Improving animal-specific radiotherapy quality assurance for kilovoltage X-ray radiotherapy using a 3D printed dog skull water phantom.

Background: Accurate dose assessment during animal radiotherapy is beneficial for veterinary medicine and medical education. Aim: To visualize the radiation treatment distribution of orthovoltage X-ray equipment in clinical practice using Monte Carlo simulations and create a dog skull water phantom for animal-specific radiotherapy. Methods: EGSnrc-based BEAMnrc and DOSXYZnrc codes were used to simulate orthovoltage dose distributions. At 10, 20, 30, 40, 50, and 80 mm in a water phantom, the depth dose was measured with waterproof Farmer dosimetry chambers, and the diagonal off-axis ratio was measured with Gafchromic EBT3 film to simulate orthovoltage dose distributions. Energy differences between orthovoltage and linear accelerated radiotherapy were assessed with a heterogeneous bone and tissue virtual phantom. The animal-specific phantom for radiotherapy quality assurance (QA) was created from CT scans of a dog and printed with a three-dimensional printer using polyamide 12 nylon, with insertion points for dosimetry chambers and Gafchromic EBT3 film. Results: Monte Carlo simulated and measured dose distributions differed by no more than 2.0% along the central axis up to a depth of 80 mm. The anode heel effect occurred in shallow areas. The orthovoltage radiotherapy percentage depth dose in bone was >40%. Build-up was >40%, with build-down after bone exit, whereas linear accelerator radiotherapy absorption changed little in the bone. A highly water-impermeable, animal-specific dog skull water phantom could be created to evaluate dose distribution. Conclusion: Animal-specific water phantoms and Monte Carlo simulated pre-treatment radiotherapy are useful QA for orthovoltage radiotherapy and yield a visually familiar phantom that will be useful for veterinary medical education.

Changes in target volume during irradiation of canine intranasal tumors can significantly impact radiation dosimetry.

Nasal tumor size can change during radiation therapy (RT). The amount of peritumoral fluid (eg, mucohemorrhagic effusions) can also fluctuate. How often this occurs and the magnitude of change are unknown. Likewise, there are no data which describe dosimetric effects of these changing volumes during a course of RT in veterinary medicine. This study addresses that gap in knowledge. Using pet dogs with nasal tumors, three CT image sets were created. Different Hounsfield units were applied to the gross tumor volume (GTV) of each image set: unchanged, -1000 (AIR), -1000 (to the portion of the GTV that actually underwent volume reduction during clinical RT; REAL). Two plans were created: 18-fraction three-dimensional conformal RT (3DCRT) and three-fraction intensity-modulated stereotactic RT (IM-SRT). For nearby normal tissues and GTV, near-maximum doses (D2% and D5% ) and volumes receiving clinically significant doses were recorded. To verify "AIR" results, thermoluminescent dosimeters recorded dose in cadavers that were irradiated using both 3DCRT and IM-SRT plans. "AIR" scenario had ≤1.5 Gray (Gy) increases in D2% and ≤3.2 cc increases of volume. "REAL" scenario had ≤0.97 Gy increases in D5% and ≤0.55 cc increases of volume at clinically relevant doses. Both were statistical significant. Results suggest that near-complete resolution of GTV warrants plan revision.

Evaluation of the i-STAT analyzer for determination of ionized calcium concentrations in bovine blood.

BACKGROUND: Information regarding the performance of the i-STAT, a point-of-care analyzer, to determine ionized calcium (iCa2+ ) concentration in bovine blood is limited. OBJECTIVE: The primary goal of this study was to evaluate the agreement of the i-STAT against a traditional bench-top blood gas analyzer (Radiometer ABL800 FLEX) in the measurement of iCa2+ in the blood of cattle with various disorders. METHODS: In this study, 121 cattle with various diseases were used. Venous blood samples were run on the i-STAT and the Radiometer ABL800 FLEX for determination of blood iCa2+ concentrations. Data were subjected to Passing-Bablok regression and Bland-Altman plots. The Radiometer ABL800 FLEX was the reference method and the i-STAT was the test method. The i-STAT performance was evaluated at two different cutoff values for iCa2+ concentrations (<1.00 and <1.18 mmol/L) using the receiver operating characteristic curve. RESULTS: The Passing-Bablok regression equation that fit the iCa2+ concentration as measured with the i-STAT (Y) and the Radiometer ABL800 FLEX (X), was Y = -0.108276 [-0.15/-0.06] + 1.103448 [1.06/1.14] × X, with a residual deviation of 0.02. The deviation from the identity line was not significant (P = 0.64). The Bland-Altman difference plot revealed no bias between the i-STAT and the Radiometer ABL 800 FLEX. The i-STAT had a sensitivity of 100% (95% CI, 87.7-100.0) and 94.8% (95% CI, 87.2-98.6) at the iCa2+ concentration cutoff values of <1.00 and <1.18 mmol/L, respectively. CONCLUSIONS: iCa2+ concentrations in bovine blood measured with the i-STAT agreed with those of the Radiometer ABL800 FLEX. In particular, the i-STAT predicted hypocalcemia with a high sensitivity.

