A patient tumour-on-a-chip system for personalised investigation of radiotherapy based treatment regimens.

Development of personalised cancer models to predict response to radiation would benefit patient care; particularly in malignancies where treatment resistance is prevalent. Herein, a robust, easy to use, tumour-on-a-chip platform which maintains precision cut head and neck cancer for the purpose of ex vivo irradiation is described. The device utilises sintered discs to separate the biopsy and medium, mimicking in vivo microvascular flow and diffusion, maintaining tissue viability for 68 h. Integrity of tissues is demonstrated by the low levels of lactate dehydrogenase release and retained histology, accompanied by assessment of cell viability by trypan blue exclusion and flow cytometry; fluid dynamic modelling validates culture conditions. An irradiation jig is described for reproducible delivery of clinically-relevant doses (5 × 2 Gy) to newly-presenting primary tumours (n = 12); the addition of concurrent cisplatin is also investigated (n = 8) with response analysed by immunohistochemistry. Fractionated irradiation reduced proliferation (BrdU, p = 0.0064), increased DNA damage (Æ´H2AX, p = 0.0043) and caspase-dependent apoptosis (caspase-cleaved cytokeratin-18) compared to control; caspase-dependent apoptosis was further increased by concurrent cisplatin compared to control (p = 0.0063). This is a proof of principle study showing the response of cancer tissue to irradiation ex vivo in a bespoke system. The novel platform described has the potential to personalise treatment for patients in a cost-effective manner with applicability to any solid tumour.

Automatic exposure control calibration and optimisation for abdomen, pelvis and lumbar spine imaging with an Agfa computed radiography system.

The use of three physical image quality metrics, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and mean effective noise equivalent quanta (eNEQm) have recently been examined by our group for their appropriateness in the calibration of an automatic exposure control (AEC) device for chest radiography with an Agfa computed radiography (CR) imaging system. This study uses the same methodology but investigates AEC calibration for abdomen, pelvis and spine CR imaging. AEC calibration curves were derived using a simple uniform phantom (equivalent to 20 cm water) to ensure each metric was held constant across the tube voltage range. Each curve was assessed for its clinical appropriateness by generating computer simulated abdomen, pelvis and spine images (created from real patient CT datasets) with appropriate detector air kermas for each tube voltage, and grading these against reference images which were reconstructed at detector air kermas correct for the constant detector dose indicator (DDI) curve currently programmed into the AEC device. All simulated images contained clinically realistic projected anatomy and were scored by experienced image evaluators. Constant DDI and CNR curves did not provide optimized performance but constant eNEQm and SNR did, with the latter being the preferred calibration metric given that it is easier to measure in practice. This result was consistent with the previous investigation for chest imaging with AEC devices. Medical physicists may therefore use a simple and easily accessible uniform water equivalent phantom to measure the SNR image quality metric described here when calibrating AEC devices for abdomen, pelvis and spine imaging with Agfa CR systems, in the confidence that clinical image quality will be sufficient for the required clinical task. However, to ensure appropriate levels of detector air kerma the advice of expert image evaluators must be sought.

Correlation between the signal-to-noise ratio improvement factor (KSNR) and clinical image quality for chest imaging with a computed radiography system.

This work assessed the appropriateness of the signal-to-noise ratio improvement factor (KSNR) as a metric for the optimisation of computed radiography (CR) of the chest. The results of a previous study in which four experienced image evaluators graded computer simulated chest images using a visual grading analysis scoring (VGAS) scheme to quantify the benefit of using an anti-scatter grid were used for the clinical image quality measurement (number of simulated patients = 80). The KSNR was used to calculate the improvement in physical image quality measured in a physical chest phantom. KSNR correlation with VGAS was assessed as a function of chest region (lung, spine and diaphragm/retrodiaphragm), and as a function of x-ray tube voltage in a given chest region. The correlation of the latter was determined by the Pearson correlation coefficient. VGAS and KSNR image quality metrics demonstrated no correlation in the lung region but did show correlation in the spine and diaphragm/retrodiaphragmatic regions. However, there was no correlation as a function of tube voltage in any region; a Pearson correlation coefficient (R) of -0.93 (p = 0.015) was found for lung, a coefficient (R) of -0.95 (p = 0.46) was found for spine, and a coefficient (R) of -0.85 (p = 0.015) was found for diaphragm. All demonstrate strong negative correlations indicating conflicting results, i.e. KSNR increases with tube voltage but VGAS decreases. Medical physicists should use the KSNR metric with caution when assessing any potential improvement in clinical chest image quality when introducing an anti-scatter grid for CR imaging, especially in the lung region. This metric may also be a limited descriptor of clinical chest image quality as a function of tube voltage when a grid is used routinely.

