A statistical, voxelised model of prostate cancer for biologically optimised radiotherapy.

Background and purpose: Radiation therapy (RT) is commonly indicated for treatment of prostate cancer (PC). Biologicallyoptimised RT for PC may improve disease-free survival. This requires accurate spatial localisation and characterisation of tumour lesions. We aimed to generate a statistical, voxelised biological model to complement in vivomultiparametric MRI data to facilitate biologically-optimised RT. Material and methods: Ex vivo prostate MRI and histopathological imaging were acquired for 63 PC patients. These data were co-registered to derive three-dimensional distributions of graded tumour lesions and cell density. Novel registration processes were used to map these data to a common reference geometry. Voxelised statistical models of tumour probability and cell density were generated to create the PC biological atlas. Cell density models were analysed using the Kullback-Leibler divergence to compare normal vs. lognormal approximations to empirical data. Results: A reference geometry was constructed using ex vivo MRI space, patient data were deformably registered using a novel anatomy-guided process. Substructure correspondence was maintained using peripheral zone definitions to address spatial variability in prostate anatomy between patients. Three distinct approaches to interpolation were designed to map contours, tumour annotations and cell density maps from histology into ex vivo MRI space. Analysis suggests a log-normal model provides a more consistent representation of cell density when compared to a linear-normal model. Conclusion: A biological model has been created that combines spatial distributions of tumour characteristics from a population into three-dimensional, voxelised, statistical models. This tool will be used to aid the development of biologically-optimised RT for PC patients.

A novel method to determine linac mechanical isocenter position and size and examples of specific QA applications.

The most important geometric characteristic of stereotactic treatment is the accuracy of positioning the target at the treatment isocenter and the accuracy of directing the radiation beam at the treatment isocenter. Commonly, the radiation isocenter is used as the reference for the treatment isocenter, but its method of localization is not strictly defined, and it depends on the linac-specific beam steering parameters. A novel method is presented for determining the linac mechanical isocenter position and size based on the localization of the collimator axis of rotation at arbitrary gantry angle. The collimator axis of rotation position is determined from the radiation beam center position corrected for the focal spot offset. The focal spot offset is determined using the image center shift method with a custom-design rigid phantom with two sets of ball-bearings. Three specific quality assurance (QA) applications and assessment methods are also presented to demonstrate the functionality of linac mechanical isocenter position and size determination in clinical practice. The first is a mechanical and radiation isocenters coincidence test suitable for quick congruence assessment of these two isocenters for a selected energy, usually required after a nonroutine linac repair and/or energy adjustment. The second is a stereotactic beam isocentricity assessment suitable for pretreatment stereotactic QA. The third is a comprehensive linac geometrical performance test suitable for routine linac QA. The uncertainties of the method for determining mechanical isocenter position and size were measured to be 0.05 mm and 0.04 mm, respectively, using four available photon energies, and were significantly smaller than those of determining the radiation isocenter position and size, which were 0.36 mm and 0.12 mm respectively. It is therefore recommended that the mechanical isocenter position and size be used as the reference linac treatment isocenter and a linac mechanical characteristic parameter respectively.

Towards zero radiation isocentre size: minimising radiation beam isocentricity on Elekta linear accelerators by means of optimising look-up tables.

The most important geometric characteristics of SRS/SBRT treatments are precise target localisation and precise aiming of the radiation beam at the target. The AAPM-RSS Medical Physics Practice Guideline 9.a. for SRS/SBRT recommends that the radiation isocentricity (i.e. beam deviation from the isocentre) should not exceed 1 mm for SRS and 1.5 mm for SBRT. Minimising the beam deviations from the treatment target, largely due to the gantry sag, can improve the accuracy of radiosurgery and stereotactic treatments and commonly beam steering parameters are optimised to achieve this objective. This study aims to investigate, as a proof of concept, if it is possible to eliminate the beam deviations on Elekta linear accelerators altogether by optimising gantry angle dependent beam steering parameters, as stored in look-up tables. The investigation used the EPID-based Winston-Lutz test at 13 gantry angles separated every 30° (from - 180° to + 180°). Elekta linacs have two look-up tables that can be customised explicitly for radial beam angle and transverse beam position. Modifications of the radial look-up table were limited by the radial beam asymmetry inhibit of more than 5%, as measured by the linac in-built ionisation chamber. Therefore, only small radial beam deviation reductions of 0.1 mm were achieved (on average from 0.37 to 0.26 mm) while radial beam symmetry changed significantly by up to ± 7%, depending on the gantry angle as measured by the IC Profiler™. The optimised transverse look-up table resulted in reduction of transverse beam deviations to almost zero (on average from 0.20 to 0.03 mm), however, that changed the transverse beam symmetry by almost a constant value of 1%, as measured by the IC Profiler™. Ideally, two additional look-up tables are needed for effective beam steering, one for radial beam position and one for transverse beam angle. Four look-up tables in total would enable customising beam centre position and beam symmetry at any gantry angle that would minimize radiation isocentre size without compromising beam symmetry.