The potential impact of ultrathin filter design on dosimetry and relative biological effectiveness in modern image-guided small animal irradiators.

OBJECTIVE:: Modern image-guided small animal irradiators like the Xstrahl Small Animal Radiation Research Platform (SARRP) are designed with ultrathin 0.15 mm Cu filters, which compared with more heavily filtrated traditional cabinet-style biological irradiators, produce X-ray spectra weighted toward lower energies, impacting the dosimetric properties and the relative biological effectiveness (RBE). This study quantifies the effect of ultrathin filter design on relative depth dose profiles, absolute dose output, and RBE using Monte Carlo techniques. METHODS:: The percent depth-dose and absolute dose output are calculated using kVDoseCalc and EGSnrc, respectively, while a tally based on the induction of double-strand breaks as a function of electron spectra invoked in PENELOPE is used to estimate the RBE. RESULTS:: The RBE increases by >2.4% in the ultrathin filter design compared to a traditional irradiator. Furthermore, minute variations in filter thickness have notable effects on the dosimetric properties of the X-ray beam, increasing the percent depth dose (at 2 cm in water) by + 0.4%/0.01 mm Cu and decreasing absolute dose (at 2 cm depth in water) by -1.8%/0.01 mm Cu for the SARRP. CONCLUSIONS:: These results show that modern image-guided irradiators are quite sensitive to small manufacturing variations in filter thickness, and show a small change in RBE compared to traditional X-ray irradiators. ADVANCES IN KNOWLEDGE:: We quantify the consequences of ultrathin filter design in modern image-guided biological irradiators on relative and absolute dose, and RBE. Our results show these to be small, but not insignificant, suggesting laboratories transitioning between irradiators should carefully design their radiobiological experiments.

EVALUATION OF THE I-STAT PORTABLE CLINICAL ANALYZER FOR MEASUREMENT OF IONIZED CALCIUM AND SELECTED BLOOD CHEMISTRY VALUES IN ASIAN ELEPHANTS (ELEPHAS MAXIMUS).

Thei-STAT® portable clinical analyzer (PCA) provides patient-side results for hematologic, biochemical, and blood gas values when immediate results are desired. This analyzer is commonly used in nondomestic animals; however, validation of this method in comparison with traditional benchtop methods should be performed for each species. In this study, the i-STAT PCA was compared with the Radiometer ABL 800 Flex benchtop analyzer using 24 heparinized whole blood samples obtained from healthy E. maximus . In addition, the effect of sample storage was evaluated on the i-STAT PCA. Analytes evaluated were hydrogen ion concentration (pH), glucose, potassium (K+), sodium (Na+), bicarbonate (HCO3-), total carbon dioxide (TCO2), partial pressure of carbon dioxide (PCO2), and ionized calcium (iCa2+). Statistical analysis using correlation coefficients, Passing-Bablok regression analysis, and Bland-Altman plots found good agreement between results from samples run immediately after phlebotomy and 4 hr postsampling on the i-STAT PCA with the exception of K+, which is known to change with sample storage. Comparison of the results from the two analyzers at 4 hr postsampling found very strong or strong correlation in all values except K+, with statistically significant bias in all values except glucose and PCO2. Despite bias, mean differences assessed via Bland-Altman plots were clinically acceptable for all analytes excluding K+. Within the reference range for iCa2+, the iCa2+ values obtained by the i-STAT PCA and Radiometer ABL 800 Flex were close in value, however in light of the constant and proportionate biases detected, overestimation at higher values and underestimation at lower values of iCa2+ by the i-STAT PCA would be of potential concern. This study supports the use of the i-STAT PCA for the evaluation of these analytes, with the exception of K+, in the Asian elephant.

Scattered Dose Calculations and Measurements in a Life-Like Mouse Phantom.