A practical method to standardise and optimise the Philips DoseRight 2.0 CT automatic exposure control system.

Given the increasing use of computed tomography (CT) in the UK over the last 30 years, it is essential to ensure that all imaging protocols are optimised to keep radiation doses as low as reasonably practicable, consistent with the intended clinical task. However, the complexity of modern CT equipment can make this task difficult to achieve in practice. Recent results of local patient dose audits have shown discrepancies between two Philips CT scanners that use the DoseRight 2.0 automatic exposure control (AEC) system in the 'automatic' mode of operation. The use of this system can result in drifting dose and image quality performance over time as it is designed to evolve based on operator technique. The purpose of this study was to develop a practical technique for configuring examination protocols on four CT scanners that use the DoseRight 2.0 AEC system in the 'manual' mode of operation. This method used a uniform phantom to generate reference images which form the basis for how the AEC system calculates exposure factors for any given patient. The results of this study have demonstrated excellent agreement in the configuration of the CT scanners in terms of average patient dose and image quality when using this technique. This work highlights the importance of CT protocol harmonisation in a modern Radiology department to ensure both consistent image quality and radiation dose. Following this study, the average radiation dose for a range of CT examinations has been reduced without any negative impact on clinical image quality.

Retrospective review of locally set tolerances for VMAT prostate patient specific QA using the COMPASS(®) system.

PURPOSE: This study retrospectively reviewed locally set pass rates/tolerances for COMPASS(®) pre-treatment quality assurance results for RapidArc prostate plans to determine if these are appropriate. This was performed via quantifying the agreement between treatment planning system calculations and measurements based on absolute dose comparisons (3% tolerance for all dose points) and global gamma index assessment (3%/3 mm criterion for 97% of points). METHOD: Seventy-three prostate one-arc RapidArc plans, delivered by four dosimetrically matched linacs, were measured using the MatriXX Evolution two-dimensional array and analysed using COMPASS(®) (v.3, IBA Dosimetry). For the planning target volumes (PTV) considered, the D99%, D50%, D1% and DMean differences were analysed. The percentage volume with gamma greater than 1, average gamma and DMean difference were investigated for all structures. Nine plans were also assessed across the linac fleet to investigate potential linac dependence of results. RESULTS AND CONCLUSIONS: Regarding PTV DMean differences, all plans fell within the 3% tolerance and mostly within 2%, although there was a relatively small systematic difference. The absolute percentage differences of average and median doses suggested a weak linac dependence of the results which was found to be clinically insignificant. New stricter tolerances were established both for dose comparisons and gamma evaluation. Correlation between the gamma pass rates and the differences in the D99%, D50% and D1% was found to be moderate suggesting that gamma analysis in isolation has questionable clinical meaning and should only be used to indicate outliers for further analysis.

Investigating the use of an antiscatter grid in chest radiography for average adults with a computed radiography imaging system.