Practical beam steering of X-ray beams on Elekta accelerators: The effect of focal spot alignment on beam (symmetry and position) and radiation isocentre (size and position).

Acceptance and commissioning of a linear accelerator is the process of preparing it for clinical use. One of the initial important dosimetric tasks for X-ray beam set-up and use is to optimise the trajectory of the electron beam before it hits the target (focal spot). The main purpose of this study is to characterise the effect of the focal spot position (offset) on the photon beam symmetry and centre position, as well as on linac radiation isocentre size and position for an Elekta Synergy® linac. For this machine, the initial electron beam steering control items 2T and Bending F were altered to steer the beam in both transverse and radial directions respectively. The IC Profiler™ was utilised to measure the photon beam symmetry and centre position; the electronic portal imaging device (EPID) and the authors' published ready-to-go procedure were used to measure the focal spot offset; and the radiation isocentre size and position were measured using the EPID, the Elekta ball-bearing phantom and in-house software. It was observed that for the 6MV beam investigated, beam symmetry shows a high dependency on the focal spot position, with correlation coefficients of 8.6%/mm and 5.6%/mm in transverse and radial directions respectively. The radiation isocentre size shows dependency of 1.7 mm/mm on focal spot position in the transverse direction only. The radiation isocentre longitudinal position shows dependency of - 1.8 mm/mm on the focal spot position in the radial direction only. The beam centre position is directly correlated with the focal spot position in both directions, but the correlation coefficient depends on the collimation used in a given direction i.e. MLC (- 1.5 mm/mm) or diaphragms (- 0.8 mm/mm). Based on the results, a fast beam steering method was proposed and used successfully on an Elekta Versa HD™ linac, utilizing the IC Profiler™ and its associated Gantry Mounting Fixture™ (GMF) to efficiently and effectively optimise beam steering parameters for clinical use. Independent validation of the method showed that focal spot offsets and beam symmetries in terms of absolute deviations were on average 0.08 ± 0.05 mm (1SD) and 0.70 ± 0.27% (1SD) respectively.

An international survey on the clinical use of rigid and deformable image registration in radiotherapy.

OBJECTIVES: Rigid image registration (RIR) and deformable image registration (DIR) are widely used in radiotherapy. This project aims to capture current international approaches to image registration. METHODS: A survey was designed to identify variations in use, resources, implementation, and decision-making criteria for clinical image registration. This was distributed to radiotherapy centers internationally in 2018. RESULTS: There were 57 responses internationally, from the Americas (46%), Australia/New Zealand (32%), Europe (12%), and Asia (10%). Rigid image registration and DIR were used clinically for computed tomography (CT)-CT registration (96% and 51%, respectively), followed by CT-PET (81% and 47%), CT-CBCT (84% and 19%), CT-MR (93% and 19%), MR-MR (49% and 5%), and CT-US (9% and 0%). Respondent centers performed DIR using dedicated software (75%) and treatment planning systems (29%), with 84% having some form of DIR software. Centers have clinically implemented DIR for atlas-based segmentation (47%), multi-modality treatment planning (65%), and dose deformation (63%). The clinical use of DIR for multi-modality treatment planning and accounting for retreatments was considered to have the highest benefit-to-risk ratio (69% and 67%, respectively). CONCLUSIONS: This survey data provides useful insights on where, when, and how image registration has been implemented in radiotherapy centers around the world. DIR is mainly in clinical use for CT-CT (51%) and CT-PET (47%) for the head and neck (43-57% over all use cases) region. The highest benefit-risk ratio for clinical use of DIR was for multi-modality treatment planning and accounting for retreatments, which also had higher clinical use than for adaptive radiotherapy and atlas-based segmentation.

