IMRT delivery to a moving target by dynamic MLC tracking: delivery for targets moving in two dimensions in the beam's eye view

A new modification of the dynamic multileaf collimator (dMLC) delivery technique for intensity-modulated therapy (IMRT) is outlined. This technique enables the tracking of a target moving through rigid-body translations in a 2D trajectory in the beam's eye view. The accuracy of the delivery versus that of deliveries with no tracking and of 1D tracking techniques is quantified with clinically derived intensity-modulated beams (IMBs). Leaf trajectories calculated in the target-reference frame were iteratively synchronized assuming regular target motion. This allowed the leaves defined in the lab-reference frame to simultaneously follow the target motion and to deliver the required IMB without violation of the leaf maximum-velocity constraint. The leaves are synchronized until the gradient of the leaf position at every instant is less than a calculated maximum. The delivered fluence in the target-reference frame was calculated with a simple primary-fluence model. The new 2D tracking technique was compared with the delivered fluence produced by no-tracking deliveries and by 1D tracking deliveries for 33 clinical IMBs. For the clinical IMBs normalized to a maximum fluence of 200 MUs, the rms difference between the desired and the delivered IMB was 15.6 +/- 3.3 MU for the case of a no-tracking delivery, 7.9 +/- 1.6 MU for the case where only the primary component of motion was corrected and 5.1 +/- 1.1 MU for the 2D tracking delivery. The residual error is due to interpolation and sampling effects. The 2D tracking delivery technique requires an increase in the delivery time evaluated as between 0 and 50% of the unsynchronized delivery time for each beam with a mean increase of 13% for the IMBs tested. The 2D tracking dMLC delivery technique allows an optimized IMB to be delivered to moving targets with increased accuracy and with acceptable increases in delivery time. When combined with real-time knowledge of the target motion at delivery time, this technique facilitates improved target conformality relative to no-tracking deliveries and allows PTV margin reduction.     

On the accuracy of a moving average algorithm for target tracking during radiation therapy treatment delivery

Real-time tumor targeting involves the continuous realignment of the radiation beam with the tumor. Real-time tumor targeting offers several advantages such as improved accuracy of tumor treatment and reduced dose to surrounding tissue. Current limitations to this technique include mechanical motion constraints. The purpose of this study was to investigate an alternative treatment scenario using a moving average algorithm. The algorithm, using a suitable averaging period, accounts for variations in the average tumor position, but respiratory induced target position variations about this average are ignored during delivery and can be treated as a random error during planning. In order to test the method a comparison between five different treatment techniques was performed: (1) moving average algorithm, (2) real-time motion tracking, (3) respiration motion gating (at both inhale and exhale), (4) moving average gating (at both inhale and exhale) and (5) static beam delivery. Two data sets were used for the purpose of this analysis: (a) external respiratory-motion traces using different coaching techniques included 331 respiration motion traces from 24 lung-cancer patients acquired using three different breathing types [free breathing (FB), audio coaching (A) and audio-visual biofeedback (AV)]; (b) 3D tumor motion included implanted fiducial motion data for over 160 treatment fractions for 46 thoracic and abdominal cancer patients obtained from the Cyberknife Synchrony. The metrics used for comparison were the group systematic error (M), the standard deviation (SD) of the systematic error (sigma) and the root mean square of the random error (sigma). Margins were calculated using the formula by Stroom et al. [Int. J. Radiat. Oncol., Biol., Phys. 43(4), 905-919 (1999)]: 2sigma + 0.7sigma. The resultant calculations for implanted fiducial motion traces (all values in cm) show that M and sigma are negligible for moving average algorithm, moving average gating, and real-time tracking (i.e., M and sigma = 0 cm) compared to static beam (M = 0.02 cm and sigma = 0.16 cm) or gated beam delivery (M = -0.05 and 0.16 cm at both exhale and inhale, respectively, and sigma = 0.17 and 0.26 cm at both exhale and inhale, respectively). Moving average algorithm sigma = 0.22 cm has a slightly lower random error than static beam delivery sigma = 0.24 cm, though gating, moving average gating, and real-time tracking have much lower random error values for implanted fiducial motion. Similar trends were also observed for the results using the external respiratory motion data. Moving average algorithm delivery significantly reduces M and sigma compared with static beam delivery. The moving average algorithm removes the nonstationary part of the respiration motion which is also achieved by AV, and thus the addition of the moving average algorithm shows little improvement with AV. Overall, a moving average algorithm shows margin reduction compared with gating and static beam delivery, and may have some mechanical advantages over real-time tracking when the beam is aligned with the target and patient compliance advantages over real-time tracking when the target is aligned to the beam.     