Anatomically accurate phantoms are useful tools for radiation dosimetry studies. In this work, we demonstrate the construction of a new generation of life-like mouse phantoms in which the methods have been generalized to be applicable to the fabrication of any small animal. The mouse phantoms, with built-in density inhomogeneity, exhibit different scattering behavior dependent on where the radiation is delivered. Computer models of the mouse phantoms and a small animal irradiation platform were devised in Monte Carlo N-Particle code (MCNP). A baseline test replicating the irradiation system in a computational model shows minimal differences from experimental results from 50 Gy down to 0.1 Gy. We observe excellent agreement between scattered dose measurements and simulation results from X-ray irradiations focused at either the lung or the abdomen within our phantoms. This study demonstrates the utility of our mouse phantoms as measurement tools with the goal of using our phantoms to verify complex computational models.

An image guided small animal stereotactic radiotherapy system.

Small animal radiotherapy studies should be performed preferably on irradiators capable of focal tumor irradiation and healthy tissue sparing. In this study, an image guided small animal arc radiation treatment system (iSMAART) was developed which can achieve highly precise radiation targeting through the utilization of onboard cone beam computed tomography (CBCT) guidance. The iSMAART employs a unique imaging and radiation geometry where animals are positioned upright. It consists of a stationary x-ray tube, a stationary flat panel detector, and a rotatable and translational animal stage. System performance was evaluated in regards to imaging, image guidance, animal positioning, and radiation targeting using phantoms and tumor bearing animals. The onboard CBCT achieved good signal, contrast, and sub-millimeter spatial resolution. The iodine contrast CBCT accurately delineated orthotopic prostate tumors. Animal positioning was evaluated with ~0.3 mm vertical displacement along superior-inferior direction. The overall targeting precision was within 0.4 mm. Stereotactic radiation beams conformal to tumor targets can be precisely delivered from multiple angles surrounding the animal. The iSMAART allows radiobiology labs to utilize an image guided precision radiation technique that can focally irradiate tumors while sparing healthy tissues at an affordable cost.

Application of computational models to estimate organ radiation dose in rainbow trout from uptake of molybdenum-99 with comparison to iodine-131.

This study compares three anatomical phantoms for rainbow trout (Oncorhynchus mykiss) for the purpose of estimating organ radiation dose and dose rates from molybdenum-99 ((99)Mo) uptake in the liver and GI tract. Model comparison and refinement is important to the process of determining accurate doses and dose rates to the whole body and the various organs. Accurate and consistent dosimetry is crucial to the determination of appropriate dose-effect relationships for use in environmental risk assessment. The computational phantoms considered are (1) a geometrically defined model employing anatomically relevant organ size and location, (2) voxel reconstruction of internal anatomy obtained from CT imaging, and (3) a new model utilizing NURBS surfaces to refine the model in (2). Dose Conversion Factors (DCFs) for whole body as well as selected organs of O. mykiss were computed using Monte Carlo modeling and combined with empirical models for predicting activity concentration to estimate dose rates and ultimately determine cumulative radiation dose (µGy) to selected organs after several half-lives of (99)Mo. The computational models provided similar results, especially for organs that were both the source and target of radiation (less than 30% difference between all models). Values in the empirical model as well as the 14 day cumulative organ doses determined from (99)Mo uptake are compared to similar models developed previously for (131)I. Finally, consideration is given to treating the GI tract as a solid organ compared to partitioning it into gut contents and GI wall, which resulted in an order of magnitude difference in estimated dose for most organs.

Pencil beam scanning dosimetry for large animal irradiation.

The space radiation environment imposes increased dangers of exposure to ionizing radiation, particularly during a solar particle event. These events consist primarily of low-energy protons that produce a highly inhomogeneous depth-dose distribution. Here we describe a novel technique that uses pencil beam scanning at extended source-to-surface distances and range shifter (RS) to provide robust but easily modifiable delivery of simulated solar particle event radiation to large animals. Thorough characterization of spot profiles as a function of energy, distance and RS position is critical to accurate treatment planning. At 105 MeV, the spot sigma is 234 mm at 4800 mm from the isocentre when the RS is installed at the nozzle. With the energy increased to 220 MeV, the spot sigma is 66 mm. At a distance of 1200 mm from the isocentre, the Gaussian sigma is 68 mm and 23 mm at 105 MeV and 220 MeV, respectively, when the RS is located on the nozzle. At lower energies, the spot sigma exhibits large differences as a function of distance and RS position. Scan areas of 1400 mm (superior-inferior) by 940 mm (anterior-posterior) and 580 mm by 320 mm are achieved at the extended distances of 4800 mm and 1200 mm, respectively, with dose inhomogeneity <2%. To treat large animals with a more sophisticated dose distribution, spot size can be reduced by placing the RS closer than 70 mm to the surface of the animals, producing spot sigmas below 6 mm.

