Propagation-based phase-contrast imaging of the breast: image quality and the effect of X-ray energy and radiation dose.

OBJECTIVES: Propagation-based phase-contrast computed tomography (PB-CT) is a new imaging technique that exploits refractive and absorption properties of X-rays to enhance soft tissue contrast and improve image quality. This study compares image quality of PB-CT and absorption-based CT (AB-CT) for breast imaging while exploring X-ray energy and radiation dose. METHODS: Thirty-nine mastectomy samples were scanned at energy levels of 28-34keV using a flat panel detector at radiation dose levels of 4mGy and 2mGy. Image quality was assessed using signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), spatial resolution (res) and visibility (vis). Statistical analysis was performed to compare PB-CT images against their corresponding AB-CT images scanned at 32keV and 4mGy. RESULTS: The PB-CT images at 4mGy, across nearly all energy levels, demonstrated superior image quality than AB-CT images at the same dose. At some energy levels, the 2mGy PB-CT images also showed better image quality in terms of CNR/Res and vis compared to the 4mGy AB-CT images. At both investigated doses, SNR and SNR/res were found to have a statistically significant difference across all energy levels. The difference in vis was statistically significant at some energy levels. CONCLUSION: This study demonstrates superior image quality of PB-CT over AB-CT, with X-ray energy playing a crucial role in determining image quality parameters. ADVANCES IN KNOWLEDGE: Our findings reveal that standard dose PB-CT outperforms standard dose AB-CT across all image quality metrics. Additionally, we demonstrate that low dose PB-CT can produce superior images compared to standard dose AB-CT in terms of CNR/Res and vis.

The design and characterization of a novel dynamic collimator system for synchrotron radiotherapy applications.

BACKGROUND: Novel synchrotron radiotherapy techniques are currently limited to using prefabricated beam-limiting blocks for field definition. For large experiments, a single square tungsten block is often used for every treatment since conformal blocks are both patient and field specific, and require long lead times for fabrication. Future synchrotron radiotherapy treatments would benefit from a dynamic collimator system. PURPOSE: We developed and tested a novel collimator design for use on the Imaging and Medical Beamline (IMBL) at the ANSTO Australian Synchrotron. METHODS: The maximum usable beam size on IMBL is 50-mm wide by 3-mm tall. Given the beam shape, targets must be vertically scanned through the synchrotron beam to cover the target volume. To shape the beam, a novel collimator design was developed, consisting of two semi-circular leaves made from 4-mm thick tungsten sheets, with each leaf capable of both vertical and horizontal movement. A software model was created to optimize motor trajectories and generate deliverable treatment fields. A series of geometric field shapes and clinical target volumes were delivered using the collimator and imaged with a digital imaging detector. Four similarity metrics (volumetric similarity, DICE, and the average and maximum Hausdorff distances) were used to measure differences between the input and planned fields, and the planned and delivered fields. RESULTS: Differences between input and planned fields increased with delivery speed, and were worse for rectangular and square fields compared to circular fields. However, the differences between planned and delivered fields were small, where the maximum average deviation between the fields was 0.25 mm (one pixel). Field repeatability was consistent with no difference (σ = 0 for all metrics) observed in consecutively delivered fields. CONCLUSIONS: We have successfully built and demonstrated a novel collimator for synchrotron radiotherapy applications on IMBL. Several design improvements have been highlighted and will be addressed in future revisions the collimator. However, in its current state, the collimator enables dynamically delivered conformal treatment fields to be utilized on IMBL, and is ready to support the forthcoming canine treatments on IMBL.

A Novel Anthropomorphic Phantom Composed of Tissue-Equivalent Materials for Use in Experimental Radiotherapy: Design, Dosimetry and Biological Pilot Study.

The production of anthropomorphic phantoms generated from tissue-equivalent materials is challenging but offers an excellent copy of the typical environment encountered in typical patients. High-quality dosimetry measurements and the correlation of the measured dose with the biological effects elicited by it are a prerequisite in preparation of clinical trials with novel radiotherapy approaches. We designed and produced a partial upper arm phantom from tissue-equivalent materials for use in experimental high-dose-rate radiotherapy. The phantom was compared to original patient data using density values and Hounsfield units obtained from CT scans. Dose simulations were conducted for broad-beam irradiation and microbeam radiotherapy (MRT) and compared to values measured in a synchrotron radiation experiment. Finally, we validated the phantom in a pilot experiment with human primary melanoma cells.