New phase-lock tracking instrument for foetal breathing monitoring

An instrument has been developed that allows foetal breathing movements to be recorded with a laboratory resolution of about 0·06 mm. The new tracking scheme is described in addition to the complete instrument incorporating a number of these tracking units for multichannel movement monitoring. The multiple tracking scheme is implemented by adapting a commercial real-time array and building a custom or special instrument to process the signals. The instrument is capable of simultaneously tracking up to six separate echo complexes selected on an electronically-switched real-time B-scan image of the foetus. It therefore can provide any permutation of three channels of differential movement at the same time. Early clinical results obtained using the new instrument are presented.     

Introduction of audio gating to further reduce organ motion in breathing synchronized radiotherapy

With breathing synchronized radiotherapy (BSRT), a voltage signal derived from an organ displacement detector is usually displayed on the vertical axis whereas the elapsed time is shown on the horizontal axis. The voltage gate window is set on the breathing voltage signal. Whenever the breathing signal falls between the two gate levels, a gate pulse is produced to enable the treatment machine. In this paper a new gating mechanism, audio (or time-sequence) gating, is introduced and is integrated into the existing voltage gating system. The audio gating takes advantage of the repetitive nature of the breathing signal when repetitive audio instruction is given to the patient. The audio gating is aimed at removing the regions of sharp rises and falls in the breathing signal that cannot be removed by the voltage gating. When the breathing signal falls between voltage gate levels as well as between audio-gate levels, the voltage- and audio-gated radiotherapy (ART) system will generate an AND gate pulse. When this gate pulse is received by a linear accelerator, the linear accelerator becomes "enabled" for beam delivery and will deliver the beam when all other interlocks are removed. This paper describes a new gating mechanism and a method of recording beam-on signal, both of which are, configured into a laptop computer. The paper also presents evidence of some clinical advantages achieved with the ART system.     

A method for the reconstruction of four-dimensional synchronized CT scans acquired during free breathing

Breathing motion is a significant source of error in radiotherapy treatment planning for the thorax and upper abdomen. Accounting for breathing motion has a profound effect on the size of conformal radiation portals employed in these sites. Breathing motion also causes artifacts and distortions in treatment planning computed tomography (CT) scans acquired during free breathing and also causes a breakdown of the assumption of the superposition of radiation portals in intensity-modulated radiation therapy, possibly leading to significant dose delivery errors. Proposed voluntary and involuntary breath-hold techniques have the potential for reducing or eliminating the effects of breathing motion, however, they are limited in practice, by the fact that many lung cancer patients cannot tolerate holding their breath. We present an alternative solution to accounting for breathing motion in radiotherapy treatment planning, where multislice CT scans are collected simultaneously with digital spirometry over many free breathing cycles to create a four-dimensional (4-D) image set, where tidal lung volume is the additional dimension. An analysis of this 4-D data leads to methods for digital-spirometry, based elimination or accounting of breathing motion artifacts in radiotherapy treatment planning for free breathing patients. The 4-D image set is generated by sorting free-breathing multislice CT scans according to user-defined tidal-volume bins. A multislice CT scanner is operated in the ciné mode, acquiring 15 scans per couch position, while the patient undergoes simultaneous digital-spirometry measurements. The spirometry is used to retrospectively sort the CT scans by their correlated tidal lung volume within the patient's normal breathing cycle. This method has been prototyped using data from three lung cancer patients. The actual tidal lung volumes agreed with the specified bin volumes within standard deviations ranging between 22 and 33 cm3. An analysis of sagittal and coronal images demonstrated relatively small (<1 cm) motion artifacts along the diaphragm, even for tidal volumes where the rate of breathing motion is greatest. While still under development, this technology has the potential for revolutionizing the radiotherapy treatment planning for the thorax and upper abdomen.     

