H Zhou

Design and evaluation of a variable aperture collimator for conformal radiotherapy of small animals using a microCT scanner

Treatment of small animals with radiation has in general been limited to planar fields shaped with lead blocks, complicating spatial localization of dose and treatment of deep-seated targets. In order to advance laboratory radiotherapy toward what is accomplished in the clinic, we have constructed a variable aperture collimator for use in shaping the beam of microCT scanner. This unit can image small animal subjects at high resolution, and is capable of delivering therapeutic doses in reasonable exposure times. The proposed collimator consists of two stages, each containing six trapezoidal brass blocks that move along a frame in a manner similar to a camera iris producing a hexagonal aperture of variable size. The two stages are offset by 30 degrees and adjusted for the divergence of the x-ray beam so as to produce a dodecagonal profile at isocenter. Slotted rotating driving plates are used to apply force to pins in the collimator blocks and effect collimator motion. This device has been investigated through both simulation and measurement. The collimator aperture size varied from 0 to 8.5 cm as the driving plate angle increased from 0 to 41 degrees. The torque required to adjust the collimator varied from 0.5 to 5 N x m, increasing with increasing driving plate angle. The transmission profiles produced by the scanner at isocenter exhibited a penumbra of approximately 10% of the collimator aperture width. Misalignment between the collimator assembly and the x-ray source could be identified on the transmission images and corrected by adjustment of the collimator location. This variable aperture collimator technology is therefore a feasible and flexible solution for adjustable shaping of radiation beams for use in small animal radiotherapy as well as other applications in which beam shaping is desired.

DEVELOPMENT OF A MICRO-COMPUTED TOMOGRAPHY-BASED IMAGE-GUIDED CONFORMAL RADIOTHERAPY SYSTEM FOR SMALL ANIMALS

PURPOSE To report on the physical aspects of a system in which radiotherapy functionality was added to a micro-computed tomography (microCT) scanner, to evaluate the accuracy of this instrument, and to and demonstrate the application of this technology for irradiating tumors growing within the lungs of mice. METHODS AND MATERIALS A GE eXplore RS120 microCT scanner was modified by the addition of a two-dimensional subject translation stage and a variable aperture collimator. Quality assurance protocols for these devices, including measurement of translation stage positioning accuracy, collimator aperture accuracy, and collimator alignment with the X-ray beam, were devised. Use of this system for image-guided radiotherapy was assessed by irradiation of a solid water phantom as well as of two mice bearing spontaneous MYC-induced lung tumors. Radiation damage was assessed ex vivo by immunohistochemical detection of gammaH2AX foci. RESULTS The positioning error of the translation stage was found to be <0.05 mm, whereas after alignment of the collimator with the X-ray axis through adjustment of its displacement and rotation, the collimator aperture error was <0.1 mm measured at isocenter. Computed tomography image-guided treatment of a solid water phantom demonstrated target localization accuracy to within 0.1 mm. Gamma-H2AX foci were detected within irradiated lung tumors in mice, with contralateral lung tissue displaying background staining. CONCLUSIONS Addition of radiotherapy functionality to a microCT scanner is an effective means of introducing image-guided radiation treatments into the preclinical setting. This approach has been shown to facilitate small-animal conformal radiotherapy while leveraging existing technology.

Commissioning of a novel microCT/RT system for small animal conformal radiotherapy

The purpose of this work was to commission a 120 kVp photon beam produced by a micro-computed tomography (microCT) scanner for use in irradiating mice to therapeutic doses. A variable-aperture collimator has been integrated with a microCT scanner to allow the delivery of beams with pseudocircular profiles of arbitrary width between 0.1 and 6.0 cm. The dose rate at the isocenter of the system was measured using ion chamber and gafchromic EBT film as 1.56-2.13 Gy min(-1) at the water surface for field diameters between 0.2 and 6.0 cm. The dose rate decreases approximately 10% per every 5 mm depth in water for field diameters between 0.5 and 1.0 cm. The flatness, symmetry and penumbra of the beam are 3.6%, 1.0% and 0.5 mm, respectively. These parameters are sufficient to accurately conform the radiation dose delivered to target organs on mice. The irradiated field size is affected principally by the divergence of the beam. In general, the beam has appropriate dosimetric characteristics to accurately deliver the dose to organs inside the mices bodies. Using multiple beams delivered from a variety of angular directions, targets as small as 2 mm may be irradiated while sparing surrounding tissue. This microCT/RT system is a feasible tool to irradiate mice using treatment planning and delivery methods analogous to those applied to humans.

