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Dose linearity and uniformity of a linear accelerator designed for implementation of multileaf collimation system-based intensity modulated radiation therapy.

The dose linearity and uniformity of a linear accelerator designed for multileaf collimation system-(MLC) based IMRT was studied as a part of commissioning and also in response to recently published data. The linear accelerator is equipped with a PRIMEVIEW, a graphical interface and a SIMTEC IM-MAXX, which is an enhanced autofield sequencer. The SIMTEC IM-MAXX sequencer permits the radiation beam to be " ON" continuously while delivering intensity modulated radiation therapy subfields at a defined gantry angle. The dose delivery is inhibited when the electron beam in the linear accelerator is forced out of phase with the microwave power while the MLC configures the field shape of a subfield. This beam switching mechanism reduces the overhead time and hence shortens the patient treatment time. The dose linearity, reproducibility, and uniformity were assessed for this type of dose delivery mechanism. The subfields with monitor units ranged from 1 MU to 100 MU were delivered using 6 MV and 23 MV photon beams. The doses were computed and converted to dose per monitor unit. The dose linearity was found to vary within 2% for both 6 MV and 23 MV photon beam using high dose rate setting (300 MU/min) except below 2 MU. The dose uniformity was assessed by delivering 4 subfields to a Kodak X-OMAT TL film using identical low monitor units. The optical density was converted to dose and found to show small variation within 3%. Our results indicate that this linear accelerator with SIMTEC IM-MAXX sequencer has better dose linearity, reproducibility, and uniformity than had been reported.

Particle Accelerators↗

Reference photon dosimetry data and reference phase space data for the 6 MV photon beam from varian clinac 2100 series linear accelerators.

The current study presents the reference photon dosimetry data (RPDD) and reference phase space data (RPSD) for the 6 MV photon beam from Varian 2100 series linear accelerators. The RPDD provide the basic photon dosimetry data, typically collected during the initial commissioning of a new linear accelerator, including output factors, depth dose data, and beam profile data in air and in water. The RPSD provide the full phase space information, such as position, direction, and energy for each particle generated inside the head of any particular linear accelerator in question. The dosimetric characteristics if the 6 MV photon beam from the majority of the aforementioned accelerators, which are unaltered from the manufacturer's original specifications, can be fully described with these two data sets within a clinically acceptable uncertainty (approximately +/-2 %). The current study also presents a detailed procedure to establish the RPDD and RPSD using measured data and Monte Carlo calculations. The RPDD were constructed by compiling our own measured data and the average data based on the analysis of more than 50 sets of measured data from the Radiological Physics Center (RPC) and 10 sets of clinical dosimetry data obtained from 10 different institutions participating in the RPC's quality assurance monitoring program. All the measured data from the RPC and the RPC-monitored institutions were found to be within a statistically tight range (i.e., 1sigma approximately 1% or less) for each dosimetric quantity. The manufacturer's standard data, except for in-air off-axis factors that are available only from the current study, were compared with the RPDD, showing that the manufacturer's standard data could also be used as the RPDD for the photon beam studied in this study. The RPSD were obtained from Monte Carlo calculations using the BEAMnrc/ DOSXYZnrc code system with 6.2 MeV (a spread of 3% full width at half maximum) and 1.0 mm full width at half maximum as the values of the energy and radial spread of a Gaussian electron pencil beam incident on the target, respectively. The RPSD were capable of generating Monte Carlo data that agreed with the RPDD within the acceptance criteria adopted in the current study (e.g., 1% or 1 mm for depth dose). A complete set of the RPDD and RPSD from the current study is available from the RPC website (http://rpc.mdanderson.org) or via mass storage media such as DVD or CD-ROM upon request.

Electrons↗

Computer interface for a linear accelerator.

A computer interface for the Clinac-18 linear accelerator has been developed, using a standard CAMAC interface plus buffer amplifiers to isolate the CAMAC from the accelerator electronics. Buffer amplifiers are employed because direct connection of the CAMAC system to the accelerator was found to affect accelerator operation. The total interface accommodates the four gantry position analog signals and thirteen digital signals describing all available treatment options. The interface also allows the computer to inhibit beam operation.

Computers↗

Characteristics of the photon beam from a new 25-MV linear accelerator.

The Therac 25 is a relatively compact therapy machine, the heart of which is a double-pass electron linear accelerator. The electron beam is injected into the accelerator at the treatment head end of the machine and is accelerated back down the arm to an energy of 13 MeV. At this end of the machine a magnet system reflects the beam back into the structure where it gains up to an additional 12 MeV of energy. After leaving the linear accelerator the beam is bent by an achromatic head magnet through 270 degrees to the treatment head. The machine produces eight electron beams and a 25-MV photon beam. In this work only the parameters of the photon beam are addressed based on measurements at the first two clinical sites. Percentage depth doses, tissue phantom ratios, and beam symmetry and stability are presented and discussed.