The Spinal Cord as Organ of Risk: Assessment for Acute and Subacute Neurological Adverse Effects after Microbeam Radiotherapy in a Rodent Model.

Microbeam radiotherapy (MRT), a high dose rate radiotherapy technique using spatial dose fractionation at the micrometre range, has shown a high therapeutic efficacy in vivo in different tumour entities, including lung cancer. We have conducted a toxicity study for the spinal cord as organ of risk during irradiation of a target in the thoracic cavity. In young adult rats, the lower thoracic spinal cord was irradiated over a length of 2 cm with an array of quasi-parallel microbeams of 50 µm width, spaced at a centre-to-centre distance of 400 µm, with MRT peak doses up to 800 Gy. No acute or subacute adverse effects were observed within the first week after irradiation up to MRT peak doses of 400 Gy. No significant differences were seen between irradiated animals and non-irradiated controls in motor function and sensitivity, open field test and somatosensory evoked potentials (SSEP). After irradiation with MRT peak doses of 450-800 Gy, dose-dependent neurologic signs occurred. Provided that long-term studies do not reveal significant morbidity due to late toxicity, an MRT dose of 400 Gy can be considered safe for the spinal cord in the tested beam geometry and field size.

Quantifying lung aeration in neonatal lambs at birth using lung ultrasound.

Background: Lung ultrasound (LUS) is a safe and non-invasive tool that can potentially assess regional lung aeration in newborn infants and reduce the need for X-ray imaging. LUS produces images with characteristic artifacts caused by the presence of air in the lung, but it is unknown if LUS can accurately detect changes in lung air volumes after birth. This study compared LUS images with lung volume measurements from high-resolution computed tomography (CT) scans to determine if LUS can accurately provide relative measures of lung aeration. Methods: Deceased near-term newborn lambs (139 days gestation, term ∼148 days) were intubated and the chest imaged using LUS (bilaterally) and phase contrast x-ray CT scans at increasing static airway pressures (0-50 cmH2O). CT scans were analyzed to calculate regional air volumes and correlated with measures from LUS images. These measures included (i) LUS grade; (ii) brightness (mean and coefficient of variation); and (iii) area under the Fourier power spectra within defined frequency ranges. Results: All LUS image analysis techniques correlated strongly with air volumes measured by CT (p < 0.01). When imaging statistics were combined in a multivariate linear regression model, LUS predicted the proportion of air in the underlying lung with moderate accuracy (95% prediction interval ± 22.15%, r 2 = 0.71). Conclusion: LUS can provide relative measures of lung aeration after birth in neonatal lambs. Future studies are needed to determine if LUS can also provide a simple means to assess air volumes and individualize aeration strategies for critically ill newborns in real time.

Modification of the Langendorff system of the isolated beating heart for experimental radiotherapy at a synchrotron: 4000†Gy in a heart beat.

Microbeam radiotherapy could help to cure malignant tumours which are currently still considered therapy-resistant. With an irradiation target in the thoracic cavity, the heart would be one of the most important organs at risk. To assess the acute adverse effects of microbeam irradiation in the heart, a powerful ex vivo tool was created by combining the Langendorff model of the isolated beating mammalian heart with X-Tream dosimetry. In a first pilot experiment conducted at the Biomedical and Imaging Beamline of the Australian Synchrotron, the system was tested at a microbeam peak dose approximately ten times higher than the anticipated future microbeam irradiation treatment doses. The entire heart was irradiated with a dose of 4000 Gy at a dose rate of >6000 Gy s-1, using an array of 50 µm-wide microbeams spaced at a centre-to-centre distance of 400 µm. Although temporary arrhythmias were seen, they reverted spontaneously to a stable rhythm and no cardiac arrest occurred. This amazing preservation of cardiac function is promising for future therapeutic approaches.

Microbeam Irradiation of the Beating Rodent Heart: An Ex Vivo Study of Acute and Subacute Effects on Cardiac Function.

