A new platform for ultra-high dose rate radiobiological research using the BELLA PW laser proton beamline.

Radiotherapy is the current standard of care for more than 50% of all cancer patients. Improvements in radiotherapy (RT) technology have increased tumor targeting and normal tissue sparing. Radiations at ultra-high dose rates required for FLASH-RT effects have sparked interest in potentially providing additional differential therapeutic benefits. We present a new experimental platform that is the first one to deliver petawatt laser-driven proton pulses of 2 MeV energy at 0.2 Hz repetition rate by means of a compact, tunable active plasma lens beamline to biological samples. Cell monolayers grown over a 10 mm diameter field were exposed to clinically relevant proton doses ranging from 7 to 35 Gy at ultra-high instantaneous dose rates of 107 Gy/s. Dose-dependent cell survival measurements of human normal and tumor cells exposed to LD protons showed significantly higher cell survival of normal-cells compared to tumor-cells for total doses of 7 Gy and higher, which was not observed to the same extent for X-ray reference irradiations at clinical dose rates. These findings provide preliminary evidence that compact LD proton sources enable a new and promising platform for investigating the physical, chemical and biological mechanisms underlying the FLASH effect.

Characterization of a custom-made 241Am alpha-source for radiobiological studies.

A compact in-house alpha particle source has been developed and fully characterized. The irradiation source is a large area, 25 cm2, 5.4 MeV average energy 241Am source, above which a Mylar dish containing a monolayer of target cells can be placed at defined positions. The source uniformity, flux, particle energy and dose rate were determined experimentally. The dose rate to the nucleus at the closest position was 1.57 Gy/min. Furthermore, a 3D printed collimator was tested and found to improve the uniformity of the energy spectra of particles reaching the target. For validation, prostate PC-3 cells were irradiated in our experimental setup with absorbed doses up to 2 Gy and for reference compared with cells irradiated with conventional X-rays with doses up to 8 Gy. The Relative Biological Effectiveness for alpha particles at 10% survival was 3.66± 0.40 agreeing with previously published data. Data presented here show the feasibility of utilising a low-cost alpha-irradiation source for accurate in vitro assays to better understand the radiobiological effects of high LET alpha particles.

STATE INSTITUTION «NATIONAL RESEARCH CENTER FOR RADIATION MEDICINE OF THE NATIONAL ACADEMY OF MEDICAL SCIENCES OF UKRAINE¼ - RESEARCH ACTIVITIES AND SCIENTIFIC ADVANCE IN 2019. / REZUL'TATY ROBOTY DU «NATsIONAL'NYI NAUKOVYI TsENTR RADIATsIINOÏ MEDYTsYNY AKADEMIÏ MEDYChNYKh NAUK UKRAÏNY¼ U 2019 ROTsI.

Research activities and scientific advance achieved in 2019 at the State Institution «National Research Center forRadiation Medicine of the National Academy of Medical Sciences of Ukraine¼ (NRCRM) concerning medical problemsof the Chornobyl disaster, radiation medicine, radiobiology, radiation hygiene and epidemiology in collaborationwith the WHO network of medical preparedness and assistance in radiation accidents are outlined in the annualreport. The report presents the results of fundamental and applied research works of the study of radiation effectsand health effects of the Chornobyl accident.The report also shows the results of scientific-organizational and health care work, staff training.The Scientific Council meeting of NAMS approved the NRCRM Annual Report.

NASA's first ground-based Galactic Cosmic Ray Simulator: Enabling a new era in space radiobiology research.