Humans↗

A prototype beam delivery system for the proton medical accelerator at Loma Linda.

A variable energy proton accelerator was commissioned at Fermi National Accelerator Laboratory for use in cancer treatment at the Loma Linda University Medical Center. The advantages of precise dose localization by proton therapy, while sparing nearby healthy tissue, are well documented [R. R. Wilson, Radiology 47, 487 (1946); M. Wagner, Med. Phys. 9, 749 (1982); M. Goitein and F. Chen, Med. Phys. 10, 831 (1983)]. One of the components of the proton therapy facility is a beam delivery system capable of delivering precise dose distributions to the target volume in the patient. To this end, a prototype beam delivery system was tested during the accelerator's commissioning period. The beam delivery system consisted of a beam spreading device to produce a large, uniform field, a range modulator to generate a spread out Bragg peak (SOBP), and various beam detectors to measure intensity, beam centering, and dose distributions. The beam delivery system provided a uniform proton dose distribution in a cylindrical volume of 20-cm-diam area and 9-cm depth. The dose variations throughout the target volume were found to be less than +/- 5%. Modifications in the range modulator should reduce this considerably. The central axis dose rate in the region of the SOBP was found to be 0.4 cGy/spill with an incident beam intensity of 6.7 x 10(9) protons/spill. With an accelerator repetition rate of 30 spills/min and expected intensity of 2.5 x 10(10) protons/spill for patient treatment, this system can provide 50 cGy/min for a 20-cm-diam field and 9-cm range modulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Equipment Design↗

Evaluation of neutron dose equivalent levels at the maze entrance of medical accelerator treatment rooms.

This paper evaluates the accuracy of Kersey's method of calculation of the dose level due to photoneutrons at the maze entrance of medical accelerators. In this study measurements and calculations of the neutron dose equivalent were made for 13 medical accelerator facilities. The group of accelerators was composed of four different models from two manufacturers. The maze length for the treatment rooms varied from 3.0 to 8.54 m and 10 of the mazes had a single 90-deg turn with the remaining having two 90-deg turns. Moderated activation detectors and a portable neutron remmeter were used for measurements in the treatment room and maze, respectively. It was found that the maximum disagreement between the measured and calculated values was a factor of 2.3 with the calculated value exceeding the measured value. The majority of the measured values were within 25% of the calculated levels. It was concluded that Kersey's method is suitable for use in designing medical accelerator mazes.

Hospital Units↗

Beam characteristics of a new model of 6-MV linear accelerator.

This paper describes the beam characteristics and dosimetry measurements performed on the 6-MV photon beam of a new model of linear accelerator, three of which were recently introduced and installed in our institution. Percent depth dose and tissue maximum ratio tables for a variety of field sizes and depths, as well as other parameters used for treatment planning are presented. These accelerators are the first of their kind using both hardware and software tools to control interlocks. Checking procedures for these interlocks are available from the authors upon request. Comparison of characteristic parameters between these three new 6-MV linear accelerators and with the 6-MV beams of two other accelerators is also made.

Calibration↗

Linear accelerator output variations and their consequences for megavoltage imaging.

An experimental study of radiation output intensity fluctuations of a Philips SL25 linear accelerator is presented. Measurements are obtained using an electronic portal imaging device, and the consequences of the measured fluctuations for various different applications of megavoltage imaging including portal imaging, transit dosimetry and megavoltage computed tomography (MVCT) are discussed with examples. Fluctuations in output of +/- 0.7% (1 SD) are seen on every radiation pulse after photon noise and uncertainties caused by the detection system have been accounted for. Large fluctuations are also seen during the initial beam stabilization period (15%), during normal accelerator operation after the beam has been on for more than 1 min (4.5%) and during are therapy as a repeatable function of gantry angle (9%). Such output intensity fluctuations are shown to produce image artifacts in portal imaging devices with scanned detector readout and can also produce systematic errors in detector calibration that would lead to uncertainty in transit dose calculations. The propagation of these intensity fluctuations through MVCT image reconstruction is shown to produce ring artifacts in the reconstructed image. Sample portal and MVCT images are presented. All observed fluctuations in accelerator output are well within the manufacturer's specifications and do not affect the total dose delivered during normal treatment. Finally, megavoltage imaging is shown to be a powerful tool for accelerator quality assurance and treatment verification.