Assessment of error in the MV radiation isocenter position calculated with the Elekta XVI software.

The assessment of the coincidence of imaging and radiation isocenters is an important task of regular quality assurance of medical linear accelerators (linacs) as recommended in national and international quality assurance guidelines. A previously reported investigation of the accuracy of the Elekta XVI software to localize the linac radiation isocenter, by comparing statistically with other independent software, has shown some discrepancies at the sub-mm level. A further investigation is carried out here using a set of reference images and mathematical operations to observe how the Elekta XVI software analyses them. Symmetric mathematical operations on reference images should result in symmetrical outcomes. Three different rotation functions are used in increasing degree of complexity to characterize the Elekta XVI software error in the linac radiation isocenter position. No independent algorithms or phantoms are used in this methodology. The magnitude and direction of the radiation isocenter localization error has been determined to be consistently 0.13 mm or 0.14 mm in the longitudinal direction towards the target depending on the case. The radiation isocenter localization error comprises two separated errors of the Ball Bearing Center by 0.13 mm and MV Field Center by either 0.00 mm or -0.01 mm in the longitudinal direction towards the target. The calculation of the MV Field Center is influenced by the polymethyl methacrylate rod supporting the ball-bearing. The precise value and the root cause of the error cannot be assessed due to the rounding effect of the results reported by the Elekta XVI software and lack of access to the source code.

Assessing the dependency of the uncertainties in the Elekta Agility MLC calibration procedure on the focal spot position.

The effectiveness of radiotherapy treatments depends on the accuracy of the dose delivery process. The majority of radiotherapy courses are delivered on linear accelerators with a Multi Leaf Collimator (MLC) in 3D conformal Radiation Therapy, Intensity Modulated Radiation Therapy (IMRT) or Volumetric Modulated Arc Therapy (VMAT) modes that require accurate MLC positioning. This study investigates the MLC calibration accuracy, following manufacturer procedures for an Elekta Synergy linac with the Agility head, against the radiation focal spot offset (alignment with the collimator axis of rotation). If the radiation focal spot is not aligned ideally with the collimator axis of rotation then a systematic error can be introduced into the calibration procedure affecting absolute MLC leaf positions. Calibration of diaphrams is equally affected; however they are not investigated here. The results indicate that an estimated 0.15 mm MLC uncertainty in all MLC leaves positions can be introduced due to uncertainty of the radiation focal spot position of 0.21 mm.

Changes in Brain Metastasis During Radiosurgical Planning.

PURPOSE: To determine whether there are any changes in brain metastases or resection cavity volumes between planning magnetic resonance imaging (MRI) and radiosurgery (RS) treatment and whether these led to a change in management or alteration in the RS plan. METHODS AND MATERIALS: Patients undergoing RS for brain metastasis or tumor resection cavities had a standardized planning MRI (MRI-1) performed and a repeat verification MRI (MRI-2) 24 hours before RS. Any change in management, including replanning based on MRI-2, was recorded. RESULTS: Thirty-four patients with a total of 59 lesions (44 metastases and 15 tumor resection cavities) were assessed with a median time between MRI-1 and MRI-2 of 7 days. Seventeen patients (50%) required a change in management based on the changes seen on MRI-2. For patients with 7 days or less between scans, 41% (9 of 22) required a change in management; among patients with 8 days or more between scans, 78% (7 of 9) required a change in management. Per lesion, 32 out of 59 lesions required replanning, including 7 of 15 (47%) cavities and 25 of 44 (57%) metastases, with the most common reason (23 lesions) being an increase in gross target volume (tumor) or clinical target volume (tumor cavity). CONCLUSIONS: Measurable changes occur in brain metastasis over a short amount of time, with a change in management required in 41% of patients with 7 days between MRI-1 and MRI-2 and in 78% of patients when there is a delay longer than 7 days. We therefore recommend that the time between planning MRI and RS treatment be as short as possible.