PURPOSE: Microbeam radiation therapy (MRT) has shown several advantages compared with conventional broad-beam radiation therapy in small animal models, including a better preservation of normal tissue function and improved drug delivery based on a rapidly increased vascular permeability in the target region. Normal tissue tolerance is the limiting factor in clinical radiation therapy. Knowledge of the normal tissue tolerance of organs at risk is therefore a prerequisite in evaluating any new radiation therapy approach. With an irradiation target in the thoracic cavity, the heart would be the most important organ at risk. METHODS AND MATERIALS: We used the ex vivo beating rodent heart in the Langendorff perfusion system at the synchrotron to administer microbeam irradiation (MBI) with a peak dose of 40 or 400 Gy. By continuously recording the electrocardiogram, the left ventricular pressure, and the aortic pressure before, during and after MBI, we were able to assess acute and subacute effects of MBI on electrophysiological and mechanical cardiac function. In addition, we analyzed histologic and ultrastructural sequelae caused by MBI. RESULTS: There were no significant changes in heart rate, heart rate variability, systolic increase of left ventricular pressure or aortic pressure. Moreover, the changes of heart rate, left ventricular pressure and aortic pressure by adding 10-5 mol/L norepinephrine to the perfusate, were also not significant between MBI and sham experiments. However, the rate-pressure product as a surrogate marker for maximum workload after MBI was significantly lower compared with sham-irradiated controls. On the structural level, no severe membranous, sarcomeric, mitochondrial or nuclear changes caused by MBI were detected by desmin immunohistochemistry and electron microscopy. CONCLUSIONS: With respect to acute and subacute toxicity, an MBI peak dose up to 400 Gy did not result in severe changes in cardiac electrophysiology or mechanics.

Designing a breast support device for phase contrast tomographic imaging: getting ready for a clinical trial.

OBJECTIVE: To design a device that can support the breast during phase-contrast tomography, and characterise its fit parameterisation and comfort rating. METHODS: 27 participants were recruited to trial a system for breast support during simulated phase contrast imaging, including being positioned on a prone imaging table while wearing the device. Participants underwent a photogrammetry analysis to establish the geometric parameterisations. All participants trialled a single-cup design while 14 participants also trialled a double-cup with suction holder and all completed a series of questionnaires to understand subjective comfort. RESULTS: Photogrammetry revealed significant positive correlations between bra cup volume and measured prone volume (p < 0.001), and between "best fit" single-cup holder volume and measured prone volume (p < 0.005). Both holders were suitable devices in terms of subjective comfort and immobilisation while stationary. However, some re-engineering to allow for quick, easy fitting in future trials where rotation through the radiation beam will occur is necessary. Light suction was well-tolerated when required. CONCLUSION: All participants indicated the table and breast support devices were comfortable, and they would continue in the trial. ADVANCES IN KNOWLEDGE: Phase contrast tomography is an emerging breast imaging modality and clinical trials are commencing internationally. This paper describes the biomedical engineering designs, in parallel with optimal imaging, that are necessary to measure breast volume so that adequate breast support can be achieved. Breast support devices have implications for comfort, motion correction and maximising breast tissue visualisation.

Full Field X-Ray Scatter Tomography.

In X-ray imaging, photons are transmitted through and absorbed by the target object, but are also scattered in significant quantities. Previous attempts to use scattered X-ray photons for imaging applications used pencil or fan beam illumination. Here we present 3D X-ray Scatter Tomography using full-field illumination for small-animal imaging. Synchrotron imaging experiments were performed on a phantom and the chest of a juvenile rat. Transmitted and scattered photons were simultaneously imaged with separate cameras; a scientific camera directly downstream of the sample stage, and a pixelated detector with a pinhole imaging system placed at 45° to the beam axis. We obtained scatter tomogram feature fidelity sufficient for segmentation of the lungs and major airways in the rat. The image contrast in the scatter tomogram slices approached that of transmission imaging, indicating robustness to the amount of multiple scattering present in our case. This opens the possibility of augmenting full-field 2D imaging systems with additional scatter detectors to obtain complementary modes or to improve the fidelity of existing images without additional dose, potentially leading to single-shot or reduced-angle tomography or overall dose reduction for live animal studies.

Effect of x-ray energy on the radiological image quality in propagation-based phase-contrast computed tomography of the breast.