With exciting new NASA plans for a sustainable return to the moon, astronauts will once again leave Earth's protective magnetosphere only to endure higher levels of radiation from galactic cosmic radiation (GCR) and the possibility of a large solar particle event (SPE). Gateway, lunar landers, and surface habitats will be designed to protect crew against SPEs with vehicle optimization, storm shelter concepts, and/or active dosimetry; however, the ever penetrating GCR will continue to pose the most significant health risks especially as lunar missions increase in duration and as NASA sets its aspirations on Mars. The primary risks of concern include carcinogenesis, central nervous system (CNS) effects resulting in potential in-mission cognitive or behavioral impairment and/or late neurological disorders, degenerative tissue effects including circulatory and heart disease, as well as potential immune system decrements impacting multiple aspects of crew health. Characterization and mitigation of these risks requires a significant reduction in the large biological uncertainties of chronic (low-dose rate) heavy-ion exposures and the validation of countermeasures in a relevant space environment. Historically, most research on understanding space radiation-induced health risks has been performed using acute exposures of monoenergetic single-ion beams. However, the space radiation environment consists of a wide variety of ion species over a broad energy range. Using the fast beam switching and controls systems technology recently developed at the NASA Space Radiation Laboratory (NSRL) at Brookhaven National Laboratory, a new era in radiobiological research is possible. NASA has developed the "GCR Simulator" to generate a spectrum of ion beams that approximates the primary and secondary GCR field experienced at human organ locations within a deep-space vehicle. The majority of the dose is delivered from protons (approximately 65%-75%) and helium ions (approximately 10%-20%) with heavier ions (Z ≥ 3) contributing the remainder. The GCR simulator exposes state-of-the art cellular and animal model systems to 33 sequential beams including 4 proton energies plus degrader, 4 helium energies plus degrader, and the 5 heavy ions of C, O, Si, Ti, and Fe. A polyethylene degrader system is used with the 100 MeV/n H and He beams to provide a nearly continuous distribution of low-energy particles. A 500 mGy exposure, delivering doses from each of the 33 beams, requires approximately 75 minutes. To more closely simulate the low-dose rates found in space, sequential field exposures can be divided into daily fractions over 2 to 6 weeks, with individual beam fractions as low as 0.1 to 0.2 mGy. In the large beam configuration (60 × 60 cm2), 54 special housing cages can accommodate 2 to 3 mice each for an approximately 75 min duration or 15 individually housed rats. On June 15, 2018, the NSRL made a significant achievement by completing the first operational run using the new GCR simulator. This paper discusses NASA's innovative technology solution for a ground-based GCR simulator at the NSRL to accelerate our understanding and mitigation of health risks faced by astronauts. Ultimately, the GCR simulator will require validation across multiple radiogenic risks, endpoints, doses, and dose rates.

Monte Carlo Processing on a Chip (MCoaC)-preliminary experiments toward the realization of optimal-hardware for TOPAS/Geant4 to drive discovery.

Amongst the scientific frameworks powered by the Monte Carlo (MC) toolkit Geant4 (Agostinelli et al., 2003), the TOPAS (Tool for Particle Simulation) (Perl et al., 2012) is one. TOPAS focuses on providing ease of use, and has significant implementation in the radiation oncology space at present. TOPAS functionality extends across the full capacity of Geant4, is freely available to non-profit users, and is being extended into radiobiology via TOPAS-nBIO (Ramos-Mendez et al., 2018). A current "grand problem" in cancer therapy is to convert the dose of treatment from physical dose to biological dose, optimized ultimately to the individual context of administration of treatment. Biology MC calculations are some of the most complex and require significant computational resources. In order to enhance TOPAS's ability to become a critical tool to explore the definition and application of biological dose in radiation therapy, we chose to explore the use of Field Programmable Gate Array (FPGA) chips to speedup the Geant4 calculations at the heart of TOPAS, because this approach called "Reconfigurable Computing" (RC), has proven able to produce significant (around 90x) (Sajish et al., 2012) speed increases in scientific computing. Here, we describe initial steps to port Geant4 and TOPAS to be used on FPGA. We provide performance analysis of the current TOPAS/Geant4 code from an RC implementation perspective. Baseline benchmarks are presented. Achievable performance figures of the subsections of the code on optimal hardware are presented; Aspects of practical implementation of "Monte Carlo on a chip" are also discussed.

Preclinical dose verification using a 3D printed mouse phantom for radiobiology experiments.

