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A leaf sequencing algorithm to enlarge treatment field length in IMRT.

With MLC-based IMRT, the maximum usable field size is often smaller than the maximum field size for conventional treatments. This is due to the constraints of the overtravel distances of MLC leaves and/or jaws. Using a new leaf sequencing algorithm, the usable IMRT field length (perpendicular to the MLC motion) can be mostly made equal to the full length of the MLC field without violating the upper jaw overtravel limit. For any given intensity pattern, a criterion was proposed to assess whether an intensity pattern can be delivered without violation of the jaw position constraints. If the criterion is met, the new algorithm will consider the jaw position constraints during the segmentation for the step and shoot delivery method. The strategy employed by the algorithm is to connect the intensity elements outside the jaw overtravel limits with those inside the jaw overtravel limits. Several methods were used to establish these connections during segmentation by modifying a previously published algorithm (areal algorithm), including changing the intensity level, alternating the leaf-sequencing direction, or limiting the segment field size. The algorithm was tested with 1000 random intensity patterns with dimensions of 21 x 27 cm2, 800 intensity patterns with higher intensity outside the jaw overtravel limit, and three different types of clinical treatment plans that were undeliverable using a segmentation method from a commercial treatment planning system. The new algorithm achieved a success rate of 100% with these test patterns. For the 1,000 random patterns, the new algorithm yields a similar average number of segments of 36.9 +/- 2.9 in comparison to 36.6 +/- 1.3 when using the areal algorithm. For the 800 patterns with higher intensities outside the jaw overtravel limits, the new algorithm results in an increase of 25% in the average number of segments compared to the areal algorithm. However, the areal algorithm fails to create deliverable segments for 90% of these patterns. Using a single isocenter, the new algorithm provides a solution to extend the usable IMRT field length from 21 to 27 cm for IMRT on a commercial linear accelerator using the step and shoot delivery method.

Algorithms↗

Dose measurements and calculations of small radiation fields for 9-MV x rays.

Measurements of dose distribution for square fields with sizes ranging from 1 X 1 to 30 X 30 cm for a 9-MV x-ray beam from a Neptune 10 linear accelerator, manufactured by CGR, are reported. Special attention was paid to field sizes smaller than 4 X 4 cm, used in radiosurgery techniques. To express the dose-monitor units relationship, total, collimator, and phantom scatter correction factors were obtained by experimental measurements. A strong dependence of these factors on the smallest field sizes (less than 4 X 4 cm) was shown. Measurements of the maximum depth dose dmax, plotted as a function of field size, showed a maximum at about 5 X 5 cm, in good agreement with previous results. dmax was also measured for the smallest fields, demonstrating that the contaminating electron component of the x-ray beam was not responsible for the dmax shift. Analysis of the penumbra width of cross dose distributions, as a function of field sizes, allowed us to postulate that the dmax shift could be due to the phantom scattered photons, which in turn were generated by the collimator scattered photons. Newly derived tissue-maximum ratio and scatter-maximum ratio data were used for dose profile calculations of 2 X 2, 4 X 4, and 10 X 10 cm field sizes. The agreement between experimental and calculated data was found to be +/- 2% within the geometrical edges of the fields and +/- 6% outside of them. A dose profile from the isocenter of a 2 X 2 cm square field moving through a 360 degree rotation arc was obtained and compared with that from the center of a 125I shielded source, as measured by Ling. Advantages and problems relating to the use of x-ray beams from linear accelerators in radiosurgery are discussed.

Humans↗

Long term variation in beam symmetry as a function of gantry angle for a computer-controlled linear accelerator.

Testing computer-controlled linear accelerators for patient safety and proper patient dose delivery requires that certain beam characteristics be monitored over an extended period of time. Computer-controlled conformal radiation therapy using asymmetric collimator jaw settings necessitates stable symmetric treatment beams. Long term beam symmetry measurements have been performed on a Philips SL20 dual energy computer-controlled linear accelerator. Symmetry in both the radial and transverse axis of each x-ray beam was monitored for eight gantry positions. These measurements were undertaken to determine the effectiveness of the SL20 beam steering system during dose delivery of 50 monitor units (MU) per field. Evaluation of the data shows that careful beam steering setup procedures result in x-ray beams in which fluctuations in symmetry as a function of gantry angle are within +/- 1.5%. Day to day instabilities produce a total overall variation in beam symmetry on the order of +/- 2.0%. Results suggest the measurement of symmetry as a function of gantry position become a routine quality assurance procedure for this accelerator.