Kilovoltage beam Monte Carlo dose calculations in submillimeter voxels for small animal radiotherapy

PURPOSE Small animal conformal radiotherapy (RT) is essential for preclinical cancer research studies and therefore various microRT systems have been recently designed. The aim of this paper is to efficiently calculate the dose delivered using our microRT system based on a microCT scanner with the Monte Carlo (MC) method and to compare the MC calculations to film measurements. METHODS Doses from 2-30 mm diameter 120 kVp photon beams deposited in a solid water phantom with 0.2 x 0.2 x 0.2 mm3 voxels are calculated using the latest versions of the EGSnrc codes BEAMNRC and DOSXYZNRC. Two dose calculation approaches are studied: a two-step approach using phase-space files and direct dose calculation with BEAMNRC simulation sources. Due to the small beam size and submillimeter voxel size resulting in long calculation times, variance reduction techniques are studied. The optimum bremsstrahlung splitting number (NBRSPL in BEAMNRC) and the optimum DOSXYZNRC photon splitting (Nsplit) number are examined for both calculation approaches and various beam sizes. The dose calculation efficiencies and the required number of histories to achieve 1% statistical uncertainty--with no particle recycling--are evaluated for 2-30 mm beams. As a final step, film dose measurements are compared to MC calculated dose distributions. RESULTS The optimum NBRSPL is approximately 1 x 10(6) for both dose calculation approaches. For the dose calculations with phase-space files, Nsplit varies only slightly for 2-30 mm beams and is established to be 300. Nsplit for the DOSXYZNRC calculation with the BEAMNRC source ranges from 300 for the 30 mm beam to 4000 for the 2 mm beam. The calculation time significantly increases for small beam sizes when the BEAMNRC simulation source is used compared to the simulations with phase-space files. For the 2 and 30 mm beams, the dose calculations with phase-space files are more efficient than the dose calculations with BEAMNRC sources by factors of 54 and 1.6, respectively. The dose calculation efficiencies converge for beams with diameters larger than 30 mm. CONCLUSIONS A very good agreement of MC calculated dose distributions to film measurements is found. The mean difference of percentage depth dose curves between calculated and measured data for 2, 5, 10, and 20 mm beams is 1.8%.

A bone composition model for Monte Carlo x-ray transport simulations.

In the megavoltage energy range although the mass attenuation coefficients of different bones do not vary by more than 10%, it has been estimated that a simple tissue model containing a single-bone composition could cause errors of up to 10% in the calculated dose distribution. In the kilovoltage energy range, the variation in mass attenuation coefficients of the bones is several times greater, and the expected error from applying this type of model could be as high as several hundred percent. Based on the observation that the calcium and phosphorus compositions of bones are strongly correlated with the bone density, the authors propose an analytical formulation of bone composition for Monte Carlo computations. Elemental compositions and densities of homogeneous adult human bones from the literature were used as references, from which the calcium and phosphorus compositions were fitted as polynomial functions of bone density and assigned to model bones together with the averaged compositions of other elements. To test this model using the Monte Carlo package DOSXYZnrc, a series of discrete model bones was generated from this formula and the radiation-tissue interaction cross-section data were calculated. The total energy released per unit mass of primary photons (terma) and Monte Carlo calculations performed using this model and the single-bone model were compared, which demonstrated that at kilovoltage energies the discrepancy could be more than 100% in bony dose and 30% in soft tissue dose. Percentage terma computed with the model agrees with that calculated on the published compositions to within 2.2% for kV spectra and 1.5% for MV spectra studied. This new bone model for Monte Carlo dose calculation may be of particular importance for dosimetry of kilovoltage radiation beams as well as for dosimetry of pediatric or animal subjects whose bone composition may differ substantially from that of adult human bones.