Design and characterization of an economical (192)Ir hemi-brain small animal irradiator.

PURPOSE: To describe the design and dosimetric characterization of a simple and economical small animal irradiator. MATERIALS AND METHODS: A high dose rate (HDR) (192)Ir brachytherapy source from a commercially available afterloader was used with a 1.3 cm thick tungsten collimator to provide sharp beam penumbra suitable for hemi-brain irradiation of mice. The unit was equipped with continuous gas anesthesia to allow robust animal immobilization. Dosimetric characterization of the device was performed with Gafchromic film measurements. RESULTS: The tungsten collimator provided a sharp penumbra suitable for hemi-brain irradiation, and dose rates on the order of 200 cGy/minute were achieved. The sharpness of the penumbra attainable with this device compares favorably to those measured experimentally for 6 MV photons, and 6 and 20 MeV electron beams from a linear accelerator, and was comparable to those measured for a 300 kVp orthovoltage beam and a Monte Carlo simulated 90 MeV proton beam. CONCLUSIONS: Due to its simplicity and low cost, the apparatus described is an attractive alternative for small animal irradiation experiments requiring steep dose gradients.

Development and dosimetry of a small animal lung irradiation platform.

Advances in large scale screening of medical countermeasures for radiation-induced normal tissue toxicity are currently hampered by animal irradiation paradigms that are both inefficient and highly variable among institutions. Here, a novel high-throughput small animal irradiation platform is introduced for use in orthovoltage small animal irradiators. Radiochromic film and metal oxide semiconductor field effect transistor detectors were used to examine several parameters, including 2D field uniformity, dose rate consistency, and shielding transmission. The authors posit that this setup will improve efficiency of drug screens by allowing for simultaneous targeted irradiation of multiple animals to improve efficiency within a single institution. Additionally, they suggest that measurement of the described parameters in all centers conducting countermeasure studies will improve the translatability of findings among institutions. The use of tissue equivalent phantoms in performing dosimetry measurements for small animal irradiation experiments was also investigated. Though these phantoms are commonly used in dosimetry, the authors recorded a significant difference in both the entrance and target tissue dose rates between euthanized rats and mice with implanted detectors and the corresponding phantom measurement. This suggests that measurements using these phantoms may not provide accurate dosimetry for in vivo experiments. Based on these measurements, the authors propose that this small animal irradiation platform can increase the capacity of animal studies by allowing for more efficient animal irradiation. They also suggest that researchers fully characterize the parameters of whatever radiation setup is in use in order to facilitate better comparison among institutions.

A portable fiberoptic ratiometric fluorescence analyzer provides rapid point-of-care determination of glomerular filtration rate in large animals.

Measurement of the glomerular filtration rate (GFR) is the gold standard for precise assessment of kidney function. A rapid, point-of-care determination of the GFR may provide advantages in the clinical setting over currently available assays. Here we demonstrate a proof of principle for such an approach in a pig and dogs, two species that approximate the vascular access and GFR results expected in humans. In both animal models, a sub-millimeter optical fiber that delivered excitation light and collected fluorescent emissions was inserted into a peripheral vein (dog) or central venous access (pig) by means of commercial intravenous catheters. A mixture of fluorescent chimeras of a small freely filterable reporter and large non-filterable plasma volume marker were infused as a bolus, excited by light-emitting diodes, and the in vivo signals detected and quantified by photomultiplier tubes in both species in less than 60 min. Concurrent standardized 6-h iohexol plasma kidney clearances validated the accuracy of our results for both physiologic and a chronic kidney disease setting. Thus, our ratiometric technique allows for both measurement of plasma vascular volume and highly accurate real-time GFR determinations, enabling clinical decision making in real time.

Skin surface temperature of broiler chickens is correlated to body core temperature and is indicative of their thermoregulatory status.

