position of scanning-pass scattering beam in carbon ion therapy

IntroductionWe developed a half-width half-maximum tilting angle convergent method to replace the conventional measurement of the virtual source position for scanning-pass scattering beam in carbon ion therapy. Materials and methodsA homemade large-format CMOS sensor and Gaf Chromic EBT3 films were used for the virtual source position measurement. The Gaf films were embedded in a self-designed rectangular plastic frame to tighten the films and set up on a treatment couch for irradiation in the air with the film perpendicular to the carbon ion beam at the nominal source-axis-distance (SAD) as well as upstream and downstream from the SAD. The radiation rectangular field size in horizontal and vertical directions on film or detector delivered by 5 carbon ion energies were analyzed separately in this study. The virtual source position was determined with film or detector at a distance upstream or downstream from the various source-film-distance by the half width half maximum tilting angle convergent method to compare the results conducted with the same measurement condition by the back projecting the FWHM to zero methods. ResultsThe determination of virtual source position by using half width half maximum tilting angle convergent method agrees with the method by back projecting the FWHM to zero, and for higher carbon ion energy has an obvious longer virtual source position since the more carbon ion beam energy, hence, the less side scatter results in the less divergent at the downstream, then the virtual source positions is distal for high energies than low energies when back projects the field sizes to zero. ConclusionWe have developed a technique capable of dealing with the virtual source position with a geometric convergent method to avoid any mistakes in the passive scatter carbon ion beam. The method for investigating the virtual source position in the carbon ion beam in this study can also be used for electrons and proton beams.

A simple method to import CAD mesh format models in FLUKA.

Monte Carlo (MC) code FLUKA possesses widespread usage and accuracy in the simulation of particle beam radiotherapy. However, the conversion from computer-aided design (CAD) mesh format models to FLUKA readable geometries could not be implemented directly and conveniently. A simple method was required to be developed. The present study proposed a simple method to voxelize CAD mesh format files by using a Python-based script and establishing geometric models in FLUKA. Five geometric models including cube, sphere, cone, ridge filter (RGF), and 1D-Ripple Filter (1D-RiFi) were created and exported as CAD mesh format files (.stl). An open-source Python-based script was used to convert them into voxels by endowing X, Y, and Z (following the Cartesian coordinates system) of solid materials in the three-dimensional (3D) grid. A FLUKA (4-2.2, CERN) predefined routine was used to establish the voxelized geometry model (VGM), while Flair (3.2-1, CERN) was used to build the direct geometry model (DGM) in FLUKA for comparison purposes. Uniform carbon ion radiation fields 8×8cm3 and 4×4cm3 were generated to transport through the five pairs of models, 2D and 3D dose distributions were compared. The integral depth dose (IDD) in water of three different energy levels of carbon ion beams transported through 1D-RiFis were also simulated and compared. Moreover, the volume between CAD mesh and VGMs, as well as the computing speed between FLUKA DGMs and VGMs were simultaneously recorded. The volume differences between VGMs and CAD mesh models were not more than 0.6%. The maximum mean point-to-point deviation of IDD distribution was 0.7%±0.51% (mean±standard deviation). The 3D dose Gamma-index passing rates were never lower than 97% with criteria of 1%-1mm. The difference in computing CPU time was 2.89%±0.22 on average. The present study proposed and verified a Python-based method for converting CAD mesh format files into VGMs and establishing them in FLUKA simply as well as accurately.

Investigation into the Operation Modes of RF Systems of Booster–Nuclotron Synchrotrons in Optimizing the Capture and Acceleration of Carbon Ion Beams

Investigation into the Operation Modes of RF Systems of Booster–Nuclotron Synchrotrons in Optimizing the Capture and Acceleration of Carbon Ion Beams

Future Perspective: Carbon Ion Radiotherapy for Head and Neck and Skull Base Malignancies.

Head and neck and base of skull malignancies are challenging for surgical and radiotherapy treatment due to the density of sensitive tissues. Carbon ion radiotherapy (CIRT) is a form of heavy particle therapy that uses accelerated carbon ions to treat malignancies that may be radioresistant or in challenging anatomic locations. CIRT has an increased biological effectiveness (ie, increased cell killing) at the end of the range of the carbon beam (ie, within the target tissue) but not in the entrance dose. This increased biological effectiveness can overcome the effects of radioresistant tumors, tissue hypoxia, and the need for radiotherapy fractionation.