Investigation of the effects of treatment planning variables in small animal radiotherapy dose distributions

PURPOSE Methods used for small animal radiation treatment have yet to achieve the same dose targeting as in clinical radiation therapy. Toward understanding how to better plan small animal radiation using a system recently developed for this purpose, the authors characterized dose distributions produced from conformal radiotherapy of small animals in a microCT scanner equipped with a variable-aperture collimator. METHODS Dose distributions delivered to a cylindrical solid water phantom were simulated using a Monte Carlo algorithm. Phase-space files for 120 kVp x-ray beams and collimator widths of 1-10 mm at isocenter were generated using BEAMnrc software, and dose distributions for evenly spaced beams numbered from 5 to 80 were generated in DOSXYZnrc for a variety of targets, including centered spherical targets in a range of sizes, spherical targets offset from centered by various distances, and various ellipsoidal targets. Dose distributions were analyzed using dose volume histograms. The dose delivered to a mouse bearing a spontaneous lung tumor was also simulated, and dose volume histograms were generated for the tumor, heart, left lung, right lung, and spinal cord. RESULTS Results indicated that for centered, symmetric targets, the number of beams required to achieve a smooth dose volume histogram decreased with increased target size. Dose distributions for noncentered, symmetric targets did not exhibit any significant loss of conformality with increasing offset from the phantom center, indicating sufficient beam penetration through the phantom for targeting superficial targets from all angles. Even with variable collimator widths, targeting of asymmetric targets was found to have less conformality than that of spherical targets. Irradiation of a mouse lung tumor with multiple beam widths was found to effectively deliver dose to the tumor volume while minimizing dose to other critical structures. CONCLUSIONS Overall, this method of generating and analyzing dose distributions provides a quantitative method for developing practical guidelines for small animal radiotherapy treatment planning. Future work should address methods to improve conformality in asymmetric targets.

TH‐C‐BRC‐09: Commissioning of a 3D MicroCT‐Based Small Animal Radiotherapy System

Purpose: We commissioned a novel microCT‐based kilovoltage 3D conformal radiotherapy system. A two‐stage, variable‐aperture collimator has been installed between the X‐ray source and the CT isocenter to confine the X‐ray beam, so that the system can be used for both imaging and treatment. Commissioning included alignment of the axes of the collimator and the X‐ray beam, measurement of the beam penumbra, measurement of the X‐ray beam dose rate in water, and measurement of the effective aperture size at isocenter. Method and Materials:Images projected to gafchromic films placed at the isocenter and the microCT detector were analyzed by software developed for this commissioning, which provided quick and precise guidance for mechanical and control‐software adjustments. The penumbra was measured by fitting the beam profile to piece‐wise linear functions. The collimator‐beam alignment, the aperture ratio of the two stages, and the absolute aperture calibration were measured with known image pixel sizes. The attenuation was measured by comparing the signals in the shielded and the exposed areas in the images. Measurement of the dose rate in water was accomplished using solid water phantoms and film, calibrated using parallel ion chamber measurements. Results: The measured penumbra width was 0.5 mm, dictated primarily by the finite x‐ray source spot size. Alignment of the collimator and X‐ray beam alignment was achieved within 0.1 mm. The beam width precision was less than 0.05 mm, guaranteed by the stage‐aperture ratio and absolute beam‐width calibration. The measured attenuation was better than 99.85%. Conclusion: The 3D‐conformal‐animal‐radiation‐system commissioning has achieved the design goals that ensure the precise delivery of x‐ray beam to deep‐seated targets in experimental animals. The techniques developed for the commissioning also provided reliable methods for future system quality assurance.

SU‐FF‐J‐162: In Vivo Biological Evaluation of Micro‐CT Based 3D Conformal Radiotherapy System