Calibration↗

Effect of positive acceleration (+gz) on electrocardiogram of subjects with vasoregulatory abnormality.

ST-T wave changes in the electrocardiogram detected during routine examination and aggravated by erect posture, hyperventilation, and exercise in apparently healthy young individuals have been termed vasoregulatory abnormalities. No evidence of ischaemic heart disease has been found in such subjects. Ten young healthy air crew with vasoregulatory abnormalities were subjected to maximal exercise on treadmill and procedure repeated after 120 mg propranolol daily for 3 days. After one week, they were subjected to a stress of positive acceleration (+gz) in a human centrifuge at 2-5 g and 3-5 g for 15 seconds each at a constant rate of rise of 0-1 g/s and the electrocardiogram was monitored during and in the post-acceleration phase. The procedure was repeated after propranolol 120 mg daily for 3 days. The stress of positive acceleration resulted in pronounced prominence of P waves and inversion of T waves (as has been reported in normal subjects) with minimal ST depression in the electrocardiogram. ST segment depression during exercise, at heart rates corresponding to those achieved during peak centrifuge runs, was significantly more pronounced. The ST, P, and T wave changes were returned to normal after propranolol. It is concluded that minimal ST segment depression after stress of positive acceleration as compared with conspicuous ST segment depression during exercise at corresponding heart rates, and their normalisation after propranolol, rules out ischaemia as an aetiological factor in subjects with vasoregulatory abnormalities.

Acceleration↗

Nonuniform activation of the agonist muscle does not covary with index finger acceleration in old adults.

This study examined the patterns of activation in the superficial and deep parts of the first dorsal interosseus muscle and in the antagonist muscle, second palmar interosseus, during postural tasks (position holding) and slow movements (position tracking) of the index finger performed by young and old adults. The position-tracking task involved the index finger lifting light loads (2.5, 10, and 35% of maximum) with shortening and lengthening contractions as steadily as possible. Steadiness was quantified in both tasks as the standard deviation of index finger acceleration. The fluctuations in acceleration during the two tasks were greater for the old subjects (62-72 yr) compared with young subjects (19-27 yr), especially with the lightest loads. The two groups of subjects activated the superficial and deep parts of first dorsal interosseus at similar intensities during the position-holding task, whereas the deep part was more active during the shortening and lengthening contractions of the position-tracking task. The nonuniform activation of first dorsal interosseus, therefore, was not associated with the difference in the standard deviation of acceleration between the young and old subjects. Furthermore, there was no association between the average level of coactivation by the antagonist muscle and the standard deviation of acceleration for either group of subjects across these tasks. Thus the greater variability in motor output exhibited by the older adults could not be explained by either the nonuniform activation of the agonist muscle or the average level of coactivation by the antagonist muscle.

Acceleration↗

Controlling human upright posture: velocity information is more accurate than position or acceleration.

The problem of how the nervous system fuses sensory information from multiple modalities for upright stance control remains largely unsolved. It is well established that the visual, vestibular, and somatosensory modalities provide position and rate (e.g., velocity, acceleration) information for estimation of body dynamics. However, it is unknown whether any particular property dominates when multisensory information is fused. Our recent stochastic analysis of postural sway during quiet stance suggested that sensory input provides more accurate information about the body's velocity than its position or acceleration. Here we tested this prediction by degrading major sources of velocity information through removal/attenuation of sensory information from vision and proprioception. Experimental measures of postural sway were compared with model predictions to determine whether sway behavior was indicative of a deficit in velocity information rather than position or acceleration information. Subjects stood with eyes closed on a support surface that was 1) fixed, 2) foam, or 3) sway-referenced. Six measures characterizing the stochastic structure of postural sway behaved in a manner consistent with model predictions of degraded velocity information. Results were inconsistent with the effect of degrading only position or acceleration information. These findings support the hypothesis that velocity information is the most accurate form of sensory information used to stabilize posture during quiet stance. Our results are consistent with the assumption that changes in sway behavior resulting from commonly used experimental manipulations (e.g., foam, sway-referencing, eyes closed) are primarily attributed to loss of accurate velocity information.

Acceleration↗

Horizontal vestibuloocular reflex evoked by high-acceleration rotations in the squirrel monkey. I. Normal responses.