OBJECTIVE: The aim of this study was to investigate via simulation a proposed change to clinical practice for chest radiography. The validity of using a scatter rejection grid across the diagnostic energy range (60-125 kVp), in conjunction with appropriate tube current-time product (mAs) for imaging with a computed radiography (CR) system was investigated. METHODS: A digitally reconstructed radiograph algorithm was used, which was capable of simulating CR chest radiographs with various tube voltages, receptor doses and scatter rejection methods. Four experienced image evaluators graded images with a grid (n = 80) at tube voltages across the diagnostic energy range and varying detector air kermas. These were scored against corresponding images reconstructed without a grid, as per current clinical protocol. RESULTS: For all patients, diagnostic image quality improved with the use of a grid, without the need to increase tube mAs (and therefore patient dose), irrespective of the tube voltage used. Increasing tube mAs by an amount determined by the Bucky factor made little difference to image quality. CONCLUSION: A virtual clinical trial has been performed with simulated chest CR images. RESULTS indicate that the use of a grid improves diagnostic image quality for average adults, without the need to increase tube mAs, even at low tube voltages. ADVANCES IN KNOWLEDGE: Validated with images containing realistic anatomical noise, it is possible to improve image quality by utilizing grids for chest radiography with CR systems without increasing patient exposure. Increasing tube mAs by an amount determined by the Bucky factor is not justified.

Validation of a technique for estimating organ doses for kilovoltage cone-beam CT of the prostate using the PCXMC 2.0 patient dose calculator.

The use of cone beam CT in common radiotherapy treatments is increasing with the growth of image guided radiotherapy. Whilst the benefits that this technology offers are clear, such as improved patient positioning prior to treatment, it is always important to consider the implications of such intensive imaging regimes on the patient, especially when considering the fundamental radiation protection requirements for justification and optimisation.The purpose of this study was to develop a technique that uses readily available dose calculation software (PCXMC 2.0) to estimate the organ and effective doses that result from these types of examination in prostate treatments on the Varian OBI system. It has been shown that by separating these types of examinations into 28 different projections, with a range of x-ray beam qualities, it is possible to reproduce the complex geometry that is used on these imaging systems in PCXMC i.e. asymmetric radiation field with a half bowtie filter rotating 360° around the patient.This new technique has been validated with thermo-luminescent dosimeter measurements in the Rando anthropomorphic phantom, and has been shown to give excellent agreement with this established method (R(2) = 0.995). This technique will prove to be valuable to radiotherapy departments that are looking to optimise their CBCT imaging protocols as it allows a rapid evaluation of the impact of any changes on patient dose. It also serves to further highlight the levels of dose that these types of patient are subject to when having daily CBCT scans as part of the treatment, which further reinforces the need for optimisation of both patient dose and image quality on these systems.

An investigation of automatic exposure control calibration for chest imaging with a computed radiography system.

The purpose of this study was to examine the use of three physical image quality metrics in the calibration of an automatic exposure control (AEC) device for chest radiography with a computed radiography (CR) imaging system. The metrics assessed were signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and mean effective noise equivalent quanta (eNEQm), all measured using a uniform chest phantom. Subsequent calibration curves were derived to ensure each metric was held constant across the tube voltage range. Each curve was assessed for its clinical appropriateness by generating computer simulated chest images with correct detector air kermas for each tube voltage, and grading these against reference images which were reconstructed at detector air kermas correct for the constant detector dose indicator (DDI) curve currently programmed into the AEC device. All simulated chest images contained clinically realistic projected anatomy and anatomical noise and were scored by experienced image evaluators. Constant DDI and CNR curves do not appear to provide optimized performance across the diagnostic energy range. Conversely, constant eNEQm and SNR do appear to provide optimized performance, with the latter being the preferred calibration metric given as it is easier to measure in practice. Medical physicists may use the SNR image quality metric described here when setting up and optimizing AEC devices for chest radiography CR systems with a degree of confidence that resulting clinical image quality will be adequate for the required clinical task. However, this must be done with close cooperation of expert image evaluators, to ensure appropriate levels of detector air kerma.

Commissioning of a new wide-bore MRI scanner for radiotherapy planning of head and neck cancer.