Coordination between breathing and forearm movements during sinusoidal tracking

Time relationships (coordination) between breathing and rhythmical limb movements were analyzed during sinusoidal tracking movements of the forearm in 11 healthy subjects. The tracking rate was varied systematically between 0.1 and 1.0 Hz in 0.1-Hz steps. The aim of the study was to elucidate whether rhythmical tracking movements can entrain breathing, and whether this entrainment depends upon the movement rate. Subjects exhibited coordination between tracking movements and breathing at various rate ratios (1:1, 1:2, 1:3). At tracking rates of between 0.2 and 0.6 Hz, 1:1 coordination occurred with a maximum at 0.3 Hz; this rate range was called the 1:1 entrainment band. Coordination of 1:2 occurred at between 0.5 and 1.0 Hz (the 1:2 coordination band) with a maximum at 0.7 Hz. Coordination of 1:3 could be detected at between 0.5 and 1.0 Hz. Different subjects showed 1:n entrainment bands at similar locations but different widths of the rate range studied. The breathing rate during tracking was significantly higher than at rest, and it was correlated positively with tracking rate. This correlation, however, depended upon the width of the entrainment bands. Breathing rates varied between 0.2 and 0.6 Hz for all coordination patterns. We conclude that the occurrence of fixed time relationships is an expression of the strength of central nervous system coupling between the two processes. The frequency of coordination between breathing and rhythmical tracking movements depends critically upon the movement rate. Accepted: 7 October 1999     

Phase-dependence of breathing and finger tracking movements during normocapnia and hypercapnia

The coordination between breathing and other motor activities usually implies that the respiratory rhythm has become entrained by the rhythm of the simultaneous movement. Our hypothesis was that by increasing the respiratory drive, e.g. by hypercapnia, we would be able to reduce the subordination of breathing to other movements and, on the other hand, enhance effects of breathing on those movements. We investigated interactions between breathing and finger flexion movements in a visually controlled step-tracking procedure which allowed us to distinguish the mutual effects and to detect the dependence of these effects on the phase-relationship between breathing and movement. In contrast to our hypothesis, we found no large increase of the respiratory influences on finger movements during hypercapnia. A noteworthy difference to normocapnia was a shortening of the finger flexion time during the final stage of expiration which was associated with an increased frequency of coincidence between the end of flexion time and the transition from expiration to inspiration. On the other hand, the response of breathing to the finger movement increased when the tracking signal was presented at the beginning of inspiration. The results of the study disproved our hypothesis and demonstrated that, during hypercapnia, breathing can be even more susceptible to influences originating from motor control. Thus, they are in agreement with the findings of a previous study that the coordination between breathing and rhythmic limb movements becomes closer during hypercapnia.     

Pursuit responses to target steps during ongoing tracking

Brief smooth eye-velocity responses to target position steps have been reported during smooth pursuit. We investigated position-error responses in eight healthy human subjects, comparing the effects of a step-ramp change in target position when imposed on steady-state smooth pursuit, vestibuloocular reflex (VOR) slow phases, or fixation. During steady-state pursuit or VOR, the target performed a step-ramp movement in the same or in the opposite direction relative to ongoing eye movements. When the step was directed backward relative to steady-state smooth pursuit, eye velocity transiently decreased (1.3 +/- 0.4 degrees /s; average peak change in amplitude +/- SD), beginning about 100 ms after the step. The amplitude of position-error responses varied inversely with the step size. In contrast, there was little or no response in trials with forward steps during steady-state smooth pursuit, when step-ramps were imposed on VOR or when smooth pursuit began from fixation. We hypothesize that during ongoing smooth tracking when a sudden shift in target position is detected the pursuit system compares the direction of ongoing eye velocity with the relative positional error on the retina. In the case of different relative directions between ongoing tracking and a new target eccentricity, a position-error response toward the new target is initiated. Such a mechanism might help the smooth pursuit system to respond better to changes in target direction. These experimental findings were simulated by a mathematical model of smooth pursuit by implementing direction-dependent behavior with a position-error gating mechanism.     