PURPOSE: Dose verification in preclinical radiotherapy is often challenged by a lack of standardization in the techniques and technologies commonly employed along with the inherent difficulty of dosimetry associated with small-field kilovoltage sources. As a consequence, the accuracy of dosimetry in radiobiological research has been called into question. Fortunately, the development and characterization of realistic small-animal phantoms has emerged as an effective and accessible means of improving dosimetric accuracy and precision in this context. The application of three-dimensional (3D) printing, in particular, has enabled substantial improvements in the conformity of representative phantoms with respect to the small animals they are modeled after. In this study, our goal was to evaluate a fully 3D printed mouse phantom for use in preclinical treatment verification of sophisticated therapies for various anatomical targets of therapeutic interest. METHODS: An anatomically realistic mouse phantom was 3D printed based on segmented microCT data of a tumor-bearing mouse. The phantom was modified to accommodate both laser-cut EBT3 radiochromic film within the mouse thorax and a plastic scintillator dosimeter (PSD), which may be placed within the brain, abdomen, or 1-cm flank subcutaneous tumor. Various treatments were delivered on an image-guided small-animal irradiator in order to determine the doses to isocenter using a PSD and validate lateral- and depth-dose distributions using film dosimeters. On-board cone-beam CT imaging was used to localize isocenter to the film plane or PSD active element prior to irradiation. The PSD irradiations comprised a 3 × 3 mm2 brain arc, 5 × 5 mm2 parallel-opposed pair (POP), and 5-beam 10 × 10 mm2 abdominal coplanar arrangement while two-dimensional (2D) film dose distributions were acquired using a 3 × 3 mm2 arc and both 5 × 5 and 10 × 10 mm2 3-beam coplanar plans. A validated Monte Carlo (MC) model of the source was used as to verify the accuracy of the film and PSD dose measurements. computer-aided design (CAD) geometries for the mouse phantom and dosimeters were imported directly into the MC code to allow for highly accurate reproduction of the physical experiment conditions. Experimental and MC-derived film data were co-registered and film dose profiles were compared for points above 90% of the dose maximum. Point dose measurements obtained with the PSD were similarly compared for each of the candidate (brain, abdomen, and tumor) treatment sites. RESULTS: For each treatment configuration and anatomical target, the MC-calculated and measured doses met the proposed 5% agreement goal for dose accuracy in radiobiology experiments. The 2D film and MC dose distributions were successfully registered and mean doses for lateral profiles were found to agree to within 2.3% in all cases. Isocentric point-dose measurements taken with the PSD were similarly consistent, with a maximum percentage deviation of 3.2%. CONCLUSIONS: Our study confirms the utility of 3D printed phantom design in providing accurate dose estimates for a variety of preclinical treatment paradigms. As a tool for pretreatment dose verification, the phantom may be of particular interest to researchers for its ability to facilitate precise dosimetry while fostering a reduction in cost for radiobiology experiments.

Simulation of a radiobiology facility for the Centre for the Clinical Application of Particles.

The Centre for the Clinical Application of Particles' Laser-hybrid Accelerator for Radiobiological Applications (LhARA) facility is being studied and requires simulation of novel accelerator components (such as the Gabor lens capture system), detector simulation and simulation of the ion beam interaction with cells. The first stage of LhARA will provide protons up to 15 MeV for in vitro studies. The second stage of LhARA will use a fixed-field accelerator to increase the energy of the particles to allow in vivo studies with protons and in vitro studies with heavier ions. BDSIM, a Geant4 based accelerator simulation tool, has been used to perform particle tracking simulations to verify the beam optics design done by BeamOptics and these show good agreement. Design parameters were defined based on an EPOCH simulation of the laser source and a series of mono-energetic input beams were generated from this by BDSIM. The tracking results show the large angular spread of the input beam (0.2 rad) can be transported with a transmission of almost 100% whilst keeping divergence at the end station very low (<0.1 mrad). The legacy of LhARA will be the demonstration of technologies that could drive a step-change in the provision of proton and light ion therapy (i.e. a laser source coupled to a Gabor lens capture and a fixed-field accelerator), and a system capable of delivering a comprehensive set of experimental data that can be used to enhance the clinical application of proton and light ion therapy.

Design and commissioning of an image-guided small animal radiation platform and quality assurance protocol for integrated proton and x-ray radiobiology research.