OBJECTIVE: A combination of CT and MRI is recommended for radiotherapy planning of head and neck cancers, and optimal spatial co-registration is achieved by imaging in the treatment position using the necessary immobilisation devices on both occasions, something which requires wide-bore scanners. Quality assurance experiments were carried out to commission a newly installed 1.5-T wide-bore MRI scanner and a dedicated, flexible six-channel phased array head and neck coil. METHODS: Signal-to-noise ratio (SNR) and spatial signal uniformity were quantified using a homogeneous aqueous phantom, and geometric distortion was quantified using a phantom with water-filled fiducials in a grid pattern. Volunteer scans were also used to determine the in vivo image quality. Clinically relevant T1 weighted and T2 weighted fat-suppressed sequences were assessed in multiple scan planes (both sequences fast spin echo based). The performance of two online signal uniformity correction schemes, one utilising low-resolution reference scans and the other not utilising low-resolution reference scans, was compared. RESULTS: Geometric distortions, for a ±35-kHz bandwidth, were <1 mm for locations within 10 cm of the isocentre rising to 1.8 mm at 18 cm away. SNR was above 50, and uniformity in the axial plane was 71% and 95% before and after uniformity correction, respectively. CONCLUSION: The combined performance of the wide-bore scanner and the dedicated coil was adjudged adequate, although superior-inferior spatial coverage was slightly limited in the lower neck. ADVANCES IN KNOWLEDGE: These results will be of interest to the increasing number of oncology centres that are seeking to incorporate MRI into planning practice using dedicated equipment.

Correlation of the clinical and physical image quality in chest radiography for average adults with a computed radiography imaging system.

OBJECTIVE: The purpose of this study was to examine the correlation between the quality of visually graded patient (clinical) chest images and a quantitative assessment of chest phantom (physical) images acquired with a computed radiography (CR) imaging system. METHODS: The results of a previously published study, in which four experienced image evaluators graded computer-simulated postero-anterior chest images using a visual grading analysis scoring (VGAS) scheme, were used for the clinical image quality measurement. Contrast-to-noise ratio (CNR) and effective dose efficiency (eDE) were used as physical image quality metrics measured in a uniform chest phantom. Although optimal values of these physical metrics for chest radiography were not derived in this work, their correlation with VGAS in images acquired without an antiscatter grid across the diagnostic range of X-ray tube voltages was determined using Pearson's correlation coefficient. RESULTS: Clinical and physical image quality metrics increased with decreasing tube voltage. Statistically significant correlations between VGAS and CNR (R=0.87, p<0.033) and eDE (R=0.77, p<0.008) were observed. CONCLUSION: Medical physics experts may use the physical image quality metrics described here in quality assurance programmes and optimisation studies with a degree of confidence that they reflect the clinical image quality in chest CR images acquired without an antiscatter grid. ADVANCES IN KNOWLEDGE: A statistically significant correlation has been found between the clinical and physical image quality in CR chest imaging. The results support the value of using CNR and eDE in the evaluation of quality in clinical thorax radiography.

Use of a digitally reconstructed radiograph-based computer simulation for the optimisation of chest radiographic techniques for computed radiography imaging systems.

OBJECTIVES: The purpose of this study was to derive an optimum radiographic technique for computed radiography (CR) chest imaging using a digitally reconstructed radiograph computer simulator. The simulator is capable of producing CR chest radiographs of adults with various tube potentials, receptor doses and scatter rejection. METHODS: Four experienced image evaluators graded images of average and obese adult patients at different potentials (average-sized, n=50; obese, n=20), receptor doses (n=10) and scatter rejection techniques (average-sized, n=20; obese, n=20). The quality of the images was evaluated using visually graded analysis. The influence of rib contrast was also assessed. RESULTS: For average-sized patients, image quality improved when tube potential was reduced compared with the reference (102 kVp). No scatter rejection was indicated. For obese patients, it has been shown that an antiscatter grid is indicated, and should be used in conjunction with as low a tube potential as possible (while allowing exposure times <20 ms). It is also possible to reduce receptor air kerma by 50% without adversely influencing image quality. Rib contrast did not interfere at any tube potential. CONCLUSIONS: A virtual clinical trial has been performed with simulated chest CR images. Results indicate that low tube potentials (<102 kVp) are optimal for average and obese adults, the former acquired without scatter rejection, the latter with an anti-scatter grid. Lower receptor (and therefore patient doses) than those used clinically are possible while maintaining adequate image quality.