Charge exchange processes during carbon ion fragmentation at an energy of 300 MeV/nucleon: comparison with models of ion-ion interactions

Experimental data are presented on the differential cross sections to produce 11Be, 12Be, and 12B isotopes at the carbon beam fragmentation with an energy of 300 MeV/nucleon in the FRAGM experiment conducted based on the ITEP-TWAС multipurpose accelerator complex. The obtained experimental data are compared with the predictions of the models of ion-ion interactions: binary cascade and quantum molecular dynamics model.

Validation of robust radiobiological optimization algorithms based on the mixed beam model for intensity-modulated carbon-ion therapy.

Currently, treatment planning systems (TPSs) that can compute the intensities of intensity-modulated carbon-ion therapy (IMCT) using scanned carbon-ion beams are limited. In the present study, the computational efficacy of the newly designed IMCT algorithms was analyzed for the first time based on the mixed beam model with respect to the physical and biological doses; moreover, the validity and effectiveness of the robust radiobiological optimization were verified. A dose calculation engine was independently generated to validate a clinical dose determined in the TPS. A biological assay was performed using the HSGc-C5 cell line to validate the calculated surviving fraction (SF). Both spot control (SC) and voxel-wise worst-case scenario (WC) algorithms were employed for robust radiobiological optimization followed by their application in a Radiation Therapy Oncology Group benchmark phantom under homogeneous and heterogeneous conditions and a clinical case for range and position errors. Importantly, for the first time, both SC and WC algorithms were implemented in the integrated TPS platform that can compute the intensities of IMCT using scanned carbon-ion beams for robust radiobiological optimization. For assessing the robustness, the difference between the maximum and minimum values of a dose-volume histogram index in the examined error scenarios was considered as a robustness index. The relative biological effectiveness (RBE) determined by the independent dose calculation engine exhibited a -0.6% difference compared with the RBE defined by the TPS at the isocenter, whereas the measured and the calculated SF were similar. Regardless of the objects, compared with the conventional IMCT, the robust radiobiological optimization enhanced the sensitivity of the examined error scenarios by up to 19% for the robustness index. The computational efficacy of the novel IMCT algorithms was verified according to the mixed beam model with respect to the physical and biological doses. The robust radiobiological optimizations lowered the impact of range and position uncertainties considerably in the examined scenarios. The robustness of the WC algorithm was more enhanced compared with that of the SC algorithm. Nevertheless, the SC algorithm can be used as an alternative to the WC IMCT algorithm with respect to the computational cost.

EXPERIMENTAL STUDY ON THE CHARGE-EXCHANGE CROSS-SECTIONS OF LOW-ENERGY CARBON IONS IN HELIUM AT GXNU

ABSTRACT Compared with nitrogen and argon, helium is lighter and can better reduce the beam loss caused by angular scattering during beam transmission. The molecular dissociation cross-section in helium is high and stable at low energies, which makes helium the prevalent stripping gas in low-energy accelerator mass spectrometry (AMS). To study the stripping behavior of 14C ions in helium at low energies, the charge state distributions of carbon ion beams with −1, +1, +2, +3, and +4 charge states were measured at energies of 70–220 keV with a compact 14C-AMS at Guangxi Normal University (GXNU). The experimental data were used to analyze the stripping characteristics of C-He in the energy range of 70–220 keV, and new charge state yields and exchange cross-sections in C-He were obtained at energies of 70–220 keV.

Heavy-ions shielding data for hadrontherapy application with Monte Carlo methods.

In hadrontherapy centers, ion beams are accelerated by a cyclotron or synchrotron through electric and magnetic fields and, once the treatment energy is reached, ions interact with the patient. The interaction of the beam with magnets, other elements of particle accelerator or with the patient generates secondary radiation and the calculation for the design of the shielding is required. A first assessment of the shielding, generally made by concrete, can be performed by using Monte Carlo simulations, in which neutron yields and the ambient dose equivalent, H*(10), spatial distribution are obtained. The aim of this work is to evaluate, with a Monte Carlo approach, ambient dose equivalent values at various concrete depths generated by the secondary radiation. Simulations are performed considering helium, lithium, carbon, oxygen and iron primary beams. For existing facilities that already accelerates carbon ion, an equivalent carbon ratio is introduced to estimate the ion currents to get, in a given point, the same ambient dose equivalent as a carbon ion. Numerical results have been obtained simulating an ion beam that impinges on a thick iron or international commission on radiation units and measurements (ICRU) tissue, respectively, representing magnets and patient. The secondary radiation is transported through a large concrete shielding where ambient dose equivalent values are calculated as function of concrete thickness.