Extreme thermal conditions may dramatically affect the performance of broilers and other domestic animals, thereby impairing animal welfare and causing economic losses. Although body core temperature is the parameter that best reflects a bird's thermal status, practical and physiological obstacles make it irrelevant as a source of information on the thermal status of commercial flocks. Advances in the technology of infrared thermal imaging have enabled highly accurate, noncontact, and noninvasive measurements of skin surface temperature. Providing that skin surface temperature correlates with body temperature, this technology could enable acquisition of reliable information on the thermal status of animals, thereby improving diagnoses of environmental stress in a flock. This study of broiler chickens found a strong positive correlation between body core temperature and facial surface temperature, as recorded by infrared thermal imaging. The correlation was equally strong at all ages from 8 to 36 d during exposure to acute heat stress with or without proper ventilation and after acclimation to chronic heat exposure. A similar correlation was found by measurements in commercial flocks of broilers. Measurements of blood plasma concentrations of corticosterone, thyroid hormones, and arginine vasotocin confirmed that metabolic activity was low after acclimation to chronic exposure to heat, whereas ventilation was at least as efficient as acclimation in reducing thermal stress but did not impair metabolism. In light of these novel results, commercial benefits of infrared thermal imaging technology are suggested, especially in climate control for commercial poultry flocks. The application of this technique to other domestic animals should be investigated in future experiments.

Commissioning a small-field biological irradiator using point, 2D, and 3D dosimetry techniques.

PURPOSE: To commission a small-field biological irradiator, the XRad225Cx from Precision x-Ray, Inc., for research use. The system produces a 225 kVp x-ray beam and is equipped with collimating cones that produce both square and circular radiation fields ranging in size from 1 to 40 mm. This work incorporates point, 2D, and 3D measurements to determine output factors (OF), percent-depth-dose (PDD) and dose profiles at multiple depths. METHODS: Three independent dosimetry systems were used: ion-chambers (a farmer chamber and a micro-ionisation chamber), 2D EBT2 radiochromic film, and a novel 3D dosimetry system (DLOS∕PRESAGE®). Reference point dose rates and output factors were determined from in-air ionization chamber measurements for fields down to ∼13 mm using the formalism of TG61. PDD, profiles, and output factors at three separate depths (0, 0.5, and 2 cm), were determined for all field sizes from EBT2 film measurements in solid water. Several film PDD curves required a scaling correction, reflecting the challenge of accurate film alignment in very small fields. PDDs, profiles, and output factors were also determined with the 3D DLOS∕PRESAGE® system which generated isotropic 0.2 mm data, in scan times of 20 min. RESULTS: Surface output factors determined by ion-chamber were observed to gradually drop by ∼9% when the field size was reduced from 40 to 13 mm. More dramatic drops were observed for the smallest fields as determined by EBT∼18% and ∼42% for the 2.5 mm and 1 mm fields, respectively. PRESAGE® and film output factors agreed well for fields <20 mm (where 3D data were available) with mean deviation of 2.2% (range 1%-4%). PDD values at 2 cm depth varied from ∼72% for the 40 mm field, down to ∼55% for the 1 mm field. EBT and PRESAGE® PDDs agreed within ∼3% in the typical therapy region (1-4 cm). At deeper depths the EBT curves were slightly steeper (2.5% at 5 cm). These results indicate good overall consistency between ion-chamber, EBT2 and PRESAGE® measured OFs, PDDs, and profiles. CONCLUSIONS: The combination of independent 2D and 3D measurements was found to be valuable to ensure accurate and comprehensive commissioning. Film measurements were time consuming and challenging due to the difficulty of film alignment in small fields. PRESAGE® 3D measurements were comprehensive and efficient, because alignment errors are negligible, and all parameters for multiple fields could be obtained from a single dosimeter and scan. However, achieving accurate superficial data (within 4 mm) is not yet feasible due to optical surface artifacts.

Inter-laboratory comparison of radiometric culture for Mycobacterium avium subsp. paratuberculosis using raw milk from known infected herds and individual dairy cattle in Victoria.