Small animal x-ray irradiation platforms are expanding the capabilities and future pathways for radiobiology research. Meanwhile, proton radiotherapy is transitioning to a standard treatment modality in the clinician's precision radiotherapy toolbox, highlighting a gap between state-of-the-art clinical radiotherapy and small animal radiobiology research. Comparative research of the biological differences between proton and x-ray beams could benefit from an integrated small animal irradiation system for in vivo experiments and corresponding quality assurance (QA) protocols to ensure rigor and reproducibility. The objective of this study is to incorporate a proton beam into a small animal radiotherapy platform while implementing QA modelled after clinical protocols. A 225 kV x-ray small animal radiation research platform (SARRP) was installed on rails to align with a modified proton experimental beamline from a 230 MeV cyclotron-based clinical system. Collimated spread out Bragg peaks (SOBP) were produced with beam parameters compatible with small animal irradiation. Proton beam characteristics were measured and alignment reproducibility with the x-ray system isocenter was evaluated. A QA protocol was designed to ensure consistent proton beam quality and alignment. As a preliminary study, cellular damage via γ-H2AX immunofluorescence staining in an irradiated mouse tumor model was used to verify the beam range in vivo. The beam line was commissioned to deliver Bragg peaks with range 4-30 mm in water at 2 Gy min-1. SOBPs were delivered with width up to 25 mm. Proton beam alignment with the x-ray system agreed within 0.5 mm. A QA phantom was created to ensure reproducible alignment of the platform and verify beam delivery. γ-H2AX staining verified expected proton range in vivo. An image-guided small animal proton/x-ray research system was developed to enable in vivo investigations of radiobiological effects of proton beams, comparative studies between proton and x-ray beams, and investigations into novel proton treatment methods.

Dosimetry and characterization of a 25-MeV proton beam line for preclinical radiobiology research.

PURPOSE: With the increase in proton therapy centers, there is a growing need to make progress in preclinical proton radiation biology to give accessible data to medical physicists and practicing radiation oncologists. METHODS: A cyclotron usually producing radioisotopes with a proton beam at an energy of about 25 MeV after acceleration, was used for radiobiology studies. Depleted silicon surface barrier detectors were used for the beam energy measurement. A complementary metal oxide semiconductor (CMOS) sensor and a plastic scintillator detector were used for fluence measurement, and compared to Geant4 and an in-house analytical dose modeling developed for this purpose. Also, from the energy measurement of each attenuated beam, the dose-averaged linear energy transfer (LETd ) was calculated with Geant4. RESULTS: The measured proton beam energy was 24.85 ± 0.14 MeV with an energy straggling of 127 ± 22 keV before scattering and extraction in air. The measured flatness was within ± 2.1% over 9 mm in diameter. A wide range of LETd is achievable: constant between the entrance and the exit of the cancer cell sample ranging from 2.2 to 8 keV/µm, beyond 20 keV/µm, and an average of 2-5 keV/µm in a scattering spread-out Bragg peak calculated for an example of a 6-mm-thick xenograft tumor. CONCLUSION: The dosimetry and the characterization of a 25-MeV proton beam line for preclinical radiobiology research was performed by measurements and modeling, demonstrating the feasibility of delivering a proton beam for preclinical in vivo and in vitro studies with LETd of clinical interest.

TRACKING DOWN ALPHA-PARTICLES: THE DESIGN, CHARACTERISATION AND TESTING OF A SHALLOW-ANGLED ALPHA-PARTICLE IRRADIATOR.

Human exposure to α-particles from radon and other radionuclides is associated with carcinogenesis, but if well controlled and targeted to cancer cells, α-particles may be used in radiotherapy. Thus, it is important to understand the biological effects of α-particles to predict cancer risk and optimise radiotherapy. To enable studies of α-particles in cells, we developed and characterised an α-particle automated irradiation rig that allows exposures at a shallow angle (70° to the normal) of cell monolayers in a 30 mm diameter dish to complement standard perpendicular irradiations. The measured incident energy of the α-particles was 3.3 ± 0.5 MeV (LET in water = 120 keV µm-1), with a maximum incident dose rate of 1.28 ± 0.02 Gy min-1, which for a 5 µm cell monolayer corresponds to a mean dose rate of 1.57 ± 0.02 Gy min-1 and a mean LET in water of 154 keV µm-1. The feasibility of resolving radiation-induced DNA double-strand breaks (DSB) foci along the track of α-particles was demonstrated using immunofluorescent labelling with γH2AX and 53BP1 in normal MRC-5 human lung cells.

