Interplay of MLC, gantry and respiratory motion during DCAT delivery

This study investigated the possible interplay effects arising from the treatment of moving targets using the dynamic conformal arc therapy (DCAT) technique. Dose from a modulated test beam was measured, with and without phantom motion and with and without a 30o arc rotation, using a diode array placed on a sinusoidally moving platform. Measurements were repeated at five different collimator angles (0, 22.5, 45, 67.5 and 90o), at two different dose rates (300 and 600 MU/min). Results showed that the effect of respiratory motion on the measured dose distribution increased slightly when the beams were delivered as arcs, rather than with a static gantry angle, and that this effect increased substantially as the collimator angle was increased from 0o (MLC motion perpendicular to respiratory motion) to 90o (MLC motion parallel to respiratory motion). The dose oscillations arising from interplay between phantom and MLC motion were found to increase in magnitude when the dose rate was increased. These results led to the development of simple recommendations for minimizing the negative effects of motion interplay on DCAT dose distributions

Development of a novel experimental model to investigate radiobiological implications of respiratory motion in advanced radiotherapy

Respiratory motion introduces complex spatio-temporal variations in the dosimetry of radiotherapy. There is a paucity of literature investigating the radiobiological consequences of intrafraction motion and concerns regarding the impact of movement when applied to cancer cell lines in vitro exist. We have addressed this by developing a novel model which accurately replicates respiratory motion under experimental conditions to allow clinically relevant irradiation of cell lines. A bespoke phantom and motor driven moving platform was adapted to accommodate flasks containing medium and cells in order to replicate respiratory motion using varying frequencies and amplitude settings. To study this effect on cell survival in vitro, dose response curves were determined for human lung cancer cell lines H1299 and H460 exposed to a uniform 6 MV radiation field under moving or stationary conditions. Cell survival curves showed no significant difference between irradiation at different dose points for these cell lines in the presence or absence of motion. These data indicate that motion of unshielded cells in vitro does not affect cell survival in the presence of uniform irradiation. This model provides a novel research platform to investigate the radiobiological consequences of respiratory motion in radiotherapy.

Investigating the influence of respiratory motion on the radiation induced bystander effect in modulated radiotherapy

Respiratory motion introduces complex spatio-temporal variations in the dosimetry of radiotherapy and may contribute towards uncertainties in radiotherapy planning. This study investigates the potential radiobiological implications occurring due to tumour motion in areas of geometric miss in lung cancer radiotherapy. A bespoke phantom and motor-driven platform to replicate respiratory motion and study the consequences on tumour cell survival in vitro was constructed. Human non-small-cell lung cancer cell lines H460 and H1299 were irradiated in modulated radiotherapy configurations in the presence and absence of respiratory motion. Clonogenic survival was calculated for irradiated and shielded regions. Direction of motion, replication of dosimetry by multi-leaf collimator (MLC) manipulation and oscillating lead shielding were investigated to confirm differences in cell survival. Respiratory motion was shown to significantly increase survival for out-of-field regions for H460/H1299 cell lines when compared with static irradiation (p <0.001). Significantly higher survival was found in the in-field region for the H460 cell line (p <0.030). Oscillating lead shielding also produced these significant differences. Respiratory motion and oscillatory delivery of radiation dose to human tumour cells has a significant impact on in- and out-of-field survival in the presence of non-uniform irradiation in this in vitro set-up. This may have important radiobiological consequences for modulated radiotherapy in lung cancer. 

Dosimetric impact of geometric errors due to respiratory motion prediction on dynamic multileaf collimator-based four-dimensional radiation delivery