Beam focal spot position determination for an Elekta linac with the Agility® head; practical guide with a ready-to-go procedure.

A novel phantomless, EPID-based method of measuring the beam focal spot offset of a linear accelerator was proposed and validated for Varian machines. In this method, one set of jaws and the MLC were utilized to form a symmetric field and then a 180o collimator rotation was utilized to determine the radiation isocenter defined by the jaws and the MLC, respectively. The difference between these two isocentres is directly correlated with the beam focal spot offset of the linear accelerator. In the current work, the method has been considered for Elekta linacs. An Elekta linac with the Agility® head does not have two set of jaws, therefore, a modified method is presented making use of one set of diaphragms, the MLC and a full 360o collimator rotation. The modified method has been tested on two Elekta Synergy® linacs with Agility® heads and independently validated. A practical guide with instructions and a MATLAB® code is attached for easy implementation.

Beam focal spot position: The forgotten linac QA parameter. An EPID-based phantomless method for routine Stereotactic linac QA.

Modern day Stereotactic treatments require high geometric accuracy of the delivered treatment. To achieve the required accuracy the IGRT imaging isocenter needs to closely coincide with the treatment beam isocenter. An influence on this isocenter coincidence and on the spatial positioning of the beam itself is the alignment of the treatment beam focal spot with collimator rotation axis. The positioning of the focal spot is dependent on the linac beam steering and on the stability of the monitor chamber and beam steering servo system. As such, there is the potential for focal spot misalignment and this should be checked on a regular basis. Traditional methods for measuring focal spot position are either indirect, inaccurate, or time consuming and hence impractical for routine use. In this study a novel, phantomless method has been developed using the EPID (Electronic Portal Imaging Device) that utilizes the different heights of the MLC and jaws. The method has been performed on four linear accelerators and benchmarked against an alternate ion chamber-based method. The method has been found to be reproducible to within ±0.012 mm (1 SD) and in agreement with the ion chamber-based method to within 0.001 ± 0.015 mm (1 SD). The method could easily be incorporated into a departmental routine linac QA (Quality Assurance) program.

Comparison of automatic image registration uncertainty for three IGRT systems using a male pelvis phantom.

A series of phantom images using the CIRS Virtual Human Male Pelvis was acquired across available dose ranges for three image-guided radiotherapy (IGRT) imaging systems: Elekta XVI CBCT, Varian TrueBeam CBCT, and TomoTherapy MV CT. Each image was registered to a fan-beam CT within the XVI software 100 times with random initial offsets. The residual registration error was analyzed to assess the role of imaging hardware and reconstruction in the uncertainty of the IGRT process. Residual translation errors were similar for all systems and < 0.5 mm. Over the clinical dose range for prostate IGRT images (10-25 mGy), all imaging systems provided acceptable matches in > 90% of registrations when incorporating residual rotational error using a dual quaternion derived distance metric. Outside normal dose settings, large uncertainties were observed at very low and very high dose levels. No trend between initial offset and residual registration error was observed. Patient images may incur higher uncertainties than this phantom study; however, these results encourage automatic matching for standard dose settings with review by treatment staff.

Alterations in anatomic and functional imaging parameters with repeated FDG PET-CT and MRI during radiotherapy for head and neck cancer: a pilot study.