The horizontal angular vestibuloocular reflex (VOR) evoked by high-frequency, high-acceleration rotations was studied in five squirrel monkeys with intact vestibular function. The VOR evoked by steps of acceleration in darkness (3,000 degrees /s(2) reaching a velocity of 150 degrees /s) began after a latency of 7.3 +/- 1.5 ms (mean +/- SD). Gain of the reflex during the acceleration was 14.2 +/- 5.2% greater than that measured once the plateau head velocity had been reached. A polynomial regression was used to analyze the trajectory of the responses to steps of acceleration. A better representation of the data was obtained from a polynomial that included a cubic term in contrast to an exclusively linear fit. For sinusoidal rotations of 0.5-15 Hz with a peak velocity of 20 degrees /s, the VOR gain measured 0.83 +/- 0.06 and did not vary across frequencies or animals. The phase of these responses was close to compensatory except at 15 Hz where a lag of 5.0 +/- 0.9 degrees was noted. The VOR gain did not vary with head velocity at 0.5 Hz but increased with velocity for rotations at frequencies of >/=4 Hz (0. 85 +/- 0.04 at 4 Hz, 20 degrees /s; 1.01 +/- 0.05 at 100 degrees /s, P < 0.0001). No responses to these rotations were noted in two animals that had undergone bilateral labyrinthectomy indicating that inertia of the eye had a negligible effect for these stimuli. We developed a mathematical model of VOR dynamics to account for these findings. The inputs to the reflex come from linear and nonlinear pathways. The linear pathway is responsible for the constant gain across frequencies at peak head velocity of 20 degrees /s and also for the phase lag at higher frequencies being less than that expected based on the reflex delay. The frequency- and velocity-dependent nonlinearity in VOR gain is accounted for by the dynamics of the nonlinear pathway. A transfer function that increases the gain of this pathway with frequency and a term related to the third power of head velocity are used to represent the dynamics of this pathway. This model accounts for the experimental findings and provides a method for interpreting responses to these stimuli after vestibular lesions.

Acceleration↗

Horizontal vestibuloocular reflex evoked by high-acceleration rotations in the squirrel monkey. II. Responses after canal plugging.

The horizontal angular vestibuloocular reflex (VOR) evoked by high-frequency, high-acceleration rotations was studied in four squirrel monkeys after unilateral plugging of the three semicircular canals. During the period (1-4 days) that animals were kept in darkness after plugging, the gain during steps of acceleration (3, 000 degrees /s(2), peak velocity = 150 degrees /s) was 0.61 +/- 0.14 (mean +/- SD) for contralesional rotations and 0.33 +/- 0.03 for ipsilesional rotations. Within 18-24 h after animals were returned to light, the VOR gain for contralesional rotations increased to 0. 88 +/- 0.05, whereas there was only a slight increase in the gain for ipsilesional rotations to 0.37 +/- 0.07. A symmetrical increase in the gain measured at the plateau of head velocity was noted after animals were returned to light. The latency of the VOR was 8.2 +/- 0. 4 ms for ipsilesional and 7.1 +/- 0.3 ms for contralesional rotations. The VOR evoked by sinusoidal rotations of 0.5-15 Hz, +/-20 degrees /s had no significant half-cycle asymmetries. The recovery of gain for these responses after plugging was greater at lower than at higher frequencies. Responses to rotations at higher velocities for frequencies >/=4 Hz showed an increase in contralesional half-cycle gain, whereas ipsilesional half-cycle gain was unchanged. A residual response that appeared to be canal and not otolith mediated was noted after plugging of all six semicircular canals. This response increased with frequency to reach a gain of 0.23 +/- 0.03 at 15 Hz, resembling that predicted based on a reduction of the dominant time constant of the canal to 32 ms after plugging. A model incorporating linear and nonlinear pathways was used to simulate the data. The coefficients of this model were determined from data in animals with intact vestibular function. Selective increases in the gain for the linear and nonlinear pathways predicted the changes in recovery observed after canal plugging. An increase in gain of the linear pathway accounted for the recovery in VOR gain for both responses at the velocity plateau of the steps of acceleration and for the sinusoidal rotations at lower peak velocities. The increase in gain for contralesional responses to steps of acceleration and sinusoidal rotations at higher frequencies and velocities was due to an increase in the gain of the nonlinear pathway. This pathway was driven into inhibitory cutoff at low velocities and therefore made no contribution for rotations toward the ipsilesional side.

Acceleration↗

Examination of the vestibular system by short-time accelerations.

Short accelerations, lasting for the split part of a second can be produced by the chair rotating with uniform speed in such a way that the chair will change its direction after each turn of 360 degrees. The accelerations of alternating directions produce ampullopetal flows in the right and the left labyrinth alternately. The nystagmus elicited will be finished during the rotation of the chair with uniform speed, thus during the stimulus-free period. The short acceleration rates render possible the multiple dosage of identical stimuli as well as the gradual increase of the intensity of the stimulus. Since the stimulus produces ampullopetal flow in the right and the left labyrinth alternately the central vestibular equilibrium will not be changed. The author applied acceleration stimuli of 20, 30, 40 and 50 degrees/sec2 doses to 20 healthy male subjects and studied the manifestations of the nystagmus elicited.