Purpose: Breast cancer is the most common cancer in women in developing and developed countries and is responsible for 15% of women's cancer deaths worldwide. Conventional absorption-based breast imaging techniques lack sufficient contrast for comprehensive diagnosis. Propagation-based phase-contrast computed tomography (PB-CT) is a developing technique that exploits a more contrast-sensitive property of x-rays: x-ray refraction. X-ray absorption, refraction, and contrast-to-noise in the corresponding images depend on the x-ray energy used, for the same/fixed radiation dose. The aim of this paper is to explore the relationship between x-ray energy and radiological image quality in PB-CT imaging. Approach: Thirty-nine mastectomy samples were scanned at the imaging and medical beamline at the Australian Synchrotron. Samples were scanned at various x-ray energies of 26, 28, 30, 32, 34, and 60 keV using a Hamamatsu Flat Panel detector at the same object-to-detector distance of 6 m and mean glandular dose of 4 mGy. A total of 132 image sets were produced for analysis. Seven observers rated PB-CT images against absorption-based CT (AB-CT) images of the same samples on a five-point scale. A visual grading characteristics (VGC) study was used to determine the difference in image quality. Results: PB-CT images produced at 28, 30, 32, and 34 keV x-ray energies demonstrated statistically significant higher image quality than reference AB-CT images. The optimum x-ray energy, 30 keV, displayed the largest area under the curve ( AUC VGC ) of 0.754 ( p = 0.009 ). This was followed by 32 keV ( AUC VGC = 0.731 , p ≤ 0.001 ), 34 keV ( AUC VGC = 0.723 , p ≤ 0.001 ), and 28 keV ( AUC VGC = 0.654 , p = 0.015 ). Conclusions: An optimum energy range (around 30 keV) in the PB-CT technique allows for higher image quality at a dose comparable to conventional mammographic techniques. This results in improved radiological image quality compared with conventional techniques, which may ultimately lead to higher diagnostic efficacy and a reduction in breast cancer mortalities.

Propagation-Based Phase-Contrast CT of the Breast Demonstrates Higher Quality Than Conventional Absorption-Based CT Even at Lower Radiation Dose.

RATIONALE AND OBJECTIVES: Propagation-based phase-contrast CT (PB-CT) is an advanced X-ray imaging technology that exploits both refraction and absorption of the transmitted X-ray beam. This study was aimed at optimizing the experimental conditions of PB-CT for breast cancer imaging and examined its performance relative to conventional absorption-based CT (AB-CT) in terms of image quality and radiation dose. MATERIALS AND METHODS: Surgically excised breast mastectomy specimens (n = 12) were scanned using both PB-CT and AB-CT techniques under varying imaging conditions. To evaluate the radiological image quality, visual grading characteristics (VGC) analysis was used in which 11 breast specialist radiologists compared the overall image quality of PB-CT images with respect to the corresponding AB-CT images. The area under the VGC curve was calculated to measure the differences between PB-CT and AB-CT images. RESULTS: The highest radiological quality was obtained for PB-CT images using a 32 keV energy X-ray beam and by applying the Homogeneous Transport of Intensity Equation phase retrieval with the value of its parameter γ set to one-half of the theoretically optimal value for the given materials. Using these optimized conditions, the image quality of PB-CT images obtained at 4 mGy and 2 mGy mean glandular dose was significantly higher than AB-CT images at 4 mGy (AUCVGC = 0.901, p = 0.001 and AUCVGC = 0.819, p = 0.011, respectively). CONCLUSION: PB-CT achieves a higher radiological image quality compared to AB-CT even at a considerably lower mean glandular dose. Successful translation of the PB-CT technique for breast cancer imaging can potentially result in improved breast cancer diagnosis.

Methods for dynamic synchrotron X-ray respiratory imaging in live animals.

Small-animal physiology studies are typically complicated, but the level of complexity is greatly increased when performing live-animal X-ray imaging studies at synchrotron and compact light sources. This group has extensive experience in these types of studies at the SPring-8 and Australian synchrotrons, as well as the Munich Compact Light Source. These experimental settings produce unique challenges. Experiments are always performed in an isolated radiation enclosure not specifically designed for live-animal imaging. This requires equipment adapted to physiological monitoring and test-substance delivery, as well as shuttering to reduce the radiation dose. Experiment designs must also take into account the fixed location, size and orientation of the X-ray beam. This article describes the techniques developed to overcome the challenges involved in respiratory X-ray imaging of live animals at synchrotrons, now enabling increasingly sophisticated imaging protocols.

