3.1. Output of the microCT/RT system
The dose rate at the isocenter of the microCT/RT system at the water surface was measured using the in-air method suggested by the AAPM protocol TG-61 (Ma et al 2001
). shows the dose rate at the isocenter at the water surface for field diameters of 4.0, 5.0 and 6.0 cm provided by the 120 kVp photon beam with the tube current operating at 25, 40 and 50 mA. The maximum standard deviation of these measurements is 0.3%. The dose rate is high enough to deliver therapeutic doses up to 8 Gy in reasonable periods of time. However, there are two technical considerations that must be taken into account when irradiating small animals with the system: (1) the duty cycle of the system and (2) generator overheating. As explained in section 2.1, measurements and calculation of the dose rate are based on the on-time only which represents approximately 10% of the full cycle time (total pulse time). Therefore, the actual time needed to irradiate a specimen is approximately ten times higher than the time calculated using the dose rate presented in .
Dose rate at the isocenter of the microCT/RT system. The dose rate is high enough to deliver therapeutic doses to mice in reasonable exposure times.
Secondly, the electrical generator of the microCT system accumulates heat during extended irradiations, eventually leading to overheating and either forced shutdown or system failure. A careful study of the heating behavior has been performed to establish irradiation protocols that avoid overstressing the generator. To avoid specimens under anesthesia for periods longer than 1 h, at this point we only deliver doses up to 8 Gy. However, our group is working in establishing a more efficient cooling system and proposing a new x-ray tube to reduce the irradiation time and increase the dose delivered.
3.2. Film dosimetry and calibration
Dosimetry for field diameters smaller than 4 cm was performed using gafchromic EBT film. shows the graph that associates the optical density and the dose delivered to the film. The films were scanned using a 16 bit flat bed scanner using transmitted light. The optical density of the film is defined as the logarithm of the light transmitted through the film. This is
Figure 3 Calibration curve used to associate the dose delivered to the film and its optical density. The curve can be fitted to a third order polynomial. The error bar represents the standard deviation in reading the film and calculating the optical density, STD (more ...)
is the light transmitted through an unused film (base + fog only) and I
is the light transmitted through the irradiated film. Log10
) and Log10
) are represented by the pixel value of the irradiated film and the unused film, respectively. The calibration curve can be fitted well with a third order polynomial.
3.3. Dose rate as a function of field diameter
shows the dose rate at the isocenter at 1 mm depth in solid water as a function of field diameter. The error bars represent the average standard deviation obtained for all points (3.6%). The dose rate ranges from 1.56 Gy min−1 to 2.08 Gy min−1 for field diameters between 0.1 and 5 cm, respectively. The dose rate decreases approximately 26% when the collimator aperture is reduced from 5.0 cm to 0.1 cm.
Figure 4 Dose rate as a function of the field diameter. The dose rate decreases as the field diameter decreases due to scatter reduction. The contribution of scatter to the primary beam is significant at the energies at which the microCT operates. The error bars (more ...)
3.4. Contribution of scatter coming from the plastic bore and collimators
Air kerma measured with the pinpoint chamber for field diameters ranging from 1.0 cm to 5.0 cm did not show any variation. This suggests that the contribution of scatter from the bore tube and the collimator to the primary beam is negligible. The standard deviation of measurements in that field diameter range was 0.9% which can be attributed to beam fluctuation. The AAPM TG-61 protocol presents backscatter factors for different energies, source–surface distances and field diameters. For the same half value layer of the microCT beam and for a source–surface distance equal to the isocenter distance, the backscatter factor for field diameters of 1.0, 2.0 and 5.0 cm are 1.059, 1.120 and 1.242, respectively. The backscatter ratios of the field diameter of 1.0 cm with respect to 2.0 and 5.0 cm are 0.945 and 0.853, respectively. The ratios of the measured dose rate of the field diameter of 1.0 cm with respect to 2.0 and 5.0 cm are 0.945 and 0.832, respectively (). This suggests that the variation of the dose rate as a function of field diameter is primarily due to the variation in the backscatter produced when photons interact with the solid water.
Backscatter factor ratio and measured dose rate ratio. The variation of the dose rate as a function of the field diameter is basically due to the variation in the backscatter produced when photons interact with the solid water.
The protocol does not present any data for field diameters smaller than 1 cm. However, if we assume the field diameter of 0.2 cm as a pencil beam, the backscatter factor would be 1.000 and the ratio with the backscatter factor for a field diameter of 5 cm would be 0.80. Using the measured dose rate, that ratio is 0.75. At very small field sizes, the penumbra is expected to limit the dose rate as the size of the beam becomes comparable to or smaller than the size of the penumbra. However, from the data we have obtained, this system is able to deliver dose rates suitable for radiotherapy at field sizes as small as 2 mm.
3.5. Dose rate as a function of depth
shows the dose rate as a function of depth for field diameters of 0.2, 0.5, 1.0 and 2.0 cm. The depth of maximum dose is between the surface and 1 mm depth. However, film has neither the spatial resolution nor the sensitivity to measure the depth of maximum dose. One millimeter depth will be taken as the depth of maximum dose based on the following assumptions: (1) 1 mm depth is the shallowest depth that we can measure using film dosimetry, (2) uncertainty on the detector is higher than any dose variation between the surface and 1 mm depth, and (3) calculations of doses delivered to small animal subjects will be done at a minimum of 1 mm depth, even for subcutaneous tumors. For field diameters of 0.5 and 1.0 cm, appropriate field sizes for mice irradiation, the dose rate decreases by about 10% per every 5 mm in depth. The dose rate is adequate to irradiate targets inside of mice considering that the widest part of the mouse abdomen has an approximate radius of about 1.25 cm. The dose rate decreases more slowly for field diameters larger than 1.0 cm, and slightly faster for field diameters smaller than 0.5 cm. The depth dose curve for 2.0 cm presents a shoulder that is not evident at a field diameter of 0.2 cm. This is due to the fact that the backscatter for field diameters of 2.0 cm is significantly higher than backscatter for 0.2 cm.