BACKGROUND: The use of imaging to implement on-treatment adaptation of radiotherapy is a promising paradigm but current data on imaging changes during radiotherapy is limited. This is a hypothesis-generating pilot study to examine the changes on multi-modality anatomic and functional imaging during (chemo)radiotherapy treatment for head and neck squamous cell carcinoma (HNSCC). METHODS: Eight patients with locally advanced HNSCC underwent imaging including computed tomography (CT), Fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET)-CT and magnetic resonance imaging (MRI) (including diffusion weighted (DW) and dynamic contrast enhanced (DCE)) at baseline and during (chemo)radiotherapy treatment (after fractions 11 and 21). Regions of interest (ROI) were drawn around the primary tumour at baseline and during treatment. Imaging parameters included gross tumour volume (GTV) assessment, SUVmax, mean ADC value and DCE-MRI parameters including Plasma Flow (PF). On treatment changes and correlations between these parameters were analysed using a Wilcoxon rank sum test and Pearson's linear correlation coefficient respectively. A p-value <0.05 was considered statistically significant. RESULTS: Statistically significant reductions in GTV-CT, GTV-MRI and GTV-DW were observed between all imaging timepoints during radiotherapy. Changes in GTV-PET during radiotherapy were heterogeneous and non-significant. Significant changes in SUVmax, mean ADC value, Plasma Flow and Plasma Volume were observed between the baseline and the fraction 11 timepoint, whilst only changes in SUVmax between baseline and the fraction 21 timepoint were statistically significant. Significant correlations were observed between multiple imaging parameters, both anatomical and functional; 20 correlations between baseline to the fraction 11 timepoint; 12 correlations between baseline and the fraction 21 timepoints; and 4 correlations between the fraction 11 and fraction 21 timepoints. CONCLUSIONS: Multi-modality imaging during radiotherapy treatment demonstrates early changes (by fraction 11) in both anatomic and functional imaging parameters. All functional imaging modalities are potentially complementary and should be considered in combination to provide multi-parametric tumour assessment, to guide potential treatment adaptation strategies. TRIAL REGISTRATION: ISRCTN Registry: ISRCTN34165059 . Registered 2nd February 2015.

X-ray volume imaging in bladder radiotherapy verification.

PURPOSE: To assess the clinical utility of X-ray volume imaging (XVI) for verification of bladder radiotherapy and to quantify geometric error in bladder radiotherapy delivery. METHODS AND MATERIALS: Twenty subjects undergoing conformal bladder radiotherapy were recruited. X-ray volume images and electronic portal images (EPIs) were acquired for the first 5 fractions and then once weekly. X-ray volume images were co-registered with the planning computed tomography scan and clinical target volume coverage assessed in three dimensions (3D). Interfraction bladder volume change was described by quantifying changes in bladder volume with time. Bony setup errors were compared from both XVI and EPI. RESULTS: The bladder boundary was clearly visible on coronal XVI views in nearly all images, allowing accurate 3D treatment verification. In 93.5% of imaged fractions, the clinical target volume was within the planning target volume. Most subjects displayed consistent bladder volumes, but 25% displayed changes that could be predicted from the first three XVIs. Bony setup errors were similar whether calculated from XVI or EPI. CONCLUSIONS: Coronal XVI can be used to verify 3D bladder radiotherapy delivery. Image-guided interventions to reduce geographic miss and normal tissue toxicity are feasible with this technology.

A feasibility study for image guided radiotherapy using low dose, high speed, cone beam X-ray volumetric imaging.

BACKGROUND AND PURPOSE: Image Guidance of patient set-up for radiotherapy can be achieved by acquiring X-ray volumetric images (XVI) with Elekta Synergy and registering these to the planning CT scan. This enables full 3D registration of structures from similar 3D imaging modalities and offers superior image quality, rotational set-up information and a large field of view. This study uses the head section of the Rando phantom to demonstrate a new paradigm of faster, lower dose XVI that still allows registration to high precision. MATERIALS AND METHODS: One high exposure XVI scan and one low exposure XVI scan were performed with a Rando Head Phantom. The second scan was used to simulate ultra low dose, fast acquisition, full and half scans by discarding a large number of projections before reconstruction. Dose measurements were performed using Thermo Luminescent Dosimeters (TLD) and an ion chamber. The reconstructed XVI scans were automatically registered with a helical CT scan of the Rando Head using the volumetric, grey-level, cross-correlation algorithm implemented in the Syntegra software package (Philips Medical Systems). Reproducibility of the registration process was investigated. RESULTS: In both XVI scans the body surface, bone-tissue and tissue air interfaces were clearly visible. Although the subjective image quality of the low dose cone beam scan was reduced, registration of both cone beam scans with the planning CT scan agreed within 0.1 mm and 0.1 degrees . Dose to the patient was reduced from 28mGy to less than 1mGy and the equivalent scan speed reduced to one minute or less. CONCLUSIONS: Automatic 3D registration of high speed, ultra low dose XVI scans with the planning CT scan can be used for precision 3D patient set-up verification/image guidance on a daily basis with out loss of accuracy when compared to higher dose XVI scans.