Impact of varying the number of irradiation fields on dose distribution: A four-dimensional scanned carbon-ion lung radiotherapy

To shorten the treatment procedure and increase the treatment efficiency, we performed planning studies to evaluate the 4D dose (4DD) distributions of different number of irradiation fields with the fixed treatment ports of scanning carbon-ion beam delivery. We enrolled 10 lung cancer patients treated with respiratory-gated scanning carbon-ion therapy. 4-field, 3-field, and 2-field plans were generated with fixed treatment ports by rotating the beam angle with a 20∼40-degree difference. For each field, the range-adapted internal target volume (raITV) was calculated. The prescription dose of 50 Gy (RBE)-weighted dose with 1 fraction was optimized on the reference phase (T50). The 4DD distributions were calculated for each patient, and dose metrics of CTV dose coverage and OARs sparing were evaluated. p < 0.05 was considered to be statistically significant by Wilcoxon signed-rank test. The sufficient CTV-D95 > 97.8% could be achieved for all the three types of treatment plan. The Dmax of skin was increased (= 19.1 ± 5.7 Gy (RBE)) for the 2-field plans as compared to 4-field plans (= 14.2 ± 6.6 Gy (RBE), p = 0.006), which is still acceptable for clinical use (<35 Gy (RBE)). And there were no differences (p > 0.076) of V20 of lung (= 15.5 ± 6.6%, 16.2 ± 7.0%, 15.6 ± 6.3%) and Dmax of spinal cord (= 3.0 ± 2.9, 3.4 ± 3.9, 3.3 ± 4.3 Gy (RBE)) among the three types of plans. Lung treatment plans under the fixed orthogonal beam ports with zero-degree couch pitch angle is feasible for clinical use to further increase the treatment efficiency and throughput.

High–Linear Energy Transfer Irradiation in Clinical Carbon-Ion Beam With the Linear Energy Transfer Painting Technique for Patients With Head and Neck Cancer

Dose-averaged linear energy transfer (LETd) is one of the important factors in determining clinical outcomes for carbon-ion radiation therapy. Innovative LET painting (LP) has been developed as an advanced form of conventional intensity modulated carbon-ion radiation therapy (IMIT) at the QST Hospital. The study had 2 motivations: to increase the minimum LETd (LETdmin) and to improve uniformity of the LETd distribution within the gross tumor volume (GTV) by using LP treatment plans for patients with head and neck cancer while maintaining the relative biologic effectiveness (RBE)-weighted dose coverage within the planning tumor volume (PTV) the same as in the conventional IMIT plan. The LP treatment plans were designed with the in-house treatment planning system. For the plans, LETd constraints and LETdmin, goal-LETd, and maximum-LETd (LETdmax) constraints for the GTV were added to the conventional dose constraints in the IMIT prescription. For 13 patients with head and neck cancer, the RBE-weighted dose to 90% (D90) and 50% (D50) of the PTV and the LETdmin, mean (LETdmean), and LETdmax values within the GTV in the LP plans were evaluated by comparing them with those in the conventional IMIT plans. The LP for 13 patients with head and neck cancer could keep D90s and D50s for the PTV within 1.0% of those by the conventional IMIT. Among the 13 patients, the mean LETdmin of the LP plans for the GTV was 59.2 ± 7.9 keV/μm, whereas that of the IMIT plans was 45.9 ± 6.0 keV/μm. The LP increased the LETdmin to 8 to 24 keV/μm for the GTV compared with IMIT. While maintaining the dose coverage to the PTV as comparable to that for IMIT, the LP increased the mean LETdmin to 13.2 keV/μm for the GTV. For a GTV up to 170 cm3, LETd > 44 keV/μm could be achieved using LP, which according to previous studies was associated with lower recurrence. In addition, the LP method delivered more uniform LETd distributions compared with IMIT.

MR-guided ion therapy: Detector response in magnetic fields during carbon ion irradiation.