Figure 5 Dose rate as a function of depth for field diameters of 2, 1, 0.5 and 0.2 cm. For field diameters of 1.0 cm and 0.5 cm, the most commonly used field diameter range used in mice irradiation, the dose rate decreases about 10% per every 5 mm in depth. The (more ...)
3.6. Flatness, symmetry, FWHM and penumbra
shows the 120 kVp photon beam dose profile at 1 mm depth for field diameters of 0.5, 1.0 and 2.0 cm. Field diameters were set at the isocenter but the film was placed at 2.5 cm above the isocenter to increase the dose rate. Therefore, the actual field diameters are 0.46, 0.93 and 1.86 cm. presents the measured values of penumbra and FWHM. It also provides the calculated values of flatness and symmetry of the beam. The beam exhibits good symmetry for field diameters smaller than 2.0 cm. The heel effect was not significant for the field diameters studied. The dose profiles exhibit shoulders, but are sufficiently flat to deliver dose homogenously at 75% of the cross-area. The beam has a very sharp penumbra. However, the observed penumbra serves to limit the dose rate beyond scatter reduction when field sizes are reduced to less than 0.2 cm.
Figure 6 (a) Dose profile at 1 mm depth for field diameters of 0.46, 0.93 and 1.86 cm (120 kVp, 50 mA photon beam). (b) Dose profile at 0.1, 1 and 2 cm depth for a field diameter of 0.93 cm. The FWHM of the beam increases to 0.95 and 1.01 cm at depths of 1 and (more ...)
Table 3 Flatness, symmetry, FWHM and penumbra for filed diameters of 0.46, 0.93 and 1.86 cm. Measurements were performed with gafchromic EBT film at 1 mm depth in solid water. In general, the photon beam has dosimetric characteristics sufficient to homogenously (more ...)
The field diameter set in the collimator and the field diameter measured with film at 1 mm depth agreed to within 1.6%. The radiation field diameter increases to 0.95 and 1.01 cm at depths of 1 and 2 cm, respectively (). This increase is mainly due to the divergence of the beam, with some contribution from lateral photon scatter. The uncertainties in penumbra and FWHM reflect the size of the pixel in the acquired images. In general, the photon beam has adequate dosimetric characteristics to homogenously irradiate targets within small animal subjects.
3.7. Dose delivery evaluation
A film–solid water phantom was irradiated with eight beams with diameters of 0.2 cm. The calculated dose delivered at the intersection of the beam axes was 1.40 Gy. Using the calibration curve and the film optical density (OD) in the intersection of the beams as the input, the measured dose delivered to the film was 1.36 Gy. The difference between the calculated and measured dose is 2.8%. shows the irradiated film and the image of the dose distribution in the film. This evaluation demonstrates that the dosimetry of the system is consistent and that it can be used to calculate irradiation time when delivering dose to experimental subjects.
Figure 7 (a) Film irradiated with eight beams with diameters of 0.2 cm. (b) Dose distribution in the film. The difference between the calculated and measured dose is 2.8%. This single dose testing proved that the dosimetry of the system was consistent and that (more ...)
3.8. Error analysis
The dose delivered to a specimen is calculated based on the air kerma rate at the isocenter of the microCT. The air kerma rate has been measured as accurately as possible, but in general, the result of the measurement is only an estimation of the true value. The result is complete only when the confidence level of the value is well known. In other words, the result must be accompanied by a quantitative statement of its uncertainty associated with the measurements (Taylor and Kuyatt 1994
). The total uncertainty should include random and systematic errors in the measurement process. The total uncertainty of the air kerma rate at the isocenter of the microCT represents the combined uncertainty of type A and type B uncertainties determined over the entire calibration procedure. It includes uncertainty due to fluctuations in the photon beam, uncertainty of the detector position and uncertainty of detector sensitivity. The uncertainties involved in the dose rate measurement, using an ion chamber, are shown in . The type A uncertainties were determined based on statistical analysis (standard deviation), whereas the type B uncertainty was based on previous measurement data, manufacturer’s specifications and data provided in calibration and other reports. Scientific judgment was also used to estimate or assign probability distributions over the limits in parameters provided by the manufacturer’s specifications. The values for the standard uncertainty types A and B are 0.3% and 2.4%, respectively. The value for the combined uncertainty is 2.4%. The expanded uncertainty at a coverage factor of k
= 2 is, therefore, 4.8%. When using film dosimetry, the overall uncertainty was estimated as 3.6%, including uncertainties in acquiring the measurements and analyzing the film. The expanded uncertainty at a cover factor of k
= 2 is therefore 7.2%.
Table 4 Uncertainty of the dose rate measured at the isocenter of the microCT using an ion chamber. Type A uncertainties are determined based on statistical analysis, whereas type B uncertainties are based on previous measurements, manufacturer’s specifications, (more ...)