Live-pig-airway surface imaging and whole-pig CT at the Australian Synchrotron Imaging and Medical Beamline.

The Australian Synchrotron Imaging and Medical Beamline (IMBL) was designed to be the world's widest synchrotron X-ray beam, partly to enable clinical imaging and therapeutic applications for humans, as well as for imaging large-animal models. Our group is currently interested in imaging the airways of newly developed cystic fibrosis (CF) animal models that display human-like lung disease, such as the CF pig. One key outcome measure for assessing the effectiveness of CF airway therapies is the ability of the lung to clear inhaled particulates by mucociliary transit (MCT). This study extends the ex vivo sheep and pig tracheal-tissue studies previously performed by the authors at the IMBL. In the present study, attempts were made to determine whether the design of the IMBL is suitable for imaging tracheal MCT in live pigs. The movement of 200 µm-diameter high-refractive-index (HRI) glass-bead marker particles deposited onto the tracheal airway surface of eight live piglets was tracked and quantified and the MCT response to aerosol delivery was examined. A high-resolution computed tomographic (CT) whole-animal post-mortem scan of one pig was also performed to verify the large sample CT capabilities of the IMBL. MCT tracking particles were visible in all animals, and the automated MCT tracking algorithms used were able to identify and track many particles, but accuracy was reduced when particles moved faster than ∼6 mm min-1 (50 pixels between exposures), or when the particles touched or overlapped. Renderings were successfully made from the CT data set. Technical issues prevented use of reliable shuttering and hence radiation doses were variable. Since dose must be carefully controlled in future studies, estimates of the minimum achievable radiation doses using this experiment design are shown. In summary, this study demonstrated the suitability of the IMBL for large-animal tracheal MCT imaging, and for whole-animal CT.

Advantages of breast cancer visualization and characterization using synchrotron radiation phase-contrast tomography.

The aim of this study was to highlight the advantages that propagation-based phase-contrast computed tomography (PB-CT) with synchrotron radiation can provide in breast cancer diagnostics. For the first time, a fresh and intact mastectomy sample from a 60 year old patient was scanned on the IMBL beamline at the Australian Synchrotron in PB-CT mode and reconstructed. The clinical picture was described and characterized by an experienced breast radiologist, who underlined the advantages of providing diagnosis on a PB-CT volume rather than conventional two-dimensional modalities. Subsequently, the image quality was assessed by 11 breast radiologists and medical imaging experts using a radiological scoring system. The results indicate that, with the radiation dose delivered to the sample being equal, the accuracy of a diagnosis made on PB-CT images is significantly higher than one using conventional techniques.

Synchrotron radiation external beam rotational radiotherapy of breast cancer: proof of principle.

The principle of rotational summation of the absorbed dose for breast cancer treatment with orthovoltage X-ray beams was proposed by J. Boone in 2012. Here, use of X-ray synchrotron radiation for image guided external beam rotational radiotherapy treatment of breast cancer is proposed. Tumor irradiation occurs with the patient in the prone position hosted on a rotating bed, with her breast hanging from a hole in the bed, which rotates around a vertical axis passing through the tumor site. Horizontal collimation of the X-ray beam provides for whole breast or partial breast irradiation, while vertical translation of the bed and successive rotations allow for irradiation of the full tumor volume, with dose rates which permit also hypofractionated treatments. In this work, which follows a previous preliminary report, results are shown of a full series of measurements on polyethylene and acrylic cylindrical phantoms carried out at the Australian Synchrotron, confirmed by Geant4 Monte Carlo simulations, intended to demonstrate the proof of principle of the technique. Dose measurements were carried out with calibrated ion chambers, radiochromic films and thermoluminescence dosimeters. The photon energy investigated was 60 keV. Image guidance may occur with the transmitted beam for contrast-enhanced breast computed tomography. For a horizontal beam collimation of 1.5 cm and rotation around the central axis of a 14 cm-diameter polyethylene phantom, a periphery-to-center dose ratio of 14% was measured. The simulations showed that under the same conditions the dose ratio decreases with increasing photon energy down to 10% at 175 keV. These values are comparable with those achievable with conventional megavoltage radiotherapy of breast cancer with a medical linear accelerator. Dose painting was demonstrated with two off-center `cancer foci' with 1.3 Gy and 0.6 Gy target doses. The use of a radiosensitizing agent for dose enhancement is foreseen.