Predictive elements in ocular interception and tracking of a moving target by untrained cats

We presented a mechanical target moving at constant velocity to awake, nontrained, head-restrained cats, in order to study how naive animals pursue objects moving at a high speed with their gaze. Eye movements were recorded while the target was moving in different directions at a constant velocity (20–80°/s) through the center of the visual field. We observed two oculomotor strategies: cats either made an interception saccade (IS) toward the target but opposite to its motion, or tracked it in the direction of motion. They used the interception strategy more frequently when the gaze position error at the onset of target motion was large, and the tracking strategy when it was small. Interception was always achieved by single saccades, which were faster than tracking saccades (TS). During tracking, cats generated sequences of two to six saccades separated by "smooth" eye movements. Tracking quality varied considerably from trial to trial. When the level of motivation was high, cats would track the target at 80°/s over up to 75% of the oculomotor range, with relatively small position errors. We compared ISs and TSs with respect to their metric properties and timing. The amplitudes of ISs positively correlated with position error existing 100 ms before saccade onset, but saccade vectors were directed to a point ahead of the target along the target's track. We conclude that, in programming the ISs, target motion is used to predict the future target position so as to assure a spatial lead of the gaze at the saccade end, instead of attempting a precise capture of the target. The amplitude of TSs did not depend on preceding position errors. TSs were usually small at the onset of the first saccade, as if cats would wait till the target arrived near the line of sight. A majority of primary TSs were initiated before the target arrived near the direction of gaze. Thus they had a direction, opposite to the position error sampled 100 ms before the saccade, but the same as the direction of target motion. Prediction of the future target position from its velocity vector should therefore contribute to the programming of TSs. In addition, we observed that TSs were faster when they were initiated with a spatial lag relative to the target and they were slower if there was a spatial lead or target velocity was reduced. Such a modulation appears to be analogous to the predictive correction of the saccade amplitude during smooth pursuit in primates. Considering strong visual motion sensitivity and motor properties of output neurons of the superior colliculus, it is likely that, in cats, the colliculus makes a major contribution to the integration of eye movement-related and target motion-related signals. Electronic Publication     

Fatigue-induced changes of impedance and performance in target tracking

Kinematic variability is caused, in part, by force fluctuations. It has been shown empirically and numerically that the effects of force fluctuations on kinematics can be suppressed by increasing joint impedance. Given that force variability increases with muscular fatigue, we hypothesized that joint impedance would increase with fatigue to retain a prescribed accuracy level. To test this hypothesis, subjects tracked a target by elbow flexion and extension both with fatigued and unfatigued elbow flexor and extensor muscles. Joint impedance was estimated from controlled perturbations to the elbow. Contrary to the hypothesis, elbow impedance decreased, whereas performance, expressed as the time-on-target, was unaffected by fatigue. Further analysis of the data revealed that subjects changed their control strategy with increasing fatigue. Although their overall kinematic variability increased, task performance was retained by staying closer to the center of the target when fatigued. In conclusion, the present study reveals a limitation of impedance modulation in the control of movement variability.     

Potential and role of a prototype amorphous silicon array electronic portal imaging device in breathing synchronized radiotherapy

Current electronic portal imaging devices (EPID) are limited in their ability to provide direct and quick verification and monitoring of patients during both setup and treatment of breathing synchronized radiotherapy (BSRT, including breathing gated, voluntary and forced breath-hold radiotherapy treatment.) These limitations are largely due to their slow image capture rate and poor image quality. An amorphous silicon array flat panel electronic portal imaging device (si-EPID) is emerging to meet the challenge. The purpose of this study is threefold: (1) to characterize the performance of a prototype si-EPID; (2) to compare image quality against that of digitized films; and (3) to evaluate the device in terms of verification of patient setup and monitoring during BSRT. In this study a Varian prototype si-EPID detector array and Clinic accelerator at the University of California Davis Cancer Center were used for imaging. Three quality assurance phantoms: a Lutz PVC phantom, a modified "Las Vegas" phantom, and a RMI model 1151 phantom, were used to characterize the imaging system. A Rando head phantom was used for anthropomorphic imaging tests. Images were obtained with the si-EPID and a Fuji RX film in a Kodak X-Omatic cassette. To investigate the clinical application, two sets of si-EPID images were collected from a lung cancer patient during a 22 s breath-hold and normal breathing. The quality of images obtained with the fast mode was found to be comparable to that obtained with the digitized films. The images with the standard mode were found to be better than the digitized film images. With this prototype si-EPID, it is possible to collect the images at the beginning, middle, and end of each breath-hold for those patients who can hold their breath for longer than 15 s. The si-EPID images can provide a quick verification of the initial patient setup and subsequent treatment position throughout the daily fractionation.     