THE RADIOBIOLOGICAL PLATFORM AT ARRONAX.

The cyclotron ARRONAX can deliver different types of particles (protons, deuterons, alpha-particles) in an energy range up to 68 MeV. One of its six experimental halls is dedicated to studying the interactions of radiation with matter including living matter. A horizontal beamline for cell irradiation has been setup and characterized. The radiobiological characterization was done in terms of V79 cells survival after irradiation with 68 MeV protons. The results demonstrate that radiobiological studies can be successfully performed confirming the high potential of the facility.

The NMBU FIGARO low dose irradiation facility.

PURPOSE: Derivation of dose-response relationships for exposed organisms and their sensitive life history stages requires in-house experiments under well-defined, controlled conditions. In the present work we describe the FIGARO low dose gamma irradiation facility at the Norwegian University of Life Sciences, Ås, Norway, which is managed by the Centre of Environmental Radioactivity (CERAD CoE). CONCLUSIONS: The CERAD/NMBU facility opened in 2003, and was upgraded to a climate controlled facility in 2012, supported by the EU DoReMi project. The 60Co irradiation source provides a continuous dose rate field from 3 Gy/hr down to 0.4 mGy/hr when maximally loaded (400 GBq). The FIGARO low dose gamma irradiation facility allows simultaneous acute to chronic exposure of organisms over the whole dose-rate field. The facility is licensed for a number of different test organisms, including GMOs, and can be used in combination with other stressors such as trace metals and UV radiation.

A framework for exposure characterization and gamma dosimetry at the NMBU FIGARO irradiation facility.

PURPOSE: The FIGARO low dose 60Co gamma irradiation facility at the Norwegian University of Life Sciences, Ås, Norway, is dedicated to the study of effects on living organisms from acute or chronic ionizing radiation exposures, either alone or in combination with other stressors such as UV radiation, metals or radionuclides. Here, we present a framework of working guidelines and computer software for characterization of absorbed dose rates and accumulated doses to organisms exposed within the continuous gamma field at FIGARO. The aims of the framework are to ensure gamma exposures are well characterized, that results from exposures are correctly interpreted in terms of absorbed dose rates and accumulated doses, and that sufficient information is available so that exposures can be reproduced later or at other facilities. METHODS: The software of the framework includes a Geant4 application for Monte Carlo radiation transport simulations and tools for dose planning, recording and reporting. The working guidelines are prepared for expert users who provide simulated, calculated or estimated absorbed dose rates and for regular users who conduct exposure experiments and are responsible for record keeping. To demonstrate the developed framework, we use a case study where 14 freshwater microcosms are exposed to four levels of gamma dose rates at FIGARO. CONCLUSION: The framework guides users towards good dosimetry practices. Lessons learned could be transferable to other gamma irradiation facilities.

STUDY FOR A PASSIVE SCATTERING LINE DEDICATED TO RADIOBIOLOGY EXPERIMENTS AT THE TRENTO PROTON THERAPY CENTER.

The recent worldwide spread of Proton Therapy centers paves the way to new opportunities for basic and applied research related to the use of accelerated proton beams. Clinical centers make use of proton beam energies up to about 230 MeV. This represents an interesting energy range for a large spectrum of applications, including detector testing, radiation shielding and space research. Additionally, radiobiology research might benefit for a larger availability of proton beams, especially in those centers where a room dedicated to research activities also exists. Here, we describe the initial activities for the setup of a radiobiology irradiation facility at the Trento Proton Therapy Center. Data referring to the characterization of the beam in air are essential to that purpose and will be presented. A basic setup for large field irradiation will be also proposed, which is needed for the majority of in vitro and in vivo radiobiology experiments.