The synchronization of dynamic multileaf collimator (DMLC) response with respiratory motion is critical to ensure the accuracy of DMLC-based four dimensional (4D) radiation delivery. In practice, however, a finite time delay (response time) between the acquisition of tumor position and multileaf collimator response necessitates predictive models of respiratory tumor motion to synchronize radiation delivery. Predicting a complex process such as respiratory motion introduces geometric errors, which have been reported in several publications. However, the dosimetric effect of such errors on 4D radiation delivery has not yet been investigated. Thus, our aim in this work was to quantify the dosimetric effects of geometric error due to prediction under several different conditions. Conformal and intensity modulated radiation therapy (IMRT) plans for a lung patient were generated for anterior-posterior/posterior-anterior (AP/PA) beam arrangements at 6 and 18 MV energies to provide planned dose distributions. Respiratory motion data was obtained from 60 diaphragm-motion fluoroscopy recordings from five patients. A linear adaptive filter was employed to predict the tumor position. The geometric error of prediction was defined as the absolute difference between predicted and actual positions at each diaphragm position. Distributions of geometric error of prediction were obtained for all of the respiratory motion data. Planned dose distributions were then convolved with distributions for the geometric error of prediction to obtain convolved dose distributions. The dosimetric effect of such geometric errors was determined as a function of several variables: response time (0-0.6 s), beam energy (6/18 MV), treatment delivery (3D/4D), treatment type (conformal/IMRT), beam direction (AP/PA), and breathing training type (free breathing/audio instruction/visual feedback). Dose difference and distance-to-agreement analysis was employed to quantify results. Based on our data, the dosimetric impact of prediction (a) increased with response time, (b) was larger for 3D radiation therapy as compared with 4D radiation therapy, (c) was relatively insensitive to change in beam energy and beam direction, (d) was greater for IMRT distributions as compared with conformal distributions, (e) was smaller than the dosimetric impact of latency, and (f) was greatest for respiration motion with audio instructions, followed by visual feedback and free breathing. Geometric errors of prediction that occur during 4D radiation delivery introduce dosimetric errors that are dependent on several factors, such as response time, treatment-delivery type, and beam energy. Even for relatively small response times of 0.6 s into the future, dosimetric errors due to prediction could approach delivery errors when respiratory motion is not accounted for at all. To reduce the dosimetric impact, better predictive models and/or shorter response times are required.

Motion correction algorithm of lung tumors for respiratory gated PET images

Respiratory gating in lung PET imaging to compensate for respiratory motion artifacts is a current research issue with broad potential impact on quantitation, diagnosis and clinical management of lung tumors. However, PET images collected at discrete bins can be significantly affected by noise as there are lower activity counts in each gated bin unless the total PET acquisition time is prolonged, so that gating methods should be combined with imaging-based motion correction and registration methods. The aim of this study was to develop and validate a fast and practical solution to the problem of respiratory motion for the detection and accurate quantitation of lung tumors in PET images. This included: (1) developing a computer-assisted algorithm for PET/CT images that automatically segments lung regions in CT images, identifies and localizes lung tumors of PET images; (2) developing and comparing different registration algorithms which processes all the information within the entire respiratory cycle and integrate all the tumor in different gated bins into a single reference bin. Four registration/integration algorithms: Centroid Based, Intensity Based, Rigid Body and Optical Flow registration were compared as well as two registration schemes: Direct Scheme and Successive Scheme. Validation was demonstrated by conducting experiments with the computerized 4D NCAT phantom and with a dynamic lung-chest phantom imaged using a GE PET/CT System. Iterations were conducted on different size simulated tumors and different noise levels. Static tumors without respiratory motion were used as gold standard; quantitative results were compared with respect to tumor activity concentration, cross-correlation coefficient, relative noise level and computation time. Comparing the results of the tumors before and after correction, the tumor activity values and tumor volumes were closer to the static tumors (gold standard). Higher correlation values and lower noise were also achieved after applying the correction algorithms. With this method the compromise between short PET scan time and reduced image noise can be achieved, while quantification and clinical analysis become fast and precise.

Motion Correction Algorithm of Lung Tumors for Respiratory Gated PET Images

Respiratory gating in lung PET imaging to compensate for respiratory motion artifacts is a current research issue with broad potential impact on quantitation, diagnosis and clinical management of lung tumors. However, PET images collected at discrete bins can be significantly affected by noise as there are lower activity counts in each gated bin unless the total PET acquisition time is prolonged, so that gating methods should be combined with imaging-based motion correction and registration methods. The aim of this study was to develop and validate a fast and practical solution to the problem of respiratory motion for the detection and accurate quantitation of lung tumors in PET images. This included: (1) developing a computer-assisted algorithm for PET/CT images that automatically segments lung regions in CT images, identifies and localizes lung tumors of PET images; (2) developing and comparing different registration algorithms which processes all the information within the entire respiratory cycle and integrate all the tumor in different gated bins into a single reference bin. Four registration/integration algorithms: Centroid Based, Intensity Based, Rigid Body and Optical Flow registration were compared as well as two registration schemes: Direct Scheme and Successive Scheme. Validation was demonstrated by conducting experiments with the computerized 4D NCAT phantom and with a dynamic lung-chest phantom imaged using a GE PET/CT System. Iterations were conducted on different size simulated tumors and different noise levels. Static tumors without respiratory motion were used as gold standard; quantitative results were compared with respect to tumor activity concentration, cross-correlation coefficient, relative noise level and computation time. Comparing the results of the tumors before and after correction, the tumor activity values and tumor volumes were closer to the static tumors (gold standard). Higher correlation values and lower noise were also achieved after applying the correction algorithms. With this method the compromise between short PET scan time and reduced image noise can be achieved, while quantification and clinical analysis become fast and precise.