Combining carbon ion therapy with on-bed MR imaging has the potential to bring particle therapy to a new level of precision. However, the introduction of magnetic fields brings challenges for dosimetry and quality assurance. For protons, a small, but significant change in detector response was shown in the presence of magnetic fields previously. For carbon ion beams, so far no such experiments have beenperformed. To investigate the influence of external magnetic fields on the response of air-filled ionizationchambers. Four commercially available ionization chambers, three thimble type (Farmer, Semiflex, and PinPoint), and a plane parallel (Bragg peak) detector were investigated. Detectors were aligned in water such that their effective point of measurement was located at 2 cm depth. Irradiations were performed using square fields for carbon ions of 186.1, 272.5, and 402.8MeV/u employing magnetic field strengths of 0, 0.25, 0.5, and 1 T. In addition, the detector response for protons and carbon ions was compared taking into account the secondary electron spectra and employing protons of 252.7 MeV forcomparison. For all four detectors, a statistically significant change in detector response, dependent on the magnetic field strength, was found. The effect was more pronounced for higher energies. The highest effects were found at 0.5 T for the PinPoint detector with a change in detector response of 1.1%. The response of different detector types appeared to be related to the cavity diameter. For proton and carbon ion irradiation with similar secondary electron spectra, the change in detector response was larger for carbon ions compared toprotons. A small, but significant dependence of the detector response was found for carbon ion irradiation in a magnetic field. The effect was found to be larger for smaller cavity diameters and at medium magnetic field strengths. Changes in detector response were more pronounced for carbon ions compared toprotons.

Regulation mechanism of lipids for extracellular yellow pigments production by Monascus purpureus BWY-5.

The biosynthesis and secretion of Monascus pigments are closely related to the integrity of the cell membrane, which determines the composition of lipids and its content in cell membrane. The present study aimed to thoroughly describe the changes of lipid profiling in Monascus purpureus BWY-5, which was screened by carbon ion beam irradiation (12C6+) to almost single yield extracellular Monascus yellow pigments (extra-MYPs), by absolute quantitative lipidomics and tandem mass tags (TMT) based quantitative proteomic. 12C6+ irradiation caused non-lipid oxidation damage to Monascus cell membrane, leading to an imbalance in cell membrane lipid homeostasis. This imbalance was attributed to significant changes not only in the composition but also in the content of lipids in Monascus, especially the inhibition of glycerophospholipid biosynthesis. Integrity of plasma membrane was maintained by the increased production of ergosterol, monogalactosylmonoacylglycerol (MGMG) and sulfoquinovosylmonoacylglycerol (SQMG), while mitochondrial membrane homeostasis was maintained by the increase of cardiolipin production. The growth and extra-MYPs production of Monascus BWY-5 have been regulated by the promotion of sphingolipids (ceramide and sulfatide) biosynthesis. Simultaneous, energy homeostasis may be achieved by increase of TG synthesis and Ca2+/Mg2+-ATPase activity. These finding suggest ergosterol, cardiolipin, sphingolipids, MGMG and SQMG play a key facilitating role in cytomembrane lipid homeostasis maintaining for Monascus purpureus BWY-5, and then it is closely related to cell growth and extra-MYPs production. KEY POINTS: 1. Energy homeostasis in Monascus purpureus BWY-5 was achieved by increase of TG synthesis and Ca2+/Mg2+-ATPase activity. 2. Integrity of plasma membrane in Monascus purpureus BWY-5 was maintained by the increased production of ergosterol. 3. Mitochondrial membrane homeostasis in Monascus purpureus BWY-5 was maintaed by the increase of cardiolipin synthesis.

Development of a SiC semiconductor-based dosimeter for evaluating clinical dose distribution in carbon ion cancer therapy fields

Dosimeters with excellent energy resolution are required to improve quality control and assurance (QA/QC) for heavy-ion cancer therapy, in which multiple species of ions are expected to be used. The conventional ionization chamber that is widely used for QA/QC generally does not support quality discrimination for different radiation species, and several types of energy-dispersive dosimeters are being studied for this application, including silicon semiconductors on insulator devices. Other wide bandgap semiconductors with good radiation hardness, including SiC and diamond, are being studied for use in cancer therapy ion fields. In this study, a 4H-SiC Schottky barrier diode was used for energy-dispersive dosimetry in the clinical carbon therapy field at Gunma University Medical Center for Heavy Ion Beam Medicine. The relative biological effectiveness was estimated from the linear energy transfer spectra for a pristine carbon beam with an energy of 290 MeV/n and a spread-out Bragg peak beam using the linear-quadratic model. The results showed that the SiC-based dosimeter could be used in the detailed characterization of the clinical dose distribution of carbon ion cancer therapy fields.