Experimental optimisation of the X-ray energy in microbeam radiation therapy.

Microbeam radiation therapy has demonstrated superior normal tissue sparing properties compared to broadbeam radiation fields. The ratio of the microbeam peak dose to the valley dose (PVDR), which is dependent on the X-ray energy/spectrum and geometry, should be maximised for an optimal therapeutic ratio. Simulation studies in the literature report the optimal energy for MRT based on the PVDR. However, most of these studies have considered different microbeam geometries to that at the Imaging and Medical Beamline (50 µm beam width with a spacing of 400 µm). We present the first fully experimental investigation of the energy dependence of PVDR and microbeam penumbra. Using monochromatic X-ray energies in the range 40-120 keV the PVDR was shown to increase with increasing energy up to 100 keV before plateauing. PVDRs measured for pink beams were consistently higher than those for monochromatic energies similar or equivalent to the average energy of the spectrum. The highest PVDR was found for a pink beam average energy of 124 keV. Conversely, the microbeam penumbra decreased with increasing energy before plateauing for energies above 90 keV. The effect of bone on the PVDR was investigated at energies 60, 95 and 120 keV. At depths greater than 20 mm beyond the bone/water interface there was almost no effect on the PVDR. In conclusion, the optimal energy range for MRT at IMBL is 90-120 keV, however when considering the IMBL flux at different energies, a spectrum with 95 keV weighted average energy was found to be the best compromise.

X-ray microbeam measurements with a high resolution scintillator fibre-optic dosimeter.

Synchrotron microbeam radiation therapy is a novel external beam therapy under investigation, that uses highly brilliant synchrotron x-rays in microbeams 50 µm width, with separation of 400 µm, as implemented here. Due to the fine spatial fractionation dosimetry of these beams is a challenging and complicated problem. In this proof-of-concept work, we present a fibre optic dosimeter that uses plastic scintillator as the radiation conversion material. We claim an ideal one-dimensional resolution of 50 µm. Using plastic scintillator and fibre optic makes this dosimeter water-equivalent, a very desirable dosimetric property. The dosimeter was tested at the Australian Synchrotron, on the Imaging and Medical Beam-Line. The individual microbeams were able to be resolved and the peak-to-valley dose ratio and the full width at half maximum of the microbeams was measured. These results are compared to a semiconductor strip detector of the same spatial resolution. A percent depth dose was measured and compared to data acquired by an ionisation chamber. The results presented demonstrate significant steps towards the development of an optical dosimeter with the potential to be applied in quality assurance of microbeam radiation therapy, which is vital if clinical trials are to be performed on human patients.

Preclinical radiotherapy at the Australian Synchrotron's Imaging and Medical Beamline: instrumentation, dosimetry and a small-animal feasibility study.

Therapeutic applications of synchrotron X-rays such as microbeam (MRT) and minibeam (MBRT) radiation therapy promise significant advantages over conventional clinical techniques for some diseases if successfully transferred to clinical practice. Preclinical studies show clear evidence that a number of normal tissues in animal models display a tolerance to much higher doses from MRT compared with conventional radiotherapy. However, a wide spread in the parameters studied makes it difficult to make any conclusions about the associated tumour control or normal tissue complication probabilities. To facilitate more systematic and reproducible preclinical synchrotron radiotherapy studies, a dedicated preclinical station including small-animal irradiation stage was designed and installed at the Imaging and Medical Beamline (IMBL) at the Australian Synchrotron. The stage was characterized in terms of the accuracy and reliability of the vertical scanning speed, as this is the key variable in dose delivery. The measured speed was found to be within 1% of the nominal speed for the range of speeds measured by an interferometer. Furthermore, dose measurements confirm the expected relationship between speed and dose and show that the measured dose is independent of the scan direction. Important dosimetric parameters such as peak dose, valley dose, the collimator output factor and peak-to-valley dose ratio are presented for 5 mm × 5 mm, 10 mm × 10 mm and 20 mm × 20 mm field sizes. Finally, a feasibility study on three glioma-bearing rats was performed. MRT and MBRT doses were prescribed to achieve an average dose of 65 Gy in the target, and magnetic resonance imaging follow-up was performed at various time points after irradiation to follow the tumour volume. Although it is impossible to draw conclusions on the different treatments with such a small number of animals, the feasibility of end-to-end preclinical synchrotron radiotherapy studies using the IMBL preclinical stage is demonstrated.