PROSPECTS FOR METROLOGY RELATED TO BIOLOGICAL RADIATION EFFECTS OF ION BEAMS.

In recent years, several approaches have been proposed to provide an understanding of the enhanced relative biological effectiveness of ion beams based on multi-scale models of their radiation effects. Among these, the BioQuaRT project was the only one which focused on developing metrology for a multi-scale characterization of particle track structure. The progress made within the BioQuaRT project has motivated the formation of a department 'Radiation Effects' at PTB dedicated to metrological research on ionizing radiation effects. This paper gives an overview of the department's present research directions and shortly discusses ideas for the future development of metrology related to biological effects of ion beams that are based on a stakeholder consultation.

Design and testing of a microcontroller that enables alpha particle irradiators to deliver complex dose rate patterns.

There is increasing interest in using alpha particle emitting radionuclides for cancer therapy because of their unique cytotoxic properties which are advantageous for eradicating tumor cells. The high linear energy transfer (LET) of alpha particles produces a correspondingly high density of ionizations along their track. Alpha particle emitting radiopharmaceuticals deposit this energy in tissues over prolonged periods with complex dose rate patterns that depend on the physical half-life of the radionuclide, and the biological uptake and clearance half-times in tumor and normal tissues. We have previously shown that the dose rate increase half-time that arises as a consequence of these biokinetics can have a profound effect on the radiotoxicity of low-LET radiation. The microcontroller hardware and software described here offer a unique way to deliver these complex dose rate patterns with a broad-beam alpha particle irradiator, thereby enabling experiments to study the radiobiology of complex dose rate patterns of alpha particles. Complex dose rate patterns were created by precise manipulation of the timing of opening and closing of the electromechanical shutters of an α-particle irradiator. An Arduino Uno and custom circuitry was implemented to control the shutters. The software that controls the circuits and shutters has a user-friendly Graphic User Interface (GUI). Alpha particle detectors were used to validate the programmed dose rate profiles. Circuit diagrams and downloadable software are provided to facilitate adoption of this technology by other radiobiology laboratories.

The REPAIR Project: Examining the Biological Impacts of Sub-Background Radiation Exposure within SNOLAB, a Deep Underground Laboratory.

Considerable attention has been given to understanding the biological effects of low-dose ionizing radiation exposure at levels slightly above background. However, relatively few studies have been performed to examine the inverse, where natural background radiation is removed. The limited available data suggest that organisms exposed to sub-background radiation environments undergo reduced growth and an impaired capacity to repair genetic damage. Shielding from background radiation is inherently difficult due to high-energy cosmic radiation. SNOLAB, located in Sudbury, Ontario, Canada, is a unique facility for examining the effects of sub-background radiation exposure. Originally constructed for astroparticle physics research, the laboratory is located within an active nickel mine at a depth of over 2,000 m. The rock overburden provides shielding equivalent to 6,000 m of water, thereby almost completely eliminating cosmic radiation. Additional features of the facility help to reduce radiological contamination from the surrounding rock. We are currently establishing a biological research program within SNOLAB: Researching the Effects of the Presence and Absence of Ionizing Radiation (REPAIR project). We hypothesize that natural background radiation is essential for life and maintains genomic stability, and that prolonged exposure to sub-background radiation environments will be detrimental to biological systems. Using a combination of whole organism and cell culture model systems, the effects of exposure to a sub-background environment will be examined on growth and development, as well as markers of genomic damage, DNA repair capacity and oxidative stress. The results of this research will provide further insight into the biological effects of low-dose radiation exposure as well as elucidate some of the processes that may drive evolution and selection in living systems. This Radiation Research focus issue contains reviews and original articles, which relate to the presence or absence of low-dose ionizing radiation exposure.