Simulation study of comparative dosimetric analysis of coplanar horizontal-port scanned carbon-ion beam therapy in the head and neck.

Carbon-ion radiotherapy (CIRT) has demonstrated success in treating radioresistant disease within the head and neck, owing to its unique physical and radiobiological properties. Construction cost remains prohibitive; a center offering only a horizontal port may bridge this difficulty, but removal of the vertical port may prohibit treatment of disease near critical organs-at-risk. Building a center only containing a horizontal treatment port has been proposed as one method for cost savings. 20 complex cases of head and neck cancer previously treated with conventional CIRT were retrospectively planned using horizontal-port-only treatment incorporating non-coplanar treatment angles to achieve greater degrees of freedom. These were dosimetrically compared with the previous plans. Comparable D95 coverage of both planning target volume and gross tumor volume with ability to meet organ-at-risk constraints were feasible with horizontal-port-only treatment. Collectively differences were noted in PTV D95, brain stem Dmax, contralateral eye Dmax and V10 Gy (RBE); further qualitative differences were noted on a plan-by-plan basis dependent on disease location. Horizontal-port-only treatment employing non-coplanar angles was feasible for complicated head and neck disease typically treated with CIRT, though careful consideration is necessary on a plan-by-plan basis. It is worth noting that non-coplanar approaches are not typically used with the current treatment gantry and may extend further the difference between horizontal port planning and a gantry-based gold-standard.

Evaluation of proton and carbon ion beam models in TReatment Planning for Particles 4D (TRiP4D) referring to a commercial treatment planning system

PurposeTo investigate the accuracy of the treatment planning system (TPS) TRiP4D in reproducing doses computed by the clinically used TPS SyngoRT. MethodsProton and carbon ion beam models in TRiP4D were converted from SyngoRT. Cubic plans with different depths in a water-tank phantom (WP) and previously treated and experimentally verified patient plans from SyngoRT were recalculated in TRiP4D. The target mean dose deviation (ΔDmean,T) and global gamma index (2%–2 mm for the absorbed dose and 3%–3mm for the RBE-weighted dose with 10% threshold) were evaluated. ResultsThe carbon and proton absorbed dose gamma passing rates (γ-PRs) were ≥99.93% and ΔDmean,T smaller than −0.22%. On average, the RBE-weighted dose Dmean,T was −1.26% lower for TRiP4D than SyngoRT for cubic plans. In TRiP4D, the faster analytical ‘low dose approximation’ (Krämer, 2006) was used, while SyngoRT used a stochastic implementation (Krämer, 2000). The average ΔDmean, T could be reduced to −0.59% when applying the same biological effect calculation algorithm. However, the dose recalculation time increased by a factor of 79–477. ΔDmean,T variation up to −2.27% and −2.79% was observed for carbon absorbed and RBE-weighted doses in patient plans. The γ-PRs were ≥93.92% and ≥91.83% for patient plans, except for one proton beam with a range shifter (γ-PR of 64.19%). ConclusionThe absorbed dose between TRiP4D and SyngoRT were identical for both proton and carbon ion plans in the WP. Compared to SyngoRT, TRiP4D underestimated the target RBE-weighted dose; however more efficient in RBE-weighted dose calculation. Large variation for proton beam with range shifter was observed. TRiP4D will be used to evaluate doses delivered to moving targets. Uncertainties inherent to the 4D-dose reconstruction calculation are expected to be significantly larger than the dose errors reported here. For this reason, the residual differences between TRiP4D and SyngoRT observed in this study are considered acceptable.The study was approved by the Institutional Research Board of Shanghai Proton and Heavy Ion Center (approval number SPHIC-MP-2020-04, RS).

The study of virtual source position with the geometric convergent ratio errors prevention management method of spot scanning beam in carbon ion therapy.