Computers↗

Method for determining photonuclear production of radioisotopes using high-energy electron beams.

Linear accelerators can produce electrons at high power and energy. These electrons can be targeted at materials to produce radionuclides. Monte Carlo simulation is used to follow the path of the linac electrons (15-35 MeV) through materials. The production of photons and their passage through the material is modeled. The method of using this Monte Carlo information to calculate activation in the materials is presented. It is found that kilowatt power levels can produce mCi amounts of radioactivity in minutes. This work permits systematic evaluation of the potential for designing linear accelerators for in-house production of radionuclides.

Computer Simulation↗

Potential therapeutic misadministration due to inappropriate electron beam field shaping.

Lead or cerrobend blocking strips are used to shape electron treatment fields when an appropriate custom insert is not available. For the Varian 2100C accelerator, the structural supports of the electron applicators impede the free placement of these field-shaping strips on the open custom insert frame while placement at the top of the applicator is unimpeded. We have investigated the dosimetric ramifications of placing field shaping strips at the top level of the 15x15 applicator for 6, 9, and 16 MeV electrons. Our results demonstrate as much as a 30% dose decrease and 2 cm penumbral increase when this is done compared to field shaping at the insert level. The magnitude of this dosimetric error qualifies as a therapeutic misadministration in many states depending on how many treatments are delivered in this manner. Based on this finding, we recommend that routine use of lead strip blocking be discouraged in favor of custom inserts due to the potential for inappropriate placement on some linear accelerators.

Electrons↗

Evaluation of useful neutron flux for accelerator boron neutron capture therapy using the 7Li(p,n) reaction.

Accelerator neutron sources for epithermal neutron capture therapy utilising the 7Li(p,n) nuclear reaction are proposed to operate in the range of 1.88 to 2.5 MeV proton energy. Operation with proton energies closer to the reaction threshold decreases neutron yield but allows for smaller reflector and moderator, with less reduction of the epithermal flux, whereas high energies allow thicker targets to be used. The neutron yields for thick lithium targets are estimated in the energy range of 1.881 MeV to 2.5 MeV and useful neutron flux determined. The optimal range of proton energy is found to be 1.89-1.95 MeV, and this is recommended for more detailed studies of neutron transport properties for accelerator BNCT.

Biophysical Phenomena↗

[20 years of experience in using high-energy electron accelerators].

The authors summed up their 20-year experience in the clinical use of a linear accelerator of electrons and a Siemens betatron (42 MeV) in the Research Institute of Oncology and Radiology, Ministry of Health of the Byelorussian SSR. Comparative advantages and shortcomings of both accelerators and the results of their technical modifications were considered. A section in the paper, devoted to the clinical aspects of tumor therapy, is concerned with the description of a number of methods of irradiation with various types of therapeutic beams, energies, field sizes, directions, various regimens of dose fractionation in time and irradiated volume. Long-term results of radiotherapy with accelerators were assessed and compared with the results of gamma-beam therapy on cobalt units. A conclusion was made that by 1991-2000 the Republic would need 10 medical accelerators.

Cobalt Radioisotopes↗

Introduction of DNA into rat liver with a hand-held gene gun: distribution of the expressed enzyme, [32P]DNA, and Ca2+ flux.

DNA-coated Au particles were accelerated by pressurized He gas to supersonic velocities for introduction of a gene into cells. Experimental and theoretical analyses both revealed a heterogeneous distribution of the particles per shot (1 mg Au = 2.4 x 10(7) particles with 2 microg [32P] DNA = 2.5 x 10(11) moles). For introduction of genes into the liver of living rats, the best results were obtained with a newly developed hand-held gene delivery system. The beta-galactosidase gene introduced into rat liver with Au particles by He at 250 psi was expressed (1.2 microunits/microg protein) in a limited area of the liver surface (8 x 8 mm, depth 0.5 mm). When the same gene gun was used on a monolayer of cultured COS7 cells (about 5 microm thick), cells were lost in the central area of heavy bombardment. Cell death caused by influx of Ca2+ was prevented by the use of the cytosol-type culture medium.