Purpose: Typically small animal irradiation is performed in the laboratory using single field techniques using lead blocks for beam shaping. This method is incapable of the accuracy of dose distribution and delivery to small regions possible in an average cancer center. To mitigate this, a collimator was installed in a microCT system which made the system capable of accurate dose delivery. By collimating the x‐ray beam from the CT, we are able to shape the beam down to 1mm at the isocenter of the system. With a bed capable of 3d movement, we are able to move the target to the isocenter of the system for treatment. We evaluated the effectiveness of dose delivery in vivo and tracked the biological effects of various doses and targets. Methods: Using multiple mice, we tested several aspects of the system. We evaluated the ability to treat a small target by using a small aperture and delivering dose to spontaneous lungtumors grown in transgenic mice. Immediately after treatment the mice were sacrificed, the tumor regions sliced for histology, and H2AX stained to evaluate double strand DNA breaks. In addition, subcutaneous teratomas expressing luciferase were also irradiated and monitored with bioluminescenceimaging to assess radiation response. Results: The system is capable of accurate dose delivery, as verified by phantom and in vivo studies. It is able to deliver dose to targeted areas while avoiding dose to others, and produce biological effects measurable by both histologic and macroscopic imaging methods. Dose fractionation allows the system to deliver a greater total dose within the dose rate constraints. Conclusion: The microCT/RT system is capable of dose delivery closely related to clinical systems. This opens many possibilities to perform pre‐clinical studies related to radiotherapy.

TH‐C‐BRC‐10: Evaluation of a Micro‐CT Based 3D Conformal Animal Radiotherapy System

Purpose: To treat small animal disease models with clinically‐relevant radiotherapy strategies, an image‐guided 3D conformal radiotherapy system based on a microCT imaging device has been constructed. Method and Materials: A variable‐aperture collimator was installed in a GE RS120 microCT, so that the beam width could be adjusted between 0 to 100 mm at the CT isocenter. The collimator was aligned with the X‐ray beam axis through film and detector measurements. A two‐dimensional translation stage was integrated with the existing z‐stage of the scanner to allow 3D positioning of a subject within the CT bore. Radiation treatment planning software is based on the RT_Image application, including tools to specify treatment parameters based on the CTimage and an EGSnrc‐based Monte Carlo dose calculation package. To test this system, two mice with spontaneous lungtumors have been irradiated to a dose of 2 Gy. Results: Automation of the system has been realized through high‐precision mechanical design and assembling of the collimator and stage, the calibration, and the control software. Geometric and dosimetric calibration of the system has resulted in beam width and position precisions better than 0.1 mm, and dose precision better than 3%. The treatment planning software development can specify treatment parameters within the coordinate frame of the CTimage, which can then be used to control the device hardware. Mice with lungtumors were irradiated with the system. Post‐mortem immunohistochemical assays demonstrated the presence of DNA double strand breaks within the radiation target. Conclusion: We have demonstrated the accuracy and utility of a novel microCT‐based image‐guided 3D conformal radiotherapy system. Clinically‐similar image‐guidedradiation therapy has been applied to small animals, facilitating future investigations of this technology in the laboratory.

SU‐FF‐J‐155: The Influence of Material Assignment On Monte Carlo Dose Calculations for Kilovoltage Small Animal Radiotherapy

Purpose: To investigate the sensitivity of tissue assignment for Monte Carlo (MC)dose calculations using a kilovoltage beam for small animal radiotherapy, and to test the feasibility of dual energy microCT (DEmCT) imaging for material determination. Method and Materials: MCdose calculations for 34 ICRU‐44 tissue types were performed in the EGSnrc/DOSXYZnrc code, using a 120kVp x‐ray beam. Each tissue type was modeled as a 5mm diameter spherical inhomogeneity in a soft tissue cylindrical phantom and a treatment plan with five 5mm diameter isocentric beams was simulated. The mean absorbed dose as a function of tissue density (r) and atomic number (Z) was studied. Two phantoms with five known materials were scanned with 70kVp and 120kVp beams and the r and Z of these materials were extracted. DEmCT tissue segmentation was also applied on 70kVp and 120kVp CTimages of a euthanized mouse. Results: The MC simulations demonstrate that inaccurate tissue segmentation can result in large dose calculation errors, up to 40% if adipose is assigned as soft tissue. The MC simulations also show a strong correlation between the Z of a tissue and the dose to the tissue. Preliminary results indicate that DEmCT material extraction using a microCT scanner is feasible; the mean error on the r and Z extraction of the five materials was 2.5% and 3.4%, respectively. The mouse DEmCT extracted tissues follow the data of ICRU‐44 tissues.Conclusions: It was demonstrated that tissue segmentation is one of the key steps in Monte Carlo treatment planning for small animal radiotherapy using a microCT scanner. Preliminary results indicate that dual energy microCT extraction has the potential to increase the accuracy of the conventional tissue segmentation scheme.