Quantitative characterization of the X-ray beam at the Australian Synchrotron Imaging and Medical Beamline (IMBL).

A critical early phase for any synchrotron beamline involves detailed testing, characterization and commissioning; this is especially true of a beamline as ambitious and complex as the Imaging & Medical Beamline (IMBL) at the Australian Synchrotron. IMBL staff and expert users have been performing precise experiments aimed at quantitative characterization of the primary polychromatic and monochromatic X-ray beams, with particular emphasis placed on the wiggler insertion devices (IDs), the primary-slit system and any in vacuo and ex vacuo filters. The findings from these studies will be described herein. These results will benefit IMBL and other users in the future, especially those for whom detailed knowledge of the X-ray beam spectrum (or `quality') and flux density is important. This information is critical for radiotherapy and radiobiology users, who ultimately need to know (to better than 5%) what X-ray dose or dose rate is being delivered to their samples. Various correction factors associated with ionization-chamber (IC) dosimetry have been accounted for, e.g. ion recombination, electron-loss effects. A new and innovative approach has been developed in this regard, which can provide confirmation of key parameter values such as the magnetic field in the wiggler and the effective thickness of key filters. IMBL commenced operation in December 2008 with an Advanced Photon Source (APS) wiggler as the (interim) ID. A superconducting multi-pole wiggler was installed and operational in January 2013. Results are obtained for both of these IDs and useful comparisons are made. A comprehensive model of the IMBL has been developed, embodied in a new computer program named spec.exe, which has been validated against a variety of experimental measurements. Having demonstrated the reliability and robustness of the model, it is then possible to use it in a practical and predictive manner. It is hoped that spec.exe will prove to be a useful resource for synchrotron science in general, and for hard X-ray beamlines, whether they are based on bending magnets or insertion devices, in particular. In due course, it is planned to make spec.exe freely available to other synchrotron scientists.

Characterization of a synthetic single crystal diamond detector for dosimetry in spatially fractionated synchrotron x-ray fields.

PURPOSE: Modern radiotherapy modalities often use small or nonstandard fields to ensure highly localized and precise dose delivery, challenging conventional clinical dosimetry protocols. The emergence of preclinical spatially fractionated synchrotron radiotherapies with high dose-rate, sub-millimetric parallel kilovoltage x-ray beams, has pushed clinical dosimetry to its limit. A commercially available synthetic single crystal diamond detector designed for small field dosimetry has been characterized to assess its potential as a dosimeter for synchrotron microbeam and minibeam radiotherapy. METHODS: Experiments were carried out using a synthetic diamond detector on the imaging and medical beamline (IMBL) at the Australian Synchrotron. The energy dependence of the detector was characterized by cross-referencing with a calibrated ionization chamber in monoenergetic beams in the energy range 30-120 keV. The dose-rate dependence was measured in the range 1-700 Gy/s. Dosimetric quantities were measured in filtered white beams, with a weighted mean energy of 95 keV, in broadbeam and spatially fractionated geometries, and compared to reference dosimeters. RESULTS: The detector exhibits an energy dependence; however, beam quality correction factors (kQ) have been measured for energies in the range 30-120 keV. The kQ factor for the weighted mean energy of the IMBL radiotherapy spectrum, 95 keV, is 1.05 ± 0.09. The detector response is independent of dose-rate in the range 1-700 Gy/s. The percentage depth dose curves measured by the diamond detector were compared to ionization chambers and agreed to within 2%. Profile measurements of microbeam and minibeam arrays were performed. The beams are well resolved and the full width at halfmaximum agrees with the nominal width of the beams. The peak to valley dose ratio (PVDR) calculated from the profiles at various depths in water agrees within experimental error with PVDR calculations from Gafchromic film data. CONCLUSIONS: The synthetic diamond detector is now well characterized and will be used to develop an experimental dosimetry protocol for spatially fractionated synchrotron radiotherapy.