Acceleration↗

Accelerator mass spectrometry in pharmaceutical research and development--a new ultrasensitive analytical method for isotope measurement.

Accelerator mass spectrometry (AMS) permits the measurement of elemental isotopes at the individual atom level. The main application of AMS in drug discovery and development will be in the analysis of 14-carbon (14C). The principle behind AMS is the separation of individual positively charged atoms through mass, charge and momentum differences. In order to obtain the high-energy charge state required for separation, negative atoms are accelerated through a high voltage field (up to 10 million volts) generated by a tandem Van de Graaff accelerator. In the middle of the accelerator, the outer valency electrons are stripped from the atom and the resulting charged species are separated and counted. For 14C, AMS counts the number of individual atoms rather than measuring radioactive decays. The result is that AMS is up to one million times more sensitive than decay counting. Radioactivity levels as low 0.0001 dpm can be detected using AMS. The exquisite sensitivity of AMS analysis means that much lower amounts of 14C can be used than for conventional counting methods. This makes it easier to use 14C for in vitro, preclinical and clinical research programmes. As 14C poses both a biological and environmental hazard, AMS permits much lower doses to be used. Human drug mass balance studies have been conducted with doses of 50 nanoCuries and below. Radioactive HPLC metabolite profiles of plasma extracts from subjects given nanoCurie doses of 14C-labelled drug have been obtained by injecting as little as 0.25 dpm onto an HPLC column. In studies of biologics, biosynthetically 14C-labelled recombinant protein has been produced with a specific radioactivity sufficient to conduct human clinical studies with AMS analysis. For one human recombinant protein an increase in sensitivity of 2,000-fold over ELISA was obtained with AMS measurement. AMS is an enabling technology that should prove of value in increasing human and environmental safety as well as allowing new research directions to be followed.

Animal Testing Alternatives↗

Responses of peripheral vestibular neurons to angular and linear accelerations in the squirrel monkey.

Peripheral neurons innervating semicircular canals can respond to constant linear accelerations. Evidence is presented that, in our preparation, the response is artifactual and arises from thermal gradients introduced by the surgical exposure. Otolith neurons do not respond to even intense angular accelerations. Canal plugging abolishes the response of the corresponding afferents to angular acceleration, without obviously affecting resting activity. The procedure does not prevent the canals from responding to linear accelerations. The latter response, unlike that seen in intact canals, is not due to thermal gradients and may be related to the mechanisms underlying the persistent component of barbecue nystagmus.

Acceleration↗

The influence of linear acceleration on optokinetic nystagmus in human subjects.

The influence of linear acceleration on optokinetic nystagmus (OKN) was studied in human subjects. Linear acceleration was applied to the subjects by means of the parallel swing and also by the transfer of the subjects in one direction, either right or left. The cortical form of OKN increased the frequency, amplitude, and eye speed of the slow phase. Of the three, the increase in eye speed was the most pronounced. The subcortical form of OKN was not only increased but was also disturbed by the linear acceleration. When the compensatory eye movement with linear acceleration and the slow phase of OKN were in the same direction, the nystagmus increased remarkably. Contrarily, when the two directions were opposed to each other, nystagmus was inhibited. These results proved that the otolithic organs are not only able to promote but also to inhibit visual function.

Acceleration↗

Subjective detection of vertical acceleration: a velocity-dependent response?

Human subjective thresholds and directional sensitivity were investigated as a function of vertical linear acceleration with head erect. A hyperbolic (r=0.94) relation emerged between threshold latency and acceleration magnitude (range 0.005 to 0.06 g). This implies that detection was determined by attainment of a given velocity (21.6+/-2.65 cm/sec) rather than the acceleration magnitude per se. Re-analysis of previous data from horizontal accelerations conducted with head erect and supine revealed similar hyperbolic relations (r=0.98 in both cases) with velocity constants of 22.6+/-1.28 and 32.4+1.96 cm/sec respectively. From these findings it is inferred that with head erect (i.e. normal attitude re gravity) the thresholds to predominantly utricular (horizontal accel.) and saccular (vert. accel.) stimulation were similar (P greater than 0.7). However, with head "supine" the saccular threshold was increased to approx. 1.5Xnormal (P less than 0.001). The results also confirmed a previously reported difficulty in the subjective detection of the direction of vertical movement.

Acceleration↗