OBJECTIVE: To compare the results of radiometric culture conducted in three Australian laboratories for Mycobacterium avium subsp. paratuberculosis (Mptb) using bulk vat and individual animal milk samples. PROCEDURE: Milk samples were collected from 15 cows exhibiting clinical signs of Johne's disease, and subsequently confirmed as infected with Mptb, and from the bulk milk vats on 91 farms running herds known to be infected with Mptb. Each milk sample was divided into three equivalent samples and one of each of the replicates was forwarded to the three participating laboratories. The identity and nature of the samples was protected from the study collaborators. The laboratories processed the samples and undertook radiometric culture for Mptb using their standard method. Results of testing were provided to the principal investigator for collation and analysis. RESULTS: In total, 2 (2.2%) of 91 vat-milk samples and 8 (53.3%) of 15 individual cows' milk samples returned positive radiometric milk culture results. Only one sample, from a clinical case of Johne's disease, was identified as positive by more than one laboratory. There were differences in the absolute frequency with which Mptb was identified in the milk samples by the collaborating laboratories. CONCLUSIONS: Mptb was cultured from a very small percentage of Australian raw bulk milk samples sourced from known infected herds. By contrast, Mptb was successfully cultured from half of the milk samples collected from clinically affected cows. There was no statistical difference between laboratories in the proportion of vat samples or individual animal milk samples in which Mptb was detected.

Background dose-rates to reference animals and plants arising from exposure to naturally occurring radionuclides in aquatic environments.

In order to put dose-rates derived in environmental impact assessments into context, the International Commission on Radiological Protection (ICRP) has recommended the structuring of effects data according to background exposure levels. The ICRP has also recommended a suite of reference animals and plants (RAPs), including seven aquatic organisms, for use within their developing framework. In light of these propositions, the objective of this work was to collate information on activity concentrations of naturally occurring primordial radionuclides for marine and freshwater ecosystems and apply appropriate dosimetry models to derive absorbed dose-rates. Although coverage of activity concentration data is comprehensive for sediment and water, few, or in some cases no, data were found for some RAPs, e.g. for frogs (Ranidae) and freshwater grasses (Poaceae) for most radionuclides. The activity concentrations for individual radionuclides in both organisms and their habitat often exhibit standard deviations that are substantially greater than arithmetic mean values, reflecting large variability in activity concentrations. To take account of variability a probabilistic approach was adopted. The dominating radionuclides contributing to exposure in the RAPs are (40)K, (210)Po and (226)Ra. The mean unweighted and weighted dose-rates for aquatic RAPs are in the ranges 0.07-0.39 microGy h(-1) and 0.37-1.9 microGy h(-1) respectively.

Predicting the radiation exposure of terrestrial wildlife in the Chernobyl exclusion zone: an international comparison of approaches.

There is now general acknowledgement that there is a requirement to demonstrate that species other than humans are protected from anthropogenic releases of radioactivity. A number of approaches have been developed for estimating the exposure of wildlife and some of these are being used to conduct regulatory assessments. There is a requirement to compare the outputs of such approaches against available data sets to ensure that they are robust and fit for purpose. In this paper we describe the application of seven approaches for predicting the whole-body ((90)Sr, (137)Cs, (241)Am and Pu isotope) activity concentrations and absorbed dose rates for a range of terrestrial species within the Chernobyl exclusion zone. Predictions are compared against available measurement data, including estimates of external dose rate recorded by thermoluminescent dosimeters attached to rodent species. Potential reasons for differences between predictions between the various approaches and the available data are explored.

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.

Dosimetric impact of daily setup variations during treatment of canine nasal tumors using intensity-modulated radiation therapy.

Intensity-modulated radiation therapy (IMRT) can be employed to yield precise dose distributions that tightly conform to targets and reduce high doses to normal structures by generating steep dose gradients. Because of these sharp gradients, daily setup variations may have an adverse effect on clinical outcome such that an adjacent normal structure may be overdosed and/or the target may be underdosed. This study provides a detailed analysis of the impact of daily setup variations on optimized IMRT canine nasal tumor treatment plans when variations are not accounted for due to the lack of image guidance. Setup histories of ten patients with nasal tumors previously treated using helical tomotherapy were replanned retrospectively to study the impact of daily setup variations on IMRT dose distributions. Daily setup shifts were applied to IMRT plans on a fraction-by-fraction basis. Using mattress immobilization and laser alignment, mean setup error magnitude in any single dimension was at least 2.5 mm (0-10.0 mm). With inclusions of all three translational coordinates, mean composite offset vector was 5.9 +/- 3.3 mm. Due to variations, a loss of equivalent uniform dose for target volumes of up to 5.6% was noted which corresponded to a potential loss in tumor control probability of 39.5%. Overdosing of eyes and brain was noted by increases in mean normalized total dose and highest normalized dose given to 2% of the volume. Findings suggest that successful implementation of canine nasal IMRT requires daily image guidance to ensure accurate delivery of precise IMRT distributions when non-rigid immobilization techniques are utilized. Unrecognized geographical misses may result in tumor recurrence and/or radiation toxicities to the eyes and brain.