Animals↗

Helios gene gun particle delivery for therapy of acid maltase deficiency.

Autosomal recessive deficiency of lysosomal acid maltase (GAA) or glycogen storage disease type II (GSDII) results in a spectrum of phenotypes including a rapidly fatal infantile disorder (Pompe's), juvenile, and a late-onset adult myopathy. The infantile onset form presents as hypotonia with massive accumulation of glycogen in skeletal and heart muscle, with death due to cardiorespiratory failure. Adult patients with the slowly progressive form develop severe skeletal muscle weakness and respiratory failure. Particle bombardment is a safe, efficient physical method in which high-density, subcellular-sized particles are accelerated to high velocity to carry DNA into cells. Because it does not depend on a specific ligand, receptor, or biochemical features on cell surfaces, particle-mediated gene transfer can be readily applied to a variety of systems. We evaluated particle bombardment as a delivery system for therapy of GSDII. We utilized a vector carrying the CMV promoter linked to the human GAA cDNA. Human GSDII cell lines (fibroblasts and lymphoid) as well as ex vivo with adult-onset peripheral blood cells (lymphocytes and monocytes) were transiently transfected by bombardment with a Helios gene gun delivering gold particles coated with the GAA expression plasmid. All cell types showed an increase in human GAA activity greater than 50% of normal activity. Subsequently, GAA -/- mice were treated every 2 weeks for 4 months by particle bombardment to the epidermis of the lower back and hind limbs. Muscle weakness in the hind and forelimbs was reversed. These data suggest that particle delivery of the GAA cDNA by the Helios gene gun may be a safe, effective treatment for GSDII.

Adult↗

Sonochemical formation of gold particles in aqueous solution.

Gold(III) ions in aqueous solutions of NaAuCl4 were reduced to form gold particles by ultrasonic irradiation. The rate of formation of gold particles was accelerated in the presence of certain organic additives such as surfactants, water-soluble polymers and aliphatic alcohols and ketones. The rates of formation of gold particles from 1 mM Au(III) ions in pure water were 3 microM min-1 under argon atmosphere and approximately zero under air, and in solutions containing additive the rates were 9-133 microM min-1 under argon and 8-40 microM min-1 under air. Surfactants stabilized the particles as colloidal state for more than several months. The rates of formation of both hydrogen atoms and hydroxyl radicals were estimated to be equal to 25 microM min-1 in the sonolysis of pure water under argon. Three reaction pathways leading to the reduction of metal ions were proposed: (1) reduction by hydrogen atoms; (2) reduction by reducing radicals formed via reactions of hydroxyl radicals or hydrogen atoms with the additives; (3) reduction by radicals formed from thermal reaction of the additives at the interfacial region between cavitation bubbles and bulk solution and/or in the cavities. The order of the contribution of these three pathways to the reduction of gold ions was (3) > (2) > (1) in most cases. The number averages of the size of gold particles formed in surfactant solutions under argon atmosphere were about 10 nm with a fairly narrow size distribution.

Argon↗

Study of moderator thickness for an accelerator-based neutron irradiation facility for boron neutron capture therapy using the 7Li(p,n) reaction near threshold.

Accelerator neutron sources for epithermal neutron capture therapy utilizing the 7Li(p,n) nuclear reaction will require a moderator even in the threshold range of 1.89 to 1.95 MeV. The corresponding neutron energies allow for a thinner reflector and moderator, with less reduction of the epithermal flux. To estimate the useful neutron flux within the epithermal range (4 eV-40 keV), the optimal thickness of a heavy water moderator was determined using the two-dimensional neutron transport S(N) code DORT. Optimized results are compared with the epithermal fluxes reported for the higher proton energy range, and are found to be inferior. Thus, this study supports the 2.5-3.0 MeV proton energy range for accelerator boron neutron capture therapy.