We developed a technique including preventing errors management method capable of dealing with the virtual source position delivered by different carbon ion energies from the pattern of spot scanning beam in this study. A homemade large-format complementary metal-oxide-semiconductor (CMOS) sensor and Gaf Chromic EBT3 films were used for the virtual source position measurement. The Gaf films were embedded in a self-designed rectangular plastic frame to tighten the films and set up on a treatment couch for irradiation in the air with the film perpendicular to the carbon ion beam at the nominal source-axis-distance (SAD) as well as upstream and downstream from the SAD. The horizontal carbon ion beam with five energies at a machine opening field size was carried out in this study. The virtual source position was determined mainly with a linear regression by back projecting the full width half maximum (FWHM) to zero at a distance upstream from the various source-film-distance and double checks additionally with a geometric convergent method to avoid any mistakes caused by manual measurement on FWHM. The virtual source position for higher carbon ion energy has an obvious longer distance from the SAD since the more carbon ion beam energy, the less spreading affected by the horizontal and vertical magnetism, therefore, the distance of virtual source positions is decreased from SAD with high to low energy. The method for investigating the virtual source position in the carbon ion beam in this study can also be used for electrons and the proton. We have developed a technique capable of dealing with the virtual source position with a geometric convergent method to avoid any mistakes in spot scanning carbon ion beam.

Heavy Ion Irradiation Reduces Vulnerability to Atrial Tachyarrhythmias - Gap Junction and Sympathetic Neural Remodeling.

Low-invasive stereotactic body radiation therapy is a novel anti-arrhythmic strategy. The mechanisms underlying its effects against ventricular tachycardia/fibrillation (VT/VF) are gradually becoming clear, whereas those underlying atrial tachycardia/fibrillation (AT/AF) remain unknown. This study investigated the effects of carbon ion beam on gap junction expression and sympathetic innervation.Methods and Results: Atrial and ventricular tachyarrhythmia models was established in 26 hypercholesterolemic (HC) 3-year-old New Zealand white rabbits; 12 rabbits were irradiated with a single 15-Gy carbon ion beam (targeted heavy ion irradiation [THIR]) and 14 were not (HC group). Eight 3-month-old rabbits (Young) were used as a reference group. In vivo induction frequencies in the Young, HC, and HC+THIR groups were 0%, 9.9%, and 1.2%, respectively, for AT/AF and 0%, 7.8%, and 1.2%, respectively, for VT/VF (P<0.01). The conduction velocity of the atria and ventricles on optical mapping was significantly reduced in the HC group; this was reversed in the HC+THIR group. Connexin-40 immunolabelling in the atria was 66.1-78.7% lower in the HC than Young group; this downregulation was less pronounced in the HC+THIR group (by 23.1-44.4%; P<0.01). Similar results were obtained for ventricular connexin-43. Sympathetic nerve densities in the atria and ventricles increased by 41.9-65.3% in the HC vs. Young group; this increase was reversed in the HC+THIR group. Heavy ion radiation reduced vulnerability to AT/AF and VT/VF in HC elderly rabbits and improved cardiac conductivity. The results suggest involvement of connexin-40/43 upregulation and suppression of sympathetic nerve sprouting.

Multi-generation study of heavy ion beam-induced mutations and agronomic trait variations to accelerate rice breeding.

Heavy ion beam (HIB) is an effective physical mutagen that has been widely used in plant mutational breeding. Systemic knowledge of the effects caused by different HIB doses at developmental and genomic levels will facilitate efficient breeding for crops. Here we examined the effects of HIB systematically. Kitaake rice seeds were irradiated by ten doses of carbon ion beams (CIB, 25 - 300 Gy), which is the most widely used HIB. We initially examined the growth, development and photosynthetic parameters of the M1 population and found that doses exceeding 125 Gy caused significant physiological damages to rice. Subsequently, we analyzed the genomic variations in 179 M2 individuals from six treatments (25 - 150 Gy) via whole-genome sequencing (WGS). The mutation rate peaks at 100 Gy (2.66×10-7/bp). Importantly, we found that mutations shared among different panicles of the same M1 individual are at low ratios, validating the hypothesis that different panicles may be derived from different progenitor cells. Furthermore, we isolated 129 mutants with distinct phenotypic variations, including changes in agronomic traits, from 11,720 M2 plants, accounting for a 1.1% mutation rate. Among them, about 50% possess stable inheritance in M3. WGS data of 11 stable M4 mutants, including three lines with higher yields, reveal their genomic mutational profiles and candidate genes. Our results demonstrate that HIB is an effective tool that facilitates breeding, that the optimal dose range for rice is 67 - 90% median lethal dose (LD50), and that the mutants isolated here can be further used for functional genomic research, genetic analysis, and breeding.