Validation of a large-scale audit technique for CT dose optimisation.

The expansion and increasing availability of computed tomography (CT) imaging means that there is a greater need for the development of efficient optimisation strategies that are able to inform clinical practice, without placing a significant burden on limited departmental resources. One of the most fundamental aspects to any optimisation programme is the collection of patient dose information, which can be compared with appropriate diagnostic reference levels. This study has investigated the implementation of a large-scale audit technique, which utilises data that already exist in the radiology information system, to determine typical doses for a range of examinations on four CT scanners. This method has been validated against what is considered the 'gold standard' technique for patient dose audits, and it has been demonstrated that results equivalent to the 'standard-sized patient' can be inferred from this much larger data set. This is particularly valuable where CT optimisation is concerned as it is considered a 'high dose' technique, and hence close monitoring of patient dose is particularly important.

A method to produce and validate a digitally reconstructed radiograph-based computer simulation for optimisation of chest radiographs acquired with a computed radiography imaging system.

OBJECTIVES: The purpose of this study was to develop and validate a computer model to produce realistic simulated computed radiography (CR) chest images using CT data sets of real patients. METHODS: Anatomical noise, which is the limiting factor in determining pathology in chest radiography, is realistically simulated by the CT data, and frequency-dependent noise has been added post-digitally reconstructed radiograph (DRR) generation to simulate exposure reduction. Realistic scatter and scatter fractions were measured in images of a chest phantom acquired on the CR system simulated by the computer model and added post-DRR calculation. RESULTS: The model has been validated with a phantom and patients and shown to provide predictions of signal-to-noise ratios (SNRs), tissue-to-rib ratios (TRRs: a measure of soft tissue pixel value to that of rib) and pixel value histograms that lie within the range of values measured with patients and the phantom. The maximum difference in measured SNR to that calculated was 10%. TRR values differed by a maximum of 1.3%. CONCLUSION: Experienced image evaluators have responded positively to the DRR images, are satisfied they contain adequate anatomical features and have deemed them clinically acceptable. Therefore, the computer model can be used by image evaluators to grade chest images presented at different tube potentials and doses in order to optimise image quality and patient dose for clinical CR chest radiographs without the need for repeat patient exposures.

Investigating the exposure class of a computed radiography system for optimisation of physical image quality for chest radiography.

The purpose of this study was to investigate whether the exposure (speed) class (EC) of an Agfa computed radiography (CR) system could be used to optimise chest radiography. The frequency-dependent normalised noise-power spectra (NNPS(f)) were determined for a range of EC settings (25-1200) for a receptor dose of 4 microGy. Signal-to-noise ratios (SNRs) were measured in the lung, heart and diaphragm areas of a chest phantom with ECs of 400 and 600 at four tube voltages (60, 75, 90 and 125 kVp). As anatomical background can be a factor in detection of lung nodules, a tissue to rib ratio (TRR), which measures the ratio of pixel values in the nodule to that of rib, was measured in the lung region of the phantom to assess the suppression of the rib at ECs of 400 and 600. The NNPS(f) at ECs lower than 400 was relatively high. The NNPS(f) at EC 600 was found to be 7% lower when averaged over all frequencies than that at EC 400. The statistical significance of this difference was verified. The EC 800 and EC 1200 settings offered no extra advantages in terms of lowering frequency-dependent noise. The EC 600 setting offered improvements in SNR of between 10% and 18% in the lung, 11% and 16% in the heart, and 15% and 20% in the diaphragm compared with EC 400. Statistical analysis verified the significant difference. The EC 600 setting increased the TRR, thereby helping to suppress rib. This work indicates that an exposure class setting of 600 is the most appropriate for standard chest radiography, but clinical verification is required.

Investigation of optimum X-ray beam tube voltage and filtration for chest radiography with a computed radiography system.