Boron Neutron Capture Therapy↗

A virtual linear accelerator for verification of treatment planning systems.

A virtual linear accelerator is implemented into a commercial pencil-beam-based treatment planning system (TPS) with the purpose of investigating the possibility of verifying the system using a Monte Carlo method. The characterization set for the TPS includes depth doses, profiles and output factors, which is generated by Monte Carlo simulations. The advantage of this method over conventional measurements is that variations in accelerator output are eliminated and more complicated geometries can be used to study the performance of a TPS. The difference between Monte Carlo simulated and TPS calculated profiles and depth doses in the characterization geometry is less than +/-2% except for the build up region. This is of the same order as previously reported results based on measurements. In an inhomogeneous, mediastinum-like case, the deviations between TPS and simulations are small in the unit-density regions. In low-density regions, the TPS overestimates the dose, and the overestimation increases with increasing energy from 3.5% for 6 MV to 9.5% for 18 MV. This result points out the widely known fact that the pencil beam concept does not handle changes in lateral electron transport, nor changes in scatter due to lateral inhomogeneitics. It is concluded that verification of a pencil-beam-based TPS with a Monte Carlo based virtual accelerator is possible, which facilitates the verification procedure.

Algorithms↗

Neutron dose measurements with the GSI ball at high-energy accelerators.

A moderator-type neutron monitor containing pairs of TLD 600/700 elements (Harshaw) modified with the addition of a lead layer (GSI ball) for the measurement of the ambient dose equivalent from neutrons at medium- and high-energy accelerators, is introduced in this work. Measurements were performed with the Gesellschaft für Schwerionenforschung (GSI) ball as well as with conventional polyethylene (PE) spheres at the high-energy accelerator SPS at European Organization for Nuclear Research [CERN (CERF)] and in Cave A of the heavy-ion synchrotron SIS at GSI. The measured dose values are compared with dose values derived from calculated neutron spectra folded with dose conversion coefficients. The estimated reading of the spheres calculated by means of the response functions and the neutron spectra is also included in the comparison. The analysis of the measurements shows that the PE/Pb sphere gives an improved estimate on the ambient dose equivalent of the neutron radiation transmitted through shielding of medium- and high-energy accelerators.

Equipment Design↗

Measurement of LINAC 90 degrees head leakage radiation TVL values.

One of the key components in modern LINAC room shielding design is the amount of 90 degrees head leakage radiation levels. With the general clinical acceptance of intensity-modulated radiation therapy (IMRT) technique, accurate knowledge of this quantity has become even more important. Measurement of 90 degrees head leakage radiation of medical linear accelerators can be technically challenging due to the low dose rate causing poor signal-to-noise ratios in most detectors. 90 degrees leakage tenth-value layer (TVL) values in concrete have not been reported for the Elekta linear accelerators. This report describes our measurements of 90 degrees leakage TVL values for 6, 10, and 18 MV x-ray beams for an Elekta Precise Treatment System. A large-volume (1000 cm3) unpressurized ionization chamber and a high sensitivity electrometer, together with a separate chamber bias power supply, were used in these measurements in order to maximize the signal-to-noise ratio. A lead enclosure, of minimum thickness 10 cm, was constructed inside the treatment room to house the ion chamber to reduce the influence of room-scattered radiation. A square aperture of 10 X 10 cm2 area was left in the shield and aimed towards the accelerator head. Measurements were performed with the chamber placed at approximately 2 m from the accelerator isocenter. Concrete slabs with individual dimensions of approximately 40 X 40 cm2 cross-sectional area and 5 cm thickness were placed between the accelerator head and the ion chamber for these measurements. The measurements were performed with total concrete thickness of up to 80 cm, so that values up to the third TVL were measured. These measurements showed thatthe first concrete TVL values are 22, 23, and 28 cm (8.6, 9.1, and 10.5 in.) for 6, 10, and 18 MV beams, while the average of the first 3 TVL's were 25, 26, and 29 cm (9.9, 10.2, and 11.5 in.). Measured values agreed to within 10% of previously reported values for Varian linear accelerators for equivalent radiation beam qualities.

Equipment Design↗