50 Years of the Radiological Research Accelerator Facility (RARAF).

The Radiological Research Accelerator Facility (RARAF) is in its 50th year of operation. It was commissioned on April 1, 1967 as a collaboration between the Radiological Research Laboratory (RRL) of Columbia University, and members of the Medical Research Center of Brookhaven National Laboratory (BNL). It was initially funded as a user facility for radiobiology and radiological physics, concentrating on monoenergetic neutrons. Facilities for irradiation with MeV light charged particles were developed in the mid-1970s. In 1980 the facility was relocated to the Nevis Laboratories of Columbia University. RARAF now has seven beam lines, each having a dedicated irradiation facility: monoenergetic neutrons, charged particle track segments, two charged particle microbeams (one electrostatically focused to <1 µm, one magnetically focused), a 4.5 keV soft X-ray microbeam, a neutron microbeam, and a facility that produces a neutron spectrum similar to that of the atomic bomb dropped at Hiroshima. Biology facilities are available on site within close proximity to the irradiation facilities, making the RARAF very user friendly.

Current Instrumentation and Technologies in Modern Radiobiology Research-Opportunities and Challenges.

There is a growing awareness of the gaps in the technical methods employed in radiation biology experiments. These quality gaps can have a substantial effect on the reliability and reproducibility of results as outlined in several recent meta-studies. This is especially true in the context of the newer laboratory irradiation technologies. These technologies allow for delivery of highly localized dose distributions and increased spatial accuracy but also present increased challenges of their own. In this article, we highlight some of the features of the new technologies and the experiments they support; this includes image-guided localized radiation systems, microirradiator systems using carbon nanotubes and physical radiation modifiers like gold nanoparticles. We discuss the key technical issues related to the consistency and quality of modern radiation biology experiments including dosimetry protocols that are essential to all experiments, quality assurance approaches, methods to validate physical radiation targeting including immunohistochemical assays and other biovalidation approaches. We highlight the future needs in terms of education and training and the creation of tools for cross-institutional benchmarking quality in preclinical studies. The demands for increased experimental rigor are challenging but can be met with an awareness and a systematic approach which ensures quality.

The effect of slice thickness on target and organs at risk volumes, dosimetric coverage and radiobiological impact in IMRT planning

Purpose: Dose-volume histogram (DVH) has become an important tool for evaluation of radiation outcome as reflected from many clinical protocols. While dosimetric accuracy in treatment planning system (TPS) is well quantified, the variability in volume estimation is uncertain due to reconstruction algorithm that is investigated in this study. In addition, the impact of dose distribution and tumor control probability (TCP) were also investigated with CT slice thickness for IMRT planning. Materials and methods: A water phantom containing various objects with accurately known volume ranging from 1 to 100 cm3 was scanned with 1, 2, 3, 5, and 10 mm slice thickness. The CT data sets were sent to Eclipse TPS for contour delineation and volume estimation. The data were compared with known volume for the estimation of error in the volume of each structure. IMRT Plans were generated on phantom containing four objects with different slice thickness (1–5 mm) to calculate TCP. ICRU-83- recommended dose points such as D2%, D50%, D98%, as well as homogeneity and conformity index were also calculated. Results: The variability of volumes with CT slice thickness was significant especially for small volume structures. A maximum error of 92 % was noticed for 1 cm3 volume of object with 10 mm slice thickness, whereas it was *19 % for 1 mm slice thickness. For 2 and 3 cm3 objects, the maximum error of 99 % was noticed with 10 mm slice thickness and *60 % with 5 mm. The differences are smaller for larger volumes with a cutoff at about 20 cm3. The calculated volume of the objects is a function of reconstruction algorithm and slice thickness. The PTV mean dose and TCP decreased with increasing slice thickness. Maximum variation of *5 % was noticed in mean dose and *2 % in TCP with change in slice thickness from 1 to 5 mm. The relative decrease in target volume receiving 95 % of the prescribed dose is *5 % with change in slice thickness from 1 to 5 mm. The homogeneity index increases up to 163 % and conformity index decreases by 4 % between 1 and 5 mm slice thickness, producing highly inhomogeneous and least conformal treatment plan. Conclusions: Estimation of a volume is dependent on CT slice thickness and the contouring algorithm in a TPS. During commissioning of TPS and for all clinical protocols, evaluation of volume should be included to provide the limit of accuracy in DVH from TPS, especially for small objects. A smaller slice thickness provides superior dosimetry with improved TCP. Thus, the smallest possible slice thickness should be used for IMRT planning, especially when smaller structures are present (AU)

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