The purpose of this study was to determine the optimum tube voltage and amount of added copper (Cu) filtration for processed chest radiographs obtained with an Agfa 75.0 Computed Radiography (CR) system. The contrast-to-noise ratio (CNR) was measured in the lung, heart/spine and diaphragm compartments of a validated chest phantom using various tube voltages and amounts of Cu filtration. The CNR was derived as a function of air kerma at the CR plate and with the effective dose. As rib contrast can interfere with detection of nodules in chest radiography, a tissue-to-rib ratio (TRR) was derived to investigate which tube voltages suppress the contrast of rib. Although processing algorithms affect the signal and noise in a way that is hard to predict, we found that, for a given set of processing parameters, the CNR was related to the plate air kerma and effective dose in a logarithmic manner (all R(2) >or=0.97). For imaging of the lung region, a low voltage (60 kVp) produced the highest CNR, whereas a high voltage (125 kVp) produced the highest TRR. In the heart/spine region, 80-125 kVp produced the highest CNR, while in the diaphragm region 60-90 kVp produced the highest CNR. For chest radiography with this CR system, the optimal tube voltage depends upon the region of interest. Of the filters tested, a 0.1 mm Cu thickness was found to provide a statistically significant increase in the CNR in the diaphragm region with tube potentials of 60 kVp and 80 kVp, without affecting the CNR in the other anatomical compartments.

Virtual reality training for radiotherapy becomes a reality.

A report in 2007 to the UK Government identified a crisis in England for training staff and students for the radiotherapy treatment of cancer. The Hull authors have developed an immersive life size virtual environment of a radiotherapy treatment room, known as VERT, to address this problem. VERT provides the trainee with models, simulation, enhanced visualization and training aids for treatment of virtual patients in a virtual treatment room. In 2007 immersive VERT systems for radiotherapy training were established for training purposes at the University Aarhus Hospital (Denmark) and the Birmingham City University (UK). This paper reports on early evaluations of VERT by these two institutions.

A method to optimize the processing algorithm of a computed radiography system for chest radiography.

A test methodology using an anthropomorphic-equivalent chest phantom is described for the optimization of the Agfa computed radiography "MUSICA" processing algorithm for chest radiography. The contrast-to-noise ratio (CNR) in the lung, heart and diaphragm regions of the phantom, and the "system modulation transfer function" (sMTF) in the lung region, were measured using test tools embedded in the phantom. Using these parameters the MUSICA processing algorithm was optimized with respect to low-contrast detectability and spatial resolution. Two optimum "MUSICA parameter sets" were derived respectively for maximizing the CNR and sMTF in each region of the phantom. Further work is required to find the relative importance of low-contrast detectability and spatial resolution in chest images, from which the definitive optimum MUSICA parameter set can then be derived. Prior to this further work, a compromised optimum MUSICA parameter set was applied to a range of clinical images. A group of experienced image evaluators scored these images alongside images produced from the same radiographs using the MUSICA parameter set in clinical use at the time. The compromised optimum MUSICA parameter set was shown to produce measurably better images.

Immersive visualization with automated collision detection for radiotherapy treatment planning.

Intensity modulated radiotherapy (IMRT) is a technique for treating cancer tumours using external delivery of radiation. To create a treatment plan the directions of the external radiation beams (typically 5 to 9) need to be specified. Normally the beams are all coplanar due to the added complexity of planning and patient set-up for non-coplanar beams. RTStar provides a virtual environment of a radiotherapy (RT) treatment room that provides a range of views and visualizations that aid a treatment planner to choose non-coplanar beam directions efficiently. RTStar also automatically warns the planner when a collision would occur during patient set-up. A study was conducted on 8 prostate IMRT cancer patients using RTStar to create RT plans using non-coplanar beams. The study demonstrated that these IMRT prostate plans with non-coplanar beams had a dosimetric advantage over their coplanar conterparts.

Treatment planning challenges in breast irradiation: the ideal and the practical.

Radiotherapy has recently undergone some interesting developments, with the introduction of new technology and techniques in many departments. Arguably, with this comes an increase in the expectation of its capability. The treatment site that continues to represent most of the workload in our departments is breast. We should consider how relevant these contemporary changes are in the treatment of breast cancer. In this paper, we review some of the challenges in planning breast treatments and how they may be addressed with contemporary radiotherapy techniques.