The effect of organ motion of radiotherapy plans

Organ motion as a result of respiration is an important field of research for medical physics. Knowledge of magnitude and direction of this motion is necessary to allow for more accurate radiotherapy treatment planning. This will result in higher doses to the tumour whilst sparing healthy tissue. This project involved human trials, where the radiation therapy patient's kidneys were CT scanned under three different conditions; whilst free breathing (FB), breath-hold at normal tidal inspiration (BHIN), and breath-hold at normal tidal expiration (BHEX). The magnitude of motion was measured by recording the outline of the kidney from a Beam's Eye View (BEV). The centre of mass of this 2D shape was calculated for each set using "ImageJ" software and the magnitude of movement determined from the change in the centroid's coordinates between the BHIN and BHEX scans. The movement ranged from, for the left and right kidneys, 4-46mm and 2-44mm in the superior/inferior (axial) plane, 1-21mm and 2- 16mm in the anterior/posterior (coronal) plane, and 0-6mm and 0-8mm in the lateral/medial (sagittal) plane. From exhale to inhale, the kidneys tended to move inferiorly, anteriorly and laterally. A standard radiotherapy plan, designed to treat the para-aortics with opposed lateral fields was performed on the free breathing (planning) CT set. The field size and arrangement was set up using the same parameters for each subject. The prescription was to deliver 45 Gray in 25 fractions. This field arrangement and prescription was then copied over to the breath hold CT sets, and the dosimetric differences were compared using Dose Volume Histograms (DVH). The point of comparison for the three sets was recorded as the percentage volume of kidney receiving less than or equal to 10 Gray. The QUASAR respiratory motion phantom was used with the range of motion determined from the human study. The phantom was imaged, planned and treated with a linear accelerator with dose determined by film. The effect of the motion was measured by the change in the penumbra of the film and compared to the penumbra from the treatment planning system.

Motion Management for Radical Radiotherapy in Non-small Cell Lung Cancer

Intrafraction tumour motion is an issue that is of increased interest in the era of image-guided radiotherapy. It is particularly relevant for non-small cell lung cancer, for which a number of recent developments are in use to aid with motion management in the delivery of radical radiotherapy. The ability to deliver hypofractionated ablative doses, such as in stereotactic radiotherapy, has been aided by improvements in the ability to analyse tumour motion and amend treatment delivery. In addition, accounting for tumour motion can enable dose escalation to occur by reducing the normal tissue being irradiated by virtue of a reduction in target volumes. Motion management for lung tumours incorporates five key components: imaging, breath-hold techniques, abdominal compression, respiratory tracking and respiratory gating. These will be described, together with the relevant benefits and associated complexities. Many studies have described improved dosimetric coverage and reduced normal tissue complication probability rates when using motion management techniques. Despite the widespread uptake of many of these techniques, there is a paucity of literature reporting improved outcome in overall survival and local control for patients whenever motion management techniques are used. This overview will review the extent of lung tumour motion, ways in which motion is detected and summarise the key methods used in motion management.

Verification of the clinical implementation of the respiratory gated beam delivery technique with synchrotron-based proton irradiation

The clinical advantage for protons over conventional high-energy x-rays stems from their unique depth-dose distribution, which delivers essentially no dose beyond the end of range. In order to achieve it, accurate localization of the tumor volume relative to the proton beam is necessary. For cases where the tumor moves with respiration, the resultant dose distribution is sensitive to such motion. One way to reduce uncertainty caused by respiratory motion is to use gated beam delivery. The main goal of this dissertation is to evaluate the respiratory gating technique in both passive scattering and scanning delivery mode. Our hypothesis for the study was that optimization of the parameters of synchrotron operation and respiratory gating can lead to greater efficiency and accuracy of respiratory gating for all modes of synchrotron-based proton treatment delivery. The hypothesis is tested in two specific aims. The specific aim #1 is to assess the efficiency of respiratory-gated proton beam delivery and optimize the synchrotron operations for the gated proton therapy. A simulation study was performed and introduced an efficient synchrotron operation pattern, called variable Tcyc. In addition, the simulation study estimated the efficiency in the respiratory gated scanning beam delivery mode as well. The specific aim #2 is to assess the accuracy of beam delivery in respiratory-gated proton therapy. The simulation study was extended to the passive scattering mode to estimate the quality of pulsed beam delivery to the residual motion for several synchrotron operation patterns with the gating technique. The results showed that variable Tcyc operation can offer good reproducible beam delivery to the residual motion at a certain phase of the motion. For respiratory gated scanning beam delivery, the impact of motion on the dose distributions by scanned beams was investigated by measurement. The results showed the threshold for motion for a variety of scan patterns and the proper number of paintings for normal and respiratory gated beam deliveries. The results of specific aims 1 and 2 provided supporting data for implementation of the respiratory gating beam delivery technique into both passive and scanning modes and the validation of the hypothesis.