On the impact of longitudinal breathing motion randomness for tomotherapy delivery

The purpose of this study is to explain the unplanned longitudinal dose modulations that appear in helical tomotherapy (HT) dose distributions in the presence of irregular patient breathing. This explanation is developed by the use of longitudinal (1D) simulations of mock and surrogate data and tested with a fully 4D HT delivered plan. The 1D simulations use a typical mock breathing function which allows more flexibility to adjust various parameters. These simplified simulations are then made more realistic by using 100 surrogate waveforms all similarly scaled to produce longitudinal breathing displacements. The results include the observation that, with many waveforms used simultaneously, a voxel-by-voxel probability of a dose error from breathing is found to be proportional to the realistically random breathing amplitude relative to the beam width if the PTV is larger than the beam width and the breathing displacement amplitude. The 4D experimental test confirms that regular breathing will not result in these modulations because of the insensitivity to leaf motion for low-frequency dynamics such as breathing. These modulations mostly result from a varying average of the breathing displacements along the beam edge gradients. Regular breathing has no displacement variation over many breathing cycles. Some low-frequency interference is also possible in real situations. In the absence of more sophisticated motion management, methods that reduce the breathing amplitude or make the breathing very regular are indicated. However, for typical breathing patterns and magnitudes, motion management techniques may not be required with HT because typical breathing occurs mostly between fundamental HT treatment temporal and spatial scales. A movement beyond only discussing margins is encouraged for intensity modulated radiotherapy such that patient and machine motion interference will be minimized and beneficial averaging maximized. These results are found for homogeneous and longitudinal on-axis delivery for unplanned longitudinal dose modulations.     

Time delay measurement for linac based treatment delivery in synchronized respiratory gating radiotherapy

A time delay in a respiratory gating system could cause an unexpected phase mismatch for synchronized gating radiotherapy. This study presents a method of identifying and measuring the time delay in a gating system. Various port films were taken for a motion phantom at different gating window levels with a very narrow window size. The time delay for the gating system was determined by comparing the motion curve (the position of a moving object versus the gating time) measured in the port films to the motion curve determined by the video cameras. The measured time delay for a linac-based gating system was 0.17+/-0.03 s. This time delay could induce target missing if it was not properly taken into account for the synchronized gating radiotherapy. Measurement/verification of the time delay should be considered as an important part of the accepting/commissioning test before the clinical use of the gating system.     

Serial linkage of target selection for orienting and tracking eye movements

Many natural actions require the coordination of two different kinds of movements. How are targets chosen under these circumstances: do central commands instruct different movement systems in parallel, or does the execution of one movement activate a serial chain that automatically chooses targets for the other movement? We examined a natural eye tracking action that consists of orienting saccades and tracking smooth pursuit eye movements, and found strong physiological evidence for a serial strategy. Monkeys chose freely between two identical spots that appeared at different sites in the visual field and moved in orthogonal directions. If a saccade was evoked to one of the moving targets by microstimulation in either the frontal eye field (FEF) or the superior colliculus (SC), then the same target was automatically chosen for pursuit. Our results imply that the neural signals responsible for saccade execution can also act as an internal command of target choice for other movement systems.     

Simulation of hippocampal afterdischarges synchronized by electrical interactions

Recent experiments have shown that hippocampal pyramidal cells can generate synchronized action potentials even when chemical synapses are blocked. The computer simulations reported here showed that communication between cells by extracellular currents could cause this synchrony, provided that (1) individual neurons were sufficiently excitable and that (2) the resistivity of the extracellular medium was sufficiently high. Synchronization was enhanced if electronic junctions were also present.